Hepatology

Exercise and a hypocaloric, Mediterranean-style diet remain first-line interventions that can benefit all patients with nonalcoholic fatty liver disease (NAFLD), according to a clinical practice update from the American Gastroenterological Association.

“[W]eight loss is associated with a reduction in liver fat, which provides a potential for reversal of disease progression,” wrote Zobair M. Younossi, MD, MPH, of Inova Fairfax Medical Campus in Falls Church, Va., with his associates. Lifestyle modifications remain “the cornerstone for management” because, even though NAFLD affects approximately 25% of individuals worldwide according to one meta-analytic assessment, interventions such as medications, bariatric endoscopy, and surgery are usually reserved for the subset of patients with severe obesity, comorbid diabetes, or nonalcoholic steatohepatitis (NASH) with at least stage 2 fibrosis, the experts wrote in Gastroenterology.

They note that clinically significant weight loss typically requires a hypocaloric diet of 1,200-1,500 kilocalories/day or a decrease of 500-1,000 kilocalories/day from baseline. A Mediterranean diet of fresh vegetables, fruits, legumes, minimally processed whole grains, fish, olive oil, nuts, and seeds is recommended because its antioxidant, anti-inflammatory effects may slow NAFLD progression. This diet minimizes or eliminates sweets, refined grains, and red and processed meats. Fructose from fruit is not associated with NAFLD, but patients should consume little or no commercially prepared fructose, which has been linked to visceral adiposity, insulin resistance, hepatic inflammation, and fibrosis progression. Other hypocaloric diets have not been studied enough to support their routine use in NAFLD treatment, according to the clinical practice update.

For patients with NASH, which is the more severe form of NAFLD and is associated with significant morbidity and mortality caused by complications from cirrhosis, hepatic decompensation, and hepatocellular carcinoma, weight loss also has a big impact: Losing at least 5% of total body weight can decrease hepatic steatosis, losing at least 7% can resolve NASH, and losing at least 10% can lessen or stabilize hepatic fibrosis, according to level 1 evidence cited by the update. Weight loss “can significantly impact all aspects of NAFLD histology including fibrosis, but a goal of 10% total body weight loss should be considered for patients with overweight or obese NAFLD,” the authors wrote. Fat loss also improves liver histology in patients with lean NAFLD (body mass index, 26 kg/m² in non-Asian patients or 24 in Asians), for whom a hypocaloric diet targeting a more modest 3%-5% total body weight loss is recommended.

Because aerobic exercise reduces hepatic fat levels independently of hypocaloric diet, patients with NAFLD should consider a weekly regimen of 150-300 minutes of moderate-intensity exercise or 75-150 minutes of vigorous activity. Resistance training can complement aerobic exercise “but [is] not a replacement,” the authors noted. In addition, patients with NAFLD should restrict alcohol consumption to reduce the risk for liver-related events, and those with advanced hepatic fibrosis should “avoid alcohol entirely.” These recommendations reflect the findings of a large prospective study in which the consumption of even low amounts of alcohol led to worse liver-related outcomes among patients with NAFLD.

Clinicians should screen for and “aggressively” manage common NAFLD comorbidities, including diabetes mellitus, hypertension, and obstructive sleep apnea, according to the clinical practice update. Patients with coexisting metabolic conditions should be risk-stratified for cardiovascular disease and treated based on guidelines from the American College of Cardiology and the American Heart Association.

It is believed that sarcopenia affects patients with NASH cirrhosis because their livers cannot effectively store, metabolize, or mobilize carbohydrates, which leads to a catabolic state in which protein and fat are used as energy sources, according to the update. To avoid exacerbations, these patients may need to optimize their protein intake – a minimum of 1.2-1.5 g/kg of body weight is recommended – from sources of branched-chain amino acids, such as chicken, fish, eggs, nuts, lentils, or soy. Patients with sarcopenic NAFLD also should consume small, frequent meals spaced no more than 4-6 hours apart. When possible, they should consult with a specialized nutritionist. Moderate-intensity exercise may also benefit patients experiencing sarcopenia.

The researchers disclosed ties to Gilead Sciences, Intercept, Bristol Myers Squibb, Novo Nordisk, and several other companies. The review was commissioned and approved by the AGA Institute’s Clinical Practice Updates Committee and the AGA Governing Board.

SOURCE: Younossi ZM et al. Gastroenterology. 2020 Dec 8. doi: 10.1053/j.gastro.2020.11.051.

This article was updated Feb. 10, 2021.

Exercise and a hypocaloric, Mediterranean-style diet remain first-line interventions that can benefit all patients with nonalcoholic fatty liver disease (NAFLD), according to a clinical practice update from the American Gastroenterological Association.

“[W]eight loss is associated with a reduction in liver fat, which provides a potential for reversal of disease progression,” wrote Zobair M. Younossi, MD, MPH, of Inova Fairfax Medical Campus in Falls Church, Va., with his associates. Lifestyle modifications remain “the cornerstone for management” because, even though NAFLD affects approximately 25% of individuals worldwide according to one meta-analytic assessment, interventions such as medications, bariatric endoscopy, and surgery are usually reserved for the subset of patients with severe obesity, comorbid diabetes, or nonalcoholic steatohepatitis (NASH) with at least stage 2 fibrosis, the experts wrote in Gastroenterology.

They note that clinically significant weight loss typically requires a hypocaloric diet of 1,200-1,500 kilocalories/day or a decrease of 500-1,000 kilocalories/day from baseline. A Mediterranean diet of fresh vegetables, fruits, legumes, minimally processed whole grains, fish, olive oil, nuts, and seeds is recommended because its antioxidant, anti-inflammatory effects may slow NAFLD progression. This diet minimizes or eliminates sweets, refined grains, and red and processed meats. Fructose from fruit is not associated with NAFLD, but patients should consume little or no commercially prepared fructose, which has been linked to visceral adiposity, insulin resistance, hepatic inflammation, and fibrosis progression. Other hypocaloric diets have not been studied enough to support their routine use in NAFLD treatment, according to the clinical practice update.

For patients with NASH, which is the more severe form of NAFLD and is associated with significant morbidity and mortality caused by complications from cirrhosis, hepatic decompensation, and hepatocellular carcinoma, weight loss also has a big impact: Losing at least 5% of total body weight can decrease hepatic steatosis, losing at least 7% can resolve NASH, and losing at least 10% can lessen or stabilize hepatic fibrosis, according to level 1 evidence cited by the update. Weight loss “can significantly impact all aspects of NAFLD histology including fibrosis, but a goal of 10% total body weight loss should be considered for patients with overweight or obese NAFLD,” the authors wrote. Fat loss also improves liver histology in patients with lean NAFLD (body mass index, 26 kg/m² in non-Asian patients or 24 in Asians), for whom a hypocaloric diet targeting a more modest 3%-5% total body weight loss is recommended.

Because aerobic exercise reduces hepatic fat levels independently of hypocaloric diet, patients with NAFLD should consider a weekly regimen of 150-300 minutes of moderate-intensity exercise or 75-150 minutes of vigorous activity. Resistance training can complement aerobic exercise “but [is] not a replacement,” the authors noted. In addition, patients with NAFLD should restrict alcohol consumption to reduce the risk for liver-related events, and those with advanced hepatic fibrosis should “avoid alcohol entirely.” These recommendations reflect the findings of a large prospective study in which the consumption of even low amounts of alcohol led to worse liver-related outcomes among patients with NAFLD.

Clinicians should screen for and “aggressively” manage common NAFLD comorbidities, including diabetes mellitus, hypertension, and obstructive sleep apnea, according to the clinical practice update. Patients with coexisting metabolic conditions should be risk-stratified for cardiovascular disease and treated based on guidelines from the American College of Cardiology and the American Heart Association.

It is believed that sarcopenia affects patients with NASH cirrhosis because their livers cannot effectively store, metabolize, or mobilize carbohydrates, which leads to a catabolic state in which protein and fat are used as energy sources, according to the update. To avoid exacerbations, these patients may need to optimize their protein intake – a minimum of 1.2-1.5 g/kg of body weight is recommended – from sources of branched-chain amino acids, such as chicken, fish, eggs, nuts, lentils, or soy. Patients with sarcopenic NAFLD also should consume small, frequent meals spaced no more than 4-6 hours apart. When possible, they should consult with a specialized nutritionist. Moderate-intensity exercise may also benefit patients experiencing sarcopenia.

The researchers disclosed ties to Gilead Sciences, Intercept, Bristol Myers Squibb, Novo Nordisk, and several other companies. The review was commissioned and approved by the AGA Institute’s Clinical Practice Updates Committee and the AGA Governing Board.

SOURCE: Younossi ZM et al. Gastroenterology. 2020 Dec 8. doi: 10.1053/j.gastro.2020.11.051.

This article was updated Feb. 10, 2021.

Exercise and a hypocaloric, Mediterranean-style diet remain first-line interventions that can benefit all patients with nonalcoholic fatty liver disease (NAFLD), according to a clinical practice update from the American Gastroenterological Association.

“[W]eight loss is associated with a reduction in liver fat, which provides a potential for reversal of disease progression,” wrote Zobair M. Younossi, MD, MPH, of Inova Fairfax Medical Campus in Falls Church, Va., with his associates. Lifestyle modifications remain “the cornerstone for management” because, even though NAFLD affects approximately 25% of individuals worldwide according to one meta-analytic assessment, interventions such as medications, bariatric endoscopy, and surgery are usually reserved for the subset of patients with severe obesity, comorbid diabetes, or nonalcoholic steatohepatitis (NASH) with at least stage 2 fibrosis, the experts wrote in Gastroenterology.

They note that clinically significant weight loss typically requires a hypocaloric diet of 1,200-1,500 kilocalories/day or a decrease of 500-1,000 kilocalories/day from baseline. A Mediterranean diet of fresh vegetables, fruits, legumes, minimally processed whole grains, fish, olive oil, nuts, and seeds is recommended because its antioxidant, anti-inflammatory effects may slow NAFLD progression. This diet minimizes or eliminates sweets, refined grains, and red and processed meats. Fructose from fruit is not associated with NAFLD, but patients should consume little or no commercially prepared fructose, which has been linked to visceral adiposity, insulin resistance, hepatic inflammation, and fibrosis progression. Other hypocaloric diets have not been studied enough to support their routine use in NAFLD treatment, according to the clinical practice update.

For patients with NASH, which is the more severe form of NAFLD and is associated with significant morbidity and mortality caused by complications from cirrhosis, hepatic decompensation, and hepatocellular carcinoma, weight loss also has a big impact: Losing at least 5% of total body weight can decrease hepatic steatosis, losing at least 7% can resolve NASH, and losing at least 10% can lessen or stabilize hepatic fibrosis, according to level 1 evidence cited by the update. Weight loss “can significantly impact all aspects of NAFLD histology including fibrosis, but a goal of 10% total body weight loss should be considered for patients with overweight or obese NAFLD,” the authors wrote. Fat loss also improves liver histology in patients with lean NAFLD (body mass index, 26 kg/m² in non-Asian patients or 24 in Asians), for whom a hypocaloric diet targeting a more modest 3%-5% total body weight loss is recommended.

Because aerobic exercise reduces hepatic fat levels independently of hypocaloric diet, patients with NAFLD should consider a weekly regimen of 150-300 minutes of moderate-intensity exercise or 75-150 minutes of vigorous activity. Resistance training can complement aerobic exercise “but [is] not a replacement,” the authors noted. In addition, patients with NAFLD should restrict alcohol consumption to reduce the risk for liver-related events, and those with advanced hepatic fibrosis should “avoid alcohol entirely.” These recommendations reflect the findings of a large prospective study in which the consumption of even low amounts of alcohol led to worse liver-related outcomes among patients with NAFLD.

Clinicians should screen for and “aggressively” manage common NAFLD comorbidities, including diabetes mellitus, hypertension, and obstructive sleep apnea, according to the clinical practice update. Patients with coexisting metabolic conditions should be risk-stratified for cardiovascular disease and treated based on guidelines from the American College of Cardiology and the American Heart Association.

It is believed that sarcopenia affects patients with NASH cirrhosis because their livers cannot effectively store, metabolize, or mobilize carbohydrates, which leads to a catabolic state in which protein and fat are used as energy sources, according to the update. To avoid exacerbations, these patients may need to optimize their protein intake – a minimum of 1.2-1.5 g/kg of body weight is recommended – from sources of branched-chain amino acids, such as chicken, fish, eggs, nuts, lentils, or soy. Patients with sarcopenic NAFLD also should consume small, frequent meals spaced no more than 4-6 hours apart. When possible, they should consult with a specialized nutritionist. Moderate-intensity exercise may also benefit patients experiencing sarcopenia.

The researchers disclosed ties to Gilead Sciences, Intercept, Bristol Myers Squibb, Novo Nordisk, and several other companies. The review was commissioned and approved by the AGA Institute’s Clinical Practice Updates Committee and the AGA Governing Board.

SOURCE: Younossi ZM et al. Gastroenterology. 2020 Dec 8. doi: 10.1053/j.gastro.2020.11.051.

This article was updated Feb. 10, 2021.

THE CASE

A 17-year-old White girl with no known past medical history presented to the emergency department (ED) with complaints of abdominal pain and pruritus. The abdominal pain had started 9 days prior and lasted for 3 days. One day after resolution, she developed bilateral lower extremity itching, which was not relieved with loratadine.

Review of systems included dark urine and yellow eyes noted for several days. The patient denied nausea, vomiting, diarrhea, constipation, fevers, chills, arthralgias, recent illness, travel, or sick contacts. Immunizations were up to date. The patient had no history of surgery or liver disease and no pertinent family history. Her current medications included ethinyl estradiol/norethindrone acetate for birth control and minocycline for acne vulgaris. She had been taking the latter medication for 2 years. No additional medications were noted, including vitamins, over-the-counter medications, or supplements. She denied smoking and alcohol or recreational drug use.

In the ED, the patient had normal vital signs. Physical exam findings included bilateral scleral icterus and scattered skin excoriations on the hands, arms, back of the neck, and feet. At the time of hospital admission, the patient’s minocycline and birth control were held under the initial presumption that one or both might be contributing to her presentation.

Pertinent laboratory findings included aspartate transaminase (AST), 828 U/L (normal range, 2-40 U/L); alanine aminotransferase (ALT), 784 U/L (normal range, 3-30 U/L); lactic acid dehydrogenase, 520 U/L (normal range, 140-280 U/L); alkaline phosphatase, 119 U/L (normal range, 44-147 U/L); total bilirubin, 1.9 µmol/L (normal range, 2-18 µmol/L); and direct bilirubin, 1.3 µmol/L (normal range, 0-4 µmol/L). Baseline liver function test results (prior to admission) were unknown. Results of a coagulation panel, complete blood count, basic metabolic panel, amylase, lipase, urine toxicology, and urinalysis all were within normal limits.

Ultrasound of the abdomen revealed a normal abdomen, liver, pancreas, gallbladder, and common bile duct. This imaging study was negative for other obstructive pathologies.

THE DIAGNOSIS

During hospital admission, a noninvasive liver work-up was pursued by Gastroenterology. A hepatitis panel, Epstein-Barr virus testing, and levels of ceruloplasmin and acetaminophen were all found to be within normal limits, excluding additional causes of liver disease. Serum antinuclear antibody (ANA) testing was significantly positive, with a titer of 1:640 (range, < 1:20) and, as noted above, liver transaminases were severely elevated, leading to a presumptive diagnosis of drug-induced liver pathology.

Continue to: During outpatient follow-up...

During outpatient follow-up with Gastroenterology 2 days after discharge, the patient’s liver transaminases and bilirubin continued to trend upward (to a maximum ALT of 871 U/L; AST, 1097 U/L; alkaline phosphatase, 122 U/L; and bilirubin, 2.9 µmol/L). Immunoglobulin G was 1342 mg/mL (normal range, 694-1618 mg/mL).

An ultrasound-guided liver biopsy was performed; it demonstrated lobular, portal, and periportal hepatitis with focal bridging necrosis, consistent with a diagnosis of autoimmune hepatitis. Mild-to-moderate focal cholestasis was demonstrated, consistent with cholestatic hepatitis.

DISCUSSION

Autoimmune hepatitis is characterized by inflammation of the liver, secondary to the presence of circulating antibodies or hypergammaglobulinemia. The pathogenesis is thought to involve a T-cell–mediated immune attack on the liver. Based on case reports,the use of minocycline is associated with risk for liver injury, although the incidence is rare.^1-4 Use of this medication may be associated with autoimmune disease in patients who are predisposed to autoimmune tendencies or who have genetic predeterminants.

Diagnosis is typically made based on abnormalities in aminotransferases (AST, ALT), elevation in serum immunoglobulins, and positive auto-antibody titers including ANA, smooth muscle antibodies, and anti-liver kidney microsomal type 1 antibodies. Although clinical presentations tend to differ, the confirmatory diagnosis is typically made histologically, with the presence of lobular and perivenular necro-inflammatory changes and plasma cell infiltration.⁵

Other infectious and metabolic causes of hepatitis should be excluded. Many medications and herbal agents have been noted to cause autoimmune hepatitis or similar syndromes that mimic the condition.

Medication history. Review of the case patient’s medication list identified ethinyl estradiol/norethindrone acetate and minocycline as potential culprits. Ethinyl estradiol/norethindrone acetate is a low-dose combination oral contraceptive pill (OCP). Although earlier formulations of OCPs were associated with hepatobiliary complications, these adverse effects are noted to be rare in the absence of predisposing conditions.⁶ In some cases, OCPs have been linked to cholestasis, chronic hepatocellular carcinoma, or hepatic adenomas, but studies have shown that these medications do not affect the course of acute liver failure.⁷

Continue to: Minocycline...

Minocyclineassociated hepatotoxicity can be due to a systemic hypersensitivity reaction, occurring within a few weeks of therapy initiation, whereas autoimmune hepatitis manifests after a year or more of exposure to the medication.

In this case, given the patient’s 2-year history of minocycline use, it is possible that she developed an acute presentation of autoimmune hepatitis. With drug-induced autoimmune liver injury, complete resolution occurs after withdrawal of the offending medication, and a response to corticosteroid therapy supports the diagnosis. Recurrence of signs or symptoms following corticosteroid cessation may indicate idiopathic autoimmune hepatitis as opposed to a drug-induced form.²

Our patient was started on steroid and immunomodulator therapy, with prednisone 40 mg/d and mycophenolate 250 mg bid. At follow-up with Gastroenterology, the patient’s symptoms and liver function test results had improved significantly (AST, 27 U/L; ALT, 14 U/L; alkaline phosphatase, 51 U/L; and total bilirubin, 0.4 µmol/L). The patient was continued on a prednisone taper while simultaneously titrating mycophenolate. The ultimate plan of care included continuing mycophenolate for a total of 4 to 5 years.

