Liver Disease

A woman presented to the emergency department with high liver enzyme levels and dark urine. She developed fever on day 2 of care, and then tested positive for the new coronavirus, researchers at Northwell Health, in Hempstead, New York, report.

The authors say the case, published online in the American Journal of Gastroenterology, is the first documented instance of a patient with COVID-19 presenting with acute hepatitis as the primary symptom before developing respiratory symptoms.

Prior data show that the most common early indications of COVID-19 are respiratory symptoms with fever, shortness of breath, sore throat, and cough, and with imaging results consistent with pneumonia. However, liver enzyme abnormalities are not uncommon in the disease course.

“In patients who are now presenting with acute hepatitis, people need to think of COVID,” senior author David Bernstein, MD, chief of the Division of Hepatology at Northwell Health, told Medscape Medical News.

In addition to Bernstein, Praneet Wander, MD, also in Northwell’s hepatology division, and Marcia Epstein, MD, with Northwell’s Department of Infectious Disease, authored the case report.

Bernstein said Northwell currently has the largest number of COVID-19 cases in the nation and that many patients are presenting with abnormal liver test results and COVID-19 symptoms.

He said that anecdotally, colleagues elsewhere in the United States are also reporting the connection.

“It seems to be that the liver enzyme elevations are part and parcel of this disease,” he said.

Case Details

According to the case report, the 59-year-old woman, who lives alone, came to the emergency department with a chief complaint of dark urine. She was given a face mask and was isolated, per protocol.

“She denied cough, sore throat, shortness of breath, diarrhea, nausea, vomiting or abdominal pain,” the authors wrote. She denied having been in contact with someone who was sick.

She had well-controlled HIV, and recent outpatient liver test results were normal. Eighteen hours after she came to the ED, she was admitted, owing to concern regarding rising liver enzyme levels in conjunction with her being HIV positive.

On presentation, her temperature was 98.9° F. There were no skin indications, lungs were normal, and “there was no jaundice, right upper quadrant tenderness, hepatomegaly or splenomegaly.”

Liver enzyme levels were as follows: aspartate aminotransferase (AST), 1230 (IU/L); alanine aminotransferase (ALT), 697 IU/L (normal for both is < 50 IU/L); alkaline phosphatase, 141 IU/L (normal, < 125 IU/L).

The patient tested negative for hepatitis A, B, C, E, cytomegalovirus, and Epstein-Barr virus. A respiratory viral panel and autoimmune markers were normal.
 

Fever Appeared on Day 2

She was admitted, and 18 hours after she came to the ED, she developed a fever of 102.2° F. A chest x-ray showed interstitial opacities in both lungs.

Nasopharyngeal samples were taken, and polymerase chain reaction test results were positive for the novel coronavirus. The patient was placed on 3 L of oxygen.

On post admission day 4, a 5-day course of hydroxychloroquine (200 mg twice a day) was initiated.

The patient was discharged to home on hospital day 8. The serum bilirubin level was 0.6 mg/dL; AST, 114 IU/L; ALT, 227 IU/L; and alkaline phosphatase, 259 IU/L.

According to Bernstein, it’s hard to tell in what order COVID-19 symptoms occur because people are staying home with other complaints. They may only present to the emergency department after they develop more typical COVID-19 symptoms, such as shortness of breath.

In this case, the patient noticed a darkening of her urine, “but if she had come the next day, she would have had fever. I think we just happened to catch it early,” Bernstein said.

He added that he saw no connection between the underlying HIV and her liver abnormalities or COVID-19 diagnosis.

Bernstein notes that most COVID-19 patients are not admitted, and he said he worries that a COVID-19 test might not be on the radar of providers in the outpatient setting when a patient presents with elevated liver enzymes levels.

If elevated liver enzyme levels can predict disease course, the information could alter how and where the disease is treated, Bernstein said.

“This is a first report. We’re really right now in the beginning of learning,” he said.

This article first appeared on Medscape.com.

A woman presented to the emergency department with high liver enzyme levels and dark urine. She developed fever on day 2 of care, and then tested positive for the new coronavirus, researchers at Northwell Health, in Hempstead, New York, report.

The authors say the case, published online in the American Journal of Gastroenterology, is the first documented instance of a patient with COVID-19 presenting with acute hepatitis as the primary symptom before developing respiratory symptoms.

Prior data show that the most common early indications of COVID-19 are respiratory symptoms with fever, shortness of breath, sore throat, and cough, and with imaging results consistent with pneumonia. However, liver enzyme abnormalities are not uncommon in the disease course.

“In patients who are now presenting with acute hepatitis, people need to think of COVID,” senior author David Bernstein, MD, chief of the Division of Hepatology at Northwell Health, told Medscape Medical News.

In addition to Bernstein, Praneet Wander, MD, also in Northwell’s hepatology division, and Marcia Epstein, MD, with Northwell’s Department of Infectious Disease, authored the case report.

Bernstein said Northwell currently has the largest number of COVID-19 cases in the nation and that many patients are presenting with abnormal liver test results and COVID-19 symptoms.

He said that anecdotally, colleagues elsewhere in the United States are also reporting the connection.

“It seems to be that the liver enzyme elevations are part and parcel of this disease,” he said.

Case Details

According to the case report, the 59-year-old woman, who lives alone, came to the emergency department with a chief complaint of dark urine. She was given a face mask and was isolated, per protocol.

“She denied cough, sore throat, shortness of breath, diarrhea, nausea, vomiting or abdominal pain,” the authors wrote. She denied having been in contact with someone who was sick.

She had well-controlled HIV, and recent outpatient liver test results were normal. Eighteen hours after she came to the ED, she was admitted, owing to concern regarding rising liver enzyme levels in conjunction with her being HIV positive.

On presentation, her temperature was 98.9° F. There were no skin indications, lungs were normal, and “there was no jaundice, right upper quadrant tenderness, hepatomegaly or splenomegaly.”

Liver enzyme levels were as follows: aspartate aminotransferase (AST), 1230 (IU/L); alanine aminotransferase (ALT), 697 IU/L (normal for both is < 50 IU/L); alkaline phosphatase, 141 IU/L (normal, < 125 IU/L).

The patient tested negative for hepatitis A, B, C, E, cytomegalovirus, and Epstein-Barr virus. A respiratory viral panel and autoimmune markers were normal.
 

Fever Appeared on Day 2

She was admitted, and 18 hours after she came to the ED, she developed a fever of 102.2° F. A chest x-ray showed interstitial opacities in both lungs.

Nasopharyngeal samples were taken, and polymerase chain reaction test results were positive for the novel coronavirus. The patient was placed on 3 L of oxygen.

On post admission day 4, a 5-day course of hydroxychloroquine (200 mg twice a day) was initiated.

The patient was discharged to home on hospital day 8. The serum bilirubin level was 0.6 mg/dL; AST, 114 IU/L; ALT, 227 IU/L; and alkaline phosphatase, 259 IU/L.

According to Bernstein, it’s hard to tell in what order COVID-19 symptoms occur because people are staying home with other complaints. They may only present to the emergency department after they develop more typical COVID-19 symptoms, such as shortness of breath.

In this case, the patient noticed a darkening of her urine, “but if she had come the next day, she would have had fever. I think we just happened to catch it early,” Bernstein said.

He added that he saw no connection between the underlying HIV and her liver abnormalities or COVID-19 diagnosis.

Bernstein notes that most COVID-19 patients are not admitted, and he said he worries that a COVID-19 test might not be on the radar of providers in the outpatient setting when a patient presents with elevated liver enzymes levels.

If elevated liver enzyme levels can predict disease course, the information could alter how and where the disease is treated, Bernstein said.

“This is a first report. We’re really right now in the beginning of learning,” he said.

This article first appeared on Medscape.com.

A woman presented to the emergency department with high liver enzyme levels and dark urine. She developed fever on day 2 of care, and then tested positive for the new coronavirus, researchers at Northwell Health, in Hempstead, New York, report.

The authors say the case, published online in the American Journal of Gastroenterology, is the first documented instance of a patient with COVID-19 presenting with acute hepatitis as the primary symptom before developing respiratory symptoms.

Prior data show that the most common early indications of COVID-19 are respiratory symptoms with fever, shortness of breath, sore throat, and cough, and with imaging results consistent with pneumonia. However, liver enzyme abnormalities are not uncommon in the disease course.

“In patients who are now presenting with acute hepatitis, people need to think of COVID,” senior author David Bernstein, MD, chief of the Division of Hepatology at Northwell Health, told Medscape Medical News.

In addition to Bernstein, Praneet Wander, MD, also in Northwell’s hepatology division, and Marcia Epstein, MD, with Northwell’s Department of Infectious Disease, authored the case report.

Bernstein said Northwell currently has the largest number of COVID-19 cases in the nation and that many patients are presenting with abnormal liver test results and COVID-19 symptoms.

He said that anecdotally, colleagues elsewhere in the United States are also reporting the connection.

“It seems to be that the liver enzyme elevations are part and parcel of this disease,” he said.

Case Details

According to the case report, the 59-year-old woman, who lives alone, came to the emergency department with a chief complaint of dark urine. She was given a face mask and was isolated, per protocol.

“She denied cough, sore throat, shortness of breath, diarrhea, nausea, vomiting or abdominal pain,” the authors wrote. She denied having been in contact with someone who was sick.

She had well-controlled HIV, and recent outpatient liver test results were normal. Eighteen hours after she came to the ED, she was admitted, owing to concern regarding rising liver enzyme levels in conjunction with her being HIV positive.

On presentation, her temperature was 98.9° F. There were no skin indications, lungs were normal, and “there was no jaundice, right upper quadrant tenderness, hepatomegaly or splenomegaly.”

Liver enzyme levels were as follows: aspartate aminotransferase (AST), 1230 (IU/L); alanine aminotransferase (ALT), 697 IU/L (normal for both is < 50 IU/L); alkaline phosphatase, 141 IU/L (normal, < 125 IU/L).

The patient tested negative for hepatitis A, B, C, E, cytomegalovirus, and Epstein-Barr virus. A respiratory viral panel and autoimmune markers were normal.
 

Fever Appeared on Day 2

She was admitted, and 18 hours after she came to the ED, she developed a fever of 102.2° F. A chest x-ray showed interstitial opacities in both lungs.

Nasopharyngeal samples were taken, and polymerase chain reaction test results were positive for the novel coronavirus. The patient was placed on 3 L of oxygen.

On post admission day 4, a 5-day course of hydroxychloroquine (200 mg twice a day) was initiated.

The patient was discharged to home on hospital day 8. The serum bilirubin level was 0.6 mg/dL; AST, 114 IU/L; ALT, 227 IU/L; and alkaline phosphatase, 259 IU/L.

According to Bernstein, it’s hard to tell in what order COVID-19 symptoms occur because people are staying home with other complaints. They may only present to the emergency department after they develop more typical COVID-19 symptoms, such as shortness of breath.

In this case, the patient noticed a darkening of her urine, “but if she had come the next day, she would have had fever. I think we just happened to catch it early,” Bernstein said.

He added that he saw no connection between the underlying HIV and her liver abnormalities or COVID-19 diagnosis.

Bernstein notes that most COVID-19 patients are not admitted, and he said he worries that a COVID-19 test might not be on the radar of providers in the outpatient setting when a patient presents with elevated liver enzymes levels.

If elevated liver enzyme levels can predict disease course, the information could alter how and where the disease is treated, Bernstein said.

“This is a first report. We’re really right now in the beginning of learning,” he said.

This article first appeared on Medscape.com.

Synbiotics can alter gut microbiota in patients with nonalcoholic fatty liver disease (NAFLD), but associated liver benefits remain unseen, according to a recent phase II study.

NAFLD patients who received a year-long regimen of fructo-oligosaccharides and Bifidobacterium animalis had no significant changes in liver fat content or fibrosis, compared with those who received placebo, reported lead author Eleonora Scorletti, MD, of the University of Pennsylvania, Philadelphia, and colleagues.

“There is recent growing interest in the role of gut microbiota in NAFLD pathogenesis, and there are several metaorganismal pathways linking altered gut microbiota ... and NAFLD,” the investigators wrote in Gastroenterology.According to the investigators, previous studies have shown that patients with NAFLD may have some characteristic alterations to their microbiota, such as increased Gram-negative bacteria or more abundant Ruminococcus species, the latter of which were associated with worse fibrosis.

“However, there is currently a lack of consistency in these findings due to the marked variance in the population studied, with differing ages, diets, and geographic locations,” the investigators wrote. “Nonetheless, despite these inconsistencies, there is the possibility that manipulation of the gut microbiota to a more favorable profile could provide a beneficial effect on liver disease in patients with NAFLD.”

To evaluate this possibility, the investigators enrolled 104 patients with NAFLD in the United Kingdom. Patients were randomly divided into a placebo (n = 49) and synbiotic group (n = 55), with the latter receiving 4 grams of fructo-oligosaccharides twice per day plus 10 billion colony-forming units of Bifidobacterium animalis subspecies lactis BB-12 on a daily basis. Treatments were given for 10-14 months.

Diagnostics were conducted across all participants at the beginning and end of the study. These included fecal microbiota analysis by 16s ribosomal DNA sequencing, liver fat measurement by proton magnetic resonance spectroscopy, biomarker-based liver fibrosis scoring, and liver stiffness assessment by vibration-controlled transient elastography.

At the end of the study, patients in the synbiotic group had increased abundance of Bifidobacterium and Faecalibacterium species and reduced proportions of Oscillibacter and Alistipes species, compared with baseline. These changes were not observed in the placebo group.

But changes in microbiota had no apparent impact on liver pathology. Although mean liver fat percentages dropped from 32.3% to 28.5% in the synbiotic group (approximately 4%), they also dropped in the placebo group, from 31.3% to 25.2% (approximately 6%), with differences between groups lacking statistical significance. Using multivariate analysis, the investigators linked these liver fat improvements, which occurred in 65% of participants, with weight loss.

“The fact that most patients had an improvement in ... liver fat, regardless of treatment allocation, is consistent with the so-called clinical trial effect, whereby participants benefit from participating in clinical trials,” the investigators wrote.

Similarly to liver fat content, no significant intergroup differences were found for liver fibrosis or stiffness, whereas, again, weight loss was linked with improvements in both disease parameters.

“Our randomized clinical trial suggests that changing the gut microbiota with this synbiotic may occur without clinically significant effects on the liver in NAFLD,” the investigators concluded.

Still, they noted that the failure of one synbiotic regimen does not discount the possibility of microbiota-based NAFLD interventions as a whole.

“Previous studies that have tested the effects of synbiotic treatment in NAFLD have also used a combination of multiple strains of probiotics as a component of the synbiotic treatment,” the investigators wrote. “Therefore, it might be possible that, because the intestine harbors trillions of bacteria, adding 1 single type of bacterium in a synbiotic may not be as effective as adding 3 or 6 different types of bacteria with the potential to influence many more bacterial species.”

The study was supported by the National Institute of Health Research, the Parnell Diabetes Trust, and Chr. Hansen Holding. One author reported funding from Chr. Hansen unrelated to this trial.

