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Patients with HBV inadequately monitored for disease activity
Chronic hepatitis B virus patients are insufficiently monitored for disease activity and hepatocellular carcinoma (HCC), according to Philip R. Spradling, MD, and his associates of the Centers for Disease Control and Prevention.
In a cohort study of 2,992 patients with CHB, 2,338 were used for assessment. Researchers used alanine aminotransferase (ALT) monitoring, HBV DNA monitoring, assessment for cirrhosis, and HBV antiviral therapy for examination. For ALT monitoring, 1,814 (78%) of patients had at least one ALT level obtained per year of follow-up. Only 876 patients (37%) had at least one HBV DNA level assessment per year of follow-up and 1,037 (44%) had less than annual testing, and 18% of patients never had an HBV DNA level assessed. Among patients with cirrhosis, 297 (54%) had HBV DNA testing done at least annually, 189 (35%) had testing done but less frequently than annually, and 61 (11%) never had an HBV DNA test done. And of the 547 patients with cirrhosis, 305 (56%) were prescribed HBV antiviral therapy.
It was noted that patients were monitored during 2006-2013. Only 68% of patients had not been prescribed treatment, and 72% had received liver-related specialty care.
“Our findings reiterate the need for clinicians who treat patients with [chronic HBV] to provide ongoing, continual assessment of disease activity based on HBV DNA and ALT levels, as well as liver imaging surveillance among patients at high risk for HCC,” researchers concluded. “As antiviral therapy for [chronic HBV] now includes potent and highly efficacious oral agents that have few contraindications and minimal side effects, as well as a high barrier to resistance, clinicians should be vigilant for opportunities to decrease the likelihood of poor clinical outcomes.”
Read the full study in Clinical Infectious Diseases here.
Chronic hepatitis B virus patients are insufficiently monitored for disease activity and hepatocellular carcinoma (HCC), according to Philip R. Spradling, MD, and his associates of the Centers for Disease Control and Prevention.
In a cohort study of 2,992 patients with CHB, 2,338 were used for assessment. Researchers used alanine aminotransferase (ALT) monitoring, HBV DNA monitoring, assessment for cirrhosis, and HBV antiviral therapy for examination. For ALT monitoring, 1,814 (78%) of patients had at least one ALT level obtained per year of follow-up. Only 876 patients (37%) had at least one HBV DNA level assessment per year of follow-up and 1,037 (44%) had less than annual testing, and 18% of patients never had an HBV DNA level assessed. Among patients with cirrhosis, 297 (54%) had HBV DNA testing done at least annually, 189 (35%) had testing done but less frequently than annually, and 61 (11%) never had an HBV DNA test done. And of the 547 patients with cirrhosis, 305 (56%) were prescribed HBV antiviral therapy.
It was noted that patients were monitored during 2006-2013. Only 68% of patients had not been prescribed treatment, and 72% had received liver-related specialty care.
“Our findings reiterate the need for clinicians who treat patients with [chronic HBV] to provide ongoing, continual assessment of disease activity based on HBV DNA and ALT levels, as well as liver imaging surveillance among patients at high risk for HCC,” researchers concluded. “As antiviral therapy for [chronic HBV] now includes potent and highly efficacious oral agents that have few contraindications and minimal side effects, as well as a high barrier to resistance, clinicians should be vigilant for opportunities to decrease the likelihood of poor clinical outcomes.”
Read the full study in Clinical Infectious Diseases here.
Chronic hepatitis B virus patients are insufficiently monitored for disease activity and hepatocellular carcinoma (HCC), according to Philip R. Spradling, MD, and his associates of the Centers for Disease Control and Prevention.
In a cohort study of 2,992 patients with CHB, 2,338 were used for assessment. Researchers used alanine aminotransferase (ALT) monitoring, HBV DNA monitoring, assessment for cirrhosis, and HBV antiviral therapy for examination. For ALT monitoring, 1,814 (78%) of patients had at least one ALT level obtained per year of follow-up. Only 876 patients (37%) had at least one HBV DNA level assessment per year of follow-up and 1,037 (44%) had less than annual testing, and 18% of patients never had an HBV DNA level assessed. Among patients with cirrhosis, 297 (54%) had HBV DNA testing done at least annually, 189 (35%) had testing done but less frequently than annually, and 61 (11%) never had an HBV DNA test done. And of the 547 patients with cirrhosis, 305 (56%) were prescribed HBV antiviral therapy.
It was noted that patients were monitored during 2006-2013. Only 68% of patients had not been prescribed treatment, and 72% had received liver-related specialty care.
“Our findings reiterate the need for clinicians who treat patients with [chronic HBV] to provide ongoing, continual assessment of disease activity based on HBV DNA and ALT levels, as well as liver imaging surveillance among patients at high risk for HCC,” researchers concluded. “As antiviral therapy for [chronic HBV] now includes potent and highly efficacious oral agents that have few contraindications and minimal side effects, as well as a high barrier to resistance, clinicians should be vigilant for opportunities to decrease the likelihood of poor clinical outcomes.”
Read the full study in Clinical Infectious Diseases here.
FROM CLINICAL INFECTIOUS DISEASES
Younger age, inconsistency of care affect antiviral adherence in hepatitis B
Patients with chronic hepatitis B who are aged under 35 years or do not see the same clinician consistently are more likely to not take their antiviral medication, finds the largest study of its kind to date.
According to the authors of the research led by Nicole Allard, PhD, from the WHO collaborative Centre for Viral Hepatitis and the Peter Doherty Institute for Infection and Immunity in Melbourne, their findings illustrate the need for clinicians to reinforce the importance of medication adherence at each patient consultation.
Furthermore, “providing more flexible and convenient care arrangements, reminder systems, and working with the individual to maximize medication adherence should be a routine part of clinical practice,” they wrote in their paper published in the Journal of Viral Hepatitis. Previous research had shown that adherence to antiviral therapy in the treatment of hepatitis B was associated with improved patient outcomes. Suboptimal adherence could lead to antiviral resistance or antiviral breakthrough, potentially leading to liver cirrhosis and liver cancer.
Understanding poor adherence in clinical settings, together with the factors associated with lower adherence, was important in informing efforts for promoting adherence, the research team said (J Viral Hepat. 2016. doi: 10.1111/jvh.12582).
In their retrospective study they assessed the pharmacy records of 1,026 patients who were dispensed antiviral therapy for hepatitis B across four Australian public hospital outpatient clinics between 2010 and 2013.
They discovered that one in five patients were “nonadherent” to therapy based on a medication possession ratio of less than 0.90 – a cutoff shown in previous studies to be correlated with virologic breakthrough.
One significant factor that affected adherence to medication was being aged under 35 years (P = .002), the research team reported.
This finding was similar to other studies of chronic diseases that had shown younger patients were at a higher risk of nonadherence, the authors noted.
“Recognition of the challenges faced by a younger person regularly taking medication at a time in their lives when they feel well is important,” they wrote.
Poor adherence was also associated with seeing multiple clinicians over shorter periods of time.
“While hospitals accommodate trainees and staffing changes occur regularly, seeking to maximize the consistency of clinical care delivery may be an important strategy to support better adherence and optimizing care for individuals,” they said.
Factors such as variations in the amount of medication, duration of treatment, sex, and cultural background did not affect adherence to medication.
“Adherence is a dynamic process and needs to be addressed regularly in a nonjudgmental way working with individuals towards improved health,” they concluded.
Patients with chronic hepatitis B who are aged under 35 years or do not see the same clinician consistently are more likely to not take their antiviral medication, finds the largest study of its kind to date.
According to the authors of the research led by Nicole Allard, PhD, from the WHO collaborative Centre for Viral Hepatitis and the Peter Doherty Institute for Infection and Immunity in Melbourne, their findings illustrate the need for clinicians to reinforce the importance of medication adherence at each patient consultation.
Furthermore, “providing more flexible and convenient care arrangements, reminder systems, and working with the individual to maximize medication adherence should be a routine part of clinical practice,” they wrote in their paper published in the Journal of Viral Hepatitis. Previous research had shown that adherence to antiviral therapy in the treatment of hepatitis B was associated with improved patient outcomes. Suboptimal adherence could lead to antiviral resistance or antiviral breakthrough, potentially leading to liver cirrhosis and liver cancer.
Understanding poor adherence in clinical settings, together with the factors associated with lower adherence, was important in informing efforts for promoting adherence, the research team said (J Viral Hepat. 2016. doi: 10.1111/jvh.12582).
In their retrospective study they assessed the pharmacy records of 1,026 patients who were dispensed antiviral therapy for hepatitis B across four Australian public hospital outpatient clinics between 2010 and 2013.
They discovered that one in five patients were “nonadherent” to therapy based on a medication possession ratio of less than 0.90 – a cutoff shown in previous studies to be correlated with virologic breakthrough.
One significant factor that affected adherence to medication was being aged under 35 years (P = .002), the research team reported.
This finding was similar to other studies of chronic diseases that had shown younger patients were at a higher risk of nonadherence, the authors noted.
“Recognition of the challenges faced by a younger person regularly taking medication at a time in their lives when they feel well is important,” they wrote.
Poor adherence was also associated with seeing multiple clinicians over shorter periods of time.
“While hospitals accommodate trainees and staffing changes occur regularly, seeking to maximize the consistency of clinical care delivery may be an important strategy to support better adherence and optimizing care for individuals,” they said.
Factors such as variations in the amount of medication, duration of treatment, sex, and cultural background did not affect adherence to medication.
“Adherence is a dynamic process and needs to be addressed regularly in a nonjudgmental way working with individuals towards improved health,” they concluded.
Patients with chronic hepatitis B who are aged under 35 years or do not see the same clinician consistently are more likely to not take their antiviral medication, finds the largest study of its kind to date.
According to the authors of the research led by Nicole Allard, PhD, from the WHO collaborative Centre for Viral Hepatitis and the Peter Doherty Institute for Infection and Immunity in Melbourne, their findings illustrate the need for clinicians to reinforce the importance of medication adherence at each patient consultation.
Furthermore, “providing more flexible and convenient care arrangements, reminder systems, and working with the individual to maximize medication adherence should be a routine part of clinical practice,” they wrote in their paper published in the Journal of Viral Hepatitis. Previous research had shown that adherence to antiviral therapy in the treatment of hepatitis B was associated with improved patient outcomes. Suboptimal adherence could lead to antiviral resistance or antiviral breakthrough, potentially leading to liver cirrhosis and liver cancer.
Understanding poor adherence in clinical settings, together with the factors associated with lower adherence, was important in informing efforts for promoting adherence, the research team said (J Viral Hepat. 2016. doi: 10.1111/jvh.12582).
In their retrospective study they assessed the pharmacy records of 1,026 patients who were dispensed antiviral therapy for hepatitis B across four Australian public hospital outpatient clinics between 2010 and 2013.
They discovered that one in five patients were “nonadherent” to therapy based on a medication possession ratio of less than 0.90 – a cutoff shown in previous studies to be correlated with virologic breakthrough.
One significant factor that affected adherence to medication was being aged under 35 years (P = .002), the research team reported.
This finding was similar to other studies of chronic diseases that had shown younger patients were at a higher risk of nonadherence, the authors noted.
“Recognition of the challenges faced by a younger person regularly taking medication at a time in their lives when they feel well is important,” they wrote.
Poor adherence was also associated with seeing multiple clinicians over shorter periods of time.
“While hospitals accommodate trainees and staffing changes occur regularly, seeking to maximize the consistency of clinical care delivery may be an important strategy to support better adherence and optimizing care for individuals,” they said.
Factors such as variations in the amount of medication, duration of treatment, sex, and cultural background did not affect adherence to medication.
“Adherence is a dynamic process and needs to be addressed regularly in a nonjudgmental way working with individuals towards improved health,” they concluded.