THE TAKEAWAY

During evaluation of a patient with new-onset liver disease, it is important to inquire about prescription medications, drugs, vitamins, and herbal supplements as possible contributors to the disease process. This case highlights the importance of monitoring patients while on minocycline and of weighing the risks vs benefits of long-term therapy. It has been suggested that liver enzymes be tested before therapy initiation and about every 3 months during long-term antibiotic treatment.⁴ Careful consideration and caution should be taken prior to the initiation of medications that have been linked to rare, but important, adverse reactions.

ACKNOWLEDGEMENT

The authors would like to thank Frank Bauer, MD, and Eva Sotil, MD, for their contributions to this case presentation.

CORRESPONDENCE

Andrea Gillis, DO, Asylum Hill Family Medicine Center, 99 Woodland Street, Hartford, CT 06105; andrea.gillis@ trinityhealthofne.org

THE CASE

A 17-year-old White girl with no known past medical history presented to the emergency department (ED) with complaints of abdominal pain and pruritus. The abdominal pain had started 9 days prior and lasted for 3 days. One day after resolution, she developed bilateral lower extremity itching, which was not relieved with loratadine.

Review of systems included dark urine and yellow eyes noted for several days. The patient denied nausea, vomiting, diarrhea, constipation, fevers, chills, arthralgias, recent illness, travel, or sick contacts. Immunizations were up to date. The patient had no history of surgery or liver disease and no pertinent family history. Her current medications included ethinyl estradiol/norethindrone acetate for birth control and minocycline for acne vulgaris. She had been taking the latter medication for 2 years. No additional medications were noted, including vitamins, over-the-counter medications, or supplements. She denied smoking and alcohol or recreational drug use.

In the ED, the patient had normal vital signs. Physical exam findings included bilateral scleral icterus and scattered skin excoriations on the hands, arms, back of the neck, and feet. At the time of hospital admission, the patient’s minocycline and birth control were held under the initial presumption that one or both might be contributing to her presentation.

Pertinent laboratory findings included aspartate transaminase (AST), 828 U/L (normal range, 2-40 U/L); alanine aminotransferase (ALT), 784 U/L (normal range, 3-30 U/L); lactic acid dehydrogenase, 520 U/L (normal range, 140-280 U/L); alkaline phosphatase, 119 U/L (normal range, 44-147 U/L); total bilirubin, 1.9 µmol/L (normal range, 2-18 µmol/L); and direct bilirubin, 1.3 µmol/L (normal range, 0-4 µmol/L). Baseline liver function test results (prior to admission) were unknown. Results of a coagulation panel, complete blood count, basic metabolic panel, amylase, lipase, urine toxicology, and urinalysis all were within normal limits.

Ultrasound of the abdomen revealed a normal abdomen, liver, pancreas, gallbladder, and common bile duct. This imaging study was negative for other obstructive pathologies.

THE DIAGNOSIS

During hospital admission, a noninvasive liver work-up was pursued by Gastroenterology. A hepatitis panel, Epstein-Barr virus testing, and levels of ceruloplasmin and acetaminophen were all found to be within normal limits, excluding additional causes of liver disease. Serum antinuclear antibody (ANA) testing was significantly positive, with a titer of 1:640 (range, < 1:20) and, as noted above, liver transaminases were severely elevated, leading to a presumptive diagnosis of drug-induced liver pathology.

Continue to: During outpatient follow-up...

During outpatient follow-up with Gastroenterology 2 days after discharge, the patient’s liver transaminases and bilirubin continued to trend upward (to a maximum ALT of 871 U/L; AST, 1097 U/L; alkaline phosphatase, 122 U/L; and bilirubin, 2.9 µmol/L). Immunoglobulin G was 1342 mg/mL (normal range, 694-1618 mg/mL).

An ultrasound-guided liver biopsy was performed; it demonstrated lobular, portal, and periportal hepatitis with focal bridging necrosis, consistent with a diagnosis of autoimmune hepatitis. Mild-to-moderate focal cholestasis was demonstrated, consistent with cholestatic hepatitis.

DISCUSSION

Autoimmune hepatitis is characterized by inflammation of the liver, secondary to the presence of circulating antibodies or hypergammaglobulinemia. The pathogenesis is thought to involve a T-cell–mediated immune attack on the liver. Based on case reports,the use of minocycline is associated with risk for liver injury, although the incidence is rare.^1-4 Use of this medication may be associated with autoimmune disease in patients who are predisposed to autoimmune tendencies or who have genetic predeterminants.

Diagnosis is typically made based on abnormalities in aminotransferases (AST, ALT), elevation in serum immunoglobulins, and positive auto-antibody titers including ANA, smooth muscle antibodies, and anti-liver kidney microsomal type 1 antibodies. Although clinical presentations tend to differ, the confirmatory diagnosis is typically made histologically, with the presence of lobular and perivenular necro-inflammatory changes and plasma cell infiltration.⁵

Other infectious and metabolic causes of hepatitis should be excluded. Many medications and herbal agents have been noted to cause autoimmune hepatitis or similar syndromes that mimic the condition.

Medication history. Review of the case patient’s medication list identified ethinyl estradiol/norethindrone acetate and minocycline as potential culprits. Ethinyl estradiol/norethindrone acetate is a low-dose combination oral contraceptive pill (OCP). Although earlier formulations of OCPs were associated with hepatobiliary complications, these adverse effects are noted to be rare in the absence of predisposing conditions.⁶ In some cases, OCPs have been linked to cholestasis, chronic hepatocellular carcinoma, or hepatic adenomas, but studies have shown that these medications do not affect the course of acute liver failure.⁷

Continue to: Minocycline...

Minocyclineassociated hepatotoxicity can be due to a systemic hypersensitivity reaction, occurring within a few weeks of therapy initiation, whereas autoimmune hepatitis manifests after a year or more of exposure to the medication.

In this case, given the patient’s 2-year history of minocycline use, it is possible that she developed an acute presentation of autoimmune hepatitis. With drug-induced autoimmune liver injury, complete resolution occurs after withdrawal of the offending medication, and a response to corticosteroid therapy supports the diagnosis. Recurrence of signs or symptoms following corticosteroid cessation may indicate idiopathic autoimmune hepatitis as opposed to a drug-induced form.²

Our patient was started on steroid and immunomodulator therapy, with prednisone 40 mg/d and mycophenolate 250 mg bid. At follow-up with Gastroenterology, the patient’s symptoms and liver function test results had improved significantly (AST, 27 U/L; ALT, 14 U/L; alkaline phosphatase, 51 U/L; and total bilirubin, 0.4 µmol/L). The patient was continued on a prednisone taper while simultaneously titrating mycophenolate. The ultimate plan of care included continuing mycophenolate for a total of 4 to 5 years.

THE TAKEAWAY

During evaluation of a patient with new-onset liver disease, it is important to inquire about prescription medications, drugs, vitamins, and herbal supplements as possible contributors to the disease process. This case highlights the importance of monitoring patients while on minocycline and of weighing the risks vs benefits of long-term therapy. It has been suggested that liver enzymes be tested before therapy initiation and about every 3 months during long-term antibiotic treatment.⁴ Careful consideration and caution should be taken prior to the initiation of medications that have been linked to rare, but important, adverse reactions.

ACKNOWLEDGEMENT

The authors would like to thank Frank Bauer, MD, and Eva Sotil, MD, for their contributions to this case presentation.

CORRESPONDENCE

Andrea Gillis, DO, Asylum Hill Family Medicine Center, 99 Woodland Street, Hartford, CT 06105; andrea.gillis@ trinityhealthofne.org

THE CASE

A 17-year-old White girl with no known past medical history presented to the emergency department (ED) with complaints of abdominal pain and pruritus. The abdominal pain had started 9 days prior and lasted for 3 days. One day after resolution, she developed bilateral lower extremity itching, which was not relieved with loratadine.

Review of systems included dark urine and yellow eyes noted for several days. The patient denied nausea, vomiting, diarrhea, constipation, fevers, chills, arthralgias, recent illness, travel, or sick contacts. Immunizations were up to date. The patient had no history of surgery or liver disease and no pertinent family history. Her current medications included ethinyl estradiol/norethindrone acetate for birth control and minocycline for acne vulgaris. She had been taking the latter medication for 2 years. No additional medications were noted, including vitamins, over-the-counter medications, or supplements. She denied smoking and alcohol or recreational drug use.

In the ED, the patient had normal vital signs. Physical exam findings included bilateral scleral icterus and scattered skin excoriations on the hands, arms, back of the neck, and feet. At the time of hospital admission, the patient’s minocycline and birth control were held under the initial presumption that one or both might be contributing to her presentation.

Pertinent laboratory findings included aspartate transaminase (AST), 828 U/L (normal range, 2-40 U/L); alanine aminotransferase (ALT), 784 U/L (normal range, 3-30 U/L); lactic acid dehydrogenase, 520 U/L (normal range, 140-280 U/L); alkaline phosphatase, 119 U/L (normal range, 44-147 U/L); total bilirubin, 1.9 µmol/L (normal range, 2-18 µmol/L); and direct bilirubin, 1.3 µmol/L (normal range, 0-4 µmol/L). Baseline liver function test results (prior to admission) were unknown. Results of a coagulation panel, complete blood count, basic metabolic panel, amylase, lipase, urine toxicology, and urinalysis all were within normal limits.

Ultrasound of the abdomen revealed a normal abdomen, liver, pancreas, gallbladder, and common bile duct. This imaging study was negative for other obstructive pathologies.

THE DIAGNOSIS

During hospital admission, a noninvasive liver work-up was pursued by Gastroenterology. A hepatitis panel, Epstein-Barr virus testing, and levels of ceruloplasmin and acetaminophen were all found to be within normal limits, excluding additional causes of liver disease. Serum antinuclear antibody (ANA) testing was significantly positive, with a titer of 1:640 (range, < 1:20) and, as noted above, liver transaminases were severely elevated, leading to a presumptive diagnosis of drug-induced liver pathology.

Continue to: During outpatient follow-up...

During outpatient follow-up with Gastroenterology 2 days after discharge, the patient’s liver transaminases and bilirubin continued to trend upward (to a maximum ALT of 871 U/L; AST, 1097 U/L; alkaline phosphatase, 122 U/L; and bilirubin, 2.9 µmol/L). Immunoglobulin G was 1342 mg/mL (normal range, 694-1618 mg/mL).

An ultrasound-guided liver biopsy was performed; it demonstrated lobular, portal, and periportal hepatitis with focal bridging necrosis, consistent with a diagnosis of autoimmune hepatitis. Mild-to-moderate focal cholestasis was demonstrated, consistent with cholestatic hepatitis.

DISCUSSION

Autoimmune hepatitis is characterized by inflammation of the liver, secondary to the presence of circulating antibodies or hypergammaglobulinemia. The pathogenesis is thought to involve a T-cell–mediated immune attack on the liver. Based on case reports,the use of minocycline is associated with risk for liver injury, although the incidence is rare.^1-4 Use of this medication may be associated with autoimmune disease in patients who are predisposed to autoimmune tendencies or who have genetic predeterminants.

Diagnosis is typically made based on abnormalities in aminotransferases (AST, ALT), elevation in serum immunoglobulins, and positive auto-antibody titers including ANA, smooth muscle antibodies, and anti-liver kidney microsomal type 1 antibodies. Although clinical presentations tend to differ, the confirmatory diagnosis is typically made histologically, with the presence of lobular and perivenular necro-inflammatory changes and plasma cell infiltration.⁵

Other infectious and metabolic causes of hepatitis should be excluded. Many medications and herbal agents have been noted to cause autoimmune hepatitis or similar syndromes that mimic the condition.

Medication history. Review of the case patient’s medication list identified ethinyl estradiol/norethindrone acetate and minocycline as potential culprits. Ethinyl estradiol/norethindrone acetate is a low-dose combination oral contraceptive pill (OCP). Although earlier formulations of OCPs were associated with hepatobiliary complications, these adverse effects are noted to be rare in the absence of predisposing conditions.⁶ In some cases, OCPs have been linked to cholestasis, chronic hepatocellular carcinoma, or hepatic adenomas, but studies have shown that these medications do not affect the course of acute liver failure.⁷

Continue to: Minocycline...

Minocyclineassociated hepatotoxicity can be due to a systemic hypersensitivity reaction, occurring within a few weeks of therapy initiation, whereas autoimmune hepatitis manifests after a year or more of exposure to the medication.

In this case, given the patient’s 2-year history of minocycline use, it is possible that she developed an acute presentation of autoimmune hepatitis. With drug-induced autoimmune liver injury, complete resolution occurs after withdrawal of the offending medication, and a response to corticosteroid therapy supports the diagnosis. Recurrence of signs or symptoms following corticosteroid cessation may indicate idiopathic autoimmune hepatitis as opposed to a drug-induced form.²

Our patient was started on steroid and immunomodulator therapy, with prednisone 40 mg/d and mycophenolate 250 mg bid. At follow-up with Gastroenterology, the patient’s symptoms and liver function test results had improved significantly (AST, 27 U/L; ALT, 14 U/L; alkaline phosphatase, 51 U/L; and total bilirubin, 0.4 µmol/L). The patient was continued on a prednisone taper while simultaneously titrating mycophenolate. The ultimate plan of care included continuing mycophenolate for a total of 4 to 5 years.

THE TAKEAWAY

During evaluation of a patient with new-onset liver disease, it is important to inquire about prescription medications, drugs, vitamins, and herbal supplements as possible contributors to the disease process. This case highlights the importance of monitoring patients while on minocycline and of weighing the risks vs benefits of long-term therapy. It has been suggested that liver enzymes be tested before therapy initiation and about every 3 months during long-term antibiotic treatment.⁴ Careful consideration and caution should be taken prior to the initiation of medications that have been linked to rare, but important, adverse reactions.

ACKNOWLEDGEMENT

The authors would like to thank Frank Bauer, MD, and Eva Sotil, MD, for their contributions to this case presentation.

CORRESPONDENCE

Andrea Gillis, DO, Asylum Hill Family Medicine Center, 99 Woodland Street, Hartford, CT 06105; andrea.gillis@ trinityhealthofne.org

Endoscopically placed intragastric balloons were safe and effective for managing nonalcoholic fatty liver disease (NAFLD), according to the findings of an open-label, prospective study of 21 patients.

Six months after balloon placement, nonalcoholic fatty liver disease activity scores (NAS) had improved in 18 of 20 biopsied patients (90%), with a median decrease of 3 points (range, 1-4 points). Magnetic resonance elastography showed that fibrosis had improved by 1.5 stages in half of patients (10 of 20). “Other than postprocedural pain (in 5% of patients), no serious adverse events were reported,” Fateh Bazerbachi, MD, of Massachusetts General Hospital in Boston, and associates wrote in Clinical Gastroenterology and Hepatology.

Nonalcoholic fatty liver disease affects approximately 70% of obese adults and half of obese children, meaning that tens of millions of individuals are affected in the United States alone. Lifestyle changes rarely induce more than 10% body weight loss, the threshold for “meaningful improvement in NASH,” and bariatric surgery is not recommended for managing mild or moderate obesity and often is not desired by patients who do qualify, the researchers noted. “Endoscopic bariatric therapies are garnering more attention as potential strategies to address these shortcomings in obesity care and its comorbidities [, but] their influences on the driving and prognostic parameters of NAFLD remain unclear.”

In all, 81% of the study participants were women, with a mean age of 54 years and an average body mass index (BMI) of 44 kg/m². At baseline, more than half had NAS scores of 4 or 5 and histologic fibrosis scores of 2 or 3. Baseline hemoglobin A1c levels averaged 7.4% (range, 5.1%-11.1%) and 29% of patients had impaired glucose tolerance. After receiving endoscopic ultrasound (EUS)–guided core liver biopsies, patients received an endoscopically placed fluid-filled intragastric balloon (Orbera, Apollo Endosurgery, Austin, Tex.). The balloon was removed 6 months later and magnetic resonance elastography and a second core biopsy were performed. One patient did not receive an exit biopsy (because of starting antithrombotic therapy) and thus was excluded from the final analysis.

Of 20 patients, 16 (80%) had at least a two-point improvement in NAS at 6 months, and half had NAS scores of less than 2, indicating remission of NASH. Three of 20 patients (15%) showed improvements in mild fibrosis, 12 showed no change, and 5 showed worsening. Patients lost an average of 11.7% of body weight (standard deviation, 7.7%; P = .01), BMI dropped by a mean of 5.2 (SD, 0.75; P = .01) and A1c fell by an average of 1.3% (SD, 0.5%; P = .02). Waist circumference also decreased significantly (mean, –14.4 cm; SD, –2.2 cm; P = .001), as did hip circumference, fasting glucose, AST, ALT, and AST-to-platelet ratio index. “Percent total body weight loss did not correlate with reductions in NAS or fibrosis,” the researchers noted.

Together, these findings suggest that intragastric balloon placement “may allow a reversal in the natural history of NAFLD and NASH, despite the short duration of the intervention,” they concluded. “The logistics of IGB [intragastric balloon] placement will enable accurate risk stratification of these patients in a safe and reproducible manner, obviating the need for additional investigations, and clarifying the real risk of patients afflicted with NAFLD.”

Apollo Endosurgery provided intragastric balloons, and Medtronic provided SharkCore needles. The senior author and two coinvestigators disclosed ties to Apollo Endosurgery, Medtronic, Metamodix, Boston Scientific, Cairn Diagnostics, Aspire Bariatrics, Johnson and Johnson, AstraZeneca, Genfit, Gila Therapeutics, and several other companies. The other investigators reported having no conflicts of interest.

SOURCE: Bazerbachi F et al. Clin Gastroenterol Hepatol. 2020 Apr 30. doi: 10.1016/j.cgh.2020.04.068.
 

Endoscopically placed intragastric balloons were safe and effective for managing nonalcoholic fatty liver disease (NAFLD), according to the findings of an open-label, prospective study of 21 patients.

Six months after balloon placement, nonalcoholic fatty liver disease activity scores (NAS) had improved in 18 of 20 biopsied patients (90%), with a median decrease of 3 points (range, 1-4 points). Magnetic resonance elastography showed that fibrosis had improved by 1.5 stages in half of patients (10 of 20). “Other than postprocedural pain (in 5% of patients), no serious adverse events were reported,” Fateh Bazerbachi, MD, of Massachusetts General Hospital in Boston, and associates wrote in Clinical Gastroenterology and Hepatology.

Nonalcoholic fatty liver disease affects approximately 70% of obese adults and half of obese children, meaning that tens of millions of individuals are affected in the United States alone. Lifestyle changes rarely induce more than 10% body weight loss, the threshold for “meaningful improvement in NASH,” and bariatric surgery is not recommended for managing mild or moderate obesity and often is not desired by patients who do qualify, the researchers noted. “Endoscopic bariatric therapies are garnering more attention as potential strategies to address these shortcomings in obesity care and its comorbidities [, but] their influences on the driving and prognostic parameters of NAFLD remain unclear.”