SOURCE: Scorletti E et al. Gastro. 2020 Jan 24. doi: 10.1053/j.gastro.2020.01.031.

Synbiotics can alter gut microbiota in patients with nonalcoholic fatty liver disease (NAFLD), but associated liver benefits remain unseen, according to a recent phase II study.

NAFLD patients who received a year-long regimen of fructo-oligosaccharides and Bifidobacterium animalis had no significant changes in liver fat content or fibrosis, compared with those who received placebo, reported lead author Eleonora Scorletti, MD, of the University of Pennsylvania, Philadelphia, and colleagues.

“There is recent growing interest in the role of gut microbiota in NAFLD pathogenesis, and there are several metaorganismal pathways linking altered gut microbiota ... and NAFLD,” the investigators wrote in Gastroenterology.According to the investigators, previous studies have shown that patients with NAFLD may have some characteristic alterations to their microbiota, such as increased Gram-negative bacteria or more abundant Ruminococcus species, the latter of which were associated with worse fibrosis.

“However, there is currently a lack of consistency in these findings due to the marked variance in the population studied, with differing ages, diets, and geographic locations,” the investigators wrote. “Nonetheless, despite these inconsistencies, there is the possibility that manipulation of the gut microbiota to a more favorable profile could provide a beneficial effect on liver disease in patients with NAFLD.”

To evaluate this possibility, the investigators enrolled 104 patients with NAFLD in the United Kingdom. Patients were randomly divided into a placebo (n = 49) and synbiotic group (n = 55), with the latter receiving 4 grams of fructo-oligosaccharides twice per day plus 10 billion colony-forming units of Bifidobacterium animalis subspecies lactis BB-12 on a daily basis. Treatments were given for 10-14 months.

Diagnostics were conducted across all participants at the beginning and end of the study. These included fecal microbiota analysis by 16s ribosomal DNA sequencing, liver fat measurement by proton magnetic resonance spectroscopy, biomarker-based liver fibrosis scoring, and liver stiffness assessment by vibration-controlled transient elastography.

At the end of the study, patients in the synbiotic group had increased abundance of Bifidobacterium and Faecalibacterium species and reduced proportions of Oscillibacter and Alistipes species, compared with baseline. These changes were not observed in the placebo group.

But changes in microbiota had no apparent impact on liver pathology. Although mean liver fat percentages dropped from 32.3% to 28.5% in the synbiotic group (approximately 4%), they also dropped in the placebo group, from 31.3% to 25.2% (approximately 6%), with differences between groups lacking statistical significance. Using multivariate analysis, the investigators linked these liver fat improvements, which occurred in 65% of participants, with weight loss.

“The fact that most patients had an improvement in ... liver fat, regardless of treatment allocation, is consistent with the so-called clinical trial effect, whereby participants benefit from participating in clinical trials,” the investigators wrote.

Similarly to liver fat content, no significant intergroup differences were found for liver fibrosis or stiffness, whereas, again, weight loss was linked with improvements in both disease parameters.

“Our randomized clinical trial suggests that changing the gut microbiota with this synbiotic may occur without clinically significant effects on the liver in NAFLD,” the investigators concluded.

Still, they noted that the failure of one synbiotic regimen does not discount the possibility of microbiota-based NAFLD interventions as a whole.

“Previous studies that have tested the effects of synbiotic treatment in NAFLD have also used a combination of multiple strains of probiotics as a component of the synbiotic treatment,” the investigators wrote. “Therefore, it might be possible that, because the intestine harbors trillions of bacteria, adding 1 single type of bacterium in a synbiotic may not be as effective as adding 3 or 6 different types of bacteria with the potential to influence many more bacterial species.”

The study was supported by the National Institute of Health Research, the Parnell Diabetes Trust, and Chr. Hansen Holding. One author reported funding from Chr. Hansen unrelated to this trial.

SOURCE: Scorletti E et al. Gastro. 2020 Jan 24. doi: 10.1053/j.gastro.2020.01.031.

Synbiotics can alter gut microbiota in patients with nonalcoholic fatty liver disease (NAFLD), but associated liver benefits remain unseen, according to a recent phase II study.

NAFLD patients who received a year-long regimen of fructo-oligosaccharides and Bifidobacterium animalis had no significant changes in liver fat content or fibrosis, compared with those who received placebo, reported lead author Eleonora Scorletti, MD, of the University of Pennsylvania, Philadelphia, and colleagues.

“There is recent growing interest in the role of gut microbiota in NAFLD pathogenesis, and there are several metaorganismal pathways linking altered gut microbiota ... and NAFLD,” the investigators wrote in Gastroenterology.According to the investigators, previous studies have shown that patients with NAFLD may have some characteristic alterations to their microbiota, such as increased Gram-negative bacteria or more abundant Ruminococcus species, the latter of which were associated with worse fibrosis.

“However, there is currently a lack of consistency in these findings due to the marked variance in the population studied, with differing ages, diets, and geographic locations,” the investigators wrote. “Nonetheless, despite these inconsistencies, there is the possibility that manipulation of the gut microbiota to a more favorable profile could provide a beneficial effect on liver disease in patients with NAFLD.”

To evaluate this possibility, the investigators enrolled 104 patients with NAFLD in the United Kingdom. Patients were randomly divided into a placebo (n = 49) and synbiotic group (n = 55), with the latter receiving 4 grams of fructo-oligosaccharides twice per day plus 10 billion colony-forming units of Bifidobacterium animalis subspecies lactis BB-12 on a daily basis. Treatments were given for 10-14 months.

Diagnostics were conducted across all participants at the beginning and end of the study. These included fecal microbiota analysis by 16s ribosomal DNA sequencing, liver fat measurement by proton magnetic resonance spectroscopy, biomarker-based liver fibrosis scoring, and liver stiffness assessment by vibration-controlled transient elastography.

At the end of the study, patients in the synbiotic group had increased abundance of Bifidobacterium and Faecalibacterium species and reduced proportions of Oscillibacter and Alistipes species, compared with baseline. These changes were not observed in the placebo group.

But changes in microbiota had no apparent impact on liver pathology. Although mean liver fat percentages dropped from 32.3% to 28.5% in the synbiotic group (approximately 4%), they also dropped in the placebo group, from 31.3% to 25.2% (approximately 6%), with differences between groups lacking statistical significance. Using multivariate analysis, the investigators linked these liver fat improvements, which occurred in 65% of participants, with weight loss.

“The fact that most patients had an improvement in ... liver fat, regardless of treatment allocation, is consistent with the so-called clinical trial effect, whereby participants benefit from participating in clinical trials,” the investigators wrote.

Similarly to liver fat content, no significant intergroup differences were found for liver fibrosis or stiffness, whereas, again, weight loss was linked with improvements in both disease parameters.

“Our randomized clinical trial suggests that changing the gut microbiota with this synbiotic may occur without clinically significant effects on the liver in NAFLD,” the investigators concluded.

Still, they noted that the failure of one synbiotic regimen does not discount the possibility of microbiota-based NAFLD interventions as a whole.

“Previous studies that have tested the effects of synbiotic treatment in NAFLD have also used a combination of multiple strains of probiotics as a component of the synbiotic treatment,” the investigators wrote. “Therefore, it might be possible that, because the intestine harbors trillions of bacteria, adding 1 single type of bacterium in a synbiotic may not be as effective as adding 3 or 6 different types of bacteria with the potential to influence many more bacterial species.”

The study was supported by the National Institute of Health Research, the Parnell Diabetes Trust, and Chr. Hansen Holding. One author reported funding from Chr. Hansen unrelated to this trial.

SOURCE: Scorletti E et al. Gastro. 2020 Jan 24. doi: 10.1053/j.gastro.2020.01.031.

Noninvasive fibrosis scores, which are widely used to predict advanced fibrosis in people with nonalcoholic fatty liver disease (NAFLD), do not do a good job of picking up advanced fibrosis in patients with underlying diabetes, according to a new study.

Advanced fibrosis is associated with an increased risk of cirrhosis, end-stage liver disease, and liver failure. Underlying diabetes is a risk factor for both advanced fibrosis and death in patients with NAFLD.

While liver biopsy remains the gold standard for detecting advanced fibrosis, high costs and risks limit its use. Noninvasive scores such as the AST/ALT ratio; AST to platelet ratio index (APRI); fibrosis-4 (FIB-4) index; and NAFLD fibrosis score (NFS) have gained popularity in recent years, as they offer the compelling advantage of using easily and cheaply attained clinical and laboratory measures to assess likelihood of disease.

But their accuracy has come into question, particularly for people with diabetes.

In research published in the Journal of Clinical Gastroenterology, Amandeep Singh, MD, and colleagues at the Cleveland Clinic looked at their center’s records for 1,157 patients with type 2 diabetes (65% women, 88% white, 85% with obesity) who had undergone a liver biopsy for suspected advanced fibrosis between 2000 and 2015. Biopsy results revealed that a third of the cohort (32%) was positive for advanced fibrosis.

The investigators then pulled patients’ laboratory results for AST, ALT, cholesterol, triglycerides, fasting glucose, hemoglobin A_1c, bilirubin, albumin, platelet count, alkaline phosphatase, albumin, and lipid levels, all collected within a year of biopsy. After plugging these into the algorithms of four different scoring systems for advanced fibrosis, they compared results with results from the biopsies.

The scores of AST/ALT greater than 1.4, APRI of at least 1.5, NFS greater than 0.676, and FIB-4 index greater than 2.67 had high specificities of 84%, 97%, 70%, and 93%, respectively, but sensitivities of only 27%, 17%, 64%, and 44%. Even when the cutoff measures were tightened, the scoring systems still missed a lot of disease. This suggests, Dr. Singh and colleagues wrote, that “the presence of diabetes could decrease the predictive value of these scores to detect advanced disease in NAFLD patients.” Reliable noninvasive biomarkers are “urgently needed” for this patient population.

In an interview, Dr. Singh advised that clinicians continue to use current noninvasive scores in patients with diabetes – preferably the NFS – “until we have a better scoring system.” If clinicians suspect advanced fibrosis based on lab tests and clinical data, then “liver biopsy should be considered,” he said.

The investigators described among the limitations of their study its retrospective, single-center design, with patients who were mostly white and from one geographic region.

Dr. Singh and colleagues reported no conflicts of interest or outside funding for their study.

[email protected]

SOURCE: Singh A et al. J Clin Gastroenterol. 2020 Mar 11. doi: 10.1097/MCG.0000000000001339.

Noninvasive fibrosis scores, which are widely used to predict advanced fibrosis in people with nonalcoholic fatty liver disease (NAFLD), do not do a good job of picking up advanced fibrosis in patients with underlying diabetes, according to a new study.

Advanced fibrosis is associated with an increased risk of cirrhosis, end-stage liver disease, and liver failure. Underlying diabetes is a risk factor for both advanced fibrosis and death in patients with NAFLD.

While liver biopsy remains the gold standard for detecting advanced fibrosis, high costs and risks limit its use. Noninvasive scores such as the AST/ALT ratio; AST to platelet ratio index (APRI); fibrosis-4 (FIB-4) index; and NAFLD fibrosis score (NFS) have gained popularity in recent years, as they offer the compelling advantage of using easily and cheaply attained clinical and laboratory measures to assess likelihood of disease.

But their accuracy has come into question, particularly for people with diabetes.

In research published in the Journal of Clinical Gastroenterology, Amandeep Singh, MD, and colleagues at the Cleveland Clinic looked at their center’s records for 1,157 patients with type 2 diabetes (65% women, 88% white, 85% with obesity) who had undergone a liver biopsy for suspected advanced fibrosis between 2000 and 2015. Biopsy results revealed that a third of the cohort (32%) was positive for advanced fibrosis.

The investigators then pulled patients’ laboratory results for AST, ALT, cholesterol, triglycerides, fasting glucose, hemoglobin A_1c, bilirubin, albumin, platelet count, alkaline phosphatase, albumin, and lipid levels, all collected within a year of biopsy. After plugging these into the algorithms of four different scoring systems for advanced fibrosis, they compared results with results from the biopsies.

The scores of AST/ALT greater than 1.4, APRI of at least 1.5, NFS greater than 0.676, and FIB-4 index greater than 2.67 had high specificities of 84%, 97%, 70%, and 93%, respectively, but sensitivities of only 27%, 17%, 64%, and 44%. Even when the cutoff measures were tightened, the scoring systems still missed a lot of disease. This suggests, Dr. Singh and colleagues wrote, that “the presence of diabetes could decrease the predictive value of these scores to detect advanced disease in NAFLD patients.” Reliable noninvasive biomarkers are “urgently needed” for this patient population.

In an interview, Dr. Singh advised that clinicians continue to use current noninvasive scores in patients with diabetes – preferably the NFS – “until we have a better scoring system.” If clinicians suspect advanced fibrosis based on lab tests and clinical data, then “liver biopsy should be considered,” he said.

The investigators described among the limitations of their study its retrospective, single-center design, with patients who were mostly white and from one geographic region.

Dr. Singh and colleagues reported no conflicts of interest or outside funding for their study.

[email protected]

SOURCE: Singh A et al. J Clin Gastroenterol. 2020 Mar 11. doi: 10.1097/MCG.0000000000001339.

Noninvasive fibrosis scores, which are widely used to predict advanced fibrosis in people with nonalcoholic fatty liver disease (NAFLD), do not do a good job of picking up advanced fibrosis in patients with underlying diabetes, according to a new study.

Advanced fibrosis is associated with an increased risk of cirrhosis, end-stage liver disease, and liver failure. Underlying diabetes is a risk factor for both advanced fibrosis and death in patients with NAFLD.

While liver biopsy remains the gold standard for detecting advanced fibrosis, high costs and risks limit its use. Noninvasive scores such as the AST/ALT ratio; AST to platelet ratio index (APRI); fibrosis-4 (FIB-4) index; and NAFLD fibrosis score (NFS) have gained popularity in recent years, as they offer the compelling advantage of using easily and cheaply attained clinical and laboratory measures to assess likelihood of disease.

But their accuracy has come into question, particularly for people with diabetes.

In research published in the Journal of Clinical Gastroenterology, Amandeep Singh, MD, and colleagues at the Cleveland Clinic looked at their center’s records for 1,157 patients with type 2 diabetes (65% women, 88% white, 85% with obesity) who had undergone a liver biopsy for suspected advanced fibrosis between 2000 and 2015. Biopsy results revealed that a third of the cohort (32%) was positive for advanced fibrosis.

The investigators then pulled patients’ laboratory results for AST, ALT, cholesterol, triglycerides, fasting glucose, hemoglobin A_1c, bilirubin, albumin, platelet count, alkaline phosphatase, albumin, and lipid levels, all collected within a year of biopsy. After plugging these into the algorithms of four different scoring systems for advanced fibrosis, they compared results with results from the biopsies.

The scores of AST/ALT greater than 1.4, APRI of at least 1.5, NFS greater than 0.676, and FIB-4 index greater than 2.67 had high specificities of 84%, 97%, 70%, and 93%, respectively, but sensitivities of only 27%, 17%, 64%, and 44%. Even when the cutoff measures were tightened, the scoring systems still missed a lot of disease. This suggests, Dr. Singh and colleagues wrote, that “the presence of diabetes could decrease the predictive value of these scores to detect advanced disease in NAFLD patients.” Reliable noninvasive biomarkers are “urgently needed” for this patient population.