FROM THE JOURNAL OF VIRAL HEPATITIS
Key clinical point: Adherence to antiviral medication is a dynamic process that clinicians need to address regularly in a nonjudgmental way at each consultation, particularly in younger patients. Providing flexible and convenient care arrangements that foster continuity of care will also improve adherence to medication.
Major finding: One in five patients with hepatitis B were nonadherent to antiviral medications. Younger age (under 35) (P = .002), and inconsistency of care predicted nonadherence.
Data Source: A retrospective study of the pharmacy records of 1,026 patients who were attending a public hospital clinic and were prescribed antiviral therapy for hepatitis B.
Disclosures: Dr. Nicole Allard is supported by an APA scholarship from the University of Melbourne. Funding for the project was provided by the Royal Melbourne Hospital lottery grant. Dr. Allard declared no conflicts of interest in the last 3 years. Several of the authors in the group reported financial ties to pharmaceutical companies.
Predisposition to overlapping AIH and PBC can exist within families
A genetic predisposition to autoimmune liver disease can cause overlapping cases of autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) within the same family, according to a case report from Japanese researchers.
A 68-year-old woman and her 49-year-old daughter were admitted to the hospital for liver dysfunction, 4 years apart. The mother had been diagnosed with PBC at a previous hospital, but was moved after treatment with 600 mg ursodeoxycholic acid (UDCA) was ineffective. The daughter had no previous diagnosis and had a variety of symptoms at admission, including jaundice, general fatigue, and darkness of the urine.
Both the mother and the daughter were negative for hepatitis A, B, and C. A simplified International Autoimmune Hepatitis Group score revealed probable AIH for both patients, and both patients were diagnosed with autoimmune liver disease with overlapping features of PBC and AIH. Treatment with UDCA and prednisolone was effective for both patients.
In a familial study, the mother and her two daughters were tested for liver function, autoantibodies, and human leukocyte antigen (HLA) haplotype. The second daughter, who was healthy with no history of liver dysfunction, had normal liver function, negative ANA, and positive AMA-M2 antibody, but had an HLA haplotype different from that of the mother and the first daughter. No difference in medication use, smoking status, alcohol consumption, or obstetric history was seen.
“The exact mechanism underlying the onset of PBC and AIH overlap within the same family remains unclear. Therefore, it is very important to monitor the healthy second daughter closely as she was positive for the AMA-M2 antibody, as this might yield further knowledge with regard to what factors influence the onset of PBC and AIH overlap within the same family,” the investigators noted.
Find the full study in the Journal of Clinical Gastroenterology (doi: 10.1007/s12328-016-0676-1)
A genetic predisposition to autoimmune liver disease can cause overlapping cases of autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) within the same family, according to a case report from Japanese researchers.
A 68-year-old woman and her 49-year-old daughter were admitted to the hospital for liver dysfunction, 4 years apart. The mother had been diagnosed with PBC at a previous hospital, but was moved after treatment with 600 mg ursodeoxycholic acid (UDCA) was ineffective. The daughter had no previous diagnosis and had a variety of symptoms at admission, including jaundice, general fatigue, and darkness of the urine.
Both the mother and the daughter were negative for hepatitis A, B, and C. A simplified International Autoimmune Hepatitis Group score revealed probable AIH for both patients, and both patients were diagnosed with autoimmune liver disease with overlapping features of PBC and AIH. Treatment with UDCA and prednisolone was effective for both patients.
In a familial study, the mother and her two daughters were tested for liver function, autoantibodies, and human leukocyte antigen (HLA) haplotype. The second daughter, who was healthy with no history of liver dysfunction, had normal liver function, negative ANA, and positive AMA-M2 antibody, but had an HLA haplotype different from that of the mother and the first daughter. No difference in medication use, smoking status, alcohol consumption, or obstetric history was seen.
“The exact mechanism underlying the onset of PBC and AIH overlap within the same family remains unclear. Therefore, it is very important to monitor the healthy second daughter closely as she was positive for the AMA-M2 antibody, as this might yield further knowledge with regard to what factors influence the onset of PBC and AIH overlap within the same family,” the investigators noted.
Find the full study in the Journal of Clinical Gastroenterology (doi: 10.1007/s12328-016-0676-1)
A genetic predisposition to autoimmune liver disease can cause overlapping cases of autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) within the same family, according to a case report from Japanese researchers.
A 68-year-old woman and her 49-year-old daughter were admitted to the hospital for liver dysfunction, 4 years apart. The mother had been diagnosed with PBC at a previous hospital, but was moved after treatment with 600 mg ursodeoxycholic acid (UDCA) was ineffective. The daughter had no previous diagnosis and had a variety of symptoms at admission, including jaundice, general fatigue, and darkness of the urine.
Both the mother and the daughter were negative for hepatitis A, B, and C. A simplified International Autoimmune Hepatitis Group score revealed probable AIH for both patients, and both patients were diagnosed with autoimmune liver disease with overlapping features of PBC and AIH. Treatment with UDCA and prednisolone was effective for both patients.
In a familial study, the mother and her two daughters were tested for liver function, autoantibodies, and human leukocyte antigen (HLA) haplotype. The second daughter, who was healthy with no history of liver dysfunction, had normal liver function, negative ANA, and positive AMA-M2 antibody, but had an HLA haplotype different from that of the mother and the first daughter. No difference in medication use, smoking status, alcohol consumption, or obstetric history was seen.
“The exact mechanism underlying the onset of PBC and AIH overlap within the same family remains unclear. Therefore, it is very important to monitor the healthy second daughter closely as she was positive for the AMA-M2 antibody, as this might yield further knowledge with regard to what factors influence the onset of PBC and AIH overlap within the same family,” the investigators noted.
Find the full study in the Journal of Clinical Gastroenterology (doi: 10.1007/s12328-016-0676-1)
FROM THE JOURNAL OF CLINICAL GASTROENTEROLOGY
Primary biliary cholangitis: Obeticholic acid reduces biomarkers
Obeticholic acid reduced alkaline phosphatase level, total bilirubin level, and other biomarkers of cholestasis, hepatocellular injury, inflammation, and apoptosis in patients with primary biliary cholangitis participating in a phase III clinical trial, which was reported online August 17 in the New England Journal of Medicine.
A study to assess the drug’s effects on clinical outcomes is currently enrolling patients (NCT02308111), said Frederik Nevens, MD, PhD, of University Hospitals Leuven (Belgium) and his associates.
They assessed treatment with obeticholic acid, a selective farnesoid X receptor agonist, in a manufacturer-sponsored double-blind randomized trial involving 217 patients treated at 59 sites in 13 countries. Participants were assigned to receive a once-daily oral placebo (73 patients), obeticholic acid at an initial dose of 5 mg with escalation to 10 mg if possible (71 patients), or a daily 10-mg dose of obeticholic acid (73 patients). All were also given standard ursodiol (13-15 mg per kg) at the same time, with the expectation that many would have to discontinue that drug due to adverse events. The study participants were treated for 1 year, when the double-blind phase of the study was completed and all were offered entry into a 5-year open-label phase.
The primary composite endpoint was 1) an alkaline phosphatase level of less than 1.67 times the upper limit of the normal range, with a reduction of at least 15% below baseline level, and 2) a total bilirubin level at or below the upper limit of the normal range. After 1 year of treatment, 46% of the 5-mg group and 47% of the 10-mg group achieved this endpoint, compared with only 10% of the placebo group. The response to treatment was rapid, with patients in the active-treatment groups showing significantly lower alkaline phosphatase and bilirubin levels than the placebo group within 2 weeks of starting therapy.
In addition, the percentage of patients who showed at least a 15% reduction in alkaline phosphatase level was significantly higher with 5-10 mg active treatment (77%) and with 10 mg active treatment (77%) than with placebo (29%). And total bilirubin level progressively decreased in both active treatment groups but progressively increased in the placebo group, Dr. Nevens and his associates said (N Engl J Med. 2016 Aug 18. doi: 10.1056/NEJMoa1509840). Obeticholic acid also reduced levels of IgM and interleukin-12, as well as levels of gamma-glutamyl transferase, alanine aminotransferase, aspartate aminotransferase, and conjugated bilirubin. It did not induce significant symptom relief as measured by a disease-specific quality of life questionnaire, and it didn’t reduce liver fibrosis as measured by noninvasive techniques.
In the open-label extension phase of the study, treatment efficacy was similar.
The most common adverse event was pruritus, which is also characteristic of the disease itself. The incidence was higher in both active-treatment groups (56% with 5-10-mg therapy and 68% with 10-mg therapy) than in the placebo group (38%). One patient (1%) in the 5-10-mg group and seven patients (10%) in the 10-mg group discontinued treatment because of pruritus, compared with no patients in the placebo group.
The treatment’s beneficial effects persisted for 2 years, but that is a relatively short follow-up for a chronic disease that will require lifelong therapy. Future research must address longer-term benefits as well as adverse events, the investigators said.
The results of this phase III clinical trial are encouraging, but we still do not know whether or how obeticholic acid impacts clinical endpoints such as hepatic decompensation, progression to cirrhosis, symptoms, or survival.
Also unknown is whether patients with this chronic disease will be able to take obeticholic acid indefinitely. And we don’t know whether to continue treating those who don’t show a biochemical response to the drug within 1 year, who comprise approximately 50% of patients, according to the results of this trial.
The price of obeticholic acid is also a concern. At present it costs approximately $70,000 per year.
Daniel S. Pratt, MD, is at the Autoimmune and Cholestatic Liver Center at Massachusetts General Hospital and at Harvard Medical School, both in Boston. He reported having no relevant financial disclosures. Dr. Pratt made these remarks in an editorial accompanying Dr. Nevens’ report (N Engl J Med. 2016 Aug 18. doi: 10.1056/NEJMe1607744).
The results of this phase III clinical trial are encouraging, but we still do not know whether or how obeticholic acid impacts clinical endpoints such as hepatic decompensation, progression to cirrhosis, symptoms, or survival.
Also unknown is whether patients with this chronic disease will be able to take obeticholic acid indefinitely. And we don’t know whether to continue treating those who don’t show a biochemical response to the drug within 1 year, who comprise approximately 50% of patients, according to the results of this trial.
The price of obeticholic acid is also a concern. At present it costs approximately $70,000 per year.
Daniel S. Pratt, MD, is at the Autoimmune and Cholestatic Liver Center at Massachusetts General Hospital and at Harvard Medical School, both in Boston. He reported having no relevant financial disclosures. Dr. Pratt made these remarks in an editorial accompanying Dr. Nevens’ report (N Engl J Med. 2016 Aug 18. doi: 10.1056/NEJMe1607744).
The results of this phase III clinical trial are encouraging, but we still do not know whether or how obeticholic acid impacts clinical endpoints such as hepatic decompensation, progression to cirrhosis, symptoms, or survival.
Also unknown is whether patients with this chronic disease will be able to take obeticholic acid indefinitely. And we don’t know whether to continue treating those who don’t show a biochemical response to the drug within 1 year, who comprise approximately 50% of patients, according to the results of this trial.
The price of obeticholic acid is also a concern. At present it costs approximately $70,000 per year.
Daniel S. Pratt, MD, is at the Autoimmune and Cholestatic Liver Center at Massachusetts General Hospital and at Harvard Medical School, both in Boston. He reported having no relevant financial disclosures. Dr. Pratt made these remarks in an editorial accompanying Dr. Nevens’ report (N Engl J Med. 2016 Aug 18. doi: 10.1056/NEJMe1607744).
Obeticholic acid reduced alkaline phosphatase level, total bilirubin level, and other biomarkers of cholestasis, hepatocellular injury, inflammation, and apoptosis in patients with primary biliary cholangitis participating in a phase III clinical trial, which was reported online August 17 in the New England Journal of Medicine.
A study to assess the drug’s effects on clinical outcomes is currently enrolling patients (NCT02308111), said Frederik Nevens, MD, PhD, of University Hospitals Leuven (Belgium) and his associates.