In all, 81% of the study participants were women, with a mean age of 54 years and an average body mass index (BMI) of 44 kg/m². At baseline, more than half had NAS scores of 4 or 5 and histologic fibrosis scores of 2 or 3. Baseline hemoglobin A1c levels averaged 7.4% (range, 5.1%-11.1%) and 29% of patients had impaired glucose tolerance. After receiving endoscopic ultrasound (EUS)–guided core liver biopsies, patients received an endoscopically placed fluid-filled intragastric balloon (Orbera, Apollo Endosurgery, Austin, Tex.). The balloon was removed 6 months later and magnetic resonance elastography and a second core biopsy were performed. One patient did not receive an exit biopsy (because of starting antithrombotic therapy) and thus was excluded from the final analysis.

Of 20 patients, 16 (80%) had at least a two-point improvement in NAS at 6 months, and half had NAS scores of less than 2, indicating remission of NASH. Three of 20 patients (15%) showed improvements in mild fibrosis, 12 showed no change, and 5 showed worsening. Patients lost an average of 11.7% of body weight (standard deviation, 7.7%; P = .01), BMI dropped by a mean of 5.2 (SD, 0.75; P = .01) and A1c fell by an average of 1.3% (SD, 0.5%; P = .02). Waist circumference also decreased significantly (mean, –14.4 cm; SD, –2.2 cm; P = .001), as did hip circumference, fasting glucose, AST, ALT, and AST-to-platelet ratio index. “Percent total body weight loss did not correlate with reductions in NAS or fibrosis,” the researchers noted.

Together, these findings suggest that intragastric balloon placement “may allow a reversal in the natural history of NAFLD and NASH, despite the short duration of the intervention,” they concluded. “The logistics of IGB [intragastric balloon] placement will enable accurate risk stratification of these patients in a safe and reproducible manner, obviating the need for additional investigations, and clarifying the real risk of patients afflicted with NAFLD.”

Apollo Endosurgery provided intragastric balloons, and Medtronic provided SharkCore needles. The senior author and two coinvestigators disclosed ties to Apollo Endosurgery, Medtronic, Metamodix, Boston Scientific, Cairn Diagnostics, Aspire Bariatrics, Johnson and Johnson, AstraZeneca, Genfit, Gila Therapeutics, and several other companies. The other investigators reported having no conflicts of interest.

SOURCE: Bazerbachi F et al. Clin Gastroenterol Hepatol. 2020 Apr 30. doi: 10.1016/j.cgh.2020.04.068.
 

Endoscopically placed intragastric balloons were safe and effective for managing nonalcoholic fatty liver disease (NAFLD), according to the findings of an open-label, prospective study of 21 patients.

Six months after balloon placement, nonalcoholic fatty liver disease activity scores (NAS) had improved in 18 of 20 biopsied patients (90%), with a median decrease of 3 points (range, 1-4 points). Magnetic resonance elastography showed that fibrosis had improved by 1.5 stages in half of patients (10 of 20). “Other than postprocedural pain (in 5% of patients), no serious adverse events were reported,” Fateh Bazerbachi, MD, of Massachusetts General Hospital in Boston, and associates wrote in Clinical Gastroenterology and Hepatology.

Nonalcoholic fatty liver disease affects approximately 70% of obese adults and half of obese children, meaning that tens of millions of individuals are affected in the United States alone. Lifestyle changes rarely induce more than 10% body weight loss, the threshold for “meaningful improvement in NASH,” and bariatric surgery is not recommended for managing mild or moderate obesity and often is not desired by patients who do qualify, the researchers noted. “Endoscopic bariatric therapies are garnering more attention as potential strategies to address these shortcomings in obesity care and its comorbidities [, but] their influences on the driving and prognostic parameters of NAFLD remain unclear.”

In all, 81% of the study participants were women, with a mean age of 54 years and an average body mass index (BMI) of 44 kg/m². At baseline, more than half had NAS scores of 4 or 5 and histologic fibrosis scores of 2 or 3. Baseline hemoglobin A1c levels averaged 7.4% (range, 5.1%-11.1%) and 29% of patients had impaired glucose tolerance. After receiving endoscopic ultrasound (EUS)–guided core liver biopsies, patients received an endoscopically placed fluid-filled intragastric balloon (Orbera, Apollo Endosurgery, Austin, Tex.). The balloon was removed 6 months later and magnetic resonance elastography and a second core biopsy were performed. One patient did not receive an exit biopsy (because of starting antithrombotic therapy) and thus was excluded from the final analysis.

Of 20 patients, 16 (80%) had at least a two-point improvement in NAS at 6 months, and half had NAS scores of less than 2, indicating remission of NASH. Three of 20 patients (15%) showed improvements in mild fibrosis, 12 showed no change, and 5 showed worsening. Patients lost an average of 11.7% of body weight (standard deviation, 7.7%; P = .01), BMI dropped by a mean of 5.2 (SD, 0.75; P = .01) and A1c fell by an average of 1.3% (SD, 0.5%; P = .02). Waist circumference also decreased significantly (mean, –14.4 cm; SD, –2.2 cm; P = .001), as did hip circumference, fasting glucose, AST, ALT, and AST-to-platelet ratio index. “Percent total body weight loss did not correlate with reductions in NAS or fibrosis,” the researchers noted.

Together, these findings suggest that intragastric balloon placement “may allow a reversal in the natural history of NAFLD and NASH, despite the short duration of the intervention,” they concluded. “The logistics of IGB [intragastric balloon] placement will enable accurate risk stratification of these patients in a safe and reproducible manner, obviating the need for additional investigations, and clarifying the real risk of patients afflicted with NAFLD.”

Apollo Endosurgery provided intragastric balloons, and Medtronic provided SharkCore needles. The senior author and two coinvestigators disclosed ties to Apollo Endosurgery, Medtronic, Metamodix, Boston Scientific, Cairn Diagnostics, Aspire Bariatrics, Johnson and Johnson, AstraZeneca, Genfit, Gila Therapeutics, and several other companies. The other investigators reported having no conflicts of interest.

SOURCE: Bazerbachi F et al. Clin Gastroenterol Hepatol. 2020 Apr 30. doi: 10.1016/j.cgh.2020.04.068.
 

Studies that address fundamental questions in hepatology and have the potential to change or improve clinical practice were the focus of a clinical debrief session from the virtual annual meeting of the American Association for the Study of Liver Diseases.

“We chose papers that had the highest level of evidence, such as randomized controlled trials, controlled studies, and large data sets – and some small data sets too,” said Tamar Taddei, MD, associate professor of medicine in the section of digestive disease at Yale University, New Haven, Conn.

Dr. Taddei and colleagues Silvia Vilarinho, MD, PhD; Simona Jakab, MD; and Ariel Jaffe, MD, all also from Yale, selected the papers from among 197 oral and 1,769 poster abstracts presented at AASLD 2020.

They highlighted the most important findings from presentations on autoimmune and cholestatic disease, transplantation, cirrhosis and portal hypertension, alcoholic liver disease, neoplasia, drug-induced liver injury, and COVID-19. They did not review studies focused primarily on nonalcoholic steatohepatitis or nonalcoholic fatty liver disease, viral hepatitis, or basic science, all of which were covered in separate debriefing sessions.
 

Cirrhosis and portal hypertension

A study from the Department of Veterans Affairs looked at the prevalence of liver disease risk factors and rates of subsequent testing for and diagnosis of cirrhosis in the Veterans Health Administration system (VHA).

The authors found that, among more than 6.65 million VHA users in 2018 with no prior diagnosis of cirrhosis, approximately half were at risk for cirrhosis, of whom about 75% were screened, and approximately 5% of those who were screened were positive for possible cirrhosis (133,636). Of the patients who screened positive, about 10% (12,566) received a diagnosis of cirrhosis, including 4,120 with liver decompensation.

“This paper underscores the importance of population-level screening in uncovering unrecognized cirrhosis, enabling intervention earlier in the course of disease,” Dr. Taddei said (Abstract #661).

A study looking at external validation of novel cirrhosis surgical risk models designed to improve prognostication for a range of common surgeries showed that the VOCAL-Penn score was superior to the Mayo Risk Score, Model for End-stage Liver Disease and MELD-sodium scores for discrimination of 30-day and 90-day postoperative mortality (Abstract #91).

“While these models are not a substitute for clinical acumen, they certainly improve our surgical risk prediction in patients with cirrhosis, a very common question in consultative hepatology,” Dr. Taddei said.

She also cited three abstracts that address the important questions regarding performing studies in patients with varices or ascites, including whether it’s safe to perform transesophageal echocardiography in patients with cirrhosis without first screening for varices, and whether nonselective beta-blockers should be continued in patients with refractory ascites.

A retrospective study of 191 patients with cirrhosis who underwent upper endoscopy within 4 years of transesophageal echocardiography had no overt gastrointestinal bleeding regardless of the presence of esophageal varices, suggesting that routine preprocedure esophagogastroduodenoscopy “is of no utility,” (Abstract #1872).

A study to determine risk of sepsis in 1,198 patients with cirrhosis found that 1-year risk of sepsis was reduced by 50% with the use of nonselective beta-blockers (Abstract #94).

The final abstract in this category touched on the use of an advance care planning video support tool to help transplant-ineligible patients with end-stage liver disease decide whether they want support measures such cardiopulmonary resuscitation or intubation. The authors found that the video decision tool was feasible and acceptable to patients, and improved their knowledge of end-of-life care. More patients randomized to the video arm opted against CPR or intubation, compared with those assigned to a verbal discussion of options (Abstract #712).
 

Alcohol

The reviewers highlighted two studies of alcohol use: The first was designed to determine the prevalence of early alcohol relapse (resumption within 3 months) in patients who presented with alcoholic hepatitis. The subjects included 478 patients enrolled in the STOPAH trial, and a validation set of 194 patients from the InTeam (Integrated Approaches for identifying Molecular Targets in Alcoholic Hepatitis) Consortium.

“They found that high-risk patients were younger, unemployed, and without a stable relationship. Intermediate risk were middle aged, employed, and in a stable relationship, and low-risk profiles were older, with known cirrhosis; they were mostly retired and in a stable relationship,” Dr. Taddei said.

The identification of nongenetic factors that predict early relapse may aid in personalization of treatment strategies, she said (Abstract #232).

The second study looked at fecal microbial transplant (FMT) for reducing cravings in adults with alcohol use disorder (AUD) and cirrhosis. The investigators saw a nonsignificant trend toward greater total abstinence at 6 months in patients randomized to FMT versus placebo.

“Future trials should be performed to determine the impact of FMT on altering the gut-brain axis in patients with AUD,” she said (Abstract #7).
 

Transplantation

The prospective controlled QUICKTRANS study by French and Belgian researchers found that patients who underwent early liver transplantation for severe alcoholic hepatitis had numerically but not significantly higher rates of relapse than patients who were transplanted after at least 6 months of abstinence, although heavy drinking was more frequent in patients who underwent early transplant.

The 2-year survival rates for both patients who underwent early transplant and those who underwent transplant after 6 months of sobriety were “identical, and excellent.” In addition, the 2-year survival rate for patients with severe alcoholic hepatitis who underwent transplant was 82.8%, compared with 28.2% for patients who were deemed ineligible for transplant according to a selection algorithm (P­ < .001).

“Perhaps most important is that studies in this population can be conducted in a controlled fashion across centers with reproducible transplant eligibility algorithms,” Dr. Taddei commented (Abstract #6).

The place of honor – Abstract # 1 – was reserved for a study looking at the effects on liver transplant practice of a new “safety net” policy from the Organ Procurement and Transplantation Network and United Network for Organ Sharing stating that patients awaiting liver transplantation who develop kidney failure may be given priority on the kidney transplant waiting list.

The investigators found that the new policy significantly increased the number of adult primary liver transplant alone candidates who where on dialysis at the time of listing, and did not affect either waiting list mortality or posttransplant outcomes.

The authors also saw a significant increase in kidney transplant listing after liver transplant, especially for patients who were on hemodialysis at the time of list.

In the period after implementation of the policy, there was a significantly higher probability of kidney transplant, and significant reduction in waiting list mortality.
 

Autoimmune & cholestatic diseases

Investigators performed an analysis of the phase 3 randomized controlled ENHANCE trial of seladelpar in patients with primary biliary cholangitis. The trial was stopped because of an adverse event ultimately deemed to be unrelated to the drug, so the analysis looked at the composite responder rate at month 3.

“The key takeaway from this study is that at the 10-mg dosage of seladelpar, 78% met a composite endpoint, 27% of patients normalized their alkaline phosphatase, and 50% normalized their ALT. There was significant improvement in pruritus,” Dr. Taddei said.

The drug was generally safe and well tolerated. A 52-week phase 3 global registration study will begin enrolling patients in early 2021 (Abstract #LO11).

In a pediatric study, investigators looked at differences in primary sclerosing cholangitis (PSC) among various population, and found that “Black and Hispanic patients have dramatically worse clinical outcomes, compared to White and Asian patients. They are more likely to be diagnosed with PSC at an advanced stage with extensive fibrosis and portal hypertensive manifestations.”

The authors suggested that the differences may be explained in part by socioeconomic disparities leading to delay in diagnosis, to a more aggressive phenotype, or both (Abstract #66).

A meta-analysis of maternal and fetal outcomes in women with autoimmune hepatitis showed that the disease is associated with increased risk of gestational diabetes, premature births, and small-for-gestational age or low-birth-weight babies.

“Pregnant women should be monitored closely before, during and after pregnancy. It’s important to know that, in the prevalence data, flares were most prevalent postpartum at 41%. These finds will help us counsel our patients with autoimmune hepatitis who become pregnant,” Dr. Taddei said (Abstract #97).
 

Drug-induced liver injury

A study of clinical outcomes following immune checkpoint inhibitor rechallenge in melanoma patients with resolved higher grade 3 or higher checkpoint inhibitor–induced hepatitis showed that 4 of 31 patients (13%) developed recurrence of grade 2 or greater hepatitis, and 15 of 31 (48%) developed an immune-related adverse event after rechallenge.

There was no difference in time to death between patients who were rechallenged and those who were not, and immune-related liver toxicities requiring drug discontinuation after rechallenge were uncommon.

“High-grade immune checkpoint inhibitor hepatitis should be reconsidered as an absolute contraindication for immune checkpoint inhibitor rechallenge,” Dr. Taddei said (Abstract # 116).
 

Neoplasia

The investigators also highlighted an abstract describing significant urban-rural and racial ethnic differences in hepatocellular carcinoma rates. A fuller description of this study can be found here (Abstract #136).

COVID-19

Finally, the reviewer highlighted a study of the clinical course of COVID-19 in patients with chronic liver disease, and to determine factors associated with adverse outcomes in patients with chronic liver disease who acquire COVID-19.

The investigators found that patients with chronic liver disease and COVID-19 have a 14% morality rate, and that alcohol-related liver disease, decompensated cirrhosis, and hepatocellular carcinoma are all risk factors for increased mortality from COVID-19.

They recommended emphasizing telemedicine, prioritizing patients with chronic liver disease for vaccination, and including these patients in prospective studies and drug trials for COVID-19 therapies.

Dr. Taddei reported having no disclosures.

Studies that address fundamental questions in hepatology and have the potential to change or improve clinical practice were the focus of a clinical debrief session from the virtual annual meeting of the American Association for the Study of Liver Diseases.

“We chose papers that had the highest level of evidence, such as randomized controlled trials, controlled studies, and large data sets – and some small data sets too,” said Tamar Taddei, MD, associate professor of medicine in the section of digestive disease at Yale University, New Haven, Conn.

Dr. Taddei and colleagues Silvia Vilarinho, MD, PhD; Simona Jakab, MD; and Ariel Jaffe, MD, all also from Yale, selected the papers from among 197 oral and 1,769 poster abstracts presented at AASLD 2020.

They highlighted the most important findings from presentations on autoimmune and cholestatic disease, transplantation, cirrhosis and portal hypertension, alcoholic liver disease, neoplasia, drug-induced liver injury, and COVID-19. They did not review studies focused primarily on nonalcoholic steatohepatitis or nonalcoholic fatty liver disease, viral hepatitis, or basic science, all of which were covered in separate debriefing sessions.
 

Cirrhosis and portal hypertension

A study from the Department of Veterans Affairs looked at the prevalence of liver disease risk factors and rates of subsequent testing for and diagnosis of cirrhosis in the Veterans Health Administration system (VHA).

The authors found that, among more than 6.65 million VHA users in 2018 with no prior diagnosis of cirrhosis, approximately half were at risk for cirrhosis, of whom about 75% were screened, and approximately 5% of those who were screened were positive for possible cirrhosis (133,636). Of the patients who screened positive, about 10% (12,566) received a diagnosis of cirrhosis, including 4,120 with liver decompensation.

“This paper underscores the importance of population-level screening in uncovering unrecognized cirrhosis, enabling intervention earlier in the course of disease,” Dr. Taddei said (Abstract #661).

A study looking at external validation of novel cirrhosis surgical risk models designed to improve prognostication for a range of common surgeries showed that the VOCAL-Penn score was superior to the Mayo Risk Score, Model for End-stage Liver Disease and MELD-sodium scores for discrimination of 30-day and 90-day postoperative mortality (Abstract #91).

“While these models are not a substitute for clinical acumen, they certainly improve our surgical risk prediction in patients with cirrhosis, a very common question in consultative hepatology,” Dr. Taddei said.

She also cited three abstracts that address the important questions regarding performing studies in patients with varices or ascites, including whether it’s safe to perform transesophageal echocardiography in patients with cirrhosis without first screening for varices, and whether nonselective beta-blockers should be continued in patients with refractory ascites.

A retrospective study of 191 patients with cirrhosis who underwent upper endoscopy within 4 years of transesophageal echocardiography had no overt gastrointestinal bleeding regardless of the presence of esophageal varices, suggesting that routine preprocedure esophagogastroduodenoscopy “is of no utility,” (Abstract #1872).

A study to determine risk of sepsis in 1,198 patients with cirrhosis found that 1-year risk of sepsis was reduced by 50% with the use of nonselective beta-blockers (Abstract #94).

The final abstract in this category touched on the use of an advance care planning video support tool to help transplant-ineligible patients with end-stage liver disease decide whether they want support measures such cardiopulmonary resuscitation or intubation. The authors found that the video decision tool was feasible and acceptable to patients, and improved their knowledge of end-of-life care. More patients randomized to the video arm opted against CPR or intubation, compared with those assigned to a verbal discussion of options (Abstract #712).
 

Alcohol

The reviewers highlighted two studies of alcohol use: The first was designed to determine the prevalence of early alcohol relapse (resumption within 3 months) in patients who presented with alcoholic hepatitis. The subjects included 478 patients enrolled in the STOPAH trial, and a validation set of 194 patients from the InTeam (Integrated Approaches for identifying Molecular Targets in Alcoholic Hepatitis) Consortium.