In an interview, Dr. Singh advised that clinicians continue to use current noninvasive scores in patients with diabetes – preferably the NFS – “until we have a better scoring system.” If clinicians suspect advanced fibrosis based on lab tests and clinical data, then “liver biopsy should be considered,” he said.

The investigators described among the limitations of their study its retrospective, single-center design, with patients who were mostly white and from one geographic region.

Dr. Singh and colleagues reported no conflicts of interest or outside funding for their study.

[email protected]

SOURCE: Singh A et al. J Clin Gastroenterol. 2020 Mar 11. doi: 10.1097/MCG.0000000000001339.

In liver transplant recipients or patients with autoimmune hepatitis on immunosuppressive therapy, acute cellular rejection or disease flare should not be presumed in the face of active coronavirus disease 2019 (COVID-19), according to the American Association for the Study of Liver Diseases (AASLD).

Signs that would normally be interpreted as flare or rejection need to be considered more cautiously now because the virus attacks the liver, and elevated aspartate aminotransferase, alanine aminotransferase, and slightly elevated bilirubin are common, ranging from a prevalence of 14% to 53% in COVID-19 patients. Acute liver injury is possible, especially in more severe cases, the group said.

The advice comes from a recently released document from AASLD, called “Clinical Insights for Hepatology and Liver Transplant Providers During the Covid-19 Pandemic,” to help hepatologists and liver transplant providers negotiate the pandemic, according to the latest data. It’s a far-ranging work that contains a lot of now familiar steps for providers to take to protect themselves and patients from the virus, but also much advice specific to liver medicine.

For instance, the group said it’s important to keep in mind that experimental treatments for the infection, including statins, remdesivir, and tocilizumab, can be hepatotoxic. Abnormal liver biochemistries are not a contraindication, but liver biochemistries need to be followed regularly in COVID-19 patients, especially those treated with remdesivir or tocilizumab, regardless of baseline values.

Also, lopinavir/ritonavir is a potent inhibitor of cytochrome P450 enzymes involved with calcineurin inhibitor metabolism, so if it’s used, AASLD said to reduce tacrolimus dosages to 1/20–1/50 of baseline.

The group cautioned against anticipatory adjustments to immunosuppressive drugs or dosages in patients without COVID-19, but if immunosuppressed liver disease patients do get the infection, prednisone doses should be reduced but kept above 10 mg/day to avoid adrenal insufficiency. In the setting of lymphopenia, fever, or worsening COVID-19 pneumonia, it advised reduction of azathioprine and mycophenolate dosages and reduction of, but not stopping, calcineurin inhibitors.

Liver transplants should not be postponed. However, to minimize exposure to the hospital environment, AASLD advised to “consider evaluating only patients with HCC [hepatocellular carcinoma] or those patients with severe disease and high MELD [model for end-stage liver disease] scores who are likely to benefit from immediate liver transplant.”

“An argument that has been put forward to justify deferring some transplants is concern about immunosuppressing patients during the COVID-19 pandemic,” the group said, but “data suggest the innate immune response may be the main driver for pulmonary injury due to COVID-19 and [that] immunosuppression may be protective. ... Posttransplant immunosuppression was not a risk factor for mortality associated with” the severe acute respiratory syndrome pandemic in 2003-2004 or the ongoing Middle East respiratory syndrome pandemic, both also caused by coronaviruses.

AASLD advised against reducing immunosuppression or stopping mycophenolate for asymptomatic patients after transplant, but COVID-19 prevention measures should be emphasized, including frequent hand washing and staying away from large crowds.

People who test positive for COVID-19 are ineligible for organ donation. Bronchoalveolar lavage is the most sensitive test (93%), followed by nasal swabs (63%) and pharyngeal swabs (32%).

In general, the group said elective procedures should be postponed, but urgent ones, such as biliary surgery and transjugular intrahepatic portosystemic shunts for bleeding varices, in addition to liver transplants, should not.

Also, HCC patients “should not wait until the pandemic abates to undergo [surveillance] imaging because the prospective duration of the pandemic is unknown. ... An arbitrary delay of 2 months is reasonable” for imaging based on patient and facility circumstances, but otherwise, “proceed with HCC treatments rather than delaying them due to the pandemic,” the group said.

As for who to bring into the office for an initial consult, “consider seeing in person only new adult and pediatric patients with urgent issues and clinically significant liver disease (e.g., jaundice, elevated ALT or AST above 500 U/L, recent onset of hepatic decompensation),” AASLD said.

[email protected]

In liver transplant recipients or patients with autoimmune hepatitis on immunosuppressive therapy, acute cellular rejection or disease flare should not be presumed in the face of active coronavirus disease 2019 (COVID-19), according to the American Association for the Study of Liver Diseases (AASLD).

Signs that would normally be interpreted as flare or rejection need to be considered more cautiously now because the virus attacks the liver, and elevated aspartate aminotransferase, alanine aminotransferase, and slightly elevated bilirubin are common, ranging from a prevalence of 14% to 53% in COVID-19 patients. Acute liver injury is possible, especially in more severe cases, the group said.

The advice comes from a recently released document from AASLD, called “Clinical Insights for Hepatology and Liver Transplant Providers During the Covid-19 Pandemic,” to help hepatologists and liver transplant providers negotiate the pandemic, according to the latest data. It’s a far-ranging work that contains a lot of now familiar steps for providers to take to protect themselves and patients from the virus, but also much advice specific to liver medicine.

For instance, the group said it’s important to keep in mind that experimental treatments for the infection, including statins, remdesivir, and tocilizumab, can be hepatotoxic. Abnormal liver biochemistries are not a contraindication, but liver biochemistries need to be followed regularly in COVID-19 patients, especially those treated with remdesivir or tocilizumab, regardless of baseline values.

Also, lopinavir/ritonavir is a potent inhibitor of cytochrome P450 enzymes involved with calcineurin inhibitor metabolism, so if it’s used, AASLD said to reduce tacrolimus dosages to 1/20–1/50 of baseline.

The group cautioned against anticipatory adjustments to immunosuppressive drugs or dosages in patients without COVID-19, but if immunosuppressed liver disease patients do get the infection, prednisone doses should be reduced but kept above 10 mg/day to avoid adrenal insufficiency. In the setting of lymphopenia, fever, or worsening COVID-19 pneumonia, it advised reduction of azathioprine and mycophenolate dosages and reduction of, but not stopping, calcineurin inhibitors.

Liver transplants should not be postponed. However, to minimize exposure to the hospital environment, AASLD advised to “consider evaluating only patients with HCC [hepatocellular carcinoma] or those patients with severe disease and high MELD [model for end-stage liver disease] scores who are likely to benefit from immediate liver transplant.”

“An argument that has been put forward to justify deferring some transplants is concern about immunosuppressing patients during the COVID-19 pandemic,” the group said, but “data suggest the innate immune response may be the main driver for pulmonary injury due to COVID-19 and [that] immunosuppression may be protective. ... Posttransplant immunosuppression was not a risk factor for mortality associated with” the severe acute respiratory syndrome pandemic in 2003-2004 or the ongoing Middle East respiratory syndrome pandemic, both also caused by coronaviruses.

AASLD advised against reducing immunosuppression or stopping mycophenolate for asymptomatic patients after transplant, but COVID-19 prevention measures should be emphasized, including frequent hand washing and staying away from large crowds.

People who test positive for COVID-19 are ineligible for organ donation. Bronchoalveolar lavage is the most sensitive test (93%), followed by nasal swabs (63%) and pharyngeal swabs (32%).

In general, the group said elective procedures should be postponed, but urgent ones, such as biliary surgery and transjugular intrahepatic portosystemic shunts for bleeding varices, in addition to liver transplants, should not.

Also, HCC patients “should not wait until the pandemic abates to undergo [surveillance] imaging because the prospective duration of the pandemic is unknown. ... An arbitrary delay of 2 months is reasonable” for imaging based on patient and facility circumstances, but otherwise, “proceed with HCC treatments rather than delaying them due to the pandemic,” the group said.

As for who to bring into the office for an initial consult, “consider seeing in person only new adult and pediatric patients with urgent issues and clinically significant liver disease (e.g., jaundice, elevated ALT or AST above 500 U/L, recent onset of hepatic decompensation),” AASLD said.

[email protected]

In liver transplant recipients or patients with autoimmune hepatitis on immunosuppressive therapy, acute cellular rejection or disease flare should not be presumed in the face of active coronavirus disease 2019 (COVID-19), according to the American Association for the Study of Liver Diseases (AASLD).

Signs that would normally be interpreted as flare or rejection need to be considered more cautiously now because the virus attacks the liver, and elevated aspartate aminotransferase, alanine aminotransferase, and slightly elevated bilirubin are common, ranging from a prevalence of 14% to 53% in COVID-19 patients. Acute liver injury is possible, especially in more severe cases, the group said.

The advice comes from a recently released document from AASLD, called “Clinical Insights for Hepatology and Liver Transplant Providers During the Covid-19 Pandemic,” to help hepatologists and liver transplant providers negotiate the pandemic, according to the latest data. It’s a far-ranging work that contains a lot of now familiar steps for providers to take to protect themselves and patients from the virus, but also much advice specific to liver medicine.

For instance, the group said it’s important to keep in mind that experimental treatments for the infection, including statins, remdesivir, and tocilizumab, can be hepatotoxic. Abnormal liver biochemistries are not a contraindication, but liver biochemistries need to be followed regularly in COVID-19 patients, especially those treated with remdesivir or tocilizumab, regardless of baseline values.

Also, lopinavir/ritonavir is a potent inhibitor of cytochrome P450 enzymes involved with calcineurin inhibitor metabolism, so if it’s used, AASLD said to reduce tacrolimus dosages to 1/20–1/50 of baseline.

The group cautioned against anticipatory adjustments to immunosuppressive drugs or dosages in patients without COVID-19, but if immunosuppressed liver disease patients do get the infection, prednisone doses should be reduced but kept above 10 mg/day to avoid adrenal insufficiency. In the setting of lymphopenia, fever, or worsening COVID-19 pneumonia, it advised reduction of azathioprine and mycophenolate dosages and reduction of, but not stopping, calcineurin inhibitors.

Liver transplants should not be postponed. However, to minimize exposure to the hospital environment, AASLD advised to “consider evaluating only patients with HCC [hepatocellular carcinoma] or those patients with severe disease and high MELD [model for end-stage liver disease] scores who are likely to benefit from immediate liver transplant.”

“An argument that has been put forward to justify deferring some transplants is concern about immunosuppressing patients during the COVID-19 pandemic,” the group said, but “data suggest the innate immune response may be the main driver for pulmonary injury due to COVID-19 and [that] immunosuppression may be protective. ... Posttransplant immunosuppression was not a risk factor for mortality associated with” the severe acute respiratory syndrome pandemic in 2003-2004 or the ongoing Middle East respiratory syndrome pandemic, both also caused by coronaviruses.

AASLD advised against reducing immunosuppression or stopping mycophenolate for asymptomatic patients after transplant, but COVID-19 prevention measures should be emphasized, including frequent hand washing and staying away from large crowds.

People who test positive for COVID-19 are ineligible for organ donation. Bronchoalveolar lavage is the most sensitive test (93%), followed by nasal swabs (63%) and pharyngeal swabs (32%).

In general, the group said elective procedures should be postponed, but urgent ones, such as biliary surgery and transjugular intrahepatic portosystemic shunts for bleeding varices, in addition to liver transplants, should not.

Also, HCC patients “should not wait until the pandemic abates to undergo [surveillance] imaging because the prospective duration of the pandemic is unknown. ... An arbitrary delay of 2 months is reasonable” for imaging based on patient and facility circumstances, but otherwise, “proceed with HCC treatments rather than delaying them due to the pandemic,” the group said.

As for who to bring into the office for an initial consult, “consider seeing in person only new adult and pediatric patients with urgent issues and clinically significant liver disease (e.g., jaundice, elevated ALT or AST above 500 U/L, recent onset of hepatic decompensation),” AASLD said.

[email protected]

Patients with COVID-19 may be at risk for liver injury, but mechanisms of damage remain unclear, according to investigators.

Proposed mechanisms include direct virus-induced effects, immune-induced damage due to excessive inflammatory responses, and drug-induced injury, reported lead author Ling Xu of Huazhong University of Science and Technology, Wuhan, China, and colleagues.

“From a clinical perspective, in addition to actively dealing with the primary disease caused by coronavirus infection, attention should also be paid to monitor the occurrence of liver injury, and to the application of drugs which may induce liver damage,” the investigators wrote in Liver International. “Patients with liver damage are advised to be treated with drugs that could both protect liver functions and inhibit inflammatory responses, such as ammonium glycyrrhizinate, which may, in turn, accelerate the process of disease recovery.”

The review of liver injury associated with major pathogenic coronaviruses included severe acute respiratory syndrome coronavirus (SARS-CoV), the Middle East respiratory syndrome coronavirus (MERS-CoV), and the newly emergent SARS-CoV-2, which causes COVID-19.

In cases of COVID-19, reported incidence of liver injury ranges from 15% to 53%, based on elevations of alanine transaminase (ALT) and aspartate aminotransferase (AST), along with slightly elevated bilirubin levels. In severe cases, albumin decreases have also been documented.

Liver injury appears to be significantly more common among those with severe infection. In one cohort of 82 patients who died from COVID-19, the incidence of liver injury was 78%, while another study of 36 nonsurvivors reported a rate of 58%.

According to the investigators, both bile duct epithelial cells and liver cells express angiotensin converting enzyme II (ACE2), which is an entry receptor for SARS-CoV-2; however, expression of ACE2 in bile duct cells is “much higher” than in liver cells, and comparable with alveolar type 2 cells in the lungs.

“Bile duct epithelial cells are known to play important roles in liver regeneration and immune response,” the investigators noted.

Beyond direct- and immune-induced effects of COVID-19, postmortem findings suggest that drug-induced liver injury may also be a possibility, with a number of theoretical culprits, including antibiotics, steroids, and antivirals. Although the investigators emphasized that data are insufficient to pinpoint an exact agent, they highlighted a recent preprint study, which reported a significantly higher rate of lopinavir/ritonavir administration among patients with abnormal liver function, compared with those who had normal liver function (56.1% vs. 25%; P = .009).

“Drug-induced liver injury during the treatment of coronavirus infection should not be ignored and needs to be carefully investigated,” the investigators concluded.

Fundamental Research Funds for the Central Universities supported the work. The investigators reported no conflicts of interest.

SOURCE: Xu L et al. Liver Int. 2020 Mar 14. doi: 10.1111/liv.14435.

Patients with COVID-19 may be at risk for liver injury, but mechanisms of damage remain unclear, according to investigators.

Proposed mechanisms include direct virus-induced effects, immune-induced damage due to excessive inflammatory responses, and drug-induced injury, reported lead author Ling Xu of Huazhong University of Science and Technology, Wuhan, China, and colleagues.