They assessed treatment with obeticholic acid, a selective farnesoid X receptor agonist, in a manufacturer-sponsored double-blind randomized trial involving 217 patients treated at 59 sites in 13 countries. Participants were assigned to receive a once-daily oral placebo (73 patients), obeticholic acid at an initial dose of 5 mg with escalation to 10 mg if possible (71 patients), or a daily 10-mg dose of obeticholic acid (73 patients). All were also given standard ursodiol (13-15 mg per kg) at the same time, with the expectation that many would have to discontinue that drug due to adverse events. The study participants were treated for 1 year, when the double-blind phase of the study was completed and all were offered entry into a 5-year open-label phase.
The primary composite endpoint was 1) an alkaline phosphatase level of less than 1.67 times the upper limit of the normal range, with a reduction of at least 15% below baseline level, and 2) a total bilirubin level at or below the upper limit of the normal range. After 1 year of treatment, 46% of the 5-mg group and 47% of the 10-mg group achieved this endpoint, compared with only 10% of the placebo group. The response to treatment was rapid, with patients in the active-treatment groups showing significantly lower alkaline phosphatase and bilirubin levels than the placebo group within 2 weeks of starting therapy.
In addition, the percentage of patients who showed at least a 15% reduction in alkaline phosphatase level was significantly higher with 5-10 mg active treatment (77%) and with 10 mg active treatment (77%) than with placebo (29%). And total bilirubin level progressively decreased in both active treatment groups but progressively increased in the placebo group, Dr. Nevens and his associates said (N Engl J Med. 2016 Aug 18. doi: 10.1056/NEJMoa1509840). Obeticholic acid also reduced levels of IgM and interleukin-12, as well as levels of gamma-glutamyl transferase, alanine aminotransferase, aspartate aminotransferase, and conjugated bilirubin. It did not induce significant symptom relief as measured by a disease-specific quality of life questionnaire, and it didn’t reduce liver fibrosis as measured by noninvasive techniques.
In the open-label extension phase of the study, treatment efficacy was similar.
The most common adverse event was pruritus, which is also characteristic of the disease itself. The incidence was higher in both active-treatment groups (56% with 5-10-mg therapy and 68% with 10-mg therapy) than in the placebo group (38%). One patient (1%) in the 5-10-mg group and seven patients (10%) in the 10-mg group discontinued treatment because of pruritus, compared with no patients in the placebo group.
The treatment’s beneficial effects persisted for 2 years, but that is a relatively short follow-up for a chronic disease that will require lifelong therapy. Future research must address longer-term benefits as well as adverse events, the investigators said.
Obeticholic acid reduced alkaline phosphatase level, total bilirubin level, and other biomarkers of cholestasis, hepatocellular injury, inflammation, and apoptosis in patients with primary biliary cholangitis participating in a phase III clinical trial, which was reported online August 17 in the New England Journal of Medicine.
A study to assess the drug’s effects on clinical outcomes is currently enrolling patients (NCT02308111), said Frederik Nevens, MD, PhD, of University Hospitals Leuven (Belgium) and his associates.
They assessed treatment with obeticholic acid, a selective farnesoid X receptor agonist, in a manufacturer-sponsored double-blind randomized trial involving 217 patients treated at 59 sites in 13 countries. Participants were assigned to receive a once-daily oral placebo (73 patients), obeticholic acid at an initial dose of 5 mg with escalation to 10 mg if possible (71 patients), or a daily 10-mg dose of obeticholic acid (73 patients). All were also given standard ursodiol (13-15 mg per kg) at the same time, with the expectation that many would have to discontinue that drug due to adverse events. The study participants were treated for 1 year, when the double-blind phase of the study was completed and all were offered entry into a 5-year open-label phase.
The primary composite endpoint was 1) an alkaline phosphatase level of less than 1.67 times the upper limit of the normal range, with a reduction of at least 15% below baseline level, and 2) a total bilirubin level at or below the upper limit of the normal range. After 1 year of treatment, 46% of the 5-mg group and 47% of the 10-mg group achieved this endpoint, compared with only 10% of the placebo group. The response to treatment was rapid, with patients in the active-treatment groups showing significantly lower alkaline phosphatase and bilirubin levels than the placebo group within 2 weeks of starting therapy.
In addition, the percentage of patients who showed at least a 15% reduction in alkaline phosphatase level was significantly higher with 5-10 mg active treatment (77%) and with 10 mg active treatment (77%) than with placebo (29%). And total bilirubin level progressively decreased in both active treatment groups but progressively increased in the placebo group, Dr. Nevens and his associates said (N Engl J Med. 2016 Aug 18. doi: 10.1056/NEJMoa1509840). Obeticholic acid also reduced levels of IgM and interleukin-12, as well as levels of gamma-glutamyl transferase, alanine aminotransferase, aspartate aminotransferase, and conjugated bilirubin. It did not induce significant symptom relief as measured by a disease-specific quality of life questionnaire, and it didn’t reduce liver fibrosis as measured by noninvasive techniques.
In the open-label extension phase of the study, treatment efficacy was similar.
The most common adverse event was pruritus, which is also characteristic of the disease itself. The incidence was higher in both active-treatment groups (56% with 5-10-mg therapy and 68% with 10-mg therapy) than in the placebo group (38%). One patient (1%) in the 5-10-mg group and seven patients (10%) in the 10-mg group discontinued treatment because of pruritus, compared with no patients in the placebo group.
The treatment’s beneficial effects persisted for 2 years, but that is a relatively short follow-up for a chronic disease that will require lifelong therapy. Future research must address longer-term benefits as well as adverse events, the investigators said.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: Obeticholic acid therapy reduced alkaline phosphatase level, total bilirubin level, and other biomarkers in primary biliary cholangitis.
Major finding: 46% of the 5-mg group and 47% of the 10-mg group achieved the primary end point, compared with only 10% of the placebo group.
Data source: A 1-year international randomized double-blind placebo-controlled phase III clinical trial involving 217 adults with primary biliary cholangitis.
Disclosures: This study was supported by Intercept Pharmaceuticals. Dr. Nevens reported having no relevant financial disclosures; his associates reported ties to numerous industry sources.
Hypoxia of obstructive sleep apnea aggravates NAFLD, NASH in adolescents
A new study has found that a strong association exists in adolescents who have obstructive sleep apnea, and their risks of developing more highly progressed forms of nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH).
“Substantial evidence suggests oxidative stress is a central mediator in NAFLD pathogenesis and progression, although the specific trigger for reactive oxygen species (ROS) generation has not been clearly delineated,” wrote the authors, led by Shikha S. Sundaram, MD of the University of Colorado at Denver, Aurora, adding that “Emerging evidence demonstrates that obesity-related obstructive sleep apnea (OSA) and intermittent nocturnal hypoxia are associated with NAFLD progression.”
Dr. Sundaram and her coinvestigators looked at patients admitted to the Children’s Hospital Colorado Pediatric Liver Center from June 2009 through January 2014. Subjects included were children ages 8-18 years, male and female, who were classified as Tanner stage 2-4 with liver biopsy evidence of NAFLD.
“In our center, a clinical liver biopsy for suspected NAFLD is performed in overweight or obese children (body mass index greater than 85% for age and gender) with chronically elevated aminotransferases in whom a diagnosis is unclear based on serologic testing,” Dr. Sundaram and her coauthors clarified regarding the screening process.
Additionally, age-matched “lean” children, that is, those with a body mass index lower than 85%, were also enrolled as controls; these subjects were included if they had no evidence of hepatomegaly or liver disease – translated to AST and ALT levels of 640 IU/L – and were also Tanner stage 2-4. The authors explained that this Tanner stage range was chosen in order to “minimize variations in insulin sensitivity that may confound the interpretation of potential associations between OSA/hypoxia and NAFLD.”
Ultimately, 36 NAFLD adolescent subjects and 14 controls completed the study. A total of 25 of the 36 NAFLD subjects (69.4%) had OSA and/or nocturnal hypoxia; of these, 15 were classified as having isolated OSA, 9 had both OSA and hypoxia, and 1 had isolated hypoxia. Polysomnograms found that all NAFLD subjects spent more than 12% of their total time asleep in REM sleep, which was deemed adequate enough to consider the findings valid.
Based on liver histology scoring, laboratory testing, urine F2-isoprostanes, and 4-hydroxynonenal liver immunohistochemistry tests that were conducted on all subjects, Dr. Sundaram and her coinvestigators found that subjects with OSA or hypoxia had more severe fibrosis than did those without. While the latter cohort were 100% stage 0-2, only 64% of those with OSA/hypoxia were stage 0-2, while the remaining 36% were stage 3 (P = .03). Additionally, higher F2-isoprostanes – used to measure lipid peroxidation – correlated with apnea/hypoxia index (r = 0.39; P = .03), and the most severe OSA/hypoxia occurred in subjects that had the greatest 4-hydroxynonenal staining (P = .03). Furthermore, an increase in both F2-isoprostanes and 4-hydroxynonenal hepatic staining was shown to lead to a higher risk of worse steatosis: r = 0.32 and r = 0.47, respectively (P = .04 and P = .007).
“These data support sleep disordered breathing as an important trigger of oxidative stress that promotes progression of pediatric NAFLD to NASH,” the authors concluded, adding that “this study confirms that OSA/hypoxia is common in pediatric NAFLD and that more severe OSA/hypoxia is associated with elevated aminotransferases, hepatic steatosis, inflammation, NAS [NAFLD activity score], and fibrosis.”
Dr. Sundaram and her coauthors call for further research to examine if “prevention or reversal of NASH following effective therapy of OSA and nocturnal hypoxia in obese patients” is viable.
This study was supported by funding from the National Institutes of Health. Dr. Sundaram and her coinvestigators did not report any relevant financial disclosures.
A new study has found that a strong association exists in adolescents who have obstructive sleep apnea, and their risks of developing more highly progressed forms of nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH).
“Substantial evidence suggests oxidative stress is a central mediator in NAFLD pathogenesis and progression, although the specific trigger for reactive oxygen species (ROS) generation has not been clearly delineated,” wrote the authors, led by Shikha S. Sundaram, MD of the University of Colorado at Denver, Aurora, adding that “Emerging evidence demonstrates that obesity-related obstructive sleep apnea (OSA) and intermittent nocturnal hypoxia are associated with NAFLD progression.”
Dr. Sundaram and her coinvestigators looked at patients admitted to the Children’s Hospital Colorado Pediatric Liver Center from June 2009 through January 2014. Subjects included were children ages 8-18 years, male and female, who were classified as Tanner stage 2-4 with liver biopsy evidence of NAFLD.
“In our center, a clinical liver biopsy for suspected NAFLD is performed in overweight or obese children (body mass index greater than 85% for age and gender) with chronically elevated aminotransferases in whom a diagnosis is unclear based on serologic testing,” Dr. Sundaram and her coauthors clarified regarding the screening process.
Additionally, age-matched “lean” children, that is, those with a body mass index lower than 85%, were also enrolled as controls; these subjects were included if they had no evidence of hepatomegaly or liver disease – translated to AST and ALT levels of 640 IU/L – and were also Tanner stage 2-4. The authors explained that this Tanner stage range was chosen in order to “minimize variations in insulin sensitivity that may confound the interpretation of potential associations between OSA/hypoxia and NAFLD.”
Ultimately, 36 NAFLD adolescent subjects and 14 controls completed the study. A total of 25 of the 36 NAFLD subjects (69.4%) had OSA and/or nocturnal hypoxia; of these, 15 were classified as having isolated OSA, 9 had both OSA and hypoxia, and 1 had isolated hypoxia. Polysomnograms found that all NAFLD subjects spent more than 12% of their total time asleep in REM sleep, which was deemed adequate enough to consider the findings valid.