“They found that high-risk patients were younger, unemployed, and without a stable relationship. Intermediate risk were middle aged, employed, and in a stable relationship, and low-risk profiles were older, with known cirrhosis; they were mostly retired and in a stable relationship,” Dr. Taddei said.

The identification of nongenetic factors that predict early relapse may aid in personalization of treatment strategies, she said (Abstract #232).

The second study looked at fecal microbial transplant (FMT) for reducing cravings in adults with alcohol use disorder (AUD) and cirrhosis. The investigators saw a nonsignificant trend toward greater total abstinence at 6 months in patients randomized to FMT versus placebo.

“Future trials should be performed to determine the impact of FMT on altering the gut-brain axis in patients with AUD,” she said (Abstract #7).
 

Transplantation

The prospective controlled QUICKTRANS study by French and Belgian researchers found that patients who underwent early liver transplantation for severe alcoholic hepatitis had numerically but not significantly higher rates of relapse than patients who were transplanted after at least 6 months of abstinence, although heavy drinking was more frequent in patients who underwent early transplant.

The 2-year survival rates for both patients who underwent early transplant and those who underwent transplant after 6 months of sobriety were “identical, and excellent.” In addition, the 2-year survival rate for patients with severe alcoholic hepatitis who underwent transplant was 82.8%, compared with 28.2% for patients who were deemed ineligible for transplant according to a selection algorithm (P­ < .001).

“Perhaps most important is that studies in this population can be conducted in a controlled fashion across centers with reproducible transplant eligibility algorithms,” Dr. Taddei commented (Abstract #6).

The place of honor – Abstract # 1 – was reserved for a study looking at the effects on liver transplant practice of a new “safety net” policy from the Organ Procurement and Transplantation Network and United Network for Organ Sharing stating that patients awaiting liver transplantation who develop kidney failure may be given priority on the kidney transplant waiting list.

The investigators found that the new policy significantly increased the number of adult primary liver transplant alone candidates who where on dialysis at the time of listing, and did not affect either waiting list mortality or posttransplant outcomes.

The authors also saw a significant increase in kidney transplant listing after liver transplant, especially for patients who were on hemodialysis at the time of list.

In the period after implementation of the policy, there was a significantly higher probability of kidney transplant, and significant reduction in waiting list mortality.
 

Autoimmune & cholestatic diseases

Investigators performed an analysis of the phase 3 randomized controlled ENHANCE trial of seladelpar in patients with primary biliary cholangitis. The trial was stopped because of an adverse event ultimately deemed to be unrelated to the drug, so the analysis looked at the composite responder rate at month 3.

“The key takeaway from this study is that at the 10-mg dosage of seladelpar, 78% met a composite endpoint, 27% of patients normalized their alkaline phosphatase, and 50% normalized their ALT. There was significant improvement in pruritus,” Dr. Taddei said.

The drug was generally safe and well tolerated. A 52-week phase 3 global registration study will begin enrolling patients in early 2021 (Abstract #LO11).

In a pediatric study, investigators looked at differences in primary sclerosing cholangitis (PSC) among various population, and found that “Black and Hispanic patients have dramatically worse clinical outcomes, compared to White and Asian patients. They are more likely to be diagnosed with PSC at an advanced stage with extensive fibrosis and portal hypertensive manifestations.”

The authors suggested that the differences may be explained in part by socioeconomic disparities leading to delay in diagnosis, to a more aggressive phenotype, or both (Abstract #66).

A meta-analysis of maternal and fetal outcomes in women with autoimmune hepatitis showed that the disease is associated with increased risk of gestational diabetes, premature births, and small-for-gestational age or low-birth-weight babies.

“Pregnant women should be monitored closely before, during and after pregnancy. It’s important to know that, in the prevalence data, flares were most prevalent postpartum at 41%. These finds will help us counsel our patients with autoimmune hepatitis who become pregnant,” Dr. Taddei said (Abstract #97).
 

Drug-induced liver injury

A study of clinical outcomes following immune checkpoint inhibitor rechallenge in melanoma patients with resolved higher grade 3 or higher checkpoint inhibitor–induced hepatitis showed that 4 of 31 patients (13%) developed recurrence of grade 2 or greater hepatitis, and 15 of 31 (48%) developed an immune-related adverse event after rechallenge.

There was no difference in time to death between patients who were rechallenged and those who were not, and immune-related liver toxicities requiring drug discontinuation after rechallenge were uncommon.

“High-grade immune checkpoint inhibitor hepatitis should be reconsidered as an absolute contraindication for immune checkpoint inhibitor rechallenge,” Dr. Taddei said (Abstract # 116).
 

Neoplasia

The investigators also highlighted an abstract describing significant urban-rural and racial ethnic differences in hepatocellular carcinoma rates. A fuller description of this study can be found here (Abstract #136).

COVID-19

Finally, the reviewer highlighted a study of the clinical course of COVID-19 in patients with chronic liver disease, and to determine factors associated with adverse outcomes in patients with chronic liver disease who acquire COVID-19.

The investigators found that patients with chronic liver disease and COVID-19 have a 14% morality rate, and that alcohol-related liver disease, decompensated cirrhosis, and hepatocellular carcinoma are all risk factors for increased mortality from COVID-19.

They recommended emphasizing telemedicine, prioritizing patients with chronic liver disease for vaccination, and including these patients in prospective studies and drug trials for COVID-19 therapies.

Dr. Taddei reported having no disclosures.

Studies that address fundamental questions in hepatology and have the potential to change or improve clinical practice were the focus of a clinical debrief session from the virtual annual meeting of the American Association for the Study of Liver Diseases.

“We chose papers that had the highest level of evidence, such as randomized controlled trials, controlled studies, and large data sets – and some small data sets too,” said Tamar Taddei, MD, associate professor of medicine in the section of digestive disease at Yale University, New Haven, Conn.

Dr. Taddei and colleagues Silvia Vilarinho, MD, PhD; Simona Jakab, MD; and Ariel Jaffe, MD, all also from Yale, selected the papers from among 197 oral and 1,769 poster abstracts presented at AASLD 2020.

They highlighted the most important findings from presentations on autoimmune and cholestatic disease, transplantation, cirrhosis and portal hypertension, alcoholic liver disease, neoplasia, drug-induced liver injury, and COVID-19. They did not review studies focused primarily on nonalcoholic steatohepatitis or nonalcoholic fatty liver disease, viral hepatitis, or basic science, all of which were covered in separate debriefing sessions.
 

Cirrhosis and portal hypertension

A study from the Department of Veterans Affairs looked at the prevalence of liver disease risk factors and rates of subsequent testing for and diagnosis of cirrhosis in the Veterans Health Administration system (VHA).

The authors found that, among more than 6.65 million VHA users in 2018 with no prior diagnosis of cirrhosis, approximately half were at risk for cirrhosis, of whom about 75% were screened, and approximately 5% of those who were screened were positive for possible cirrhosis (133,636). Of the patients who screened positive, about 10% (12,566) received a diagnosis of cirrhosis, including 4,120 with liver decompensation.

“This paper underscores the importance of population-level screening in uncovering unrecognized cirrhosis, enabling intervention earlier in the course of disease,” Dr. Taddei said (Abstract #661).

A study looking at external validation of novel cirrhosis surgical risk models designed to improve prognostication for a range of common surgeries showed that the VOCAL-Penn score was superior to the Mayo Risk Score, Model for End-stage Liver Disease and MELD-sodium scores for discrimination of 30-day and 90-day postoperative mortality (Abstract #91).

“While these models are not a substitute for clinical acumen, they certainly improve our surgical risk prediction in patients with cirrhosis, a very common question in consultative hepatology,” Dr. Taddei said.

She also cited three abstracts that address the important questions regarding performing studies in patients with varices or ascites, including whether it’s safe to perform transesophageal echocardiography in patients with cirrhosis without first screening for varices, and whether nonselective beta-blockers should be continued in patients with refractory ascites.

A retrospective study of 191 patients with cirrhosis who underwent upper endoscopy within 4 years of transesophageal echocardiography had no overt gastrointestinal bleeding regardless of the presence of esophageal varices, suggesting that routine preprocedure esophagogastroduodenoscopy “is of no utility,” (Abstract #1872).

A study to determine risk of sepsis in 1,198 patients with cirrhosis found that 1-year risk of sepsis was reduced by 50% with the use of nonselective beta-blockers (Abstract #94).

The final abstract in this category touched on the use of an advance care planning video support tool to help transplant-ineligible patients with end-stage liver disease decide whether they want support measures such cardiopulmonary resuscitation or intubation. The authors found that the video decision tool was feasible and acceptable to patients, and improved their knowledge of end-of-life care. More patients randomized to the video arm opted against CPR or intubation, compared with those assigned to a verbal discussion of options (Abstract #712).
 

Alcohol

The reviewers highlighted two studies of alcohol use: The first was designed to determine the prevalence of early alcohol relapse (resumption within 3 months) in patients who presented with alcoholic hepatitis. The subjects included 478 patients enrolled in the STOPAH trial, and a validation set of 194 patients from the InTeam (Integrated Approaches for identifying Molecular Targets in Alcoholic Hepatitis) Consortium.

“They found that high-risk patients were younger, unemployed, and without a stable relationship. Intermediate risk were middle aged, employed, and in a stable relationship, and low-risk profiles were older, with known cirrhosis; they were mostly retired and in a stable relationship,” Dr. Taddei said.

The identification of nongenetic factors that predict early relapse may aid in personalization of treatment strategies, she said (Abstract #232).

The second study looked at fecal microbial transplant (FMT) for reducing cravings in adults with alcohol use disorder (AUD) and cirrhosis. The investigators saw a nonsignificant trend toward greater total abstinence at 6 months in patients randomized to FMT versus placebo.

“Future trials should be performed to determine the impact of FMT on altering the gut-brain axis in patients with AUD,” she said (Abstract #7).
 

Transplantation

The prospective controlled QUICKTRANS study by French and Belgian researchers found that patients who underwent early liver transplantation for severe alcoholic hepatitis had numerically but not significantly higher rates of relapse than patients who were transplanted after at least 6 months of abstinence, although heavy drinking was more frequent in patients who underwent early transplant.

The 2-year survival rates for both patients who underwent early transplant and those who underwent transplant after 6 months of sobriety were “identical, and excellent.” In addition, the 2-year survival rate for patients with severe alcoholic hepatitis who underwent transplant was 82.8%, compared with 28.2% for patients who were deemed ineligible for transplant according to a selection algorithm (P­ < .001).

“Perhaps most important is that studies in this population can be conducted in a controlled fashion across centers with reproducible transplant eligibility algorithms,” Dr. Taddei commented (Abstract #6).

The place of honor – Abstract # 1 – was reserved for a study looking at the effects on liver transplant practice of a new “safety net” policy from the Organ Procurement and Transplantation Network and United Network for Organ Sharing stating that patients awaiting liver transplantation who develop kidney failure may be given priority on the kidney transplant waiting list.

The investigators found that the new policy significantly increased the number of adult primary liver transplant alone candidates who where on dialysis at the time of listing, and did not affect either waiting list mortality or posttransplant outcomes.

The authors also saw a significant increase in kidney transplant listing after liver transplant, especially for patients who were on hemodialysis at the time of list.

In the period after implementation of the policy, there was a significantly higher probability of kidney transplant, and significant reduction in waiting list mortality.
 

Autoimmune & cholestatic diseases

Investigators performed an analysis of the phase 3 randomized controlled ENHANCE trial of seladelpar in patients with primary biliary cholangitis. The trial was stopped because of an adverse event ultimately deemed to be unrelated to the drug, so the analysis looked at the composite responder rate at month 3.

“The key takeaway from this study is that at the 10-mg dosage of seladelpar, 78% met a composite endpoint, 27% of patients normalized their alkaline phosphatase, and 50% normalized their ALT. There was significant improvement in pruritus,” Dr. Taddei said.

The drug was generally safe and well tolerated. A 52-week phase 3 global registration study will begin enrolling patients in early 2021 (Abstract #LO11).

In a pediatric study, investigators looked at differences in primary sclerosing cholangitis (PSC) among various population, and found that “Black and Hispanic patients have dramatically worse clinical outcomes, compared to White and Asian patients. They are more likely to be diagnosed with PSC at an advanced stage with extensive fibrosis and portal hypertensive manifestations.”

The authors suggested that the differences may be explained in part by socioeconomic disparities leading to delay in diagnosis, to a more aggressive phenotype, or both (Abstract #66).

A meta-analysis of maternal and fetal outcomes in women with autoimmune hepatitis showed that the disease is associated with increased risk of gestational diabetes, premature births, and small-for-gestational age or low-birth-weight babies.

“Pregnant women should be monitored closely before, during and after pregnancy. It’s important to know that, in the prevalence data, flares were most prevalent postpartum at 41%. These finds will help us counsel our patients with autoimmune hepatitis who become pregnant,” Dr. Taddei said (Abstract #97).
 

Drug-induced liver injury

A study of clinical outcomes following immune checkpoint inhibitor rechallenge in melanoma patients with resolved higher grade 3 or higher checkpoint inhibitor–induced hepatitis showed that 4 of 31 patients (13%) developed recurrence of grade 2 or greater hepatitis, and 15 of 31 (48%) developed an immune-related adverse event after rechallenge.

There was no difference in time to death between patients who were rechallenged and those who were not, and immune-related liver toxicities requiring drug discontinuation after rechallenge were uncommon.

“High-grade immune checkpoint inhibitor hepatitis should be reconsidered as an absolute contraindication for immune checkpoint inhibitor rechallenge,” Dr. Taddei said (Abstract # 116).
 

Neoplasia

The investigators also highlighted an abstract describing significant urban-rural and racial ethnic differences in hepatocellular carcinoma rates. A fuller description of this study can be found here (Abstract #136).

COVID-19

Finally, the reviewer highlighted a study of the clinical course of COVID-19 in patients with chronic liver disease, and to determine factors associated with adverse outcomes in patients with chronic liver disease who acquire COVID-19.

The investigators found that patients with chronic liver disease and COVID-19 have a 14% morality rate, and that alcohol-related liver disease, decompensated cirrhosis, and hepatocellular carcinoma are all risk factors for increased mortality from COVID-19.

They recommended emphasizing telemedicine, prioritizing patients with chronic liver disease for vaccination, and including these patients in prospective studies and drug trials for COVID-19 therapies.

Dr. Taddei reported having no disclosures.

For patients with chronic hepatitis B, the protective effects of aspirin against hepatocellular carcinoma (HCC) can vary with cirrhosis status and statin treatment, a pair of new studies finds.

One study showed that, although aspirin is linked to a reduction in risk for HCC in these patients, comedication with statins could explain some of that effect. The other showed that cirrhosis dampens the risk-reduction benefit of aspirin.

Currently, there is a link between a reduction in HCC risk and aspirin or statins in patients with chronic hepatitis B, said investigator Won-Mook Choi, MD, PhD, from the University of Ulsan College of Medicine, in Seoul, Republic of Korea.

In one of their analyses, Choi and his colleagues teased out the contribution of each drug and found that the decrease in HCC risk conferred by statins is similar whether or not patients also take aspirin.

“Only statins showed consistent and significant dose-dependent reductions in the risk of HCC, regardless of study design,” said Choi, who presented the findings at The Liver Meeting 2020.

The second study, which looked at the association between aspirin and the risk for HCC in patients with and without cirrhosis, was presented by Heejoon Jang, MD, from the Seoul National University College of Medicine.

Aspirin was shown to be associated with a reduced risk for HCC, but cirrhosis “had a substantial effect on this association,” erasing the benefit of aspirin, Jang reported.
 

Statins and aspirin

Statins and aspirin are more likely to be prescribed together for patients with chronic hepatitis B but no cirrhosis, said Choi. For that reason, he and his colleagues analyzed data from the Korean National Health Insurance Service database from 2005 to 2015.

In their nested case-control analysis, 17,150 patients with HCC were matched for sex, age, and other factors to 817,675 patients without HCC. All participants had chronic hepatitis B without cirrhosis and had never received antiviral treatment.

The team also analyzed the incidence of HCC in two historic cohorts of patients with chronic hepatitis B but no cirrhosis, one consisting of 673,107 people who took aspirin and the other with 588,045 who took statins.

The nested case-control analysis showed an 11% risk reduction with aspirin use (adjusted odds ratio [OR], 0.89; 95% CI, 0.85 - 0.94) and a 61% risk reduction with statin use (adjusted OR, 0.39; 95% CI, 0.36 - 0.40). There was a dose-response effect with statins, but not with aspirin.

The historic cohort analysis showed a 33% reduction in the risk for HCC with aspirin (adjusted hazard ratio [HR], 0.67; 95% CI, 0.63 - 0.72) and a 67% reduction with statins (adjusted HR, 0.33; 95% CI, 0.30 - 0.37). However, stratified analyses by drug showed a statin benefit with or without aspirin (P < .001 for both), but no aspirin benefit without statins.
 

Cirrhosis and aspirin

To assess the interaction between cirrhosis and aspirin, Jang and his colleagues identified 329,635 patients with chronic hepatitis B in the Korean National Health Insurance Service database.

A total of 20,200 had taken aspirin for at least 90 consecutive days, and the rest had never received antiplatelet therapy. Treated and untreated patients were matched for several factors, and HCC incidence was assessed after a median follow-up of 6.7 years.

Among the 2,697 patients who developed HCC during follow-up, the cumulative incidence of HCC was significantly lower for those who took aspirin than for those who did not (P < .001). There was a 15% reduction in the risk for HCC in the aspirin group (adjusted HR, 0.85; 95% CI, 0.78 - 0.92).

However, in patients with cirrhosis, the benefit of aspirin disappeared. Patients without cirrhosis still had a 13% reduction in risk for HCC (adjusted HR, 0.87: 95% CI, 0.79 - 0.95). This group also had a slightly elevated risk for major bleeding (adjusted HR, 1.1; 95% CI, 1.03 - 1.28).

The findings from these two studies add to a growing body of literature that shows the promise of statins and aspirin, which are both readily available and relatively safe, said Amit Singal, MD, from the UT Southwestern Medical Center in Dallas, who was not involved with either study.

“The studies are relatively simple but really do tackle an area of immense need in the field,” he said. Short of having higher-quality data, however, statins and aspirin aren’t quite ready to become bespoke chemotherapies in the clinic, he added, although the results show promise for future randomized trials.

The subgroup analyses that looked at cirrhosis and the interplay of aspirin and statins can help with the planning of such trials, which “is really important for trial design,” Singal noted.

He also pointed to studies that, unlike these results, have found a benefit of aspirin in patients with cirrhosis, underscoring the need for randomized trials. However, “each study does provide a data point that can help to inform those trials,” he said.