“From a clinical perspective, in addition to actively dealing with the primary disease caused by coronavirus infection, attention should also be paid to monitor the occurrence of liver injury, and to the application of drugs which may induce liver damage,” the investigators wrote in Liver International. “Patients with liver damage are advised to be treated with drugs that could both protect liver functions and inhibit inflammatory responses, such as ammonium glycyrrhizinate, which may, in turn, accelerate the process of disease recovery.”

The review of liver injury associated with major pathogenic coronaviruses included severe acute respiratory syndrome coronavirus (SARS-CoV), the Middle East respiratory syndrome coronavirus (MERS-CoV), and the newly emergent SARS-CoV-2, which causes COVID-19.

In cases of COVID-19, reported incidence of liver injury ranges from 15% to 53%, based on elevations of alanine transaminase (ALT) and aspartate aminotransferase (AST), along with slightly elevated bilirubin levels. In severe cases, albumin decreases have also been documented.

Liver injury appears to be significantly more common among those with severe infection. In one cohort of 82 patients who died from COVID-19, the incidence of liver injury was 78%, while another study of 36 nonsurvivors reported a rate of 58%.

According to the investigators, both bile duct epithelial cells and liver cells express angiotensin converting enzyme II (ACE2), which is an entry receptor for SARS-CoV-2; however, expression of ACE2 in bile duct cells is “much higher” than in liver cells, and comparable with alveolar type 2 cells in the lungs.

“Bile duct epithelial cells are known to play important roles in liver regeneration and immune response,” the investigators noted.

Beyond direct- and immune-induced effects of COVID-19, postmortem findings suggest that drug-induced liver injury may also be a possibility, with a number of theoretical culprits, including antibiotics, steroids, and antivirals. Although the investigators emphasized that data are insufficient to pinpoint an exact agent, they highlighted a recent preprint study, which reported a significantly higher rate of lopinavir/ritonavir administration among patients with abnormal liver function, compared with those who had normal liver function (56.1% vs. 25%; P = .009).

“Drug-induced liver injury during the treatment of coronavirus infection should not be ignored and needs to be carefully investigated,” the investigators concluded.

Fundamental Research Funds for the Central Universities supported the work. The investigators reported no conflicts of interest.

SOURCE: Xu L et al. Liver Int. 2020 Mar 14. doi: 10.1111/liv.14435.

Patients with COVID-19 may be at risk for liver injury, but mechanisms of damage remain unclear, according to investigators.

Proposed mechanisms include direct virus-induced effects, immune-induced damage due to excessive inflammatory responses, and drug-induced injury, reported lead author Ling Xu of Huazhong University of Science and Technology, Wuhan, China, and colleagues.

“From a clinical perspective, in addition to actively dealing with the primary disease caused by coronavirus infection, attention should also be paid to monitor the occurrence of liver injury, and to the application of drugs which may induce liver damage,” the investigators wrote in Liver International. “Patients with liver damage are advised to be treated with drugs that could both protect liver functions and inhibit inflammatory responses, such as ammonium glycyrrhizinate, which may, in turn, accelerate the process of disease recovery.”

The review of liver injury associated with major pathogenic coronaviruses included severe acute respiratory syndrome coronavirus (SARS-CoV), the Middle East respiratory syndrome coronavirus (MERS-CoV), and the newly emergent SARS-CoV-2, which causes COVID-19.

In cases of COVID-19, reported incidence of liver injury ranges from 15% to 53%, based on elevations of alanine transaminase (ALT) and aspartate aminotransferase (AST), along with slightly elevated bilirubin levels. In severe cases, albumin decreases have also been documented.

Liver injury appears to be significantly more common among those with severe infection. In one cohort of 82 patients who died from COVID-19, the incidence of liver injury was 78%, while another study of 36 nonsurvivors reported a rate of 58%.

According to the investigators, both bile duct epithelial cells and liver cells express angiotensin converting enzyme II (ACE2), which is an entry receptor for SARS-CoV-2; however, expression of ACE2 in bile duct cells is “much higher” than in liver cells, and comparable with alveolar type 2 cells in the lungs.

“Bile duct epithelial cells are known to play important roles in liver regeneration and immune response,” the investigators noted.

Beyond direct- and immune-induced effects of COVID-19, postmortem findings suggest that drug-induced liver injury may also be a possibility, with a number of theoretical culprits, including antibiotics, steroids, and antivirals. Although the investigators emphasized that data are insufficient to pinpoint an exact agent, they highlighted a recent preprint study, which reported a significantly higher rate of lopinavir/ritonavir administration among patients with abnormal liver function, compared with those who had normal liver function (56.1% vs. 25%; P = .009).

“Drug-induced liver injury during the treatment of coronavirus infection should not be ignored and needs to be carefully investigated,” the investigators concluded.

Fundamental Research Funds for the Central Universities supported the work. The investigators reported no conflicts of interest.

SOURCE: Xu L et al. Liver Int. 2020 Mar 14. doi: 10.1111/liv.14435.

The first randomized trial to see if a short course of a direct-acting antiviral works as well for acute hepatitis C virus (HCV) infection as the standard 12-week course was stopped early after it became clear that it did not, according to a report at the Conference on Retroviruses & Opportunistic Infections.

In the end, 6 weeks of sofosbuvir-velpatasvir (Epclusa) “was inferior” to 12 weeks, said investigators led by Gail Matthews, MD, PhD, an associate professor in the Viral Hepatitis Clinical Research Program at the Kirby Institute, in Sydney, New South Wales, Australia.

Guidelines recommend 12 weeks of direct-acting antiviral treatment, but a few observational studies have suggested that 6 weeks might be enough. Since that would make it easier for physicians and patients, and would save money, Dr. Matthews and her team set out to resolve the uncertainty with a randomized trial.

Enrollment was halted short of the 250 target because of an “unacceptably high” relapse rate of 9.7% among 93 people randomized to 6 weeks of sofosbuvir-velpatasvir versus 2% among 99 subjects randomized to the standard 12-week regimen. All the relapse patients except for one in the 12-week arm were more than 95% adherent to treatment, she at the meeting, which was scheduled to be in Boston, but was held online this year because of concerns about spreading the COVID-19 virus.

There were 17 treatment failures (18.3%) in the short arm: two deaths, three reinfections, three lost to follow-up, and the nine relapses 12 weeks out from the end of treatment. There were eight failures (8%) in the long arm, including two reinfections, two lost to follow-up, and the two relapses, but no deaths. Excluding patients with no virologic reason for failure, Dr. Matthews said, “we see the difference in the two arms even more clearly,” with viral RNA undetectable in 98% of the 12-week patients – which is in keeping with label data – versus 89% in the short arm.

The groups were well balanced. Almost all the subjects were men and the majority were white; the median age was 43 years. Almost two-thirds had a primary infection at baseline and HCV genotype 1 a/b was the most common in both groups. Patients had been infected for a year or less, with a median of 25 weeks.

The majority of subjects picked up the virus through homosexual sex, but about 20% by injection drug use. Over two-thirds had well-controlled HIV. There were no treatment related discontinuations, and all the relapsed patients were successfully treated with subsequent therapy, Dr. Matthews said.

The study was conducted in the United States, Europe, Canada, New Zealand, and Australia, and funded by the National Institutes of Health. Dr. Matthews reported research grants to her institution form Abbvie and Gilead, maker of Epclusa.

[email protected]

SOURCE: Matthews G. CROI 2020 abstract 121.

The first randomized trial to see if a short course of a direct-acting antiviral works as well for acute hepatitis C virus (HCV) infection as the standard 12-week course was stopped early after it became clear that it did not, according to a report at the Conference on Retroviruses & Opportunistic Infections.

In the end, 6 weeks of sofosbuvir-velpatasvir (Epclusa) “was inferior” to 12 weeks, said investigators led by Gail Matthews, MD, PhD, an associate professor in the Viral Hepatitis Clinical Research Program at the Kirby Institute, in Sydney, New South Wales, Australia.

Guidelines recommend 12 weeks of direct-acting antiviral treatment, but a few observational studies have suggested that 6 weeks might be enough. Since that would make it easier for physicians and patients, and would save money, Dr. Matthews and her team set out to resolve the uncertainty with a randomized trial.

Enrollment was halted short of the 250 target because of an “unacceptably high” relapse rate of 9.7% among 93 people randomized to 6 weeks of sofosbuvir-velpatasvir versus 2% among 99 subjects randomized to the standard 12-week regimen. All the relapse patients except for one in the 12-week arm were more than 95% adherent to treatment, she at the meeting, which was scheduled to be in Boston, but was held online this year because of concerns about spreading the COVID-19 virus.

There were 17 treatment failures (18.3%) in the short arm: two deaths, three reinfections, three lost to follow-up, and the nine relapses 12 weeks out from the end of treatment. There were eight failures (8%) in the long arm, including two reinfections, two lost to follow-up, and the two relapses, but no deaths. Excluding patients with no virologic reason for failure, Dr. Matthews said, “we see the difference in the two arms even more clearly,” with viral RNA undetectable in 98% of the 12-week patients – which is in keeping with label data – versus 89% in the short arm.

The groups were well balanced. Almost all the subjects were men and the majority were white; the median age was 43 years. Almost two-thirds had a primary infection at baseline and HCV genotype 1 a/b was the most common in both groups. Patients had been infected for a year or less, with a median of 25 weeks.

The majority of subjects picked up the virus through homosexual sex, but about 20% by injection drug use. Over two-thirds had well-controlled HIV. There were no treatment related discontinuations, and all the relapsed patients were successfully treated with subsequent therapy, Dr. Matthews said.

The study was conducted in the United States, Europe, Canada, New Zealand, and Australia, and funded by the National Institutes of Health. Dr. Matthews reported research grants to her institution form Abbvie and Gilead, maker of Epclusa.

[email protected]

SOURCE: Matthews G. CROI 2020 abstract 121.

The first randomized trial to see if a short course of a direct-acting antiviral works as well for acute hepatitis C virus (HCV) infection as the standard 12-week course was stopped early after it became clear that it did not, according to a report at the Conference on Retroviruses & Opportunistic Infections.

In the end, 6 weeks of sofosbuvir-velpatasvir (Epclusa) “was inferior” to 12 weeks, said investigators led by Gail Matthews, MD, PhD, an associate professor in the Viral Hepatitis Clinical Research Program at the Kirby Institute, in Sydney, New South Wales, Australia.

Guidelines recommend 12 weeks of direct-acting antiviral treatment, but a few observational studies have suggested that 6 weeks might be enough. Since that would make it easier for physicians and patients, and would save money, Dr. Matthews and her team set out to resolve the uncertainty with a randomized trial.

Enrollment was halted short of the 250 target because of an “unacceptably high” relapse rate of 9.7% among 93 people randomized to 6 weeks of sofosbuvir-velpatasvir versus 2% among 99 subjects randomized to the standard 12-week regimen. All the relapse patients except for one in the 12-week arm were more than 95% adherent to treatment, she at the meeting, which was scheduled to be in Boston, but was held online this year because of concerns about spreading the COVID-19 virus.

There were 17 treatment failures (18.3%) in the short arm: two deaths, three reinfections, three lost to follow-up, and the nine relapses 12 weeks out from the end of treatment. There were eight failures (8%) in the long arm, including two reinfections, two lost to follow-up, and the two relapses, but no deaths. Excluding patients with no virologic reason for failure, Dr. Matthews said, “we see the difference in the two arms even more clearly,” with viral RNA undetectable in 98% of the 12-week patients – which is in keeping with label data – versus 89% in the short arm.

The groups were well balanced. Almost all the subjects were men and the majority were white; the median age was 43 years. Almost two-thirds had a primary infection at baseline and HCV genotype 1 a/b was the most common in both groups. Patients had been infected for a year or less, with a median of 25 weeks.

The majority of subjects picked up the virus through homosexual sex, but about 20% by injection drug use. Over two-thirds had well-controlled HIV. There were no treatment related discontinuations, and all the relapsed patients were successfully treated with subsequent therapy, Dr. Matthews said.

The study was conducted in the United States, Europe, Canada, New Zealand, and Australia, and funded by the National Institutes of Health. Dr. Matthews reported research grants to her institution form Abbvie and Gilead, maker of Epclusa.

[email protected]

SOURCE: Matthews G. CROI 2020 abstract 121.

The risk of liver cancer and liver-related death in patients with chronic viral hepatitis was substantially reduced with the use of low-dose aspirin, results from a nationwide study from Sweden suggest.

The risk of hepatocellular carcinoma (HCC) was reduced by 31% compared with no aspirin use, and liver-related mortality dropped by 27%, as long as aspirin use continued.

“We were excited to find for the first time in a nationwide Western population that low-dose aspirin use was associated with substantial reduction in risk of developing incident HCC,” lead author Tracey G. Simon, MD, MPH, of Massachusetts General Hospital and Harvard Medical School in Boston, told Medscape Medical News.

The study was published in the March 12 issue of the New England Journal of Medicine.

HCC is the fourth-leading cause of cancer mortality worldwide, and is driven mostly by viral hepatitis B (HBV) and viral hepatitis C (HCV) infection, noted Jennifer A. Flemming, MD, of Queen’s University, Kingston, Canada, an expert not involved with the study. HCC is also one of the only cancers to show a rising incidence over the past several decades, she added .

However, the results of this do not change clinical practice. “It is premature to prescribe low dose ASA [acetylsalicylic acid] in patients with viral hepatitis for the sole indication of HCC prevention in routine clinical practice without support from prospective randomized data,” she said.

“The results of this study make it clear that a prospective randomized study comparing ASA to placebo in patients with viral hepatitis without an indication for low-dose ASA is justified to evaluate the risk of incident HCC,” she told Medscape Medical News.

The study authors agree, and they also emphasize that the findings from this observational study “should not yet change clinical practice.”

More research is needed in populations with compensated and decompensated cirrhosis to determine the optimal timing of aspirin initiation — or cessation of therapy — that will maximize benefit and prevent adverse events, said Simon.

Study Details

Although several earlier studies have suggested a duration-dependent benefit of aspirin use in preventing HCC in smaller populations, this study is the first to confirm a duration-response relationship with low-dose aspirin use in an unselected European population with confirmed viral hepatitis, Simon pointed out.

For their study, Simon and colleagues used the Swedish Register for Surveillance of Communicable Diseases database to identify 50,275 adults diagnosed between 2005 and 2015 with acute and chronic HBV and HCV infection. Some 13,276 adults had HBV and 36,999 had HCV, and this included 14,205 low-dose (75 mg or 160 mg) aspirin users and 36,070 nonusers.

The analysis showed that in aspirin users, the 10-year cumulative incidence of HCC was 4% compared with 8.3% in nonusers. After multivariable adjustment, aspirin users had a risk of HCC that was 31% lower compared with nonusers (adjusted subhazard ratio, 0.69; 95% confidence interval [CI], 0.62 - 0.76).

Patients taking low-dose aspirin had a 10-year liver-related mortality of 11% compared with 17.9% among nonusers. The adjusted risk of liver-related mortality was 27% lower in aspirin users than in nonusers.