Based on liver histology scoring, laboratory testing, urine F2-isoprostanes, and 4-hydroxynonenal liver immunohistochemistry tests that were conducted on all subjects, Dr. Sundaram and her coinvestigators found that subjects with OSA or hypoxia had more severe fibrosis than did those without. While the latter cohort were 100% stage 0-2, only 64% of those with OSA/hypoxia were stage 0-2, while the remaining 36% were stage 3 (P = .03). Additionally, higher F2-isoprostanes – used to measure lipid peroxidation – correlated with apnea/hypoxia index (r = 0.39; P = .03), and the most severe OSA/hypoxia occurred in subjects that had the greatest 4-hydroxynonenal staining (P = .03). Furthermore, an increase in both F2-isoprostanes and 4-hydroxynonenal hepatic staining was shown to lead to a higher risk of worse steatosis: r = 0.32 and r = 0.47, respectively (P = .04 and P = .007).
“These data support sleep disordered breathing as an important trigger of oxidative stress that promotes progression of pediatric NAFLD to NASH,” the authors concluded, adding that “this study confirms that OSA/hypoxia is common in pediatric NAFLD and that more severe OSA/hypoxia is associated with elevated aminotransferases, hepatic steatosis, inflammation, NAS [NAFLD activity score], and fibrosis.”
Dr. Sundaram and her coauthors call for further research to examine if “prevention or reversal of NASH following effective therapy of OSA and nocturnal hypoxia in obese patients” is viable.
This study was supported by funding from the National Institutes of Health. Dr. Sundaram and her coinvestigators did not report any relevant financial disclosures.
A new study has found that a strong association exists in adolescents who have obstructive sleep apnea, and their risks of developing more highly progressed forms of nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH).
“Substantial evidence suggests oxidative stress is a central mediator in NAFLD pathogenesis and progression, although the specific trigger for reactive oxygen species (ROS) generation has not been clearly delineated,” wrote the authors, led by Shikha S. Sundaram, MD of the University of Colorado at Denver, Aurora, adding that “Emerging evidence demonstrates that obesity-related obstructive sleep apnea (OSA) and intermittent nocturnal hypoxia are associated with NAFLD progression.”
Dr. Sundaram and her coinvestigators looked at patients admitted to the Children’s Hospital Colorado Pediatric Liver Center from June 2009 through January 2014. Subjects included were children ages 8-18 years, male and female, who were classified as Tanner stage 2-4 with liver biopsy evidence of NAFLD.
“In our center, a clinical liver biopsy for suspected NAFLD is performed in overweight or obese children (body mass index greater than 85% for age and gender) with chronically elevated aminotransferases in whom a diagnosis is unclear based on serologic testing,” Dr. Sundaram and her coauthors clarified regarding the screening process.
Additionally, age-matched “lean” children, that is, those with a body mass index lower than 85%, were also enrolled as controls; these subjects were included if they had no evidence of hepatomegaly or liver disease – translated to AST and ALT levels of 640 IU/L – and were also Tanner stage 2-4. The authors explained that this Tanner stage range was chosen in order to “minimize variations in insulin sensitivity that may confound the interpretation of potential associations between OSA/hypoxia and NAFLD.”
Ultimately, 36 NAFLD adolescent subjects and 14 controls completed the study. A total of 25 of the 36 NAFLD subjects (69.4%) had OSA and/or nocturnal hypoxia; of these, 15 were classified as having isolated OSA, 9 had both OSA and hypoxia, and 1 had isolated hypoxia. Polysomnograms found that all NAFLD subjects spent more than 12% of their total time asleep in REM sleep, which was deemed adequate enough to consider the findings valid.
Based on liver histology scoring, laboratory testing, urine F2-isoprostanes, and 4-hydroxynonenal liver immunohistochemistry tests that were conducted on all subjects, Dr. Sundaram and her coinvestigators found that subjects with OSA or hypoxia had more severe fibrosis than did those without. While the latter cohort were 100% stage 0-2, only 64% of those with OSA/hypoxia were stage 0-2, while the remaining 36% were stage 3 (P = .03). Additionally, higher F2-isoprostanes – used to measure lipid peroxidation – correlated with apnea/hypoxia index (r = 0.39; P = .03), and the most severe OSA/hypoxia occurred in subjects that had the greatest 4-hydroxynonenal staining (P = .03). Furthermore, an increase in both F2-isoprostanes and 4-hydroxynonenal hepatic staining was shown to lead to a higher risk of worse steatosis: r = 0.32 and r = 0.47, respectively (P = .04 and P = .007).
“These data support sleep disordered breathing as an important trigger of oxidative stress that promotes progression of pediatric NAFLD to NASH,” the authors concluded, adding that “this study confirms that OSA/hypoxia is common in pediatric NAFLD and that more severe OSA/hypoxia is associated with elevated aminotransferases, hepatic steatosis, inflammation, NAS [NAFLD activity score], and fibrosis.”
Dr. Sundaram and her coauthors call for further research to examine if “prevention or reversal of NASH following effective therapy of OSA and nocturnal hypoxia in obese patients” is viable.
This study was supported by funding from the National Institutes of Health. Dr. Sundaram and her coinvestigators did not report any relevant financial disclosures.
FROM THE JOURNAL OF HEPATOLOGY
Key clinical point: Adolescents with obstructive sleep apnea have a higher risk for nonalcoholic fatty liver disease, because of liver tissue scarring.
Major finding: The cohort of subjects with OSA had more severe fibrosis (64%, stages 0-2; 36% stage 3) than those without OSA (100%, stages 0-2) (P = .03).
Data source: Prospective cohort study of 36 adolescents with NAFLD and 14 lean controls.
Disclosures: Funding provided by the NIH. Authors reported no relevant financial disclosures.
Study finds clues to fibrosis progression in chronic HCV infection
Fibrosis progression in hepatitis C virus–infected individuals is not linear, is associated with Clues to fibrosis progression in chronic hepatitis C infectionClues to fibrosis progression in chronic hepatitis C infection–related flares, and varies according to stage, with those who are least fibrotic tending to have the highest progression, according to a study.
Identifying which patients with hepatitis C virus (HCV) infection will likely progress to cirrhosis has historically been a challenge, creating some difficulty adhering to guidelines recommending that patients at greater risk of fibrosis be among those prioritized for treatment. Having an ability to more accurately diagnose those most at risk could help to better guide treatment prioritization and clinical management.
To that end, Marija Zeremski, PhD, and her colleagues at Weill Cornell Medical School, New York, analyzed 936 biopsies taken from 378 patients seen at a single site between 1997 and 2013. At the time of the first biopsy, nearly two-thirds of the patients were white men in their late 40s to mid-50s, with chronic HCV infection. Nearly 88% of all patients were HCV genotype 1 infected (J Infect Dis. 2016. doi: 10.1093/infdis/jiw332).
In the study, investigators found that between the first and a follow-up biopsy, 57.4% of patients progressed by at least one fibrosis stage, 16.1% of patients had more severe fibrosis progressions of at least two stages, and 10.6% developed either stage 3-4 or 4, with nearly 6% of patients progressing to cirrhosis. Fibrosis progression between the first and last biopsies was associated with less fibrosis on the first biopsy (P less than .001).
Increased necroinflammation and the presence of at least one alanine aminotransferase (ALT) flare greater than 200 U/L during follow-up was also significantly associated with fibrosis progression (odds ratio [OR], 2.64, P less than .007). HCV genotype 3–infected patients were significantly more likely to progress to cirrhosis (P less than .001).
Intrahepatic inflammation at the time of the initial biopsy was at grade 1 or lower in 36.4% of patients, while 56.9% of patients had grade 2 (moderate) inflammation. Severe inflammation (grade 3 or higher) was found in 6.7% of patients reviewed. There was no fibrosis in 11.9% of patients, stage 1 level of fibrosis in 32.3%, stage 2 in 39.4%, and stage 3 in 16.4% of patients.
Moderate to severe fibrosis, defined as equal to or greater than stage 2, was significantly associated with elevated inflammation (greater or equal to grade 2) on the initial biopsy (OR, 9.00; P less than .001). Steatosis testing was performed on 222 patients; 59% tested positive for it. This was significantly associated with stage 2 or higher fibrosis (OR, 2.39; P = .002), and grade 2 or higher levels of inflammation (OR, 4.07; P less than .001) on the initial biopsy.
The highest fibrosis progression rate occurred between stages 0 and 1; the lowest, between stages 2 and 3.
Consecutive biopsies were separated by at least 1 year; patients were either HCV treatment naive or were treatment nonresponders. There were a total of 558 consecutive biopsy pairs available to analyze stage progression. The time between the first and last biopsies was 6.5 years (plus or minus 3 years), while the mean duration between adjacent biopsies was 4.4 years (plus or minus 1.9 years). Data regarding HCV treatment between liver biopsies were available for all but 45 patients. Forty-three percent of the remaining patients did not achieve a sustained virologic response after treatment.
Patients who’d had a cirrhosis diagnosis according to the first biopsy, those for whom treatment induced viral eradication, or those who’d had liver transplantation between biopsies were all excluded from the review.
The investigators wrote that their finding about the association between genotype 3 and cirrhosis should be “interpreted cautiously” because of the low number of these patients in their study.
This article was updated August 17, 2016.
On Twitter @whitneymcknight
Fibrosis progression in hepatitis C virus–infected individuals is not linear, is associated with Clues to fibrosis progression in chronic hepatitis C infectionClues to fibrosis progression in chronic hepatitis C infection–related flares, and varies according to stage, with those who are least fibrotic tending to have the highest progression, according to a study.
Identifying which patients with hepatitis C virus (HCV) infection will likely progress to cirrhosis has historically been a challenge, creating some difficulty adhering to guidelines recommending that patients at greater risk of fibrosis be among those prioritized for treatment. Having an ability to more accurately diagnose those most at risk could help to better guide treatment prioritization and clinical management.
To that end, Marija Zeremski, PhD, and her colleagues at Weill Cornell Medical School, New York, analyzed 936 biopsies taken from 378 patients seen at a single site between 1997 and 2013. At the time of the first biopsy, nearly two-thirds of the patients were white men in their late 40s to mid-50s, with chronic HCV infection. Nearly 88% of all patients were HCV genotype 1 infected (J Infect Dis. 2016. doi: 10.1093/infdis/jiw332).
In the study, investigators found that between the first and a follow-up biopsy, 57.4% of patients progressed by at least one fibrosis stage, 16.1% of patients had more severe fibrosis progressions of at least two stages, and 10.6% developed either stage 3-4 or 4, with nearly 6% of patients progressing to cirrhosis. Fibrosis progression between the first and last biopsies was associated with less fibrosis on the first biopsy (P less than .001).
Increased necroinflammation and the presence of at least one alanine aminotransferase (ALT) flare greater than 200 U/L during follow-up was also significantly associated with fibrosis progression (odds ratio [OR], 2.64, P less than .007). HCV genotype 3–infected patients were significantly more likely to progress to cirrhosis (P less than .001).
Intrahepatic inflammation at the time of the initial biopsy was at grade 1 or lower in 36.4% of patients, while 56.9% of patients had grade 2 (moderate) inflammation. Severe inflammation (grade 3 or higher) was found in 6.7% of patients reviewed. There was no fibrosis in 11.9% of patients, stage 1 level of fibrosis in 32.3%, stage 2 in 39.4%, and stage 3 in 16.4% of patients.
Moderate to severe fibrosis, defined as equal to or greater than stage 2, was significantly associated with elevated inflammation (greater or equal to grade 2) on the initial biopsy (OR, 9.00; P less than .001). Steatosis testing was performed on 222 patients; 59% tested positive for it. This was significantly associated with stage 2 or higher fibrosis (OR, 2.39; P = .002), and grade 2 or higher levels of inflammation (OR, 4.07; P less than .001) on the initial biopsy.
The highest fibrosis progression rate occurred between stages 0 and 1; the lowest, between stages 2 and 3.