Choi and Jang have disclosed no relevant financial relationships. Singal is a consultant for Genentech, Bayer, Eisai, Exelixis, Bristol-Myers Squibb, Roche, Glycotest, FujiFilm, GRAIL, and Exact Sciences, primarily in relation to HCC treatment and screening, not chemoprevention.

This article first appeared on Medscape.com.

For patients with chronic hepatitis B, the protective effects of aspirin against hepatocellular carcinoma (HCC) can vary with cirrhosis status and statin treatment, a pair of new studies finds.

One study showed that, although aspirin is linked to a reduction in risk for HCC in these patients, comedication with statins could explain some of that effect. The other showed that cirrhosis dampens the risk-reduction benefit of aspirin.

Currently, there is a link between a reduction in HCC risk and aspirin or statins in patients with chronic hepatitis B, said investigator Won-Mook Choi, MD, PhD, from the University of Ulsan College of Medicine, in Seoul, Republic of Korea.

In one of their analyses, Choi and his colleagues teased out the contribution of each drug and found that the decrease in HCC risk conferred by statins is similar whether or not patients also take aspirin.

“Only statins showed consistent and significant dose-dependent reductions in the risk of HCC, regardless of study design,” said Choi, who presented the findings at The Liver Meeting 2020.

The second study, which looked at the association between aspirin and the risk for HCC in patients with and without cirrhosis, was presented by Heejoon Jang, MD, from the Seoul National University College of Medicine.

Aspirin was shown to be associated with a reduced risk for HCC, but cirrhosis “had a substantial effect on this association,” erasing the benefit of aspirin, Jang reported.
 

Statins and aspirin

Statins and aspirin are more likely to be prescribed together for patients with chronic hepatitis B but no cirrhosis, said Choi. For that reason, he and his colleagues analyzed data from the Korean National Health Insurance Service database from 2005 to 2015.

In their nested case-control analysis, 17,150 patients with HCC were matched for sex, age, and other factors to 817,675 patients without HCC. All participants had chronic hepatitis B without cirrhosis and had never received antiviral treatment.

The team also analyzed the incidence of HCC in two historic cohorts of patients with chronic hepatitis B but no cirrhosis, one consisting of 673,107 people who took aspirin and the other with 588,045 who took statins.

The nested case-control analysis showed an 11% risk reduction with aspirin use (adjusted odds ratio [OR], 0.89; 95% CI, 0.85 - 0.94) and a 61% risk reduction with statin use (adjusted OR, 0.39; 95% CI, 0.36 - 0.40). There was a dose-response effect with statins, but not with aspirin.

The historic cohort analysis showed a 33% reduction in the risk for HCC with aspirin (adjusted hazard ratio [HR], 0.67; 95% CI, 0.63 - 0.72) and a 67% reduction with statins (adjusted HR, 0.33; 95% CI, 0.30 - 0.37). However, stratified analyses by drug showed a statin benefit with or without aspirin (P < .001 for both), but no aspirin benefit without statins.
 

Cirrhosis and aspirin

To assess the interaction between cirrhosis and aspirin, Jang and his colleagues identified 329,635 patients with chronic hepatitis B in the Korean National Health Insurance Service database.

A total of 20,200 had taken aspirin for at least 90 consecutive days, and the rest had never received antiplatelet therapy. Treated and untreated patients were matched for several factors, and HCC incidence was assessed after a median follow-up of 6.7 years.

Among the 2,697 patients who developed HCC during follow-up, the cumulative incidence of HCC was significantly lower for those who took aspirin than for those who did not (P < .001). There was a 15% reduction in the risk for HCC in the aspirin group (adjusted HR, 0.85; 95% CI, 0.78 - 0.92).

However, in patients with cirrhosis, the benefit of aspirin disappeared. Patients without cirrhosis still had a 13% reduction in risk for HCC (adjusted HR, 0.87: 95% CI, 0.79 - 0.95). This group also had a slightly elevated risk for major bleeding (adjusted HR, 1.1; 95% CI, 1.03 - 1.28).

The findings from these two studies add to a growing body of literature that shows the promise of statins and aspirin, which are both readily available and relatively safe, said Amit Singal, MD, from the UT Southwestern Medical Center in Dallas, who was not involved with either study.

“The studies are relatively simple but really do tackle an area of immense need in the field,” he said. Short of having higher-quality data, however, statins and aspirin aren’t quite ready to become bespoke chemotherapies in the clinic, he added, although the results show promise for future randomized trials.

The subgroup analyses that looked at cirrhosis and the interplay of aspirin and statins can help with the planning of such trials, which “is really important for trial design,” Singal noted.

He also pointed to studies that, unlike these results, have found a benefit of aspirin in patients with cirrhosis, underscoring the need for randomized trials. However, “each study does provide a data point that can help to inform those trials,” he said.

Choi and Jang have disclosed no relevant financial relationships. Singal is a consultant for Genentech, Bayer, Eisai, Exelixis, Bristol-Myers Squibb, Roche, Glycotest, FujiFilm, GRAIL, and Exact Sciences, primarily in relation to HCC treatment and screening, not chemoprevention.

This article first appeared on Medscape.com.

For patients with chronic hepatitis B, the protective effects of aspirin against hepatocellular carcinoma (HCC) can vary with cirrhosis status and statin treatment, a pair of new studies finds.

One study showed that, although aspirin is linked to a reduction in risk for HCC in these patients, comedication with statins could explain some of that effect. The other showed that cirrhosis dampens the risk-reduction benefit of aspirin.

Currently, there is a link between a reduction in HCC risk and aspirin or statins in patients with chronic hepatitis B, said investigator Won-Mook Choi, MD, PhD, from the University of Ulsan College of Medicine, in Seoul, Republic of Korea.

In one of their analyses, Choi and his colleagues teased out the contribution of each drug and found that the decrease in HCC risk conferred by statins is similar whether or not patients also take aspirin.

“Only statins showed consistent and significant dose-dependent reductions in the risk of HCC, regardless of study design,” said Choi, who presented the findings at The Liver Meeting 2020.

The second study, which looked at the association between aspirin and the risk for HCC in patients with and without cirrhosis, was presented by Heejoon Jang, MD, from the Seoul National University College of Medicine.

Aspirin was shown to be associated with a reduced risk for HCC, but cirrhosis “had a substantial effect on this association,” erasing the benefit of aspirin, Jang reported.
 

Statins and aspirin

Statins and aspirin are more likely to be prescribed together for patients with chronic hepatitis B but no cirrhosis, said Choi. For that reason, he and his colleagues analyzed data from the Korean National Health Insurance Service database from 2005 to 2015.

In their nested case-control analysis, 17,150 patients with HCC were matched for sex, age, and other factors to 817,675 patients without HCC. All participants had chronic hepatitis B without cirrhosis and had never received antiviral treatment.

The team also analyzed the incidence of HCC in two historic cohorts of patients with chronic hepatitis B but no cirrhosis, one consisting of 673,107 people who took aspirin and the other with 588,045 who took statins.

The nested case-control analysis showed an 11% risk reduction with aspirin use (adjusted odds ratio [OR], 0.89; 95% CI, 0.85 - 0.94) and a 61% risk reduction with statin use (adjusted OR, 0.39; 95% CI, 0.36 - 0.40). There was a dose-response effect with statins, but not with aspirin.

The historic cohort analysis showed a 33% reduction in the risk for HCC with aspirin (adjusted hazard ratio [HR], 0.67; 95% CI, 0.63 - 0.72) and a 67% reduction with statins (adjusted HR, 0.33; 95% CI, 0.30 - 0.37). However, stratified analyses by drug showed a statin benefit with or without aspirin (P < .001 for both), but no aspirin benefit without statins.
 

Cirrhosis and aspirin

To assess the interaction between cirrhosis and aspirin, Jang and his colleagues identified 329,635 patients with chronic hepatitis B in the Korean National Health Insurance Service database.

A total of 20,200 had taken aspirin for at least 90 consecutive days, and the rest had never received antiplatelet therapy. Treated and untreated patients were matched for several factors, and HCC incidence was assessed after a median follow-up of 6.7 years.

Among the 2,697 patients who developed HCC during follow-up, the cumulative incidence of HCC was significantly lower for those who took aspirin than for those who did not (P < .001). There was a 15% reduction in the risk for HCC in the aspirin group (adjusted HR, 0.85; 95% CI, 0.78 - 0.92).

However, in patients with cirrhosis, the benefit of aspirin disappeared. Patients without cirrhosis still had a 13% reduction in risk for HCC (adjusted HR, 0.87: 95% CI, 0.79 - 0.95). This group also had a slightly elevated risk for major bleeding (adjusted HR, 1.1; 95% CI, 1.03 - 1.28).

The findings from these two studies add to a growing body of literature that shows the promise of statins and aspirin, which are both readily available and relatively safe, said Amit Singal, MD, from the UT Southwestern Medical Center in Dallas, who was not involved with either study.

“The studies are relatively simple but really do tackle an area of immense need in the field,” he said. Short of having higher-quality data, however, statins and aspirin aren’t quite ready to become bespoke chemotherapies in the clinic, he added, although the results show promise for future randomized trials.

The subgroup analyses that looked at cirrhosis and the interplay of aspirin and statins can help with the planning of such trials, which “is really important for trial design,” Singal noted.

He also pointed to studies that, unlike these results, have found a benefit of aspirin in patients with cirrhosis, underscoring the need for randomized trials. However, “each study does provide a data point that can help to inform those trials,” he said.

Choi and Jang have disclosed no relevant financial relationships. Singal is a consultant for Genentech, Bayer, Eisai, Exelixis, Bristol-Myers Squibb, Roche, Glycotest, FujiFilm, GRAIL, and Exact Sciences, primarily in relation to HCC treatment and screening, not chemoprevention.

This article first appeared on Medscape.com.

Loss of the hepatitis B surface antigen (HBsAg), a marker for functional cure of hepatitis B infection, is nearly six times more common among White patients than Asian patients following cessation of therapy with a nucleotide or nucleoside analogue, investigators in the RETRACT-B study group report.

Among 1,541 patients in a global retrospective cohort, the cumulative rate of HBsAg loss 4 years after cessation of therapy with entecavir (ETV), tenofovir disoproxil fumarate (TDF), or other nucleoside/nucleotide analogue (“nuc” or NA) was 11% in Asian patients, compared with 41% in Whites, which translated in multivariate analysis into a hazard ratio (HR) of 5.8 (P < .001), said Grishma Hirode, a clinical research associate and PhD candidate at the Toronto Centre for Liver Disease.

“On univariate Cox regression, the rate of S [antigen] loss was significantly higher among older patients, among [Whites], and among tenofovir-treated patients prior to stopping,” she said during the virtual annual meeting of the American Association for the Study of Liver Diseases.

Although NAs are effective at suppressing hepatitis B viral activity, functional cure as indicated by HBsAg loss is uncommon, Ms. Hirode noted.

“Finite use of antiviral therapy has been proposed as an alternative to long-term therapy, and the rationale for stopping nuc therapy is to induce a durable virologic remission in the form of an inactive carrier state, and ideally a functional cure,” she said.

The RETRACT-B (Response after End of Treatment with Antivirals in Chronic Hepatitis B) study group, comprising liver treatment centers in Canada, Europe, Hong Kong, and Taiwan, studies outcomes following cessation of nucleos(t)ide analogue therapy.

The investigators looked at data on 1,541 patients, including those with both hepatitis B e-antigen (HBeAg) positive and HBeAg-negative disease at the start of therapy, all of whom were HBeAg negative at the time of antiviral cessation and had undetectable serum HBV DNA. Patients with hepatitis C, hepatitis D and/or HIV co-infection were excluded, as were patients who had received interferon treatment less than 12 months before stopping.

The mean age at baseline was 53 years. Men comprised 73% of the sample. In all, 88% of patients were Asian, 10% White, and 2% other.

In patients for whom genotype data was known, 0.5% had type A, 43% type B, 11% type C, and 2% type D.

Nearly two-thirds of patients (60%) were on ETV at the time of drug cessation, 29% were on TDF, and 11% were on other agents.

In all, 5% of patients had cirrhosis at the time of nucleos(t)ide cessation, the mean HBsAg was 2.6 log₁₀ IU/mL, and the mean alanine aminotransferase (ALT) level was 0.6 times the upper limit of normal.

The median duration of NA therapy was 3 years.

The cumulative rates of HBsAg loss over time among all patients was 3% at 1 year, 8% at 2 years. 12% at 3 years, and 14% at 4 years. Cumulative rates of antigen loss at year 4 were significantly greater for patients 50 and older vs. those younger than 50 (18% vs. 9%, respectively, P = .01), Whites vs. Asians (41% vs. 11%, P < .001), and in those who had been on TDF vs. ETV (17% vs. 12%, P = .001). There was no significant difference in cumulative HBsAg loss between patients who were HBeAg positive or negative at the start of NA therapy.

Cumulative rates of retreatment were 30% at 1 year, 43% at 2 years, 50% at 3 years, and 56% at 4 years. The only significant predictor for retreatment was age, with patients 50 and older being significantly more likely to be retreated by year 4 (63% vs. 45%, respectively, P < .001).

In a univariate model for HBsAg loss, the HR for age 50 and older was 1.7 (P = .01), the HR for White vs. Asian patients was 5.5 (P < .001), and the HR for TDF vs. ETV was 2.0 (P = .001).

A univariate model for retreatment showed an HR of 1.6 for patients 50 and older; all other parameters (sex, race, NA type, and HBeAg status at start of therapy) were not significantly different.

In multivariate models, only race/ethnicity remained significant as a predictor for HBsAg loss, with a HR of 5.8 for Whites vs. Asians (P < .001), and only age 50 and older remained significant as a predictor for retreatment, with a HR of 1.6 (P < .001).

The 4-year cumulative rate of virologic relapse, defined as an HBV DNA of 2000 IU/mL or higher) was 74%, the rate of combined DNA plus ALT relapse (ALT 2 or more times the upper limit of normal) was 56%, and the rate of ALT flares (5 or more times the upper limit of normal) was 33%.

In all, 15 patients (1%) experienced hepatic decompensation, and 12 (0.96%) died, with 9 of the deaths reported as liver-related.
 

Race/ethnicity differences previously seen

Liver specialist Anna Suk-Fong Lok, MD, professor of medicine at the University of Michigan in Ann Arbor, who was not involved in the study, said that the findings are not especially surprising.

“When the studies came out from Asian countries showing that patients who were taken off treatment had a higher rate of S antigen loss than patients who stayed on treatment, the rate of S antigen loss was not all that impressive, but when you look at the European studies the rate of S antigen loss was very high,” she said in an interview.

“The question of course is ‘Why?’ I don’t think we understand completely why. We can speculate, but none of these type studies give us a definitive answer,” she said.

Possible reasons for the racial differences in HBsAg loss include differences in hepatitis B genotype, she said.

“Another possibility is that Asian patients may have been infected either at the time of birth or as a young kid, so they may have been infected for a much longer period of time than [Whites], who usually acquire infections as adults,” Dr. Lok said.

There may also be differences between patient populations in immune responses following cessation of antiviral therapy, she added.

The study was supported by the RETRACT-B group. Ms. Hirode and Dr. Lok reported no relevant disclosures.

SOURCE: Hirode G et al. AASLD 2020. Abstract 23.

Loss of the hepatitis B surface antigen (HBsAg), a marker for functional cure of hepatitis B infection, is nearly six times more common among White patients than Asian patients following cessation of therapy with a nucleotide or nucleoside analogue, investigators in the RETRACT-B study group report.

Among 1,541 patients in a global retrospective cohort, the cumulative rate of HBsAg loss 4 years after cessation of therapy with entecavir (ETV), tenofovir disoproxil fumarate (TDF), or other nucleoside/nucleotide analogue (“nuc” or NA) was 11% in Asian patients, compared with 41% in Whites, which translated in multivariate analysis into a hazard ratio (HR) of 5.8 (P < .001), said Grishma Hirode, a clinical research associate and PhD candidate at the Toronto Centre for Liver Disease.

“On univariate Cox regression, the rate of S [antigen] loss was significantly higher among older patients, among [Whites], and among tenofovir-treated patients prior to stopping,” she said during the virtual annual meeting of the American Association for the Study of Liver Diseases.

Although NAs are effective at suppressing hepatitis B viral activity, functional cure as indicated by HBsAg loss is uncommon, Ms. Hirode noted.

“Finite use of antiviral therapy has been proposed as an alternative to long-term therapy, and the rationale for stopping nuc therapy is to induce a durable virologic remission in the form of an inactive carrier state, and ideally a functional cure,” she said.

The RETRACT-B (Response after End of Treatment with Antivirals in Chronic Hepatitis B) study group, comprising liver treatment centers in Canada, Europe, Hong Kong, and Taiwan, studies outcomes following cessation of nucleos(t)ide analogue therapy.

The investigators looked at data on 1,541 patients, including those with both hepatitis B e-antigen (HBeAg) positive and HBeAg-negative disease at the start of therapy, all of whom were HBeAg negative at the time of antiviral cessation and had undetectable serum HBV DNA. Patients with hepatitis C, hepatitis D and/or HIV co-infection were excluded, as were patients who had received interferon treatment less than 12 months before stopping.

The mean age at baseline was 53 years. Men comprised 73% of the sample. In all, 88% of patients were Asian, 10% White, and 2% other.

In patients for whom genotype data was known, 0.5% had type A, 43% type B, 11% type C, and 2% type D.

Nearly two-thirds of patients (60%) were on ETV at the time of drug cessation, 29% were on TDF, and 11% were on other agents.

In all, 5% of patients had cirrhosis at the time of nucleos(t)ide cessation, the mean HBsAg was 2.6 log₁₀ IU/mL, and the mean alanine aminotransferase (ALT) level was 0.6 times the upper limit of normal.

The median duration of NA therapy was 3 years.

The cumulative rates of HBsAg loss over time among all patients was 3% at 1 year, 8% at 2 years. 12% at 3 years, and 14% at 4 years. Cumulative rates of antigen loss at year 4 were significantly greater for patients 50 and older vs. those younger than 50 (18% vs. 9%, respectively, P = .01), Whites vs. Asians (41% vs. 11%, P < .001), and in those who had been on TDF vs. ETV (17% vs. 12%, P = .001). There was no significant difference in cumulative HBsAg loss between patients who were HBeAg positive or negative at the start of NA therapy.

Cumulative rates of retreatment were 30% at 1 year, 43% at 2 years, 50% at 3 years, and 56% at 4 years. The only significant predictor for retreatment was age, with patients 50 and older being significantly more likely to be retreated by year 4 (63% vs. 45%, respectively, P < .001).

In a univariate model for HBsAg loss, the HR for age 50 and older was 1.7 (P = .01), the HR for White vs. Asian patients was 5.5 (P < .001), and the HR for TDF vs. ETV was 2.0 (P = .001).