There was no significant difference in the 10-year risk of gastrointestinal bleeding between users and nonusers of aspirin (7.8% and 6.9%, respectively). In addition, the analysis showed that the risks of any gastrointestinal bleeding were similar among aspirin-users with compensated cirrhosis and those without cirrhosis (8.3% and 7.5%, respectively).

Notably, the risk of HCC was significantly lower after 3 to 5 years of aspirin use and after 5 or more years of use (adjusted hazard ratio [HR], 0.66, 0.57, respectively) compared with short-term use (3 months to <1 year; adjusted HR, 0.90) or with intermittent, discontinued, or no aspirin use. But when those with chronic viral hepatitis stopped taking aspirin, their risk of HCC rose to become 22% higher compared with peers who continued to use aspirin.

The risk of liver-related death also rose by 31% in aspirin users who stopped taking aspirin compared with those who did not stop (subhazard ratio, 1.31). Again, this relationship appeared to be duration-dependent, with the risk of incident HCC rising sharply among those who discontinued aspirin and increasing in magnitude over time.

The consistency of aspirin use also influenced risk. In individuals who had an on-again, off-again pattern of aspirin use, the incidence of HCC was 5.9% compared with 1.1% in those who used it consistently.

“Our results were consistent regardless of sex, cause of hepatitis, or underlying compensated cirrhosis,” the authors write. “The consistent duration-response associations lend further credence to a potential causal relationship.”

Limitations of the Study

The current study findings are not new, but this is the best-designed study to date, commented Flemming. Still, there were a number of limitations, she noted. Although cirrhosis is the strongest risk factor for HCC in patients with viral hepatitis, for instance, it was assessed only at cohort entry, and not during the median 8 years of follow-up. There was also a lack of information about sustained virologic response (SVR) rates.

Since less than 25% of patients with HCV received HCV therapy, this indicates they were likely treated with interferon-based therapy, Flemming suggested. Interferon-based therapy is associated with much lower SVR rates than direct acting antiviral (DAA) therapy, which can produce SVR in approximately 95% of patients, she pointed out.

“Therefore, a large proportion of the study patients were likely viremic and at a higher baseline risk of HCC than contemporary HCV populations.”

Evidence from a number of studies indicates that achieving SVR with DAA therapy is associated with a 70% risk reduction for incident HCC and liver-related events, Flemming said. “Whether the use of ASA in patients who have achieved SVR provides the same HCC risk reduction and decrease in hepatic outcomes is unknown.”

Also, the study did not provide information on the specific type of HBV therapy used in patients with HBV, Flemming noted. When considering the prevention of HCC in patients with chronic HBV infection, recent data support a differential protective effect of tenofovir disoproxil fumarate (multiple brands) compared with entecavir (Baraclude, Bristol-Myers Squibb), she pointed out. As previously reported by Medscape Medical News, these data also indicate that tenofovir may be more effective than entecavir in reducing the risk of liver failure and all-cause mortality.

This study was funded by the US National Institutes of Health, Nyckelfonden, Region Stockholm County, the American Association for the Study of Liver Diseases, Boston Nutrition Obesity Research Council, Region Örebro County, and Karolinska Institutet. Simon has disclosed no relevant financial relationships. A number of study coauthors disclosed having relationships with industry; the full list can be found with the original article. Flemming reported relationships with Gilead Sciences Canada, AbbVie, and Lupin Pharmaceuticals.

This article first appeared on Medscape.com.

N Engl J Med. 2020 Mar 12. doi: 10.1056/NEJMoa1912035.

The risk of liver cancer and liver-related death in patients with chronic viral hepatitis was substantially reduced with the use of low-dose aspirin, results from a nationwide study from Sweden suggest.

The risk of hepatocellular carcinoma (HCC) was reduced by 31% compared with no aspirin use, and liver-related mortality dropped by 27%, as long as aspirin use continued.

“We were excited to find for the first time in a nationwide Western population that low-dose aspirin use was associated with substantial reduction in risk of developing incident HCC,” lead author Tracey G. Simon, MD, MPH, of Massachusetts General Hospital and Harvard Medical School in Boston, told Medscape Medical News.

The study was published in the March 12 issue of the New England Journal of Medicine.

HCC is the fourth-leading cause of cancer mortality worldwide, and is driven mostly by viral hepatitis B (HBV) and viral hepatitis C (HCV) infection, noted Jennifer A. Flemming, MD, of Queen’s University, Kingston, Canada, an expert not involved with the study. HCC is also one of the only cancers to show a rising incidence over the past several decades, she added .

However, the results of this do not change clinical practice. “It is premature to prescribe low dose ASA [acetylsalicylic acid] in patients with viral hepatitis for the sole indication of HCC prevention in routine clinical practice without support from prospective randomized data,” she said.

“The results of this study make it clear that a prospective randomized study comparing ASA to placebo in patients with viral hepatitis without an indication for low-dose ASA is justified to evaluate the risk of incident HCC,” she told Medscape Medical News.

The study authors agree, and they also emphasize that the findings from this observational study “should not yet change clinical practice.”

More research is needed in populations with compensated and decompensated cirrhosis to determine the optimal timing of aspirin initiation — or cessation of therapy — that will maximize benefit and prevent adverse events, said Simon.

Study Details

Although several earlier studies have suggested a duration-dependent benefit of aspirin use in preventing HCC in smaller populations, this study is the first to confirm a duration-response relationship with low-dose aspirin use in an unselected European population with confirmed viral hepatitis, Simon pointed out.

For their study, Simon and colleagues used the Swedish Register for Surveillance of Communicable Diseases database to identify 50,275 adults diagnosed between 2005 and 2015 with acute and chronic HBV and HCV infection. Some 13,276 adults had HBV and 36,999 had HCV, and this included 14,205 low-dose (75 mg or 160 mg) aspirin users and 36,070 nonusers.

The analysis showed that in aspirin users, the 10-year cumulative incidence of HCC was 4% compared with 8.3% in nonusers. After multivariable adjustment, aspirin users had a risk of HCC that was 31% lower compared with nonusers (adjusted subhazard ratio, 0.69; 95% confidence interval [CI], 0.62 - 0.76).

Patients taking low-dose aspirin had a 10-year liver-related mortality of 11% compared with 17.9% among nonusers. The adjusted risk of liver-related mortality was 27% lower in aspirin users than in nonusers.

There was no significant difference in the 10-year risk of gastrointestinal bleeding between users and nonusers of aspirin (7.8% and 6.9%, respectively). In addition, the analysis showed that the risks of any gastrointestinal bleeding were similar among aspirin-users with compensated cirrhosis and those without cirrhosis (8.3% and 7.5%, respectively).

Notably, the risk of HCC was significantly lower after 3 to 5 years of aspirin use and after 5 or more years of use (adjusted hazard ratio [HR], 0.66, 0.57, respectively) compared with short-term use (3 months to <1 year; adjusted HR, 0.90) or with intermittent, discontinued, or no aspirin use. But when those with chronic viral hepatitis stopped taking aspirin, their risk of HCC rose to become 22% higher compared with peers who continued to use aspirin.

The risk of liver-related death also rose by 31% in aspirin users who stopped taking aspirin compared with those who did not stop (subhazard ratio, 1.31). Again, this relationship appeared to be duration-dependent, with the risk of incident HCC rising sharply among those who discontinued aspirin and increasing in magnitude over time.

The consistency of aspirin use also influenced risk. In individuals who had an on-again, off-again pattern of aspirin use, the incidence of HCC was 5.9% compared with 1.1% in those who used it consistently.

“Our results were consistent regardless of sex, cause of hepatitis, or underlying compensated cirrhosis,” the authors write. “The consistent duration-response associations lend further credence to a potential causal relationship.”

Limitations of the Study

The current study findings are not new, but this is the best-designed study to date, commented Flemming. Still, there were a number of limitations, she noted. Although cirrhosis is the strongest risk factor for HCC in patients with viral hepatitis, for instance, it was assessed only at cohort entry, and not during the median 8 years of follow-up. There was also a lack of information about sustained virologic response (SVR) rates.

Since less than 25% of patients with HCV received HCV therapy, this indicates they were likely treated with interferon-based therapy, Flemming suggested. Interferon-based therapy is associated with much lower SVR rates than direct acting antiviral (DAA) therapy, which can produce SVR in approximately 95% of patients, she pointed out.

“Therefore, a large proportion of the study patients were likely viremic and at a higher baseline risk of HCC than contemporary HCV populations.”

Evidence from a number of studies indicates that achieving SVR with DAA therapy is associated with a 70% risk reduction for incident HCC and liver-related events, Flemming said. “Whether the use of ASA in patients who have achieved SVR provides the same HCC risk reduction and decrease in hepatic outcomes is unknown.”

Also, the study did not provide information on the specific type of HBV therapy used in patients with HBV, Flemming noted. When considering the prevention of HCC in patients with chronic HBV infection, recent data support a differential protective effect of tenofovir disoproxil fumarate (multiple brands) compared with entecavir (Baraclude, Bristol-Myers Squibb), she pointed out. As previously reported by Medscape Medical News, these data also indicate that tenofovir may be more effective than entecavir in reducing the risk of liver failure and all-cause mortality.

This study was funded by the US National Institutes of Health, Nyckelfonden, Region Stockholm County, the American Association for the Study of Liver Diseases, Boston Nutrition Obesity Research Council, Region Örebro County, and Karolinska Institutet. Simon has disclosed no relevant financial relationships. A number of study coauthors disclosed having relationships with industry; the full list can be found with the original article. Flemming reported relationships with Gilead Sciences Canada, AbbVie, and Lupin Pharmaceuticals.

This article first appeared on Medscape.com.

N Engl J Med. 2020 Mar 12. doi: 10.1056/NEJMoa1912035.

The risk of liver cancer and liver-related death in patients with chronic viral hepatitis was substantially reduced with the use of low-dose aspirin, results from a nationwide study from Sweden suggest.

The risk of hepatocellular carcinoma (HCC) was reduced by 31% compared with no aspirin use, and liver-related mortality dropped by 27%, as long as aspirin use continued.

“We were excited to find for the first time in a nationwide Western population that low-dose aspirin use was associated with substantial reduction in risk of developing incident HCC,” lead author Tracey G. Simon, MD, MPH, of Massachusetts General Hospital and Harvard Medical School in Boston, told Medscape Medical News.

The study was published in the March 12 issue of the New England Journal of Medicine.

HCC is the fourth-leading cause of cancer mortality worldwide, and is driven mostly by viral hepatitis B (HBV) and viral hepatitis C (HCV) infection, noted Jennifer A. Flemming, MD, of Queen’s University, Kingston, Canada, an expert not involved with the study. HCC is also one of the only cancers to show a rising incidence over the past several decades, she added .

However, the results of this do not change clinical practice. “It is premature to prescribe low dose ASA [acetylsalicylic acid] in patients with viral hepatitis for the sole indication of HCC prevention in routine clinical practice without support from prospective randomized data,” she said.

“The results of this study make it clear that a prospective randomized study comparing ASA to placebo in patients with viral hepatitis without an indication for low-dose ASA is justified to evaluate the risk of incident HCC,” she told Medscape Medical News.

The study authors agree, and they also emphasize that the findings from this observational study “should not yet change clinical practice.”

More research is needed in populations with compensated and decompensated cirrhosis to determine the optimal timing of aspirin initiation — or cessation of therapy — that will maximize benefit and prevent adverse events, said Simon.

Study Details

Although several earlier studies have suggested a duration-dependent benefit of aspirin use in preventing HCC in smaller populations, this study is the first to confirm a duration-response relationship with low-dose aspirin use in an unselected European population with confirmed viral hepatitis, Simon pointed out.

For their study, Simon and colleagues used the Swedish Register for Surveillance of Communicable Diseases database to identify 50,275 adults diagnosed between 2005 and 2015 with acute and chronic HBV and HCV infection. Some 13,276 adults had HBV and 36,999 had HCV, and this included 14,205 low-dose (75 mg or 160 mg) aspirin users and 36,070 nonusers.

The analysis showed that in aspirin users, the 10-year cumulative incidence of HCC was 4% compared with 8.3% in nonusers. After multivariable adjustment, aspirin users had a risk of HCC that was 31% lower compared with nonusers (adjusted subhazard ratio, 0.69; 95% confidence interval [CI], 0.62 - 0.76).

Patients taking low-dose aspirin had a 10-year liver-related mortality of 11% compared with 17.9% among nonusers. The adjusted risk of liver-related mortality was 27% lower in aspirin users than in nonusers.

There was no significant difference in the 10-year risk of gastrointestinal bleeding between users and nonusers of aspirin (7.8% and 6.9%, respectively). In addition, the analysis showed that the risks of any gastrointestinal bleeding were similar among aspirin-users with compensated cirrhosis and those without cirrhosis (8.3% and 7.5%, respectively).

Notably, the risk of HCC was significantly lower after 3 to 5 years of aspirin use and after 5 or more years of use (adjusted hazard ratio [HR], 0.66, 0.57, respectively) compared with short-term use (3 months to <1 year; adjusted HR, 0.90) or with intermittent, discontinued, or no aspirin use. But when those with chronic viral hepatitis stopped taking aspirin, their risk of HCC rose to become 22% higher compared with peers who continued to use aspirin.

The risk of liver-related death also rose by 31% in aspirin users who stopped taking aspirin compared with those who did not stop (subhazard ratio, 1.31). Again, this relationship appeared to be duration-dependent, with the risk of incident HCC rising sharply among those who discontinued aspirin and increasing in magnitude over time.

The consistency of aspirin use also influenced risk. In individuals who had an on-again, off-again pattern of aspirin use, the incidence of HCC was 5.9% compared with 1.1% in those who used it consistently.

“Our results were consistent regardless of sex, cause of hepatitis, or underlying compensated cirrhosis,” the authors write. “The consistent duration-response associations lend further credence to a potential causal relationship.”

Limitations of the Study

The current study findings are not new, but this is the best-designed study to date, commented Flemming. Still, there were a number of limitations, she noted. Although cirrhosis is the strongest risk factor for HCC in patients with viral hepatitis, for instance, it was assessed only at cohort entry, and not during the median 8 years of follow-up. There was also a lack of information about sustained virologic response (SVR) rates.

Since less than 25% of patients with HCV received HCV therapy, this indicates they were likely treated with interferon-based therapy, Flemming suggested. Interferon-based therapy is associated with much lower SVR rates than direct acting antiviral (DAA) therapy, which can produce SVR in approximately 95% of patients, she pointed out.

“Therefore, a large proportion of the study patients were likely viremic and at a higher baseline risk of HCC than contemporary HCV populations.”

Evidence from a number of studies indicates that achieving SVR with DAA therapy is associated with a 70% risk reduction for incident HCC and liver-related events, Flemming said. “Whether the use of ASA in patients who have achieved SVR provides the same HCC risk reduction and decrease in hepatic outcomes is unknown.”