Consecutive biopsies were separated by at least 1 year; patients were either HCV treatment naive or were treatment nonresponders. There were a total of 558 consecutive biopsy pairs available to analyze stage progression. The time between the first and last biopsies was 6.5 years (plus or minus 3 years), while the mean duration between adjacent biopsies was 4.4 years (plus or minus 1.9 years). Data regarding HCV treatment between liver biopsies were available for all but 45 patients. Forty-three percent of the remaining patients did not achieve a sustained virologic response after treatment.
Patients who’d had a cirrhosis diagnosis according to the first biopsy, those for whom treatment induced viral eradication, or those who’d had liver transplantation between biopsies were all excluded from the review.
The investigators wrote that their finding about the association between genotype 3 and cirrhosis should be “interpreted cautiously” because of the low number of these patients in their study.
This article was updated August 17, 2016.
On Twitter @whitneymcknight
Fibrosis progression in hepatitis C virus–infected individuals is not linear, is associated with Clues to fibrosis progression in chronic hepatitis C infectionClues to fibrosis progression in chronic hepatitis C infection–related flares, and varies according to stage, with those who are least fibrotic tending to have the highest progression, according to a study.
Identifying which patients with hepatitis C virus (HCV) infection will likely progress to cirrhosis has historically been a challenge, creating some difficulty adhering to guidelines recommending that patients at greater risk of fibrosis be among those prioritized for treatment. Having an ability to more accurately diagnose those most at risk could help to better guide treatment prioritization and clinical management.
To that end, Marija Zeremski, PhD, and her colleagues at Weill Cornell Medical School, New York, analyzed 936 biopsies taken from 378 patients seen at a single site between 1997 and 2013. At the time of the first biopsy, nearly two-thirds of the patients were white men in their late 40s to mid-50s, with chronic HCV infection. Nearly 88% of all patients were HCV genotype 1 infected (J Infect Dis. 2016. doi: 10.1093/infdis/jiw332).
In the study, investigators found that between the first and a follow-up biopsy, 57.4% of patients progressed by at least one fibrosis stage, 16.1% of patients had more severe fibrosis progressions of at least two stages, and 10.6% developed either stage 3-4 or 4, with nearly 6% of patients progressing to cirrhosis. Fibrosis progression between the first and last biopsies was associated with less fibrosis on the first biopsy (P less than .001).
Increased necroinflammation and the presence of at least one alanine aminotransferase (ALT) flare greater than 200 U/L during follow-up was also significantly associated with fibrosis progression (odds ratio [OR], 2.64, P less than .007). HCV genotype 3–infected patients were significantly more likely to progress to cirrhosis (P less than .001).
Intrahepatic inflammation at the time of the initial biopsy was at grade 1 or lower in 36.4% of patients, while 56.9% of patients had grade 2 (moderate) inflammation. Severe inflammation (grade 3 or higher) was found in 6.7% of patients reviewed. There was no fibrosis in 11.9% of patients, stage 1 level of fibrosis in 32.3%, stage 2 in 39.4%, and stage 3 in 16.4% of patients.
Moderate to severe fibrosis, defined as equal to or greater than stage 2, was significantly associated with elevated inflammation (greater or equal to grade 2) on the initial biopsy (OR, 9.00; P less than .001). Steatosis testing was performed on 222 patients; 59% tested positive for it. This was significantly associated with stage 2 or higher fibrosis (OR, 2.39; P = .002), and grade 2 or higher levels of inflammation (OR, 4.07; P less than .001) on the initial biopsy.
The highest fibrosis progression rate occurred between stages 0 and 1; the lowest, between stages 2 and 3.
Consecutive biopsies were separated by at least 1 year; patients were either HCV treatment naive or were treatment nonresponders. There were a total of 558 consecutive biopsy pairs available to analyze stage progression. The time between the first and last biopsies was 6.5 years (plus or minus 3 years), while the mean duration between adjacent biopsies was 4.4 years (plus or minus 1.9 years). Data regarding HCV treatment between liver biopsies were available for all but 45 patients. Forty-three percent of the remaining patients did not achieve a sustained virologic response after treatment.
Patients who’d had a cirrhosis diagnosis according to the first biopsy, those for whom treatment induced viral eradication, or those who’d had liver transplantation between biopsies were all excluded from the review.
The investigators wrote that their finding about the association between genotype 3 and cirrhosis should be “interpreted cautiously” because of the low number of these patients in their study.
This article was updated August 17, 2016.
On Twitter @whitneymcknight
FROM THE JOURNAL OF INFECTIOUS DISEASES
Key clinical point: Fibrosis progression is not linear in chronic HCV infection.
Major finding: Between the first and follow-up biopsy, 57.4% of patients progressed by at least one fibrosis stage, 16.1% of patients had more severe fibrosis progressions of at least two stages, and 10.6% developed either stage 3-4 or 4, with nearly 6% of patients progressing to cirrhosis.
Data source: A review of 936 biopsies taken from 378 patients seen at a single site between 1997 and 2013.
Disclosures: Dr. Talal and Dr. Jacobson disclosed numerous industry relationships, including with Abbott, AbbVie, and Gilead. The study was supported by the Troup Fund of the Kaleida Health Foundation and the Greenberg Foundation for Medical Research.
Hepatitis outlook: July 2016
If you work on the front lines of medical care treating patients with hepatitis, you may not have time to review all the hepatitis research that enters the medical literature every month. Here’s a quick look at some notable news items and journal articles published over the past month, covering a variety of the major hepatitis viruses.
Although hepatitis E virus infections are increasingly recognized as a global public health problem, there are “few methods for prevention and treatment that are widely available,” according to a recent analysis.
A “suboptimal plasma level of the antiviral drug daclatasvir allows the selection of resistance-associated variants” and fails to contribute to antiviral activity in HIV-hepatitis C virus (HCV) coinfected patients, according to a recent study, although no definite reason for the low daclatasvir level was found.
The new preservative-free inactivated hepatitis A vaccine (Healive) in two doses showed better persistence of antibody concentrations for 5 years after full-course immunization among children, compared with Havrix. The endurance of protective immunogenicity was estimated for at least 20 years.
Because of transplacental transfer of antihepatitis B virus antibodies (anti-HBVs), high levels of maternal anti-HBVs may suppress infants’ immune response to standard HBV vaccination, according to an analysis in the Journal of Viral Hepatitis.
The gamma-glutamyl transpeptidase-to-platelet ratio (GPR) is “a new serum model for the diagnosis” of liver fibrosis and cirrhosis, according to a recent study. Researchers said it shows advantages in Chinese hepatitis Be antigen (HBeAg)-positive patients with hepatitis B virus DNA greater than or equal to 5 log10 copies/mL and ALT less than or equal to two times ULN (upper limit of normal), compared with APRI (aspartate aminotransferase to platelet ratio index) and Fibrosis-4.
A baseline quantitative hepatitis B surface antigen (HBsAg) threshold of 3.141 log10 IU/mL and a baseline quantitative hepatitis B core-related antigen 3.450 log10 U/mL threshold, used separately or in combination, allow prediction of response to pegylated interferon-alpha-2a (PegIFN)-based “precision therapy” for hepatitis B virus infection, a new study found.
Male sex, age over 40 years, cirrhotic liver, and long length of stay are significant factors associated with death in hepatitis A virus-hospitalized cases, according to a study in the Journal of Viral Hepatitis.
Chronic kidney disease patients receiving three doses of hepatitis B adjuvanted vaccine were three times more likely to seroconvert than patients immunized with nonadjuvanted vaccines, according to results of a Spanish study. This meant fewer patients needed a second course of HBV vaccination and there were fewer outpatient visits.
Acute kidney injury is closely linked with increased short-term mortality in Chinese hepatitis B virus-related, acute-on-chronic liver failure patients, according to a study in the Journal of Viral Hepatitis.
Italian investigators attempted “to predict susceptibility of healthy patients to de novo HBV infection using a cultured IFN-gamma enzyme-linked immunospot (ELISPOT) assay.” Although the prognostic value of the assay was not demonstrated, data suggested that the subjects may be at risk for HBV infection.
Investigators demonstrated that treatment with sofosbuvir and simeprevir was effective in a real-life cohort of patients with hepatitis C virus genotype 4 infection and advanced liver fibrosis/cirrhosis. They said that adding ribavirin could be considered in treatment-experienced patients.
The presence of specific anti-envelope antibodies may be a factor that helps individuals at high risk of hepatitis C virus to resist infection, according to a study in the Journal of Viral Hepatitis.
A Chinese study determined that certain social network structural characteristics are related to hepatitis C virus infections in people who inject drugs, and used the data to identify the most susceptible individuals for HCV transmission in a network of people who inject drugs.
Drug resistance analyses of protease inhibitors that treat hepatitis C virus infection can be useful and essential in revealing the particular variants responsible for pretreatment natural resistance and also the particular mutations responsible for the viral breakthrough that may develop during the treatment, according to a study in the International Journal of Infectious Diseases.
Routine vaccination of toddlers against hepatitis A virus would be cost effective in Mexico using a single-dose vaccination strategy, according to a recent study, although the authors said the cost efficacy of a second dose depends on the assumptions of added safeguards by immune memory protection and the time horizon over which the analysis is enacted.
Hepatitis C virus-infected patients undergoing ribavirin-free sofosbuvir and velpatasvir regimens had significantly better patient-reported outcome scores during therapy, compared with those undergoing the ribavirin-containing regimen, a recent study found.
An analysis in Infectious Diseases in Clinical Practice reported the first case of visual hallucinations during chronic hepatitis C treatment with sofosbuvir and simeprevir. Investigators said hallucinations stopped upon starting antipsychotic medication, and the remainder of treatment was safe.
Sustained virologic response can be attained with pegylated interferon-alpha plus ribavirin combination therapy in hepatitis C virus–infected patients, but a relapse may occur in some patients, according to a recent study.
A quantitative HBsAg test can be used to ascertain high levels of hepatitis B viremia in women who might transmit the virus to their children, rather than a test for HBeAg or HBV DNA, according to a research letter in Hepatology.
The prevalence of antihepatitis E virus (HEV) antibodies was 49% (153/313) among blood donors in central Italy, according to a study published in Eurosurveillance. The authors said HEV infection is hyperendemic among blood donors (80% men, 18- to 64-years-old) from central Italy and associated with local dietary habits, such as eating raw dried pig liver sausage.
On Twitter @richpizzi
If you work on the front lines of medical care treating patients with hepatitis, you may not have time to review all the hepatitis research that enters the medical literature every month. Here’s a quick look at some notable news items and journal articles published over the past month, covering a variety of the major hepatitis viruses.
Although hepatitis E virus infections are increasingly recognized as a global public health problem, there are “few methods for prevention and treatment that are widely available,” according to a recent analysis.
A “suboptimal plasma level of the antiviral drug daclatasvir allows the selection of resistance-associated variants” and fails to contribute to antiviral activity in HIV-hepatitis C virus (HCV) coinfected patients, according to a recent study, although no definite reason for the low daclatasvir level was found.
The new preservative-free inactivated hepatitis A vaccine (Healive) in two doses showed better persistence of antibody concentrations for 5 years after full-course immunization among children, compared with Havrix. The endurance of protective immunogenicity was estimated for at least 20 years.
Because of transplacental transfer of antihepatitis B virus antibodies (anti-HBVs), high levels of maternal anti-HBVs may suppress infants’ immune response to standard HBV vaccination, according to an analysis in the Journal of Viral Hepatitis.
The gamma-glutamyl transpeptidase-to-platelet ratio (GPR) is “a new serum model for the diagnosis” of liver fibrosis and cirrhosis, according to a recent study. Researchers said it shows advantages in Chinese hepatitis Be antigen (HBeAg)-positive patients with hepatitis B virus DNA greater than or equal to 5 log10 copies/mL and ALT less than or equal to two times ULN (upper limit of normal), compared with APRI (aspartate aminotransferase to platelet ratio index) and Fibrosis-4.