A univariate model for retreatment showed an HR of 1.6 for patients 50 and older; all other parameters (sex, race, NA type, and HBeAg status at start of therapy) were not significantly different.

In multivariate models, only race/ethnicity remained significant as a predictor for HBsAg loss, with a HR of 5.8 for Whites vs. Asians (P < .001), and only age 50 and older remained significant as a predictor for retreatment, with a HR of 1.6 (P < .001).

The 4-year cumulative rate of virologic relapse, defined as an HBV DNA of 2000 IU/mL or higher) was 74%, the rate of combined DNA plus ALT relapse (ALT 2 or more times the upper limit of normal) was 56%, and the rate of ALT flares (5 or more times the upper limit of normal) was 33%.

In all, 15 patients (1%) experienced hepatic decompensation, and 12 (0.96%) died, with 9 of the deaths reported as liver-related.
 

Race/ethnicity differences previously seen

Liver specialist Anna Suk-Fong Lok, MD, professor of medicine at the University of Michigan in Ann Arbor, who was not involved in the study, said that the findings are not especially surprising.

“When the studies came out from Asian countries showing that patients who were taken off treatment had a higher rate of S antigen loss than patients who stayed on treatment, the rate of S antigen loss was not all that impressive, but when you look at the European studies the rate of S antigen loss was very high,” she said in an interview.

“The question of course is ‘Why?’ I don’t think we understand completely why. We can speculate, but none of these type studies give us a definitive answer,” she said.

Possible reasons for the racial differences in HBsAg loss include differences in hepatitis B genotype, she said.

“Another possibility is that Asian patients may have been infected either at the time of birth or as a young kid, so they may have been infected for a much longer period of time than [Whites], who usually acquire infections as adults,” Dr. Lok said.

There may also be differences between patient populations in immune responses following cessation of antiviral therapy, she added.

The study was supported by the RETRACT-B group. Ms. Hirode and Dr. Lok reported no relevant disclosures.

SOURCE: Hirode G et al. AASLD 2020. Abstract 23.

Loss of the hepatitis B surface antigen (HBsAg), a marker for functional cure of hepatitis B infection, is nearly six times more common among White patients than Asian patients following cessation of therapy with a nucleotide or nucleoside analogue, investigators in the RETRACT-B study group report.

Among 1,541 patients in a global retrospective cohort, the cumulative rate of HBsAg loss 4 years after cessation of therapy with entecavir (ETV), tenofovir disoproxil fumarate (TDF), or other nucleoside/nucleotide analogue (“nuc” or NA) was 11% in Asian patients, compared with 41% in Whites, which translated in multivariate analysis into a hazard ratio (HR) of 5.8 (P < .001), said Grishma Hirode, a clinical research associate and PhD candidate at the Toronto Centre for Liver Disease.

“On univariate Cox regression, the rate of S [antigen] loss was significantly higher among older patients, among [Whites], and among tenofovir-treated patients prior to stopping,” she said during the virtual annual meeting of the American Association for the Study of Liver Diseases.

Although NAs are effective at suppressing hepatitis B viral activity, functional cure as indicated by HBsAg loss is uncommon, Ms. Hirode noted.

“Finite use of antiviral therapy has been proposed as an alternative to long-term therapy, and the rationale for stopping nuc therapy is to induce a durable virologic remission in the form of an inactive carrier state, and ideally a functional cure,” she said.

The RETRACT-B (Response after End of Treatment with Antivirals in Chronic Hepatitis B) study group, comprising liver treatment centers in Canada, Europe, Hong Kong, and Taiwan, studies outcomes following cessation of nucleos(t)ide analogue therapy.

The investigators looked at data on 1,541 patients, including those with both hepatitis B e-antigen (HBeAg) positive and HBeAg-negative disease at the start of therapy, all of whom were HBeAg negative at the time of antiviral cessation and had undetectable serum HBV DNA. Patients with hepatitis C, hepatitis D and/or HIV co-infection were excluded, as were patients who had received interferon treatment less than 12 months before stopping.

The mean age at baseline was 53 years. Men comprised 73% of the sample. In all, 88% of patients were Asian, 10% White, and 2% other.

In patients for whom genotype data was known, 0.5% had type A, 43% type B, 11% type C, and 2% type D.

Nearly two-thirds of patients (60%) were on ETV at the time of drug cessation, 29% were on TDF, and 11% were on other agents.

In all, 5% of patients had cirrhosis at the time of nucleos(t)ide cessation, the mean HBsAg was 2.6 log₁₀ IU/mL, and the mean alanine aminotransferase (ALT) level was 0.6 times the upper limit of normal.

The median duration of NA therapy was 3 years.

The cumulative rates of HBsAg loss over time among all patients was 3% at 1 year, 8% at 2 years. 12% at 3 years, and 14% at 4 years. Cumulative rates of antigen loss at year 4 were significantly greater for patients 50 and older vs. those younger than 50 (18% vs. 9%, respectively, P = .01), Whites vs. Asians (41% vs. 11%, P < .001), and in those who had been on TDF vs. ETV (17% vs. 12%, P = .001). There was no significant difference in cumulative HBsAg loss between patients who were HBeAg positive or negative at the start of NA therapy.

Cumulative rates of retreatment were 30% at 1 year, 43% at 2 years, 50% at 3 years, and 56% at 4 years. The only significant predictor for retreatment was age, with patients 50 and older being significantly more likely to be retreated by year 4 (63% vs. 45%, respectively, P < .001).

In a univariate model for HBsAg loss, the HR for age 50 and older was 1.7 (P = .01), the HR for White vs. Asian patients was 5.5 (P < .001), and the HR for TDF vs. ETV was 2.0 (P = .001).

A univariate model for retreatment showed an HR of 1.6 for patients 50 and older; all other parameters (sex, race, NA type, and HBeAg status at start of therapy) were not significantly different.

In multivariate models, only race/ethnicity remained significant as a predictor for HBsAg loss, with a HR of 5.8 for Whites vs. Asians (P < .001), and only age 50 and older remained significant as a predictor for retreatment, with a HR of 1.6 (P < .001).

The 4-year cumulative rate of virologic relapse, defined as an HBV DNA of 2000 IU/mL or higher) was 74%, the rate of combined DNA plus ALT relapse (ALT 2 or more times the upper limit of normal) was 56%, and the rate of ALT flares (5 or more times the upper limit of normal) was 33%.

In all, 15 patients (1%) experienced hepatic decompensation, and 12 (0.96%) died, with 9 of the deaths reported as liver-related.
 

Race/ethnicity differences previously seen

Liver specialist Anna Suk-Fong Lok, MD, professor of medicine at the University of Michigan in Ann Arbor, who was not involved in the study, said that the findings are not especially surprising.

“When the studies came out from Asian countries showing that patients who were taken off treatment had a higher rate of S antigen loss than patients who stayed on treatment, the rate of S antigen loss was not all that impressive, but when you look at the European studies the rate of S antigen loss was very high,” she said in an interview.

“The question of course is ‘Why?’ I don’t think we understand completely why. We can speculate, but none of these type studies give us a definitive answer,” she said.

Possible reasons for the racial differences in HBsAg loss include differences in hepatitis B genotype, she said.

“Another possibility is that Asian patients may have been infected either at the time of birth or as a young kid, so they may have been infected for a much longer period of time than [Whites], who usually acquire infections as adults,” Dr. Lok said.

There may also be differences between patient populations in immune responses following cessation of antiviral therapy, she added.

The study was supported by the RETRACT-B group. Ms. Hirode and Dr. Lok reported no relevant disclosures.

SOURCE: Hirode G et al. AASLD 2020. Abstract 23.

The incidence rate of hepatocellular carcinoma in urban areas of the United States began to slow in 2009, but the rate in rural areas of the nation continued to rise at a steady pace, especially among non-Hispanic Whites and Blacks, investigators have found.

Although overall hepatocellular carcinoma (HCC) incidence rates were consistently lower among people living in nonmetro (rural) versus metro (urban) areas, the average annual percentage change in urban areas began to slow from 5.3% for the period of 1995 through 2009 to 2.7% thereafter. In contrast, the average annual percentage change in rural areas remained steady at 5.7%, a disparity that remained even after adjusting for differences among subgroups, reported Christina Gainey, MD, a third-year resident in internal medicine at the University of Southern California Medical Center, Los Angeles.

“We found that there are striking urban-rural disparities in HCC incidence trends that vary by race and ethnicity, and these disparities are growing over time,” she said during the virtual annual meeting of the American Association for the Study of Liver Diseases.

“Our study really highlights a critical public health issue that’s disproportionately affecting rural Americans. They already face considerable health inequities when it comes to access to care, health outcomes, and public health infrastructure and resources, and as of now we still don’t know why cases of HCC continue to rise in these areas,” she said.

Dr. Gainey noted that HCC is the fastest-growing cancer in the United States, according to the 2020 Annual Report to the Nation on the Status of Cancer, issued jointly by the Centers for Disease Control and Prevention, the North American Association of Central Cancer Registries, the American Cancer Society, and the National Cancer Institute.

Previous studies have identified disparities between urban and rural regions in care of patients with cervical cancer, colorectal cancer, and other malignancies, but there are very few data on urban-rural differences in HCC incidence, she said.
 

Incidence trends

To better understand whether such differences exists, the investigators compared trends in age-adjusted incidence rates of HCC in both rural and urban areas of the United States from 1995 to 2016, with stratification of trends by race/ethnicity and other demographic factors.

They drew from the NAACR database, which captures 93% of the U.S. population, in contrast to the CDC’s Surveillance, Epidemiology, and End Results (SEER) database which samples just 18% of the population.

Patients with HCC were defined by diagnostic codes, with diagnoses of intrahepatic bile duct cancers excluded.

They used 2013 U.S. Department of Agriculture Rural-Urban Continuum Codes to identify rural areas (regions of open countryside with town populations fewer than 2,500 people) and urban areas (populations ranging from 2,500 to 49,999, but not part of a larger labor market area).

The investigators identified a total of 310,635 HCC cases, 85% in urban areas and 15% in rural areas. Three-fourths of the patients (77%) were male. The median age ranged from 55-59 years.

There were notable demographic differences between the regions with non-Hispanic Whites comprising only 57% of the urban sample, but 82% of the rural sample. The urban sample included 16% non-Hispanic Blacks, 10% Asian/Pacific Islanders, and 17% Hispanics. The respective proportions in the rural areas were 8%, 2%, and 8%.

As noted before, age-adjusted incidence rates (adjusted to the year 2000 U.S. population) were lower in rural areas, at 4.9 per 100,000 population, compared with 6.9/100,000 in urban areas.

But when they looked at the average annual percentage changes using jointpoint regression, they saw that beginning in 2009 the AAPC in urban areas began to slow, from 5.3% for the period prior to 2009 to 2.7% thereafter, while the average annual percentage change in urban areas remained steady at 5.7%.

The largest increase in incidence over the course of the study was among rural non-Hispanic Whites, with an AAPC of 5.7%. Among urban non-Hispanic Blacks, the AAPC rose by 6.6% from 1995 to 2009, but slowed thereafter.

In contrast, among rural non-Hispanic Blacks the AAPC remained steady, at 5.4%.

The only group to see a decline in incidence was urban Asians/Pacific Islanders, who had an overall decline of 1%.

Among all groups, rural Hispanics had the highest age-adjusted incidence rates, at 14.9 per 100,000 in 2016.
 

Awareness gap?

 Lewis R. Roberts, MB, ChB, PhD, a hepatobiliary cancer researcher at the Mayo Clinic in Rochester, Minn., who was not involved in the study, said in an interview that the difference in incidence rates between cities and the country may be attributable to a number of factors, including the opioid crisis, which can lead to an increase in injectable drug use or sexual behaviors resulting in increases in chronic hepatitis C infections and cirrhosis, known risk factors for HCC, as well as a lack of awareness of infections as a risk factor.

“In order for people to find these diseases, they have to be looking, and many of these are hidden diseases in our community,” he said. “What the study made me wonder was whether it just happens to be that they are in some ways more hidden in a rural community than they are in an urban community.”

He noted that clinicians in urban communities are more accustomed to treating more diverse populations who may have higher susceptibility to viral hepatitis, for example, and that screening and treatment for hepatitis C may be more common in urban areas than rural areas, he said.

No funding source for the study was reported. Dr. Gainey and Dr. Roberts reported having no conflicts of interest to disclose.

SOURCE: Gainey C et al. Liver Meeting 2020, Abstract 136.

The incidence rate of hepatocellular carcinoma in urban areas of the United States began to slow in 2009, but the rate in rural areas of the nation continued to rise at a steady pace, especially among non-Hispanic Whites and Blacks, investigators have found.

Although overall hepatocellular carcinoma (HCC) incidence rates were consistently lower among people living in nonmetro (rural) versus metro (urban) areas, the average annual percentage change in urban areas began to slow from 5.3% for the period of 1995 through 2009 to 2.7% thereafter. In contrast, the average annual percentage change in rural areas remained steady at 5.7%, a disparity that remained even after adjusting for differences among subgroups, reported Christina Gainey, MD, a third-year resident in internal medicine at the University of Southern California Medical Center, Los Angeles.

“We found that there are striking urban-rural disparities in HCC incidence trends that vary by race and ethnicity, and these disparities are growing over time,” she said during the virtual annual meeting of the American Association for the Study of Liver Diseases.

“Our study really highlights a critical public health issue that’s disproportionately affecting rural Americans. They already face considerable health inequities when it comes to access to care, health outcomes, and public health infrastructure and resources, and as of now we still don’t know why cases of HCC continue to rise in these areas,” she said.

Dr. Gainey noted that HCC is the fastest-growing cancer in the United States, according to the 2020 Annual Report to the Nation on the Status of Cancer, issued jointly by the Centers for Disease Control and Prevention, the North American Association of Central Cancer Registries, the American Cancer Society, and the National Cancer Institute.

Previous studies have identified disparities between urban and rural regions in care of patients with cervical cancer, colorectal cancer, and other malignancies, but there are very few data on urban-rural differences in HCC incidence, she said.
 

Incidence trends

To better understand whether such differences exists, the investigators compared trends in age-adjusted incidence rates of HCC in both rural and urban areas of the United States from 1995 to 2016, with stratification of trends by race/ethnicity and other demographic factors.

They drew from the NAACR database, which captures 93% of the U.S. population, in contrast to the CDC’s Surveillance, Epidemiology, and End Results (SEER) database which samples just 18% of the population.

Patients with HCC were defined by diagnostic codes, with diagnoses of intrahepatic bile duct cancers excluded.

They used 2013 U.S. Department of Agriculture Rural-Urban Continuum Codes to identify rural areas (regions of open countryside with town populations fewer than 2,500 people) and urban areas (populations ranging from 2,500 to 49,999, but not part of a larger labor market area).

The investigators identified a total of 310,635 HCC cases, 85% in urban areas and 15% in rural areas. Three-fourths of the patients (77%) were male. The median age ranged from 55-59 years.

There were notable demographic differences between the regions with non-Hispanic Whites comprising only 57% of the urban sample, but 82% of the rural sample. The urban sample included 16% non-Hispanic Blacks, 10% Asian/Pacific Islanders, and 17% Hispanics. The respective proportions in the rural areas were 8%, 2%, and 8%.

As noted before, age-adjusted incidence rates (adjusted to the year 2000 U.S. population) were lower in rural areas, at 4.9 per 100,000 population, compared with 6.9/100,000 in urban areas.

But when they looked at the average annual percentage changes using jointpoint regression, they saw that beginning in 2009 the AAPC in urban areas began to slow, from 5.3% for the period prior to 2009 to 2.7% thereafter, while the average annual percentage change in urban areas remained steady at 5.7%.

The largest increase in incidence over the course of the study was among rural non-Hispanic Whites, with an AAPC of 5.7%. Among urban non-Hispanic Blacks, the AAPC rose by 6.6% from 1995 to 2009, but slowed thereafter.

In contrast, among rural non-Hispanic Blacks the AAPC remained steady, at 5.4%.

The only group to see a decline in incidence was urban Asians/Pacific Islanders, who had an overall decline of 1%.

Among all groups, rural Hispanics had the highest age-adjusted incidence rates, at 14.9 per 100,000 in 2016.
 

Awareness gap?

 Lewis R. Roberts, MB, ChB, PhD, a hepatobiliary cancer researcher at the Mayo Clinic in Rochester, Minn., who was not involved in the study, said in an interview that the difference in incidence rates between cities and the country may be attributable to a number of factors, including the opioid crisis, which can lead to an increase in injectable drug use or sexual behaviors resulting in increases in chronic hepatitis C infections and cirrhosis, known risk factors for HCC, as well as a lack of awareness of infections as a risk factor.

“In order for people to find these diseases, they have to be looking, and many of these are hidden diseases in our community,” he said. “What the study made me wonder was whether it just happens to be that they are in some ways more hidden in a rural community than they are in an urban community.”

He noted that clinicians in urban communities are more accustomed to treating more diverse populations who may have higher susceptibility to viral hepatitis, for example, and that screening and treatment for hepatitis C may be more common in urban areas than rural areas, he said.

No funding source for the study was reported. Dr. Gainey and Dr. Roberts reported having no conflicts of interest to disclose.

SOURCE: Gainey C et al. Liver Meeting 2020, Abstract 136.

The incidence rate of hepatocellular carcinoma in urban areas of the United States began to slow in 2009, but the rate in rural areas of the nation continued to rise at a steady pace, especially among non-Hispanic Whites and Blacks, investigators have found.

Although overall hepatocellular carcinoma (HCC) incidence rates were consistently lower among people living in nonmetro (rural) versus metro (urban) areas, the average annual percentage change in urban areas began to slow from 5.3% for the period of 1995 through 2009 to 2.7% thereafter. In contrast, the average annual percentage change in rural areas remained steady at 5.7%, a disparity that remained even after adjusting for differences among subgroups, reported Christina Gainey, MD, a third-year resident in internal medicine at the University of Southern California Medical Center, Los Angeles.

“We found that there are striking urban-rural disparities in HCC incidence trends that vary by race and ethnicity, and these disparities are growing over time,” she said during the virtual annual meeting of the American Association for the Study of Liver Diseases.

“Our study really highlights a critical public health issue that’s disproportionately affecting rural Americans. They already face considerable health inequities when it comes to access to care, health outcomes, and public health infrastructure and resources, and as of now we still don’t know why cases of HCC continue to rise in these areas,” she said.

Dr. Gainey noted that HCC is the fastest-growing cancer in the United States, according to the 2020 Annual Report to the Nation on the Status of Cancer, issued jointly by the Centers for Disease Control and Prevention, the North American Association of Central Cancer Registries, the American Cancer Society, and the National Cancer Institute.