Also, the study did not provide information on the specific type of HBV therapy used in patients with HBV, Flemming noted. When considering the prevention of HCC in patients with chronic HBV infection, recent data support a differential protective effect of tenofovir disoproxil fumarate (multiple brands) compared with entecavir (Baraclude, Bristol-Myers Squibb), she pointed out. As previously reported by Medscape Medical News, these data also indicate that tenofovir may be more effective than entecavir in reducing the risk of liver failure and all-cause mortality.

This study was funded by the US National Institutes of Health, Nyckelfonden, Region Stockholm County, the American Association for the Study of Liver Diseases, Boston Nutrition Obesity Research Council, Region Örebro County, and Karolinska Institutet. Simon has disclosed no relevant financial relationships. A number of study coauthors disclosed having relationships with industry; the full list can be found with the original article. Flemming reported relationships with Gilead Sciences Canada, AbbVie, and Lupin Pharmaceuticals.

This article first appeared on Medscape.com.

N Engl J Med. 2020 Mar 12. doi: 10.1056/NEJMoa1912035.

For patients with nonalcoholic steatohepatitis (NASH) with cirrhosis and portal hypertension, belapectin therapy was safe but did not significantly improve fibrosis or hepatic venous pressure gradient, compared with placebo, according to the results of a multicenter phase 2b study.

After 52 weeks of infusions, the change in hepatic venous pressure gradient did not significantly differ between the 2-mg/kg group (–0.28 mm Hg) and the placebo group (0.10 mm Hg) or between the 8-mg/kg group (–0.25 mm Hg) and the placebo group (P = .1 for both comparisons). Belapectin also did not significantly improve fibrosis, nonalcoholic fatty liver disease activity score, or the frequency of various complications of cirrhosis. “However, in a subgroup analysis of patients without esophageal varices, 2 mg/kg belapectin did reduce hepatic venous pressure gradient and development of varices,” wrote Naga Chalasani, MD, of Indiana University in Indianapolis and his associates. The findings were published in Gastroenterology.

NASH leads to portal hypertension, variceal bleeding, ascites with bacterial peritonitis, hepatic encephalopathy, and liver-related death and is a leading reason for liver transplantation among women and men. Galectin-3, which is primarily secreted by macrophages, is elevated in patients with NASH and has been linked to the pathophysiology of liver fibrosis in mice. Belapectin (GR-MD-02), a complex carbohydrate that targets and disrupts galectin-3, has been found to reduce liver fibrosis and portal hypertension in rats and was safe and well tolerated in phase 1 studies.

For this double-blind trial, the researchers randomly assigned 162 patients with NASH, cirrhosis, and portal hypertension (hepatic venous pressure gradient at least 6 mm Hg) to receive biweekly infusions of belapectin 2 mg/kg (54 patients), belapectin 8 mg/kg (54 patients), or placebo (54 patients). Patients were treated for 52 weeks. The primary endpoint was change from baseline in hepatic venous pressure gradient.

In a post-hoc analysis of the 81 patients who had no esophageal varices at baseline, 2 mg/kg belapectin was associated with an average 1.61-mm Hg reduction in hepatic venous pressure gradient from baseline (P = .02) and with a reduction in the development of new varices (P = .03).These effects did not extend to subgroups of patients with varices at baseline, clinically significant portal hypertension, or mild portal hypertension. Moreover, 2 mg/kg belapectin did not improve fibrosis, and the higher dose of belapectin (8 mg/kg) met neither the primary endpoint nor the secondary endpoints in the overall cohort or in subgroup analyses. In the subgroup with no varices at baseline, Galectin Technologies is proceeding to initiating a phase 3 clinical trial.

“Interestingly and somewhat unexpectedly, belapectin was associated with an improvement in hepatocyte ballooning,” which “is considered fundamental to the pathogenesis of disease progression in nonalcoholic steatohepatitis,” the researchers wrote. “The significance of such improvement in hepatocyte ballooning in the absence of improvement of other histological components, especially inflammation, is unknown.”

Galectin Therapeutics provided funding. Dr. Chalasani disclosed grant support from Galectin Therapeutics and relevant consulting relationships with NuSirt, AbbVie, Afimmune (DS Biopharma), and several other pharmaceutical companies. Sixteen coinvestigators also disclosed relationships with pharmaceutical companies, of whom eight disclosed consulting relationships, received research funding, or were employed by Galectin.

SOURCE: Chalasani N et al. Gastroenterology. 2019 Dec 5. doi: 10.1053/j.gastro.2019.11.296.

*This story was updated on 3/18/2020.

For patients with nonalcoholic steatohepatitis (NASH) with cirrhosis and portal hypertension, belapectin therapy was safe but did not significantly improve fibrosis or hepatic venous pressure gradient, compared with placebo, according to the results of a multicenter phase 2b study.

After 52 weeks of infusions, the change in hepatic venous pressure gradient did not significantly differ between the 2-mg/kg group (–0.28 mm Hg) and the placebo group (0.10 mm Hg) or between the 8-mg/kg group (–0.25 mm Hg) and the placebo group (P = .1 for both comparisons). Belapectin also did not significantly improve fibrosis, nonalcoholic fatty liver disease activity score, or the frequency of various complications of cirrhosis. “However, in a subgroup analysis of patients without esophageal varices, 2 mg/kg belapectin did reduce hepatic venous pressure gradient and development of varices,” wrote Naga Chalasani, MD, of Indiana University in Indianapolis and his associates. The findings were published in Gastroenterology.

NASH leads to portal hypertension, variceal bleeding, ascites with bacterial peritonitis, hepatic encephalopathy, and liver-related death and is a leading reason for liver transplantation among women and men. Galectin-3, which is primarily secreted by macrophages, is elevated in patients with NASH and has been linked to the pathophysiology of liver fibrosis in mice. Belapectin (GR-MD-02), a complex carbohydrate that targets and disrupts galectin-3, has been found to reduce liver fibrosis and portal hypertension in rats and was safe and well tolerated in phase 1 studies.

For this double-blind trial, the researchers randomly assigned 162 patients with NASH, cirrhosis, and portal hypertension (hepatic venous pressure gradient at least 6 mm Hg) to receive biweekly infusions of belapectin 2 mg/kg (54 patients), belapectin 8 mg/kg (54 patients), or placebo (54 patients). Patients were treated for 52 weeks. The primary endpoint was change from baseline in hepatic venous pressure gradient.

In a post-hoc analysis of the 81 patients who had no esophageal varices at baseline, 2 mg/kg belapectin was associated with an average 1.61-mm Hg reduction in hepatic venous pressure gradient from baseline (P = .02) and with a reduction in the development of new varices (P = .03).These effects did not extend to subgroups of patients with varices at baseline, clinically significant portal hypertension, or mild portal hypertension. Moreover, 2 mg/kg belapectin did not improve fibrosis, and the higher dose of belapectin (8 mg/kg) met neither the primary endpoint nor the secondary endpoints in the overall cohort or in subgroup analyses. In the subgroup with no varices at baseline, Galectin Technologies is proceeding to initiating a phase 3 clinical trial.

“Interestingly and somewhat unexpectedly, belapectin was associated with an improvement in hepatocyte ballooning,” which “is considered fundamental to the pathogenesis of disease progression in nonalcoholic steatohepatitis,” the researchers wrote. “The significance of such improvement in hepatocyte ballooning in the absence of improvement of other histological components, especially inflammation, is unknown.”

Galectin Therapeutics provided funding. Dr. Chalasani disclosed grant support from Galectin Therapeutics and relevant consulting relationships with NuSirt, AbbVie, Afimmune (DS Biopharma), and several other pharmaceutical companies. Sixteen coinvestigators also disclosed relationships with pharmaceutical companies, of whom eight disclosed consulting relationships, received research funding, or were employed by Galectin.

SOURCE: Chalasani N et al. Gastroenterology. 2019 Dec 5. doi: 10.1053/j.gastro.2019.11.296.

*This story was updated on 3/18/2020.

For patients with nonalcoholic steatohepatitis (NASH) with cirrhosis and portal hypertension, belapectin therapy was safe but did not significantly improve fibrosis or hepatic venous pressure gradient, compared with placebo, according to the results of a multicenter phase 2b study.

After 52 weeks of infusions, the change in hepatic venous pressure gradient did not significantly differ between the 2-mg/kg group (–0.28 mm Hg) and the placebo group (0.10 mm Hg) or between the 8-mg/kg group (–0.25 mm Hg) and the placebo group (P = .1 for both comparisons). Belapectin also did not significantly improve fibrosis, nonalcoholic fatty liver disease activity score, or the frequency of various complications of cirrhosis. “However, in a subgroup analysis of patients without esophageal varices, 2 mg/kg belapectin did reduce hepatic venous pressure gradient and development of varices,” wrote Naga Chalasani, MD, of Indiana University in Indianapolis and his associates. The findings were published in Gastroenterology.

NASH leads to portal hypertension, variceal bleeding, ascites with bacterial peritonitis, hepatic encephalopathy, and liver-related death and is a leading reason for liver transplantation among women and men. Galectin-3, which is primarily secreted by macrophages, is elevated in patients with NASH and has been linked to the pathophysiology of liver fibrosis in mice. Belapectin (GR-MD-02), a complex carbohydrate that targets and disrupts galectin-3, has been found to reduce liver fibrosis and portal hypertension in rats and was safe and well tolerated in phase 1 studies.

For this double-blind trial, the researchers randomly assigned 162 patients with NASH, cirrhosis, and portal hypertension (hepatic venous pressure gradient at least 6 mm Hg) to receive biweekly infusions of belapectin 2 mg/kg (54 patients), belapectin 8 mg/kg (54 patients), or placebo (54 patients). Patients were treated for 52 weeks. The primary endpoint was change from baseline in hepatic venous pressure gradient.

In a post-hoc analysis of the 81 patients who had no esophageal varices at baseline, 2 mg/kg belapectin was associated with an average 1.61-mm Hg reduction in hepatic venous pressure gradient from baseline (P = .02) and with a reduction in the development of new varices (P = .03).These effects did not extend to subgroups of patients with varices at baseline, clinically significant portal hypertension, or mild portal hypertension. Moreover, 2 mg/kg belapectin did not improve fibrosis, and the higher dose of belapectin (8 mg/kg) met neither the primary endpoint nor the secondary endpoints in the overall cohort or in subgroup analyses. In the subgroup with no varices at baseline, Galectin Technologies is proceeding to initiating a phase 3 clinical trial.

“Interestingly and somewhat unexpectedly, belapectin was associated with an improvement in hepatocyte ballooning,” which “is considered fundamental to the pathogenesis of disease progression in nonalcoholic steatohepatitis,” the researchers wrote. “The significance of such improvement in hepatocyte ballooning in the absence of improvement of other histological components, especially inflammation, is unknown.”

Galectin Therapeutics provided funding. Dr. Chalasani disclosed grant support from Galectin Therapeutics and relevant consulting relationships with NuSirt, AbbVie, Afimmune (DS Biopharma), and several other pharmaceutical companies. Sixteen coinvestigators also disclosed relationships with pharmaceutical companies, of whom eight disclosed consulting relationships, received research funding, or were employed by Galectin.

SOURCE: Chalasani N et al. Gastroenterology. 2019 Dec 5. doi: 10.1053/j.gastro.2019.11.296.

*This story was updated on 3/18/2020.

Adults aged 18-79 years should be screened for hepatitis C virus infection, according to an updated grade B recommendation from the U.S. Preventive Services Task Force.

Cases of acute hepatitis C virus (HCV) infection have spiked in the last decade, in part because of increased use of injection drugs and in part because of better surveillance, Douglas K. Owens, MD, of Stanford (Calif.) University, and colleagues wrote in the recommendation statement published in JAMA.

The recommendation applies to all asymptomatic adults aged 18-79 years without known liver disease, and expands on the 2013 recommendation to screen adults born between 1945 and 1965. The grade B designation means that the task force concluded with moderate certainty that HCV screening for adults aged 18-79 years had “substantial net benefit.”

The recommendations are based on an evidence report including 8 randomized, controlled trials, 48 other treatment studies, and 33 cohort studies published through February 2019 for a total of 179,230 individuals.

The screening is a one-time procedure for most adults, according to the task force, but clinicians should periodically screen individuals at increased risk, such as those with a past or current history of injection drug use. In addition, clinicians should consider screening individuals at increased risk who are above or below the recommended age range.

Although the task force identified no direct evidence on the benefit of screening for HCV infection in asymptomatic adults, a notable finding was that the newer direct-acting antiviral (DAA) regimens are sufficiently effective to support the expanded screening recommendation, they said. However, clinicians should inform patients that screening is voluntary and conducted only with the patient’s knowledge. Clinicians should educate patients about hepatitis C and give them an opportunity to ask questions and to make a decision about screening, according to the task force.

In the evidence report, a total of 49 studies including 10,181 individuals showed DAA treatment associated with pooled sustained virologic response rates greater than 95% across all virus genotypes, and a short-term serious adverse event rate of 1.9%. In addition, sustained virologic response following an antiviral therapy was associated with a reduction in risk of all-cause mortality (pooled hazard ratio 0.40) and of hepatocellular carcinoma (pooled HR 0.29) compared with cases of no sustained virologic response.

The evidence report findings were limited by several factors, including the relatively small number of randomized trials involving current DAA treatments, limited data on baseline symptoms, limited data on adolescents, and limited evidence on potential long-term harms of DAA therapy, noted Richard Chou, MD, of Oregon Health & Science University, Portland, and colleagues. However, new pooled evidence “indicates that SVR rates with currently recommended all-oral DAA regimens are substantially higher (more than 95%) than with interferon-based therapies evaluated in the prior review (68%-78%),” they said.

Several editorials were published concurrently with the recommendation.

In an editorial published in JAMA, Camilla S. Graham, MD, of Harvard Medical School, Boston, and Stacey Trooskin, MD, of the University of Pennsylvania, Philadelphia, wrote that the new recommendation reflects changes in hepatitis C virus management.

“With the approvals of sofosbuvir and simeprevir in 2013, patients with hepatitis C, a chronic viral illness associated with the deaths of more U.S. patients than the next 60 reportable infectious diseases combined, including HIV and tuberculosis, could expect a greater than 90% rate of achieving sustained virologic response (SVR, defined as undetectable HCV levels 12 weeks or longer after treatment completion, which is consistent with virologic cure of HCV infection) following 12 weeks of treatment,” they said.

These medications are effective but expensive; however, the combination of the availability of generic medications and the ongoing opioid epidemic in the United States are important contributors to the expanded recommendations, which “are welcome,” and may help meeting WHO 2030 targets for reducing new HCV infections, they said.

Dr. Graham disclosed personal fees from UpToDate. Dr. Trooskin disclosed grants from Gilead Sciences and personal fees from Merck, AbbVie, and Gilead Sciences.