A baseline quantitative hepatitis B surface antigen (HBsAg) threshold of 3.141 log10 IU/mL and a baseline quantitative hepatitis B core-related antigen 3.450 log10 U/mL threshold, used separately or in combination, allow prediction of response to pegylated interferon-alpha-2a (PegIFN)-based “precision therapy” for hepatitis B virus infection, a new study found.
Male sex, age over 40 years, cirrhotic liver, and long length of stay are significant factors associated with death in hepatitis A virus-hospitalized cases, according to a study in the Journal of Viral Hepatitis.
Chronic kidney disease patients receiving three doses of hepatitis B adjuvanted vaccine were three times more likely to seroconvert than patients immunized with nonadjuvanted vaccines, according to results of a Spanish study. This meant fewer patients needed a second course of HBV vaccination and there were fewer outpatient visits.
Acute kidney injury is closely linked with increased short-term mortality in Chinese hepatitis B virus-related, acute-on-chronic liver failure patients, according to a study in the Journal of Viral Hepatitis.
Italian investigators attempted “to predict susceptibility of healthy patients to de novo HBV infection using a cultured IFN-gamma enzyme-linked immunospot (ELISPOT) assay.” Although the prognostic value of the assay was not demonstrated, data suggested that the subjects may be at risk for HBV infection.
Investigators demonstrated that treatment with sofosbuvir and simeprevir was effective in a real-life cohort of patients with hepatitis C virus genotype 4 infection and advanced liver fibrosis/cirrhosis. They said that adding ribavirin could be considered in treatment-experienced patients.
The presence of specific anti-envelope antibodies may be a factor that helps individuals at high risk of hepatitis C virus to resist infection, according to a study in the Journal of Viral Hepatitis.
A Chinese study determined that certain social network structural characteristics are related to hepatitis C virus infections in people who inject drugs, and used the data to identify the most susceptible individuals for HCV transmission in a network of people who inject drugs.
Drug resistance analyses of protease inhibitors that treat hepatitis C virus infection can be useful and essential in revealing the particular variants responsible for pretreatment natural resistance and also the particular mutations responsible for the viral breakthrough that may develop during the treatment, according to a study in the International Journal of Infectious Diseases.
Routine vaccination of toddlers against hepatitis A virus would be cost effective in Mexico using a single-dose vaccination strategy, according to a recent study, although the authors said the cost efficacy of a second dose depends on the assumptions of added safeguards by immune memory protection and the time horizon over which the analysis is enacted.
Hepatitis C virus-infected patients undergoing ribavirin-free sofosbuvir and velpatasvir regimens had significantly better patient-reported outcome scores during therapy, compared with those undergoing the ribavirin-containing regimen, a recent study found.
An analysis in Infectious Diseases in Clinical Practice reported the first case of visual hallucinations during chronic hepatitis C treatment with sofosbuvir and simeprevir. Investigators said hallucinations stopped upon starting antipsychotic medication, and the remainder of treatment was safe.
Sustained virologic response can be attained with pegylated interferon-alpha plus ribavirin combination therapy in hepatitis C virus–infected patients, but a relapse may occur in some patients, according to a recent study.
A quantitative HBsAg test can be used to ascertain high levels of hepatitis B viremia in women who might transmit the virus to their children, rather than a test for HBeAg or HBV DNA, according to a research letter in Hepatology.
The prevalence of antihepatitis E virus (HEV) antibodies was 49% (153/313) among blood donors in central Italy, according to a study published in Eurosurveillance. The authors said HEV infection is hyperendemic among blood donors (80% men, 18- to 64-years-old) from central Italy and associated with local dietary habits, such as eating raw dried pig liver sausage.
On Twitter @richpizzi
If you work on the front lines of medical care treating patients with hepatitis, you may not have time to review all the hepatitis research that enters the medical literature every month. Here’s a quick look at some notable news items and journal articles published over the past month, covering a variety of the major hepatitis viruses.
Although hepatitis E virus infections are increasingly recognized as a global public health problem, there are “few methods for prevention and treatment that are widely available,” according to a recent analysis.
A “suboptimal plasma level of the antiviral drug daclatasvir allows the selection of resistance-associated variants” and fails to contribute to antiviral activity in HIV-hepatitis C virus (HCV) coinfected patients, according to a recent study, although no definite reason for the low daclatasvir level was found.
The new preservative-free inactivated hepatitis A vaccine (Healive) in two doses showed better persistence of antibody concentrations for 5 years after full-course immunization among children, compared with Havrix. The endurance of protective immunogenicity was estimated for at least 20 years.
Because of transplacental transfer of antihepatitis B virus antibodies (anti-HBVs), high levels of maternal anti-HBVs may suppress infants’ immune response to standard HBV vaccination, according to an analysis in the Journal of Viral Hepatitis.
The gamma-glutamyl transpeptidase-to-platelet ratio (GPR) is “a new serum model for the diagnosis” of liver fibrosis and cirrhosis, according to a recent study. Researchers said it shows advantages in Chinese hepatitis Be antigen (HBeAg)-positive patients with hepatitis B virus DNA greater than or equal to 5 log10 copies/mL and ALT less than or equal to two times ULN (upper limit of normal), compared with APRI (aspartate aminotransferase to platelet ratio index) and Fibrosis-4.
A baseline quantitative hepatitis B surface antigen (HBsAg) threshold of 3.141 log10 IU/mL and a baseline quantitative hepatitis B core-related antigen 3.450 log10 U/mL threshold, used separately or in combination, allow prediction of response to pegylated interferon-alpha-2a (PegIFN)-based “precision therapy” for hepatitis B virus infection, a new study found.
Male sex, age over 40 years, cirrhotic liver, and long length of stay are significant factors associated with death in hepatitis A virus-hospitalized cases, according to a study in the Journal of Viral Hepatitis.
Chronic kidney disease patients receiving three doses of hepatitis B adjuvanted vaccine were three times more likely to seroconvert than patients immunized with nonadjuvanted vaccines, according to results of a Spanish study. This meant fewer patients needed a second course of HBV vaccination and there were fewer outpatient visits.
Acute kidney injury is closely linked with increased short-term mortality in Chinese hepatitis B virus-related, acute-on-chronic liver failure patients, according to a study in the Journal of Viral Hepatitis.
Italian investigators attempted “to predict susceptibility of healthy patients to de novo HBV infection using a cultured IFN-gamma enzyme-linked immunospot (ELISPOT) assay.” Although the prognostic value of the assay was not demonstrated, data suggested that the subjects may be at risk for HBV infection.
Investigators demonstrated that treatment with sofosbuvir and simeprevir was effective in a real-life cohort of patients with hepatitis C virus genotype 4 infection and advanced liver fibrosis/cirrhosis. They said that adding ribavirin could be considered in treatment-experienced patients.
The presence of specific anti-envelope antibodies may be a factor that helps individuals at high risk of hepatitis C virus to resist infection, according to a study in the Journal of Viral Hepatitis.
A Chinese study determined that certain social network structural characteristics are related to hepatitis C virus infections in people who inject drugs, and used the data to identify the most susceptible individuals for HCV transmission in a network of people who inject drugs.
Drug resistance analyses of protease inhibitors that treat hepatitis C virus infection can be useful and essential in revealing the particular variants responsible for pretreatment natural resistance and also the particular mutations responsible for the viral breakthrough that may develop during the treatment, according to a study in the International Journal of Infectious Diseases.
Routine vaccination of toddlers against hepatitis A virus would be cost effective in Mexico using a single-dose vaccination strategy, according to a recent study, although the authors said the cost efficacy of a second dose depends on the assumptions of added safeguards by immune memory protection and the time horizon over which the analysis is enacted.
Hepatitis C virus-infected patients undergoing ribavirin-free sofosbuvir and velpatasvir regimens had significantly better patient-reported outcome scores during therapy, compared with those undergoing the ribavirin-containing regimen, a recent study found.
An analysis in Infectious Diseases in Clinical Practice reported the first case of visual hallucinations during chronic hepatitis C treatment with sofosbuvir and simeprevir. Investigators said hallucinations stopped upon starting antipsychotic medication, and the remainder of treatment was safe.
Sustained virologic response can be attained with pegylated interferon-alpha plus ribavirin combination therapy in hepatitis C virus–infected patients, but a relapse may occur in some patients, according to a recent study.
A quantitative HBsAg test can be used to ascertain high levels of hepatitis B viremia in women who might transmit the virus to their children, rather than a test for HBeAg or HBV DNA, according to a research letter in Hepatology.
The prevalence of antihepatitis E virus (HEV) antibodies was 49% (153/313) among blood donors in central Italy, according to a study published in Eurosurveillance. The authors said HEV infection is hyperendemic among blood donors (80% men, 18- to 64-years-old) from central Italy and associated with local dietary habits, such as eating raw dried pig liver sausage.
On Twitter @richpizzi
Hepatitis outlook: July 2016
If you work on the front lines of medical care treating patients with hepatitis, you may not have time to review all the hepatitis research that enters the medical literature every month. Here’s a quick look at some notable news items and journal articles published over the past month, covering a variety of the major hepatitis viruses.
Although hepatitis E virus infections are increasingly recognized as a global public health problem, there are “few methods for prevention and treatment that are widely available,” according to a recent analysis.
| ©Zerbor/Thinkstock |
A “suboptimal plasma level of the antiviral drug daclatasvir allows the selection of resistance-associated variants” and fails to contribute to antiviral activity in HIV-hepatitis C virus (HCV) coinfected patients, according to a recent study, although no definite reason for the low daclatasvir level was found.
The new preservative-free inactivated hepatitis A vaccine (Healive) in two doses showed better persistence of antibody concentrations for 5 years after full-course immunization among children, compared with Havrix. The endurance of protective immunogenicity was estimated for at least 20 years.
Because of transplacental transfer of antihepatitis B virus antibodies (anti-HBVs), high levels of maternal anti-HBVs may suppress infants’ immune response to standard HBV vaccination, according to an analysis in the Journal of Viral Hepatitis.
The gamma-glutamyl transpeptidase-to-platelet ratio (GPR) is “a new serum model for the diagnosis” of liver fibrosis and cirrhosis, according to a recent study. Researchers said it shows advantages in Chinese hepatitis Be antigen (HBeAg)-positive patients with hepatitis B virus DNA greater than or equal to 5 log10 copies/mL and ALT less than or equal to two times ULN (upper limit of normal), compared with APRI (aspartate aminotransferase to platelet ratio index) and Fibrosis-4.
A baseline quantitative hepatitis B surface antigen (HBsAg) threshold of 3.141 log10 IU/mL and a baseline quantitative hepatitis B core-related antigen 3.450 log10 U/mL threshold, used separately or in combination, allow prediction of response to pegylated interferon-alpha-2a (PegIFN)-based “precision therapy” for hepatitis B virus infection, a new study found.
Male sex, age over 40 years, cirrhotic liver, and long length of stay are significant factors associated with death in hepatitis A virus-hospitalized cases, according to a study in the Journal of Viral Hepatitis.
Chronic kidney disease patients receiving three doses of hepatitis B adjuvanted vaccine were three times more likely to seroconvert than patients immunized with nonadjuvanted vaccines, according to results of a Spanish study. This meant fewer patients needed a second course of HBV vaccination and there were fewer outpatient visits.
Acute kidney injury is closely linked with increased short-term mortality in Chinese hepatitis B virus-related, acute-on-chronic liver failure patients, according to a study in the Journal of Viral Hepatitis.
Italian investigators attempted “to predict susceptibility of healthy patients to de novo HBV infection using a cultured IFN-gamma enzyme-linked immunospot (ELISPOT) assay.” Although the prognostic value of the assay was not demonstrated, data suggested that the subjects may be at risk for HBV infection.
Investigators demonstrated that treatment with sofosbuvir and simeprevir was effective in a real-life cohort of patients with hepatitis C virus genotype 4 infection and advanced liver fibrosis/cirrhosis. They said that adding ribavirin could be considered in treatment-experienced patients.
The presence of specific anti-envelope antibodies may be a factor that helps individuals at high risk of hepatitis C virus to resist infection, according to a study in the Journal of Viral Hepatitis.