Previous studies have identified disparities between urban and rural regions in care of patients with cervical cancer, colorectal cancer, and other malignancies, but there are very few data on urban-rural differences in HCC incidence, she said.
 

Incidence trends

To better understand whether such differences exists, the investigators compared trends in age-adjusted incidence rates of HCC in both rural and urban areas of the United States from 1995 to 2016, with stratification of trends by race/ethnicity and other demographic factors.

They drew from the NAACR database, which captures 93% of the U.S. population, in contrast to the CDC’s Surveillance, Epidemiology, and End Results (SEER) database which samples just 18% of the population.

Patients with HCC were defined by diagnostic codes, with diagnoses of intrahepatic bile duct cancers excluded.

They used 2013 U.S. Department of Agriculture Rural-Urban Continuum Codes to identify rural areas (regions of open countryside with town populations fewer than 2,500 people) and urban areas (populations ranging from 2,500 to 49,999, but not part of a larger labor market area).

The investigators identified a total of 310,635 HCC cases, 85% in urban areas and 15% in rural areas. Three-fourths of the patients (77%) were male. The median age ranged from 55-59 years.

There were notable demographic differences between the regions with non-Hispanic Whites comprising only 57% of the urban sample, but 82% of the rural sample. The urban sample included 16% non-Hispanic Blacks, 10% Asian/Pacific Islanders, and 17% Hispanics. The respective proportions in the rural areas were 8%, 2%, and 8%.

As noted before, age-adjusted incidence rates (adjusted to the year 2000 U.S. population) were lower in rural areas, at 4.9 per 100,000 population, compared with 6.9/100,000 in urban areas.

But when they looked at the average annual percentage changes using jointpoint regression, they saw that beginning in 2009 the AAPC in urban areas began to slow, from 5.3% for the period prior to 2009 to 2.7% thereafter, while the average annual percentage change in urban areas remained steady at 5.7%.

The largest increase in incidence over the course of the study was among rural non-Hispanic Whites, with an AAPC of 5.7%. Among urban non-Hispanic Blacks, the AAPC rose by 6.6% from 1995 to 2009, but slowed thereafter.

In contrast, among rural non-Hispanic Blacks the AAPC remained steady, at 5.4%.

The only group to see a decline in incidence was urban Asians/Pacific Islanders, who had an overall decline of 1%.

Among all groups, rural Hispanics had the highest age-adjusted incidence rates, at 14.9 per 100,000 in 2016.
 

Awareness gap?

 Lewis R. Roberts, MB, ChB, PhD, a hepatobiliary cancer researcher at the Mayo Clinic in Rochester, Minn., who was not involved in the study, said in an interview that the difference in incidence rates between cities and the country may be attributable to a number of factors, including the opioid crisis, which can lead to an increase in injectable drug use or sexual behaviors resulting in increases in chronic hepatitis C infections and cirrhosis, known risk factors for HCC, as well as a lack of awareness of infections as a risk factor.

“In order for people to find these diseases, they have to be looking, and many of these are hidden diseases in our community,” he said. “What the study made me wonder was whether it just happens to be that they are in some ways more hidden in a rural community than they are in an urban community.”

He noted that clinicians in urban communities are more accustomed to treating more diverse populations who may have higher susceptibility to viral hepatitis, for example, and that screening and treatment for hepatitis C may be more common in urban areas than rural areas, he said.

No funding source for the study was reported. Dr. Gainey and Dr. Roberts reported having no conflicts of interest to disclose.

SOURCE: Gainey C et al. Liver Meeting 2020, Abstract 136.

Individuals living with hepatitis C virus (HCV) infection face several challenges in accessing care, many of which are shared by patients in the HIV community.

Better linkage to care with providers who are familiar with both the HCV and HIV treatment cascade may not only improve access to HCV treatment, but it may also support patient retention, treatment adherence, and achievement of sustained virologic response (SVR) and viral suppression, said Stephanie LaMoy, CAN Community Health, North Point, Florida. She presented the results of a pilot study at the virtual Association of Nurses in AIDS Care 2020 Annual Meeting.

In an effort to identify strategies most important for improving care access among their patients with HCV, LaMoy and her colleagues assessed 12-month patient data collected from three of their clinics. These data were evaluated for HCV treatment access, engagement, and outcomes.

The pilot study included 126 patients who were reactive and another 24 HCV-positive patients who were referred from other sources. Active HCV infections requiring treatment were reported in 144 patients.

A total of 59 patients were linked to care but did not initiate treatment for their active infection. LaMoy said there were multiple causes, including homelessness, substance abuse, and inability to maintain contact.

In contrast, 85 patients with HCV infection started treatment, but 35 of these patients did not complete their regimen. Out of the 50 patients who reported completing treatment, 30 did not return to the clinic to confirm sustained viral suppression.

According to LaMoy, this raised a red flag, causing the investigators to consider a different approach to care.
 

HIV care continuum model and its role in HCV

To improve the rate at which patients with HCV infection complete treatment within their clinics, the researchers formed a panel to determine necessary interventions that could reduce barriers to care.

The HIV care continuum came into play. They chose this model based on knowledge that HCV and HIV share the same care continuum with similar goals in diagnosis, linkage to care, retention, and suppression.

Based on the consensus of the panel and consideration of the HIV care continuum model, they identified a number of interventions needed to mitigate HCV treatment barriers. These included the incorporation of peer navigators or linkage-to-care (LCC) coordinators, use of the mobile medical unit, greater implementation of onsite lab visits, and medication-assisted treatment.

The LCC coordinators proved to be particularly important, as these team members helped assist patients with social and financial support to address challenges with access to treatment. These coordinators can also help  patients gain access to specialized providers, ultimately improving the chance of successful HCV management.

Additionally, LCC coordinators may help identify and reduce barriers associated with housing, transportation, and nutrition. Frequent patient contact by the LCC coordinators can encourage adherence and promote risk reduction education, such as providing referrals to needle exchange services.

“Linking individuals to care with providers who are familiar with the treatment cascade could help improve retention and should be a top priority for those involved in HCV screening and treatment,” said LaMoy. “An environment with knowledge, lack of judgment, and a tenacious need to heal the community that welcomes those with barriers to care is exactly what is needed for the patients in our program.”
 

National, community challenges fuel barriers to HCV treatment access

Substance use, trauma histories, and mental health problems can negatively affect care engagement and must be addressed before the benefits of HCV therapy can be realized.

Addressing these issues isn’t always easy, said Kathleen Bernock, FNP-BC, AACRN, AAHIVS, of the Bedford-Stuyvesant Family Health Center in New York City, in an email to Medscape Medical News. She pointed out that several states have harsh restrictions on who is able to access HCV treatment, and some states will not approve certain medications for people who actively use drugs.

“Even for states without these restrictions, many health systems are difficult to navigate and may not be welcoming to persons actively using,” said Bernock. Trauma-informed care can also be difficult to translate into clinics, she added.

“Decentralizing care to the communities most affected would greatly help mitigate these barriers,” suggested Bernock. Decentralization, she explained, might include co-locating services such as syringe exchanges, utilizing community health workers and patient navigators, and expanding capacity-to-treat to community-based providers.

“[And] with the expansion of telehealth services in the US,” said Bernock, “we now have even more avenues to reach people that we never had before.”

LaMoy and Bernock have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Individuals living with hepatitis C virus (HCV) infection face several challenges in accessing care, many of which are shared by patients in the HIV community.

Better linkage to care with providers who are familiar with both the HCV and HIV treatment cascade may not only improve access to HCV treatment, but it may also support patient retention, treatment adherence, and achievement of sustained virologic response (SVR) and viral suppression, said Stephanie LaMoy, CAN Community Health, North Point, Florida. She presented the results of a pilot study at the virtual Association of Nurses in AIDS Care 2020 Annual Meeting.

In an effort to identify strategies most important for improving care access among their patients with HCV, LaMoy and her colleagues assessed 12-month patient data collected from three of their clinics. These data were evaluated for HCV treatment access, engagement, and outcomes.

The pilot study included 126 patients who were reactive and another 24 HCV-positive patients who were referred from other sources. Active HCV infections requiring treatment were reported in 144 patients.

A total of 59 patients were linked to care but did not initiate treatment for their active infection. LaMoy said there were multiple causes, including homelessness, substance abuse, and inability to maintain contact.

In contrast, 85 patients with HCV infection started treatment, but 35 of these patients did not complete their regimen. Out of the 50 patients who reported completing treatment, 30 did not return to the clinic to confirm sustained viral suppression.

According to LaMoy, this raised a red flag, causing the investigators to consider a different approach to care.
 

HIV care continuum model and its role in HCV

To improve the rate at which patients with HCV infection complete treatment within their clinics, the researchers formed a panel to determine necessary interventions that could reduce barriers to care.

The HIV care continuum came into play. They chose this model based on knowledge that HCV and HIV share the same care continuum with similar goals in diagnosis, linkage to care, retention, and suppression.

Based on the consensus of the panel and consideration of the HIV care continuum model, they identified a number of interventions needed to mitigate HCV treatment barriers. These included the incorporation of peer navigators or linkage-to-care (LCC) coordinators, use of the mobile medical unit, greater implementation of onsite lab visits, and medication-assisted treatment.

The LCC coordinators proved to be particularly important, as these team members helped assist patients with social and financial support to address challenges with access to treatment. These coordinators can also help  patients gain access to specialized providers, ultimately improving the chance of successful HCV management.

Additionally, LCC coordinators may help identify and reduce barriers associated with housing, transportation, and nutrition. Frequent patient contact by the LCC coordinators can encourage adherence and promote risk reduction education, such as providing referrals to needle exchange services.

“Linking individuals to care with providers who are familiar with the treatment cascade could help improve retention and should be a top priority for those involved in HCV screening and treatment,” said LaMoy. “An environment with knowledge, lack of judgment, and a tenacious need to heal the community that welcomes those with barriers to care is exactly what is needed for the patients in our program.”
 

National, community challenges fuel barriers to HCV treatment access

Substance use, trauma histories, and mental health problems can negatively affect care engagement and must be addressed before the benefits of HCV therapy can be realized.

Addressing these issues isn’t always easy, said Kathleen Bernock, FNP-BC, AACRN, AAHIVS, of the Bedford-Stuyvesant Family Health Center in New York City, in an email to Medscape Medical News. She pointed out that several states have harsh restrictions on who is able to access HCV treatment, and some states will not approve certain medications for people who actively use drugs.

“Even for states without these restrictions, many health systems are difficult to navigate and may not be welcoming to persons actively using,” said Bernock. Trauma-informed care can also be difficult to translate into clinics, she added.

“Decentralizing care to the communities most affected would greatly help mitigate these barriers,” suggested Bernock. Decentralization, she explained, might include co-locating services such as syringe exchanges, utilizing community health workers and patient navigators, and expanding capacity-to-treat to community-based providers.

“[And] with the expansion of telehealth services in the US,” said Bernock, “we now have even more avenues to reach people that we never had before.”

LaMoy and Bernock have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Individuals living with hepatitis C virus (HCV) infection face several challenges in accessing care, many of which are shared by patients in the HIV community.

Better linkage to care with providers who are familiar with both the HCV and HIV treatment cascade may not only improve access to HCV treatment, but it may also support patient retention, treatment adherence, and achievement of sustained virologic response (SVR) and viral suppression, said Stephanie LaMoy, CAN Community Health, North Point, Florida. She presented the results of a pilot study at the virtual Association of Nurses in AIDS Care 2020 Annual Meeting.

In an effort to identify strategies most important for improving care access among their patients with HCV, LaMoy and her colleagues assessed 12-month patient data collected from three of their clinics. These data were evaluated for HCV treatment access, engagement, and outcomes.

The pilot study included 126 patients who were reactive and another 24 HCV-positive patients who were referred from other sources. Active HCV infections requiring treatment were reported in 144 patients.

A total of 59 patients were linked to care but did not initiate treatment for their active infection. LaMoy said there were multiple causes, including homelessness, substance abuse, and inability to maintain contact.

In contrast, 85 patients with HCV infection started treatment, but 35 of these patients did not complete their regimen. Out of the 50 patients who reported completing treatment, 30 did not return to the clinic to confirm sustained viral suppression.

According to LaMoy, this raised a red flag, causing the investigators to consider a different approach to care.
 

HIV care continuum model and its role in HCV

To improve the rate at which patients with HCV infection complete treatment within their clinics, the researchers formed a panel to determine necessary interventions that could reduce barriers to care.

The HIV care continuum came into play. They chose this model based on knowledge that HCV and HIV share the same care continuum with similar goals in diagnosis, linkage to care, retention, and suppression.

Based on the consensus of the panel and consideration of the HIV care continuum model, they identified a number of interventions needed to mitigate HCV treatment barriers. These included the incorporation of peer navigators or linkage-to-care (LCC) coordinators, use of the mobile medical unit, greater implementation of onsite lab visits, and medication-assisted treatment.

The LCC coordinators proved to be particularly important, as these team members helped assist patients with social and financial support to address challenges with access to treatment. These coordinators can also help  patients gain access to specialized providers, ultimately improving the chance of successful HCV management.

Additionally, LCC coordinators may help identify and reduce barriers associated with housing, transportation, and nutrition. Frequent patient contact by the LCC coordinators can encourage adherence and promote risk reduction education, such as providing referrals to needle exchange services.

“Linking individuals to care with providers who are familiar with the treatment cascade could help improve retention and should be a top priority for those involved in HCV screening and treatment,” said LaMoy. “An environment with knowledge, lack of judgment, and a tenacious need to heal the community that welcomes those with barriers to care is exactly what is needed for the patients in our program.”
 

National, community challenges fuel barriers to HCV treatment access

Substance use, trauma histories, and mental health problems can negatively affect care engagement and must be addressed before the benefits of HCV therapy can be realized.

Addressing these issues isn’t always easy, said Kathleen Bernock, FNP-BC, AACRN, AAHIVS, of the Bedford-Stuyvesant Family Health Center in New York City, in an email to Medscape Medical News. She pointed out that several states have harsh restrictions on who is able to access HCV treatment, and some states will not approve certain medications for people who actively use drugs.

“Even for states without these restrictions, many health systems are difficult to navigate and may not be welcoming to persons actively using,” said Bernock. Trauma-informed care can also be difficult to translate into clinics, she added.

“Decentralizing care to the communities most affected would greatly help mitigate these barriers,” suggested Bernock. Decentralization, she explained, might include co-locating services such as syringe exchanges, utilizing community health workers and patient navigators, and expanding capacity-to-treat to community-based providers.

“[And] with the expansion of telehealth services in the US,” said Bernock, “we now have even more avenues to reach people that we never had before.”

LaMoy and Bernock have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Patients with primary biliary cholangitis experienced rapid improvements in itch and quality of life after treatment with linerixibat in a randomized, placebo-controlled trial of the safety, efficacy, and tolerability of the small-molecule drug.

Moderate to severe pruritus “affects patients’ quality of life and is a huge burden for them,” said investigator Cynthia Levy, MD, from the University of Miami Health System.

“Finally having a medication that controls those symptoms is really important,” she said in an interview.

With a twice-daily mid-range dose of the drug for 12 weeks, patients with moderate to severe itch reported significantly less itch and better social and emotional quality of life, Dr. Levy reported at the Liver Meeting, where she presented findings from the phase 2 GLIMMER trial.

After a single-blind 4-week placebo run-in period for patients with itch scores of at least 4 on a 10-point rating scale, those with itch scores of at least 3 were then randomly assigned to one of five treatment regimens – once-daily linerixibat at doses of 20 mg, 90 mg, or 180 mg, or twice-daily doses of 40 mg or 90 mg – or to placebo.

After 12 weeks of treatment, all 147 participants once again received placebo for 4 weeks.

During the trial, participants recorded itch levels twice daily. The worst of these daily scores was averaged every 7 days to determine the mean worst daily itch.

The primary study endpoint was the change in worst daily itch from baseline after 12 weeks of treatment. Participants whose self-rated itch improved by 2 points on the 10-point scale were considered to have had a response to the drug.

Participants also completed the PBC-40, an instrument to measure quality of life in patients with primary biliary cholangitis, answering questions about itch and social and emotional status.

Reductions in worst daily itch from baseline to 12 weeks were steepest in the 40-mg twice-daily group, at 2.86 points, and in the 90-mg twice-daily group, at 2.25 points. In the placebo group, the mean decrease was 1.73 points.

During the subsequent 4 weeks of placebo, after treatment ended, the itch relief faded in all groups.

Scores on the PBC-40 itch domain improved significantly in every group, including placebo. However, only those in the twice-daily 40-mg group saw significant improvements on the social (P = .0016) and emotional (P = .0025) domains.
 

‘Between incremental and revolutionary’

The results are on a “kind of continuum between incremental and revolutionary,” said Jonathan A. Dranoff, MD, from the University of Arkansas for Medical Sciences, Little Rock, who was not involved in the study. “It doesn’t hit either extreme, but it’s the first new drug for this purpose in forever, which by itself is a good thing.”

The placebo effect suggests that “maybe the actual contribution of the noncognitive brain to pruritus is bigger than we thought, and that’s worth noting,” he added. Nevertheless, “the drug still appears to have effects that are statistically different from placebo.”

The placebo effect in itching studies is always high but tends to wane over time, said Dr. Levy. This trial had a 4-week placebo run-in period to allow that effect to fade somewhat, she explained.

About 10% of the study cohort experienced drug-related diarrhea, which was expected, and about 10% dropped out of the trial because of drug-related adverse events.

Linerixibat is an ileal sodium-dependent bile acid transporter inhibitor, so the gut has to deal with the excess bile acid fallout, but the diarrhea is likely manageable with antidiarrheals, said Dr. Levy.

It is unlikely that diarrhea will deter patients with severe itch from using an effective drug when other drugs have failed them. “These patients are consumed by itch most of the time,” said Dr. Dranoff. “I think for people who don’t regularly treat patients with primary biliary cholangitis, it’s one of the underappreciated aspects of the disease.”

The improvements in social and emotional quality of life seen with linerixibat are not only statistically significant, they are also clinically significant, said Dr. Levy. “We are really expecting this to impact the lives of our patients and are looking forward to phase 3.”

Dr. Levy disclosed support from GlaxoSmithKline. Dr. Dranoff disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Patients with primary biliary cholangitis experienced rapid improvements in itch and quality of life after treatment with linerixibat in a randomized, placebo-controlled trial of the safety, efficacy, and tolerability of the small-molecule drug.

Moderate to severe pruritus “affects patients’ quality of life and is a huge burden for them,” said investigator Cynthia Levy, MD, from the University of Miami Health System.

“Finally having a medication that controls those symptoms is really important,” she said in an interview.

With a twice-daily mid-range dose of the drug for 12 weeks, patients with moderate to severe itch reported significantly less itch and better social and emotional quality of life, Dr. Levy reported at the Liver Meeting, where she presented findings from the phase 2 GLIMMER trial.