In an editorial published in JAMA Internal Medicine, Jennifer C. Price, MD, and Danielle Brandman, MD, both of the University of California, San Francisco, wrote that “the advancements in HCV diagnosis and treatment have been extraordinary,” but that the new recommendation does not go far enough. “Implementation of HCV screening and linkage to treatment requires large-scale coordinated efforts, innovation, and resources. For example, point-of-care HCV RNA testing would enable scale-up of HCV screening and confirmatory testing among individuals at greatest risk of HCV infection,” they said. “Additionally, barriers remain between diagnosis and treatment, such as access to a health care provider who can treat HCV and authorization to receive affordable DAAs,” they noted. “Although the USPSTF HCV screening recommendation is a step forward for controlling HCV infection in the U.S., it will take a coordinated and funded effort to ensure that the anticipated benefits are realized,” they concluded.

Dr. Price disclosed research funding from Gilead Sciences and Merck. Dr. Brandman disclosed research funding from Gilead Sciences, Pfizer, Conatus, Allergan, and Grifols, as well as personal fees from Alnylam.

In an editorial published in JAMA Network Open, Eli S. Rosenberg, PhD, of the University at Albany (N.Y.) School of Public Health, and Joshua A. Barocas, MD, of Boston University, emphasized the need to change the stigma surrounding HCV infection in the United States.

“Given the changing epidemiology of HCV infection, new public health priorities, advancements in treatment, and unmet diagnostic needs, it is wise to periodically reevaluate screening recommendations to ensure that they are maximally addressing these areas and patients’ individual needs,” they said. “The Affordable Care Act requires private insurers and Medicaid to cover preventive services recommended by the USPSTF with a grade of A or B with no cost sharing (i.e., no deductible or copayment),” they noted. Although the new recommendation for one-time screening will likely identify more cases, improve outcomes, and reduce deaths, the editorialists cautioned that “one-time screening should not be interpreted like catch-up vaccinations, whereby we immunize someone at any age for hepatitis B virus, for example, and they are then immunized for the remainder of their life,” and that reassessments are needed, especially for younger adults.

In addition, they emphasized the need to reduce the stigma surrounding HCV and allow for recommendations based on risk, rather than age. “We have forced the USPSTF to adopt age-based screening recommendations because we, as a society, have created a culture in which we have stigmatized these behaviors and we, as practitioners, have proven to be inadequate at eliciting HCV risk behaviors,” they said. “Our responsibility as a society and practice community is to address structural and individual factors that limit our ability to most precisely address the needs of our patients and truly move toward HCV elimination,” they concluded.

The USPSTF is supported by the Agency for Healthcare Research and Quality. The task force researchers had no financial conflicts to disclose.

SOURCES: Owens DK et al. JAMA. 2020 Mar 2. doi: 10.1001/jama.2020.1123; Chou R et al. JAMA. 2020 Mar 2. doi: 10.1001/jama.2019.20788; Graham CS, Trooskin S. JAMA. 2020 Mar 2. doi: 10.1001/jama.2019.22313; Price JC and Brandman D. JAMA Intern Med. 2020 Mar 2. doi: 10.1001/jamainternmed.2019.7334; Rosenberg ES, Barocas JA. JAMA Network Open. 2020 Mar 2. doi: 10.1001/jamanetworkopen.2020.0538.

Use AGA patient education to help your patients better understand HCV, including their risk and treatment options, at https://www.gastro.org/practice-guidance/gi-patient-center/topic/hepatitis-c-hcv.

Adults aged 18-79 years should be screened for hepatitis C virus infection, according to an updated grade B recommendation from the U.S. Preventive Services Task Force.

Cases of acute hepatitis C virus (HCV) infection have spiked in the last decade, in part because of increased use of injection drugs and in part because of better surveillance, Douglas K. Owens, MD, of Stanford (Calif.) University, and colleagues wrote in the recommendation statement published in JAMA.

The recommendation applies to all asymptomatic adults aged 18-79 years without known liver disease, and expands on the 2013 recommendation to screen adults born between 1945 and 1965. The grade B designation means that the task force concluded with moderate certainty that HCV screening for adults aged 18-79 years had “substantial net benefit.”

The recommendations are based on an evidence report including 8 randomized, controlled trials, 48 other treatment studies, and 33 cohort studies published through February 2019 for a total of 179,230 individuals.

The screening is a one-time procedure for most adults, according to the task force, but clinicians should periodically screen individuals at increased risk, such as those with a past or current history of injection drug use. In addition, clinicians should consider screening individuals at increased risk who are above or below the recommended age range.

Although the task force identified no direct evidence on the benefit of screening for HCV infection in asymptomatic adults, a notable finding was that the newer direct-acting antiviral (DAA) regimens are sufficiently effective to support the expanded screening recommendation, they said. However, clinicians should inform patients that screening is voluntary and conducted only with the patient’s knowledge. Clinicians should educate patients about hepatitis C and give them an opportunity to ask questions and to make a decision about screening, according to the task force.

In the evidence report, a total of 49 studies including 10,181 individuals showed DAA treatment associated with pooled sustained virologic response rates greater than 95% across all virus genotypes, and a short-term serious adverse event rate of 1.9%. In addition, sustained virologic response following an antiviral therapy was associated with a reduction in risk of all-cause mortality (pooled hazard ratio 0.40) and of hepatocellular carcinoma (pooled HR 0.29) compared with cases of no sustained virologic response.

The evidence report findings were limited by several factors, including the relatively small number of randomized trials involving current DAA treatments, limited data on baseline symptoms, limited data on adolescents, and limited evidence on potential long-term harms of DAA therapy, noted Richard Chou, MD, of Oregon Health & Science University, Portland, and colleagues. However, new pooled evidence “indicates that SVR rates with currently recommended all-oral DAA regimens are substantially higher (more than 95%) than with interferon-based therapies evaluated in the prior review (68%-78%),” they said.

Several editorials were published concurrently with the recommendation.

In an editorial published in JAMA, Camilla S. Graham, MD, of Harvard Medical School, Boston, and Stacey Trooskin, MD, of the University of Pennsylvania, Philadelphia, wrote that the new recommendation reflects changes in hepatitis C virus management.

“With the approvals of sofosbuvir and simeprevir in 2013, patients with hepatitis C, a chronic viral illness associated with the deaths of more U.S. patients than the next 60 reportable infectious diseases combined, including HIV and tuberculosis, could expect a greater than 90% rate of achieving sustained virologic response (SVR, defined as undetectable HCV levels 12 weeks or longer after treatment completion, which is consistent with virologic cure of HCV infection) following 12 weeks of treatment,” they said.

These medications are effective but expensive; however, the combination of the availability of generic medications and the ongoing opioid epidemic in the United States are important contributors to the expanded recommendations, which “are welcome,” and may help meeting WHO 2030 targets for reducing new HCV infections, they said.

Dr. Graham disclosed personal fees from UpToDate. Dr. Trooskin disclosed grants from Gilead Sciences and personal fees from Merck, AbbVie, and Gilead Sciences.

In an editorial published in JAMA Internal Medicine, Jennifer C. Price, MD, and Danielle Brandman, MD, both of the University of California, San Francisco, wrote that “the advancements in HCV diagnosis and treatment have been extraordinary,” but that the new recommendation does not go far enough. “Implementation of HCV screening and linkage to treatment requires large-scale coordinated efforts, innovation, and resources. For example, point-of-care HCV RNA testing would enable scale-up of HCV screening and confirmatory testing among individuals at greatest risk of HCV infection,” they said. “Additionally, barriers remain between diagnosis and treatment, such as access to a health care provider who can treat HCV and authorization to receive affordable DAAs,” they noted. “Although the USPSTF HCV screening recommendation is a step forward for controlling HCV infection in the U.S., it will take a coordinated and funded effort to ensure that the anticipated benefits are realized,” they concluded.

Dr. Price disclosed research funding from Gilead Sciences and Merck. Dr. Brandman disclosed research funding from Gilead Sciences, Pfizer, Conatus, Allergan, and Grifols, as well as personal fees from Alnylam.

In an editorial published in JAMA Network Open, Eli S. Rosenberg, PhD, of the University at Albany (N.Y.) School of Public Health, and Joshua A. Barocas, MD, of Boston University, emphasized the need to change the stigma surrounding HCV infection in the United States.

“Given the changing epidemiology of HCV infection, new public health priorities, advancements in treatment, and unmet diagnostic needs, it is wise to periodically reevaluate screening recommendations to ensure that they are maximally addressing these areas and patients’ individual needs,” they said. “The Affordable Care Act requires private insurers and Medicaid to cover preventive services recommended by the USPSTF with a grade of A or B with no cost sharing (i.e., no deductible or copayment),” they noted. Although the new recommendation for one-time screening will likely identify more cases, improve outcomes, and reduce deaths, the editorialists cautioned that “one-time screening should not be interpreted like catch-up vaccinations, whereby we immunize someone at any age for hepatitis B virus, for example, and they are then immunized for the remainder of their life,” and that reassessments are needed, especially for younger adults.

In addition, they emphasized the need to reduce the stigma surrounding HCV and allow for recommendations based on risk, rather than age. “We have forced the USPSTF to adopt age-based screening recommendations because we, as a society, have created a culture in which we have stigmatized these behaviors and we, as practitioners, have proven to be inadequate at eliciting HCV risk behaviors,” they said. “Our responsibility as a society and practice community is to address structural and individual factors that limit our ability to most precisely address the needs of our patients and truly move toward HCV elimination,” they concluded.

The USPSTF is supported by the Agency for Healthcare Research and Quality. The task force researchers had no financial conflicts to disclose.

SOURCES: Owens DK et al. JAMA. 2020 Mar 2. doi: 10.1001/jama.2020.1123; Chou R et al. JAMA. 2020 Mar 2. doi: 10.1001/jama.2019.20788; Graham CS, Trooskin S. JAMA. 2020 Mar 2. doi: 10.1001/jama.2019.22313; Price JC and Brandman D. JAMA Intern Med. 2020 Mar 2. doi: 10.1001/jamainternmed.2019.7334; Rosenberg ES, Barocas JA. JAMA Network Open. 2020 Mar 2. doi: 10.1001/jamanetworkopen.2020.0538.

Use AGA patient education to help your patients better understand HCV, including their risk and treatment options, at https://www.gastro.org/practice-guidance/gi-patient-center/topic/hepatitis-c-hcv.

Adults aged 18-79 years should be screened for hepatitis C virus infection, according to an updated grade B recommendation from the U.S. Preventive Services Task Force.

Cases of acute hepatitis C virus (HCV) infection have spiked in the last decade, in part because of increased use of injection drugs and in part because of better surveillance, Douglas K. Owens, MD, of Stanford (Calif.) University, and colleagues wrote in the recommendation statement published in JAMA.

The recommendation applies to all asymptomatic adults aged 18-79 years without known liver disease, and expands on the 2013 recommendation to screen adults born between 1945 and 1965. The grade B designation means that the task force concluded with moderate certainty that HCV screening for adults aged 18-79 years had “substantial net benefit.”

The recommendations are based on an evidence report including 8 randomized, controlled trials, 48 other treatment studies, and 33 cohort studies published through February 2019 for a total of 179,230 individuals.

The screening is a one-time procedure for most adults, according to the task force, but clinicians should periodically screen individuals at increased risk, such as those with a past or current history of injection drug use. In addition, clinicians should consider screening individuals at increased risk who are above or below the recommended age range.

Although the task force identified no direct evidence on the benefit of screening for HCV infection in asymptomatic adults, a notable finding was that the newer direct-acting antiviral (DAA) regimens are sufficiently effective to support the expanded screening recommendation, they said. However, clinicians should inform patients that screening is voluntary and conducted only with the patient’s knowledge. Clinicians should educate patients about hepatitis C and give them an opportunity to ask questions and to make a decision about screening, according to the task force.

In the evidence report, a total of 49 studies including 10,181 individuals showed DAA treatment associated with pooled sustained virologic response rates greater than 95% across all virus genotypes, and a short-term serious adverse event rate of 1.9%. In addition, sustained virologic response following an antiviral therapy was associated with a reduction in risk of all-cause mortality (pooled hazard ratio 0.40) and of hepatocellular carcinoma (pooled HR 0.29) compared with cases of no sustained virologic response.

The evidence report findings were limited by several factors, including the relatively small number of randomized trials involving current DAA treatments, limited data on baseline symptoms, limited data on adolescents, and limited evidence on potential long-term harms of DAA therapy, noted Richard Chou, MD, of Oregon Health & Science University, Portland, and colleagues. However, new pooled evidence “indicates that SVR rates with currently recommended all-oral DAA regimens are substantially higher (more than 95%) than with interferon-based therapies evaluated in the prior review (68%-78%),” they said.

Several editorials were published concurrently with the recommendation.

In an editorial published in JAMA, Camilla S. Graham, MD, of Harvard Medical School, Boston, and Stacey Trooskin, MD, of the University of Pennsylvania, Philadelphia, wrote that the new recommendation reflects changes in hepatitis C virus management.

“With the approvals of sofosbuvir and simeprevir in 2013, patients with hepatitis C, a chronic viral illness associated with the deaths of more U.S. patients than the next 60 reportable infectious diseases combined, including HIV and tuberculosis, could expect a greater than 90% rate of achieving sustained virologic response (SVR, defined as undetectable HCV levels 12 weeks or longer after treatment completion, which is consistent with virologic cure of HCV infection) following 12 weeks of treatment,” they said.

These medications are effective but expensive; however, the combination of the availability of generic medications and the ongoing opioid epidemic in the United States are important contributors to the expanded recommendations, which “are welcome,” and may help meeting WHO 2030 targets for reducing new HCV infections, they said.

Dr. Graham disclosed personal fees from UpToDate. Dr. Trooskin disclosed grants from Gilead Sciences and personal fees from Merck, AbbVie, and Gilead Sciences.

In an editorial published in JAMA Internal Medicine, Jennifer C. Price, MD, and Danielle Brandman, MD, both of the University of California, San Francisco, wrote that “the advancements in HCV diagnosis and treatment have been extraordinary,” but that the new recommendation does not go far enough. “Implementation of HCV screening and linkage to treatment requires large-scale coordinated efforts, innovation, and resources. For example, point-of-care HCV RNA testing would enable scale-up of HCV screening and confirmatory testing among individuals at greatest risk of HCV infection,” they said. “Additionally, barriers remain between diagnosis and treatment, such as access to a health care provider who can treat HCV and authorization to receive affordable DAAs,” they noted. “Although the USPSTF HCV screening recommendation is a step forward for controlling HCV infection in the U.S., it will take a coordinated and funded effort to ensure that the anticipated benefits are realized,” they concluded.

Dr. Price disclosed research funding from Gilead Sciences and Merck. Dr. Brandman disclosed research funding from Gilead Sciences, Pfizer, Conatus, Allergan, and Grifols, as well as personal fees from Alnylam.

In an editorial published in JAMA Network Open, Eli S. Rosenberg, PhD, of the University at Albany (N.Y.) School of Public Health, and Joshua A. Barocas, MD, of Boston University, emphasized the need to change the stigma surrounding HCV infection in the United States.