A Chinese study determined that certain social network structural characteristics are related to hepatitis C virus infections in people who inject drugs, and used the data to identify the most susceptible individuals for HCV transmission in a network of people who inject drugs.
Drug resistance analyses of protease inhibitors that treat hepatitis C virus infection can be useful and essential in revealing the particular variants responsible for pretreatment natural resistance and also the particular mutations responsible for the viral breakthrough that may develop during the treatment, according to a study in the International Journal of Infectious Diseases.
Routine vaccination of toddlers against hepatitis A virus would be cost effective in Mexico using a single-dose vaccination strategy, according to a recent study, although the authors said the cost efficacy of a second dose depends on the assumptions of added safeguards by immune memory protection and the time horizon over which the analysis is enacted.
Hepatitis C virus-infected patients undergoing ribavirin-free sofosbuvir and velpatasvir regimens had significantly better patient-reported outcome scores during therapy, compared with those undergoing the ribavirin-containing regimen, a recent study found.
An analysis in Infectious Diseases in Clinical Practice reported the first case of visual hallucinations during chronic hepatitis C treatment with sofosbuvir and simeprevir. Investigators said hallucinations stopped upon starting antipsychotic medication, and the remainder of treatment was safe.
Sustained virologic response can be attained with pegylated interferon-alpha plus ribavirin combination therapy in hepatitis C virus–infected patients, but a relapse may occur in some patients, according to a recent study.
A quantitative HBsAg test can be used to ascertain high levels of hepatitis B viremia in women who might transmit the virus to their children, rather than a test for HBeAg or HBV DNA, according to a research letter in Hepatology.
A Chinese study found a robust relationship between Helicobacter pylori infection and chronic hepatitis B. This is especially true during hepatitis B virus progression.
The prevalence of antihepatitis E virus (HEV) antibodies was 49% (153/313) among blood donors in central Italy, according to a study published in Eurosurveillance. The authors said HEV infection is hyperendemic among blood donors (80% men, 18- to 64-years-old) from central Italy and associated with local dietary habits, such as eating raw dried pig liver sausage.
AGA Resource
Through the HCV Clinical Service Line, AGA offers tools to help you become more efficient, understand quality standards and improve the process of care for patients. Visit http://www.gastro.org/patient-care/conditions-diseases/hepatitis-c to learn more.
On Twitter @richpizzi
If you work on the front lines of medical care treating patients with hepatitis, you may not have time to review all the hepatitis research that enters the medical literature every month. Here’s a quick look at some notable news items and journal articles published over the past month, covering a variety of the major hepatitis viruses.
Although hepatitis E virus infections are increasingly recognized as a global public health problem, there are “few methods for prevention and treatment that are widely available,” according to a recent analysis.
| ©Zerbor/Thinkstock |
A “suboptimal plasma level of the antiviral drug daclatasvir allows the selection of resistance-associated variants” and fails to contribute to antiviral activity in HIV-hepatitis C virus (HCV) coinfected patients, according to a recent study, although no definite reason for the low daclatasvir level was found.
The new preservative-free inactivated hepatitis A vaccine (Healive) in two doses showed better persistence of antibody concentrations for 5 years after full-course immunization among children, compared with Havrix. The endurance of protective immunogenicity was estimated for at least 20 years.
Because of transplacental transfer of antihepatitis B virus antibodies (anti-HBVs), high levels of maternal anti-HBVs may suppress infants’ immune response to standard HBV vaccination, according to an analysis in the Journal of Viral Hepatitis.
The gamma-glutamyl transpeptidase-to-platelet ratio (GPR) is “a new serum model for the diagnosis” of liver fibrosis and cirrhosis, according to a recent study. Researchers said it shows advantages in Chinese hepatitis Be antigen (HBeAg)-positive patients with hepatitis B virus DNA greater than or equal to 5 log10 copies/mL and ALT less than or equal to two times ULN (upper limit of normal), compared with APRI (aspartate aminotransferase to platelet ratio index) and Fibrosis-4.
A baseline quantitative hepatitis B surface antigen (HBsAg) threshold of 3.141 log10 IU/mL and a baseline quantitative hepatitis B core-related antigen 3.450 log10 U/mL threshold, used separately or in combination, allow prediction of response to pegylated interferon-alpha-2a (PegIFN)-based “precision therapy” for hepatitis B virus infection, a new study found.
Male sex, age over 40 years, cirrhotic liver, and long length of stay are significant factors associated with death in hepatitis A virus-hospitalized cases, according to a study in the Journal of Viral Hepatitis.
Chronic kidney disease patients receiving three doses of hepatitis B adjuvanted vaccine were three times more likely to seroconvert than patients immunized with nonadjuvanted vaccines, according to results of a Spanish study. This meant fewer patients needed a second course of HBV vaccination and there were fewer outpatient visits.
Acute kidney injury is closely linked with increased short-term mortality in Chinese hepatitis B virus-related, acute-on-chronic liver failure patients, according to a study in the Journal of Viral Hepatitis.
Italian investigators attempted “to predict susceptibility of healthy patients to de novo HBV infection using a cultured IFN-gamma enzyme-linked immunospot (ELISPOT) assay.” Although the prognostic value of the assay was not demonstrated, data suggested that the subjects may be at risk for HBV infection.
Investigators demonstrated that treatment with sofosbuvir and simeprevir was effective in a real-life cohort of patients with hepatitis C virus genotype 4 infection and advanced liver fibrosis/cirrhosis. They said that adding ribavirin could be considered in treatment-experienced patients.
The presence of specific anti-envelope antibodies may be a factor that helps individuals at high risk of hepatitis C virus to resist infection, according to a study in the Journal of Viral Hepatitis.
A Chinese study determined that certain social network structural characteristics are related to hepatitis C virus infections in people who inject drugs, and used the data to identify the most susceptible individuals for HCV transmission in a network of people who inject drugs.
Drug resistance analyses of protease inhibitors that treat hepatitis C virus infection can be useful and essential in revealing the particular variants responsible for pretreatment natural resistance and also the particular mutations responsible for the viral breakthrough that may develop during the treatment, according to a study in the International Journal of Infectious Diseases.
Routine vaccination of toddlers against hepatitis A virus would be cost effective in Mexico using a single-dose vaccination strategy, according to a recent study, although the authors said the cost efficacy of a second dose depends on the assumptions of added safeguards by immune memory protection and the time horizon over which the analysis is enacted.
Hepatitis C virus-infected patients undergoing ribavirin-free sofosbuvir and velpatasvir regimens had significantly better patient-reported outcome scores during therapy, compared with those undergoing the ribavirin-containing regimen, a recent study found.
An analysis in Infectious Diseases in Clinical Practice reported the first case of visual hallucinations during chronic hepatitis C treatment with sofosbuvir and simeprevir. Investigators said hallucinations stopped upon starting antipsychotic medication, and the remainder of treatment was safe.
Sustained virologic response can be attained with pegylated interferon-alpha plus ribavirin combination therapy in hepatitis C virus–infected patients, but a relapse may occur in some patients, according to a recent study.
A quantitative HBsAg test can be used to ascertain high levels of hepatitis B viremia in women who might transmit the virus to their children, rather than a test for HBeAg or HBV DNA, according to a research letter in Hepatology.
A Chinese study found a robust relationship between Helicobacter pylori infection and chronic hepatitis B. This is especially true during hepatitis B virus progression.
The prevalence of antihepatitis E virus (HEV) antibodies was 49% (153/313) among blood donors in central Italy, according to a study published in Eurosurveillance. The authors said HEV infection is hyperendemic among blood donors (80% men, 18- to 64-years-old) from central Italy and associated with local dietary habits, such as eating raw dried pig liver sausage.
AGA Resource
Through the HCV Clinical Service Line, AGA offers tools to help you become more efficient, understand quality standards and improve the process of care for patients. Visit http://www.gastro.org/patient-care/conditions-diseases/hepatitis-c to learn more.
On Twitter @richpizzi
If you work on the front lines of medical care treating patients with hepatitis, you may not have time to review all the hepatitis research that enters the medical literature every month. Here’s a quick look at some notable news items and journal articles published over the past month, covering a variety of the major hepatitis viruses.
Although hepatitis E virus infections are increasingly recognized as a global public health problem, there are “few methods for prevention and treatment that are widely available,” according to a recent analysis.
| ©Zerbor/Thinkstock |
A “suboptimal plasma level of the antiviral drug daclatasvir allows the selection of resistance-associated variants” and fails to contribute to antiviral activity in HIV-hepatitis C virus (HCV) coinfected patients, according to a recent study, although no definite reason for the low daclatasvir level was found.
The new preservative-free inactivated hepatitis A vaccine (Healive) in two doses showed better persistence of antibody concentrations for 5 years after full-course immunization among children, compared with Havrix. The endurance of protective immunogenicity was estimated for at least 20 years.
Because of transplacental transfer of antihepatitis B virus antibodies (anti-HBVs), high levels of maternal anti-HBVs may suppress infants’ immune response to standard HBV vaccination, according to an analysis in the Journal of Viral Hepatitis.
The gamma-glutamyl transpeptidase-to-platelet ratio (GPR) is “a new serum model for the diagnosis” of liver fibrosis and cirrhosis, according to a recent study. Researchers said it shows advantages in Chinese hepatitis Be antigen (HBeAg)-positive patients with hepatitis B virus DNA greater than or equal to 5 log10 copies/mL and ALT less than or equal to two times ULN (upper limit of normal), compared with APRI (aspartate aminotransferase to platelet ratio index) and Fibrosis-4.
A baseline quantitative hepatitis B surface antigen (HBsAg) threshold of 3.141 log10 IU/mL and a baseline quantitative hepatitis B core-related antigen 3.450 log10 U/mL threshold, used separately or in combination, allow prediction of response to pegylated interferon-alpha-2a (PegIFN)-based “precision therapy” for hepatitis B virus infection, a new study found.
Male sex, age over 40 years, cirrhotic liver, and long length of stay are significant factors associated with death in hepatitis A virus-hospitalized cases, according to a study in the Journal of Viral Hepatitis.
Chronic kidney disease patients receiving three doses of hepatitis B adjuvanted vaccine were three times more likely to seroconvert than patients immunized with nonadjuvanted vaccines, according to results of a Spanish study. This meant fewer patients needed a second course of HBV vaccination and there were fewer outpatient visits.
Acute kidney injury is closely linked with increased short-term mortality in Chinese hepatitis B virus-related, acute-on-chronic liver failure patients, according to a study in the Journal of Viral Hepatitis.
Italian investigators attempted “to predict susceptibility of healthy patients to de novo HBV infection using a cultured IFN-gamma enzyme-linked immunospot (ELISPOT) assay.” Although the prognostic value of the assay was not demonstrated, data suggested that the subjects may be at risk for HBV infection.
Investigators demonstrated that treatment with sofosbuvir and simeprevir was effective in a real-life cohort of patients with hepatitis C virus genotype 4 infection and advanced liver fibrosis/cirrhosis. They said that adding ribavirin could be considered in treatment-experienced patients.
The presence of specific anti-envelope antibodies may be a factor that helps individuals at high risk of hepatitis C virus to resist infection, according to a study in the Journal of Viral Hepatitis.
A Chinese study determined that certain social network structural characteristics are related to hepatitis C virus infections in people who inject drugs, and used the data to identify the most susceptible individuals for HCV transmission in a network of people who inject drugs.
Drug resistance analyses of protease inhibitors that treat hepatitis C virus infection can be useful and essential in revealing the particular variants responsible for pretreatment natural resistance and also the particular mutations responsible for the viral breakthrough that may develop during the treatment, according to a study in the International Journal of Infectious Diseases.
Routine vaccination of toddlers against hepatitis A virus would be cost effective in Mexico using a single-dose vaccination strategy, according to a recent study, although the authors said the cost efficacy of a second dose depends on the assumptions of added safeguards by immune memory protection and the time horizon over which the analysis is enacted.