After a single-blind 4-week placebo run-in period for patients with itch scores of at least 4 on a 10-point rating scale, those with itch scores of at least 3 were then randomly assigned to one of five treatment regimens – once-daily linerixibat at doses of 20 mg, 90 mg, or 180 mg, or twice-daily doses of 40 mg or 90 mg – or to placebo.

After 12 weeks of treatment, all 147 participants once again received placebo for 4 weeks.

During the trial, participants recorded itch levels twice daily. The worst of these daily scores was averaged every 7 days to determine the mean worst daily itch.

The primary study endpoint was the change in worst daily itch from baseline after 12 weeks of treatment. Participants whose self-rated itch improved by 2 points on the 10-point scale were considered to have had a response to the drug.

Participants also completed the PBC-40, an instrument to measure quality of life in patients with primary biliary cholangitis, answering questions about itch and social and emotional status.

Reductions in worst daily itch from baseline to 12 weeks were steepest in the 40-mg twice-daily group, at 2.86 points, and in the 90-mg twice-daily group, at 2.25 points. In the placebo group, the mean decrease was 1.73 points.

During the subsequent 4 weeks of placebo, after treatment ended, the itch relief faded in all groups.

Scores on the PBC-40 itch domain improved significantly in every group, including placebo. However, only those in the twice-daily 40-mg group saw significant improvements on the social (P = .0016) and emotional (P = .0025) domains.
 

‘Between incremental and revolutionary’

The results are on a “kind of continuum between incremental and revolutionary,” said Jonathan A. Dranoff, MD, from the University of Arkansas for Medical Sciences, Little Rock, who was not involved in the study. “It doesn’t hit either extreme, but it’s the first new drug for this purpose in forever, which by itself is a good thing.”

The placebo effect suggests that “maybe the actual contribution of the noncognitive brain to pruritus is bigger than we thought, and that’s worth noting,” he added. Nevertheless, “the drug still appears to have effects that are statistically different from placebo.”

The placebo effect in itching studies is always high but tends to wane over time, said Dr. Levy. This trial had a 4-week placebo run-in period to allow that effect to fade somewhat, she explained.

About 10% of the study cohort experienced drug-related diarrhea, which was expected, and about 10% dropped out of the trial because of drug-related adverse events.

Linerixibat is an ileal sodium-dependent bile acid transporter inhibitor, so the gut has to deal with the excess bile acid fallout, but the diarrhea is likely manageable with antidiarrheals, said Dr. Levy.

It is unlikely that diarrhea will deter patients with severe itch from using an effective drug when other drugs have failed them. “These patients are consumed by itch most of the time,” said Dr. Dranoff. “I think for people who don’t regularly treat patients with primary biliary cholangitis, it’s one of the underappreciated aspects of the disease.”

The improvements in social and emotional quality of life seen with linerixibat are not only statistically significant, they are also clinically significant, said Dr. Levy. “We are really expecting this to impact the lives of our patients and are looking forward to phase 3.”

Dr. Levy disclosed support from GlaxoSmithKline. Dr. Dranoff disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Patients with primary biliary cholangitis experienced rapid improvements in itch and quality of life after treatment with linerixibat in a randomized, placebo-controlled trial of the safety, efficacy, and tolerability of the small-molecule drug.

Moderate to severe pruritus “affects patients’ quality of life and is a huge burden for them,” said investigator Cynthia Levy, MD, from the University of Miami Health System.

“Finally having a medication that controls those symptoms is really important,” she said in an interview.

With a twice-daily mid-range dose of the drug for 12 weeks, patients with moderate to severe itch reported significantly less itch and better social and emotional quality of life, Dr. Levy reported at the Liver Meeting, where she presented findings from the phase 2 GLIMMER trial.

After a single-blind 4-week placebo run-in period for patients with itch scores of at least 4 on a 10-point rating scale, those with itch scores of at least 3 were then randomly assigned to one of five treatment regimens – once-daily linerixibat at doses of 20 mg, 90 mg, or 180 mg, or twice-daily doses of 40 mg or 90 mg – or to placebo.

After 12 weeks of treatment, all 147 participants once again received placebo for 4 weeks.

During the trial, participants recorded itch levels twice daily. The worst of these daily scores was averaged every 7 days to determine the mean worst daily itch.

The primary study endpoint was the change in worst daily itch from baseline after 12 weeks of treatment. Participants whose self-rated itch improved by 2 points on the 10-point scale were considered to have had a response to the drug.

Participants also completed the PBC-40, an instrument to measure quality of life in patients with primary biliary cholangitis, answering questions about itch and social and emotional status.

Reductions in worst daily itch from baseline to 12 weeks were steepest in the 40-mg twice-daily group, at 2.86 points, and in the 90-mg twice-daily group, at 2.25 points. In the placebo group, the mean decrease was 1.73 points.

During the subsequent 4 weeks of placebo, after treatment ended, the itch relief faded in all groups.

Scores on the PBC-40 itch domain improved significantly in every group, including placebo. However, only those in the twice-daily 40-mg group saw significant improvements on the social (P = .0016) and emotional (P = .0025) domains.
 

‘Between incremental and revolutionary’

The results are on a “kind of continuum between incremental and revolutionary,” said Jonathan A. Dranoff, MD, from the University of Arkansas for Medical Sciences, Little Rock, who was not involved in the study. “It doesn’t hit either extreme, but it’s the first new drug for this purpose in forever, which by itself is a good thing.”

The placebo effect suggests that “maybe the actual contribution of the noncognitive brain to pruritus is bigger than we thought, and that’s worth noting,” he added. Nevertheless, “the drug still appears to have effects that are statistically different from placebo.”

The placebo effect in itching studies is always high but tends to wane over time, said Dr. Levy. This trial had a 4-week placebo run-in period to allow that effect to fade somewhat, she explained.

About 10% of the study cohort experienced drug-related diarrhea, which was expected, and about 10% dropped out of the trial because of drug-related adverse events.

Linerixibat is an ileal sodium-dependent bile acid transporter inhibitor, so the gut has to deal with the excess bile acid fallout, but the diarrhea is likely manageable with antidiarrheals, said Dr. Levy.

It is unlikely that diarrhea will deter patients with severe itch from using an effective drug when other drugs have failed them. “These patients are consumed by itch most of the time,” said Dr. Dranoff. “I think for people who don’t regularly treat patients with primary biliary cholangitis, it’s one of the underappreciated aspects of the disease.”

The improvements in social and emotional quality of life seen with linerixibat are not only statistically significant, they are also clinically significant, said Dr. Levy. “We are really expecting this to impact the lives of our patients and are looking forward to phase 3.”

Dr. Levy disclosed support from GlaxoSmithKline. Dr. Dranoff disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

About one-third of patients with chronic hepatitis B maintained a profile consistent with inactive disease 1 year after withdrawal from treatment in the randomized HBRN trial, which compared tenofovir with and without pegylated interferon (PEG-IFN). The two treatment groups, however, had similarly low rates of hepatitis B surface antigen (HBsAg) loss, the trial’s primary end point.

The successful withdrawals could inform discussions with patients who are “very motivated to have a finite treatment course,” said investigator Norah Terrault, MD, from the University of Southern California, Los Angeles. The results might “help patients in talking about expectations,” she said, because “there’s a one in three chance they won’t go back on treatment” if they meet specific metrics.

In HBRN, the metrics for withdrawal from treatment after 192 weeks included low levels of viral DNA (<1,000 IU/mL) for at least 24 weeks, no cirrhosis, negative week 144 test results for the hepatitis B envelope antigen (HBeAg), and week 180 conversion to anti-HBe positivity.

Of 102 patients who received tenofovir monotherapy for 192 weeks and who completed the trial, 51 met these criteria. After withdrawal from treatment, 30% still had DNA levels below 1,000 IU/mL and normal ALT at week 240, which is consistent with inactive chronic hepatitis B.

Of the 99 participants in the combination group – who received PEG-IFN for the first 24 of 192 weeks in addition to tenofovir – 60 met the withdrawal criteria at 192 weeks. At week 240, 39% of this withdrawal group still had DNA and ALT values consistent with inactive disease.

Rates of HBsAg loss, which signals functional cure, were low in the two groups, however. At week 240, fewer patients in the tenofovir monotherapy group tested negative for HBsAg than in the tenofovir plus PEG-IFN combination group, but the difference was not significant (4.5% vs. 5.7%).

The timing of HBsAg loss differed between the groups. In the combination group, the loss largely occurred before treatment withdrawal, likely because of the antiviral effects of interferon, Dr. Terrault said in an interview. In the monotherapy group, the loss occurred after 192 weeks, possibly reflecting the immunologic consequences of treatment withdrawal.

The timing of ALT flares also differed between groups. In the combination group, 58% of flares occurred during the 24-week PEG-IFN period. In the monotherapy group, 70% of flares occurred after tenofovir was stopped at 192 weeks.

The flare picture is a tricky one, said Dr. Terrault. The episodes might be a positive factor in HBsAg loss, but severe flares carry a risk for decompensation. Good predictors of the severity of flares are lacking, and “that is the hurdle” to finding a balance with these trade-offs.
 

‘Partially a failure and partially a success’

The findings are “partially a failure and partially a success,” said Robert Gish, MD, from Loma Linda (Calif.) University of Health, who was not involved in the study.

The low rates of HBsAg loss and the similarity between the two treatment groups represent the failure, he explained. The success is for the patients who were HBeAg-positive when the study began because they had high HBeAg loss rates in both the monotherapy and combination groups (41% vs. 61%; P = .06).

Loss of HBeAg was numerically higher in the combination group because of the interferon effect. That could be viewed as a “subjective benefit” of PEG-IFN, even though the difference wasn’t statistically significant, said Dr. Gish.

The low rates of HBsAg loss could relate to two features of the patient profile, he explained. At study entry, the participants had moderately high levels of quantitative HBsAg and were predominately of Asian ancestry, which are predisposing factors for limited HBsAg loss.

Previous studies have suggested that peak HBsAg loss could take 2-3 years to develop after treatment withdrawal in a trial population. In the HBRN trial, rates almost 1 year after withdrawal are similar to 1-year rates from other studies, Dr. Terrault said. How these results for HBsAg loss in the two treatment groups will look at the 3-year mark is not known.

The trial design standardized withdrawal protocol and the length of time patients were on treatment before withdrawal was attempted, which are strengths of this study, said Dr. Terrault. And “a triumph of this study is execution of a standard for nucleic acid treatment in a protocolized way, followed by withdrawal. That is something we are happy about.”

Dr. Terrault reported receiving institutional grant support from Roche/Genentech and Gilead Sciences. Dr. Gish reported receiving research support from Gilead Sciences and serving as a consultant and on advisory boards for several pharmaceutical companies.

This article first appeared on Medscape.com.

About one-third of patients with chronic hepatitis B maintained a profile consistent with inactive disease 1 year after withdrawal from treatment in the randomized HBRN trial, which compared tenofovir with and without pegylated interferon (PEG-IFN). The two treatment groups, however, had similarly low rates of hepatitis B surface antigen (HBsAg) loss, the trial’s primary end point.

The successful withdrawals could inform discussions with patients who are “very motivated to have a finite treatment course,” said investigator Norah Terrault, MD, from the University of Southern California, Los Angeles. The results might “help patients in talking about expectations,” she said, because “there’s a one in three chance they won’t go back on treatment” if they meet specific metrics.

In HBRN, the metrics for withdrawal from treatment after 192 weeks included low levels of viral DNA (<1,000 IU/mL) for at least 24 weeks, no cirrhosis, negative week 144 test results for the hepatitis B envelope antigen (HBeAg), and week 180 conversion to anti-HBe positivity.

Of 102 patients who received tenofovir monotherapy for 192 weeks and who completed the trial, 51 met these criteria. After withdrawal from treatment, 30% still had DNA levels below 1,000 IU/mL and normal ALT at week 240, which is consistent with inactive chronic hepatitis B.

Of the 99 participants in the combination group – who received PEG-IFN for the first 24 of 192 weeks in addition to tenofovir – 60 met the withdrawal criteria at 192 weeks. At week 240, 39% of this withdrawal group still had DNA and ALT values consistent with inactive disease.

Rates of HBsAg loss, which signals functional cure, were low in the two groups, however. At week 240, fewer patients in the tenofovir monotherapy group tested negative for HBsAg than in the tenofovir plus PEG-IFN combination group, but the difference was not significant (4.5% vs. 5.7%).

The timing of HBsAg loss differed between the groups. In the combination group, the loss largely occurred before treatment withdrawal, likely because of the antiviral effects of interferon, Dr. Terrault said in an interview. In the monotherapy group, the loss occurred after 192 weeks, possibly reflecting the immunologic consequences of treatment withdrawal.

The timing of ALT flares also differed between groups. In the combination group, 58% of flares occurred during the 24-week PEG-IFN period. In the monotherapy group, 70% of flares occurred after tenofovir was stopped at 192 weeks.

The flare picture is a tricky one, said Dr. Terrault. The episodes might be a positive factor in HBsAg loss, but severe flares carry a risk for decompensation. Good predictors of the severity of flares are lacking, and “that is the hurdle” to finding a balance with these trade-offs.
 

‘Partially a failure and partially a success’

The findings are “partially a failure and partially a success,” said Robert Gish, MD, from Loma Linda (Calif.) University of Health, who was not involved in the study.

The low rates of HBsAg loss and the similarity between the two treatment groups represent the failure, he explained. The success is for the patients who were HBeAg-positive when the study began because they had high HBeAg loss rates in both the monotherapy and combination groups (41% vs. 61%; P = .06).

Loss of HBeAg was numerically higher in the combination group because of the interferon effect. That could be viewed as a “subjective benefit” of PEG-IFN, even though the difference wasn’t statistically significant, said Dr. Gish.

The low rates of HBsAg loss could relate to two features of the patient profile, he explained. At study entry, the participants had moderately high levels of quantitative HBsAg and were predominately of Asian ancestry, which are predisposing factors for limited HBsAg loss.

Previous studies have suggested that peak HBsAg loss could take 2-3 years to develop after treatment withdrawal in a trial population. In the HBRN trial, rates almost 1 year after withdrawal are similar to 1-year rates from other studies, Dr. Terrault said. How these results for HBsAg loss in the two treatment groups will look at the 3-year mark is not known.

The trial design standardized withdrawal protocol and the length of time patients were on treatment before withdrawal was attempted, which are strengths of this study, said Dr. Terrault. And “a triumph of this study is execution of a standard for nucleic acid treatment in a protocolized way, followed by withdrawal. That is something we are happy about.”

Dr. Terrault reported receiving institutional grant support from Roche/Genentech and Gilead Sciences. Dr. Gish reported receiving research support from Gilead Sciences and serving as a consultant and on advisory boards for several pharmaceutical companies.

This article first appeared on Medscape.com.

About one-third of patients with chronic hepatitis B maintained a profile consistent with inactive disease 1 year after withdrawal from treatment in the randomized HBRN trial, which compared tenofovir with and without pegylated interferon (PEG-IFN). The two treatment groups, however, had similarly low rates of hepatitis B surface antigen (HBsAg) loss, the trial’s primary end point.

The successful withdrawals could inform discussions with patients who are “very motivated to have a finite treatment course,” said investigator Norah Terrault, MD, from the University of Southern California, Los Angeles. The results might “help patients in talking about expectations,” she said, because “there’s a one in three chance they won’t go back on treatment” if they meet specific metrics.

In HBRN, the metrics for withdrawal from treatment after 192 weeks included low levels of viral DNA (<1,000 IU/mL) for at least 24 weeks, no cirrhosis, negative week 144 test results for the hepatitis B envelope antigen (HBeAg), and week 180 conversion to anti-HBe positivity.

Of 102 patients who received tenofovir monotherapy for 192 weeks and who completed the trial, 51 met these criteria. After withdrawal from treatment, 30% still had DNA levels below 1,000 IU/mL and normal ALT at week 240, which is consistent with inactive chronic hepatitis B.

Of the 99 participants in the combination group – who received PEG-IFN for the first 24 of 192 weeks in addition to tenofovir – 60 met the withdrawal criteria at 192 weeks. At week 240, 39% of this withdrawal group still had DNA and ALT values consistent with inactive disease.

Rates of HBsAg loss, which signals functional cure, were low in the two groups, however. At week 240, fewer patients in the tenofovir monotherapy group tested negative for HBsAg than in the tenofovir plus PEG-IFN combination group, but the difference was not significant (4.5% vs. 5.7%).

The timing of HBsAg loss differed between the groups. In the combination group, the loss largely occurred before treatment withdrawal, likely because of the antiviral effects of interferon, Dr. Terrault said in an interview. In the monotherapy group, the loss occurred after 192 weeks, possibly reflecting the immunologic consequences of treatment withdrawal.

The timing of ALT flares also differed between groups. In the combination group, 58% of flares occurred during the 24-week PEG-IFN period. In the monotherapy group, 70% of flares occurred after tenofovir was stopped at 192 weeks.

The flare picture is a tricky one, said Dr. Terrault. The episodes might be a positive factor in HBsAg loss, but severe flares carry a risk for decompensation. Good predictors of the severity of flares are lacking, and “that is the hurdle” to finding a balance with these trade-offs.
 

‘Partially a failure and partially a success’

The findings are “partially a failure and partially a success,” said Robert Gish, MD, from Loma Linda (Calif.) University of Health, who was not involved in the study.

The low rates of HBsAg loss and the similarity between the two treatment groups represent the failure, he explained. The success is for the patients who were HBeAg-positive when the study began because they had high HBeAg loss rates in both the monotherapy and combination groups (41% vs. 61%; P = .06).

Loss of HBeAg was numerically higher in the combination group because of the interferon effect. That could be viewed as a “subjective benefit” of PEG-IFN, even though the difference wasn’t statistically significant, said Dr. Gish.

The low rates of HBsAg loss could relate to two features of the patient profile, he explained. At study entry, the participants had moderately high levels of quantitative HBsAg and were predominately of Asian ancestry, which are predisposing factors for limited HBsAg loss.

Previous studies have suggested that peak HBsAg loss could take 2-3 years to develop after treatment withdrawal in a trial population. In the HBRN trial, rates almost 1 year after withdrawal are similar to 1-year rates from other studies, Dr. Terrault said. How these results for HBsAg loss in the two treatment groups will look at the 3-year mark is not known.

The trial design standardized withdrawal protocol and the length of time patients were on treatment before withdrawal was attempted, which are strengths of this study, said Dr. Terrault. And “a triumph of this study is execution of a standard for nucleic acid treatment in a protocolized way, followed by withdrawal. That is something we are happy about.”

Dr. Terrault reported receiving institutional grant support from Roche/Genentech and Gilead Sciences. Dr. Gish reported receiving research support from Gilead Sciences and serving as a consultant and on advisory boards for several pharmaceutical companies.

This article first appeared on Medscape.com.