“Given the changing epidemiology of HCV infection, new public health priorities, advancements in treatment, and unmet diagnostic needs, it is wise to periodically reevaluate screening recommendations to ensure that they are maximally addressing these areas and patients’ individual needs,” they said. “The Affordable Care Act requires private insurers and Medicaid to cover preventive services recommended by the USPSTF with a grade of A or B with no cost sharing (i.e., no deductible or copayment),” they noted. Although the new recommendation for one-time screening will likely identify more cases, improve outcomes, and reduce deaths, the editorialists cautioned that “one-time screening should not be interpreted like catch-up vaccinations, whereby we immunize someone at any age for hepatitis B virus, for example, and they are then immunized for the remainder of their life,” and that reassessments are needed, especially for younger adults.

In addition, they emphasized the need to reduce the stigma surrounding HCV and allow for recommendations based on risk, rather than age. “We have forced the USPSTF to adopt age-based screening recommendations because we, as a society, have created a culture in which we have stigmatized these behaviors and we, as practitioners, have proven to be inadequate at eliciting HCV risk behaviors,” they said. “Our responsibility as a society and practice community is to address structural and individual factors that limit our ability to most precisely address the needs of our patients and truly move toward HCV elimination,” they concluded.

The USPSTF is supported by the Agency for Healthcare Research and Quality. The task force researchers had no financial conflicts to disclose.

SOURCES: Owens DK et al. JAMA. 2020 Mar 2. doi: 10.1001/jama.2020.1123; Chou R et al. JAMA. 2020 Mar 2. doi: 10.1001/jama.2019.20788; Graham CS, Trooskin S. JAMA. 2020 Mar 2. doi: 10.1001/jama.2019.22313; Price JC and Brandman D. JAMA Intern Med. 2020 Mar 2. doi: 10.1001/jamainternmed.2019.7334; Rosenberg ES, Barocas JA. JAMA Network Open. 2020 Mar 2. doi: 10.1001/jamanetworkopen.2020.0538.

Use AGA patient education to help your patients better understand HCV, including their risk and treatment options, at https://www.gastro.org/practice-guidance/gi-patient-center/topic/hepatitis-c-hcv.

MAUI, HAWAII – Alcohol use and deaths related to alcohol-use disorders are increasing, and young adults might be the group to watch, said Norah Terrault, MD, MPH, professor at the Keck School of Medicine of USC in Los Angeles.

“A lot of young people are drinking large amounts and they don’t know they’re at risk. They may not drink much during the week but then drink 30 drinks on the weekend,” Dr. Terrault told Medscape Medical News.

The largest relative increase in deaths from alcoholic cirrhosis – 10.5% from 2009 to 2016 – was in the 25- to 34-year age group, she reported here at the Gastroenterology Updates IBD Liver Disease Conference 2020.

This highlights the importance of asking for details about alcohol use during primary care visits; not only how much, but also what time of day, for instance, she explained.

Dr. Terrault’s team at Keck is part of the ACCELERATE-AH consortium, a group of 12 transplant centers looking at patterns of alcohol use before and after liver transplantation.

In their retrospective study of 147 consecutive transplant patients from 2006 to 2018, they found that young age, a history of multiple rehab attempts, and overt encephalopathy at time of transplantation were predictors of alcohol use after the procedure.

Corticosteroids remain the only proven therapy for alcoholic hepatitis. “We have not seen a new therapy in this arena in decades,” said Dr. Terrault. “We really have nothing to offer these patients, yet it’s an incredibly common presentation with a high mortality.”
 

More treatment options

The good news is that some phase 2 data look promising for new therapies, she reported.

“Some of them are targeting injury and regeneration primarily. Others are looking at the anti-inflammatory and antifibrotic effects. Some are also looking at how gut permeability and the microbiome are influencing outcomes,” she explained.

Transplantation has become very important for patients who do not respond to current therapy, and selection criteria have evolved over the years to take this into account, she pointed out.

In the early 1980s, alcoholic hepatitis was considered an inappropriate indication for liver transplantation. In the early 2000s, the guidance moved to setting 6 months of alcohol abstinence as a criterion for transplantation. The 6-month rule effectively eliminated patients with severe alcoholic hepatitis, who, by the time they needed a new liver, would not have 6 months to live.

Recently, guidelines have added the option of transplantation for patients with alcoholic hepatitis. The option was always there for people who developed alcohol cirrhosis or liver cancer, but now alcoholic hepatitis is recognized as a potential indication for transplantation, Dr. Terrault explained.

Today, transplant centers are moving away from the 6-month rule for two main reasons, she said. One is that few data support the 6-month time period as the duration that makes a difference.

“There is nothing magical about 6 months vs. 3 months or 12 months,” she said, adding that studies have shown that other factors might be better indicators, such as family support and whether the person is employed.

Second, recent studies have shown that rates of 3-year survival are similar in people who did not abstain at all before the procedure and those who undergo transplantation for other reasons.

The ACCELERATE-AH consortium also found that 70% of patients with severe alcoholic hepatitis remained abstinent up to 3 years after transplantation.

Anytime we give an organ to anyone on the list, someone else may die without one. Every year, 20% of patients on the list die without a transplant.

The selection process remains complicated and controversial, Dr. Terrault acknowledged.

“Anytime we give an organ to anyone on the list, someone else may die without one. Every year, 20% of patients on the list die without a transplant,” she said.

And there is concern that because patients with severe alcoholic hepatitis present with severe illness, they get moved to the top of the wait list. The rationale for that, she explained, is that it is done that way in other acute situations.

“We transplant individuals who have an acetaminophen overdose, for example. That’s common in many programs,” she said.

“My issue is that some patients with acute alcoholic hepatitis that have a very high severity score, but some of them, just with abstinence, will get better,” said Guadalupe Garcia-Tsao, MD, professor of medicine at Yale University in New Haven, Conn.

There are cases in which acute alcoholic hepatitis will resolve with abstinence, “and patients can return to an entirely compensated state of cirrhosis, in which they are entirely asymptomatic and they can live,” she told Medscape Medical News.

But it’s hard to know without a control group which patients would have that kind of success with just abstinence, she acknowledged.

Terrault said she agreed, and added that “our tools are not that good,” so determining which patients can be “pulled back from the brink” without transplantation is a challenge.

“There’s still a lot to learn about how we do this, and how we do it well,” she said.

Alcoholic hepatitis as an indication for liver transplantation is rare – less than 1% – but growing.

“This is a potential therapy for your patient who is sick in the ICU with a high severity of disease who has failed steroids. We should call out to see if there’s a transplant program that might be willing to evaluate them,” she said.
 

This article first appeared on Medscape.com.

MAUI, HAWAII – Alcohol use and deaths related to alcohol-use disorders are increasing, and young adults might be the group to watch, said Norah Terrault, MD, MPH, professor at the Keck School of Medicine of USC in Los Angeles.

“A lot of young people are drinking large amounts and they don’t know they’re at risk. They may not drink much during the week but then drink 30 drinks on the weekend,” Dr. Terrault told Medscape Medical News.

The largest relative increase in deaths from alcoholic cirrhosis – 10.5% from 2009 to 2016 – was in the 25- to 34-year age group, she reported here at the Gastroenterology Updates IBD Liver Disease Conference 2020.

This highlights the importance of asking for details about alcohol use during primary care visits; not only how much, but also what time of day, for instance, she explained.

Dr. Terrault’s team at Keck is part of the ACCELERATE-AH consortium, a group of 12 transplant centers looking at patterns of alcohol use before and after liver transplantation.

In their retrospective study of 147 consecutive transplant patients from 2006 to 2018, they found that young age, a history of multiple rehab attempts, and overt encephalopathy at time of transplantation were predictors of alcohol use after the procedure.

Corticosteroids remain the only proven therapy for alcoholic hepatitis. “We have not seen a new therapy in this arena in decades,” said Dr. Terrault. “We really have nothing to offer these patients, yet it’s an incredibly common presentation with a high mortality.”
 

More treatment options

The good news is that some phase 2 data look promising for new therapies, she reported.

“Some of them are targeting injury and regeneration primarily. Others are looking at the anti-inflammatory and antifibrotic effects. Some are also looking at how gut permeability and the microbiome are influencing outcomes,” she explained.

Transplantation has become very important for patients who do not respond to current therapy, and selection criteria have evolved over the years to take this into account, she pointed out.

In the early 1980s, alcoholic hepatitis was considered an inappropriate indication for liver transplantation. In the early 2000s, the guidance moved to setting 6 months of alcohol abstinence as a criterion for transplantation. The 6-month rule effectively eliminated patients with severe alcoholic hepatitis, who, by the time they needed a new liver, would not have 6 months to live.

Recently, guidelines have added the option of transplantation for patients with alcoholic hepatitis. The option was always there for people who developed alcohol cirrhosis or liver cancer, but now alcoholic hepatitis is recognized as a potential indication for transplantation, Dr. Terrault explained.

Today, transplant centers are moving away from the 6-month rule for two main reasons, she said. One is that few data support the 6-month time period as the duration that makes a difference.

“There is nothing magical about 6 months vs. 3 months or 12 months,” she said, adding that studies have shown that other factors might be better indicators, such as family support and whether the person is employed.

Second, recent studies have shown that rates of 3-year survival are similar in people who did not abstain at all before the procedure and those who undergo transplantation for other reasons.

The ACCELERATE-AH consortium also found that 70% of patients with severe alcoholic hepatitis remained abstinent up to 3 years after transplantation.

Anytime we give an organ to anyone on the list, someone else may die without one. Every year, 20% of patients on the list die without a transplant.

The selection process remains complicated and controversial, Dr. Terrault acknowledged.

“Anytime we give an organ to anyone on the list, someone else may die without one. Every year, 20% of patients on the list die without a transplant,” she said.

And there is concern that because patients with severe alcoholic hepatitis present with severe illness, they get moved to the top of the wait list. The rationale for that, she explained, is that it is done that way in other acute situations.

“We transplant individuals who have an acetaminophen overdose, for example. That’s common in many programs,” she said.

“My issue is that some patients with acute alcoholic hepatitis that have a very high severity score, but some of them, just with abstinence, will get better,” said Guadalupe Garcia-Tsao, MD, professor of medicine at Yale University in New Haven, Conn.

There are cases in which acute alcoholic hepatitis will resolve with abstinence, “and patients can return to an entirely compensated state of cirrhosis, in which they are entirely asymptomatic and they can live,” she told Medscape Medical News.

But it’s hard to know without a control group which patients would have that kind of success with just abstinence, she acknowledged.

Terrault said she agreed, and added that “our tools are not that good,” so determining which patients can be “pulled back from the brink” without transplantation is a challenge.

“There’s still a lot to learn about how we do this, and how we do it well,” she said.

Alcoholic hepatitis as an indication for liver transplantation is rare – less than 1% – but growing.

“This is a potential therapy for your patient who is sick in the ICU with a high severity of disease who has failed steroids. We should call out to see if there’s a transplant program that might be willing to evaluate them,” she said.
 

This article first appeared on Medscape.com.

MAUI, HAWAII – Alcohol use and deaths related to alcohol-use disorders are increasing, and young adults might be the group to watch, said Norah Terrault, MD, MPH, professor at the Keck School of Medicine of USC in Los Angeles.

“A lot of young people are drinking large amounts and they don’t know they’re at risk. They may not drink much during the week but then drink 30 drinks on the weekend,” Dr. Terrault told Medscape Medical News.

The largest relative increase in deaths from alcoholic cirrhosis – 10.5% from 2009 to 2016 – was in the 25- to 34-year age group, she reported here at the Gastroenterology Updates IBD Liver Disease Conference 2020.

This highlights the importance of asking for details about alcohol use during primary care visits; not only how much, but also what time of day, for instance, she explained.

Dr. Terrault’s team at Keck is part of the ACCELERATE-AH consortium, a group of 12 transplant centers looking at patterns of alcohol use before and after liver transplantation.

In their retrospective study of 147 consecutive transplant patients from 2006 to 2018, they found that young age, a history of multiple rehab attempts, and overt encephalopathy at time of transplantation were predictors of alcohol use after the procedure.

Corticosteroids remain the only proven therapy for alcoholic hepatitis. “We have not seen a new therapy in this arena in decades,” said Dr. Terrault. “We really have nothing to offer these patients, yet it’s an incredibly common presentation with a high mortality.”
 

More treatment options

The good news is that some phase 2 data look promising for new therapies, she reported.

“Some of them are targeting injury and regeneration primarily. Others are looking at the anti-inflammatory and antifibrotic effects. Some are also looking at how gut permeability and the microbiome are influencing outcomes,” she explained.

Transplantation has become very important for patients who do not respond to current therapy, and selection criteria have evolved over the years to take this into account, she pointed out.

In the early 1980s, alcoholic hepatitis was considered an inappropriate indication for liver transplantation. In the early 2000s, the guidance moved to setting 6 months of alcohol abstinence as a criterion for transplantation. The 6-month rule effectively eliminated patients with severe alcoholic hepatitis, who, by the time they needed a new liver, would not have 6 months to live.

Recently, guidelines have added the option of transplantation for patients with alcoholic hepatitis. The option was always there for people who developed alcohol cirrhosis or liver cancer, but now alcoholic hepatitis is recognized as a potential indication for transplantation, Dr. Terrault explained.

Today, transplant centers are moving away from the 6-month rule for two main reasons, she said. One is that few data support the 6-month time period as the duration that makes a difference.

“There is nothing magical about 6 months vs. 3 months or 12 months,” she said, adding that studies have shown that other factors might be better indicators, such as family support and whether the person is employed.

Second, recent studies have shown that rates of 3-year survival are similar in people who did not abstain at all before the procedure and those who undergo transplantation for other reasons.

The ACCELERATE-AH consortium also found that 70% of patients with severe alcoholic hepatitis remained abstinent up to 3 years after transplantation.

Anytime we give an organ to anyone on the list, someone else may die without one. Every year, 20% of patients on the list die without a transplant.

The selection process remains complicated and controversial, Dr. Terrault acknowledged.

“Anytime we give an organ to anyone on the list, someone else may die without one. Every year, 20% of patients on the list die without a transplant,” she said.

And there is concern that because patients with severe alcoholic hepatitis present with severe illness, they get moved to the top of the wait list. The rationale for that, she explained, is that it is done that way in other acute situations.

“We transplant individuals who have an acetaminophen overdose, for example. That’s common in many programs,” she said.

“My issue is that some patients with acute alcoholic hepatitis that have a very high severity score, but some of them, just with abstinence, will get better,” said Guadalupe Garcia-Tsao, MD, professor of medicine at Yale University in New Haven, Conn.

There are cases in which acute alcoholic hepatitis will resolve with abstinence, “and patients can return to an entirely compensated state of cirrhosis, in which they are entirely asymptomatic and they can live,” she told Medscape Medical News.

But it’s hard to know without a control group which patients would have that kind of success with just abstinence, she acknowledged.

Terrault said she agreed, and added that “our tools are not that good,” so determining which patients can be “pulled back from the brink” without transplantation is a challenge.

“There’s still a lot to learn about how we do this, and how we do it well,” she said.

Alcoholic hepatitis as an indication for liver transplantation is rare – less than 1% – but growing.

“This is a potential therapy for your patient who is sick in the ICU with a high severity of disease who has failed steroids. We should call out to see if there’s a transplant program that might be willing to evaluate them,” she said.
 

This article first appeared on Medscape.com.