Hepatitis C virus-infected patients undergoing ribavirin-free sofosbuvir and velpatasvir regimens had significantly better patient-reported outcome scores during therapy, compared with those undergoing the ribavirin-containing regimen, a recent study found.
An analysis in Infectious Diseases in Clinical Practice reported the first case of visual hallucinations during chronic hepatitis C treatment with sofosbuvir and simeprevir. Investigators said hallucinations stopped upon starting antipsychotic medication, and the remainder of treatment was safe.
Sustained virologic response can be attained with pegylated interferon-alpha plus ribavirin combination therapy in hepatitis C virus–infected patients, but a relapse may occur in some patients, according to a recent study.
A quantitative HBsAg test can be used to ascertain high levels of hepatitis B viremia in women who might transmit the virus to their children, rather than a test for HBeAg or HBV DNA, according to a research letter in Hepatology.
A Chinese study found a robust relationship between Helicobacter pylori infection and chronic hepatitis B. This is especially true during hepatitis B virus progression.
The prevalence of antihepatitis E virus (HEV) antibodies was 49% (153/313) among blood donors in central Italy, according to a study published in Eurosurveillance. The authors said HEV infection is hyperendemic among blood donors (80% men, 18- to 64-years-old) from central Italy and associated with local dietary habits, such as eating raw dried pig liver sausage.
AGA Resource
Through the HCV Clinical Service Line, AGA offers tools to help you become more efficient, understand quality standards and improve the process of care for patients. Visit http://www.gastro.org/patient-care/conditions-diseases/hepatitis-c to learn more.
On Twitter @richpizzi
Links found between NAFLD, type 2 diabetes, and NASH in children
Nearly one in three children with nonalcoholic fatty liver disease have abnormal glucose metabolism, and this co-morbidity is also associated with a greater risk of nonalcoholic steatohepatitis, according to a cross-sectional study published online Aug. 1 in JAMA Pediatrics.
The study used data from 675 children with biopsy-confirmed nonalcoholic fatty liver disease (NAFLD) who were enrolled in the NASH Clinical Research Network. The mean age of the children was 12.6 years, and they had a mean BMI of 32.5. Most of the children in the study were boys and Hispanic.
Overall, 23.4% of study participants had prediabetes and 6.5% met the clinical criteria for type 2 diabetes. However, girls with NAFLD had a 60% greater risk of prediabetes and a fivefold greater risk of type 2 diabetes than boys, even after controlling for BMI and waist circumference (JAMA Pediatr. 2016 Aug 1. doi: 10.1001/jamapediatrics.2016.1971), reported Dr. Kimberly P. Newton and her coauthors.
The researchers also noted a significant association between nonalcoholic steatohepatitis (NASH) and glucose metabolism. Individuals with type 2 diabetes were three times more likely to also have NASH, while those with prediabetes had a 90% higher incidence of NASH, compared with individuals with normal glucose metabolism. They also found that those with NASH had significantly higher mean fasting glucose and insulin concentrations than children without NASH.
Dr. Newton, of the University of California, San Diego, and her coauthors wrote that while abnormal glucose metabolism is known to be common in adults with NAFLD, and that type diabetes is a risk factor for progression to NASH and liver-related mortality, the association in children with NAFLD is less well understood.
“Among our cohort, the prevalence of children with type 2 diabetes was much higher than would be expected based on contributions from obesity alone,” they wrote. “Although systemic insulin resistance is believed be important in the pathogenesis of both pediatric NAFLD and type 2 diabetes, to our knowledge, there are no longitudinal studies that evaluate the cause-effect relationship between these two associated conditions.”
The authors drew particular attention to the threefold higher odds of NASH in children with NAFLD and type 2 diabetes, pointing out that while the prognostic implications of NASH in childhood are not fully known, the NASH phenotype is associated with a “substantially” greater risk of cirrhosis. This risk is likely to be compounded by the presence of type 2 diabetes.
“Our study advances the literature by showing that as early as childhood, prediabetes and type 2 diabetes emerge as clear risk factors for NASH with potential downstream implications for future morbidity and mortality.”
Commenting on the greater incidence of prediabetes and type 2 diabetes among girls with NAFLD, the authors said this had been observed in other studies and that sex differences represented a major unmet research need.
The Nonalcoholic Steatohepatitis Clinical Research Network is supported by the National Institute of Diabetes and Digestive and Kidney Diseases. Additional support was received from the National Center for Advancing Translational Sciences. The researchers reported no conflicts of interest.
Nearly one in three children with nonalcoholic fatty liver disease have abnormal glucose metabolism, and this co-morbidity is also associated with a greater risk of nonalcoholic steatohepatitis, according to a cross-sectional study published online Aug. 1 in JAMA Pediatrics.
The study used data from 675 children with biopsy-confirmed nonalcoholic fatty liver disease (NAFLD) who were enrolled in the NASH Clinical Research Network. The mean age of the children was 12.6 years, and they had a mean BMI of 32.5. Most of the children in the study were boys and Hispanic.
Overall, 23.4% of study participants had prediabetes and 6.5% met the clinical criteria for type 2 diabetes. However, girls with NAFLD had a 60% greater risk of prediabetes and a fivefold greater risk of type 2 diabetes than boys, even after controlling for BMI and waist circumference (JAMA Pediatr. 2016 Aug 1. doi: 10.1001/jamapediatrics.2016.1971), reported Dr. Kimberly P. Newton and her coauthors.
The researchers also noted a significant association between nonalcoholic steatohepatitis (NASH) and glucose metabolism. Individuals with type 2 diabetes were three times more likely to also have NASH, while those with prediabetes had a 90% higher incidence of NASH, compared with individuals with normal glucose metabolism. They also found that those with NASH had significantly higher mean fasting glucose and insulin concentrations than children without NASH.
Dr. Newton, of the University of California, San Diego, and her coauthors wrote that while abnormal glucose metabolism is known to be common in adults with NAFLD, and that type diabetes is a risk factor for progression to NASH and liver-related mortality, the association in children with NAFLD is less well understood.
“Among our cohort, the prevalence of children with type 2 diabetes was much higher than would be expected based on contributions from obesity alone,” they wrote. “Although systemic insulin resistance is believed be important in the pathogenesis of both pediatric NAFLD and type 2 diabetes, to our knowledge, there are no longitudinal studies that evaluate the cause-effect relationship between these two associated conditions.”
The authors drew particular attention to the threefold higher odds of NASH in children with NAFLD and type 2 diabetes, pointing out that while the prognostic implications of NASH in childhood are not fully known, the NASH phenotype is associated with a “substantially” greater risk of cirrhosis. This risk is likely to be compounded by the presence of type 2 diabetes.
“Our study advances the literature by showing that as early as childhood, prediabetes and type 2 diabetes emerge as clear risk factors for NASH with potential downstream implications for future morbidity and mortality.”
Commenting on the greater incidence of prediabetes and type 2 diabetes among girls with NAFLD, the authors said this had been observed in other studies and that sex differences represented a major unmet research need.
The Nonalcoholic Steatohepatitis Clinical Research Network is supported by the National Institute of Diabetes and Digestive and Kidney Diseases. Additional support was received from the National Center for Advancing Translational Sciences. The researchers reported no conflicts of interest.
Nearly one in three children with nonalcoholic fatty liver disease have abnormal glucose metabolism, and this co-morbidity is also associated with a greater risk of nonalcoholic steatohepatitis, according to a cross-sectional study published online Aug. 1 in JAMA Pediatrics.
The study used data from 675 children with biopsy-confirmed nonalcoholic fatty liver disease (NAFLD) who were enrolled in the NASH Clinical Research Network. The mean age of the children was 12.6 years, and they had a mean BMI of 32.5. Most of the children in the study were boys and Hispanic.
Overall, 23.4% of study participants had prediabetes and 6.5% met the clinical criteria for type 2 diabetes. However, girls with NAFLD had a 60% greater risk of prediabetes and a fivefold greater risk of type 2 diabetes than boys, even after controlling for BMI and waist circumference (JAMA Pediatr. 2016 Aug 1. doi: 10.1001/jamapediatrics.2016.1971), reported Dr. Kimberly P. Newton and her coauthors.
The researchers also noted a significant association between nonalcoholic steatohepatitis (NASH) and glucose metabolism. Individuals with type 2 diabetes were three times more likely to also have NASH, while those with prediabetes had a 90% higher incidence of NASH, compared with individuals with normal glucose metabolism. They also found that those with NASH had significantly higher mean fasting glucose and insulin concentrations than children without NASH.
Dr. Newton, of the University of California, San Diego, and her coauthors wrote that while abnormal glucose metabolism is known to be common in adults with NAFLD, and that type diabetes is a risk factor for progression to NASH and liver-related mortality, the association in children with NAFLD is less well understood.
“Among our cohort, the prevalence of children with type 2 diabetes was much higher than would be expected based on contributions from obesity alone,” they wrote. “Although systemic insulin resistance is believed be important in the pathogenesis of both pediatric NAFLD and type 2 diabetes, to our knowledge, there are no longitudinal studies that evaluate the cause-effect relationship between these two associated conditions.”
The authors drew particular attention to the threefold higher odds of NASH in children with NAFLD and type 2 diabetes, pointing out that while the prognostic implications of NASH in childhood are not fully known, the NASH phenotype is associated with a “substantially” greater risk of cirrhosis. This risk is likely to be compounded by the presence of type 2 diabetes.
“Our study advances the literature by showing that as early as childhood, prediabetes and type 2 diabetes emerge as clear risk factors for NASH with potential downstream implications for future morbidity and mortality.”
Commenting on the greater incidence of prediabetes and type 2 diabetes among girls with NAFLD, the authors said this had been observed in other studies and that sex differences represented a major unmet research need.
The Nonalcoholic Steatohepatitis Clinical Research Network is supported by the National Institute of Diabetes and Digestive and Kidney Diseases. Additional support was received from the National Center for Advancing Translational Sciences. The researchers reported no conflicts of interest.
FROM JAMA PEDIATRICS
Key clinical point: Nearly one in three children with nonalcoholic fatty liver disease have abnormal glucose metabolism, and this combination also is associated with a greater risk of nonalcoholic steatohepatitis.
Major finding: Among children with biopsy-diagnosed non-alcoholic fatty liver disease, 23.4% had prediabetes and 6.5% met the clinical criteria for type 2 diabetes.
Data source: Cross-sectional study of 675 children with biopsy-confirmed nonalcoholic fatty liver disease enrolled in the NASH Clinical Research Network.
Disclosures: The Nonalcoholic Steatohepatitis Clinical Research Network is supported by the National Institute of Diabetes and Digestive and Kidney Diseases. Additional support was received from the National Center for Advancing Translational Sciences. The researchers reported no conflicts of interest.
WHO analysis: Cost of new HCV meds unaffordable globally
The cost of new medicines for patients infected with hepatitis C virus vary widely around the globe, especially when adjusted for national wealth, results from an economic analysis led by World Health Organization officials suggest.
“These prices threaten the sustainability of health systems in many countries and prevent large-scale provision of treatment,” Suzanne Hill, PhD, of the World Health Organization, Geneva, and her associates wrote (PLoS Med. 2016 May 31;[5]:e1002032. doi:10.1371/journal.pmed.1002032).
“Stakeholders should implement a fairer pricing framework to deliver lower prices that take account of affordability. Without lower prices, countries are unlikely to be able to increase investment to minimize the burden of hepatitis C.”
In an effort to calculate the potential total cost of sofosbuvir and ledipasvir/sofosbuvir for different national health systems and individual patients in 30 countries, the researchers obtained 2015 prices for a 12-week course of treatment with the medications for as many countries as possible. Sources of reference were the Pharma Price Information service of the Austrian public health institute Gesundheit Österreich GmbH, national government and drug reimbursement authority website, and press releases.
Using data compiled between July 17, 2015, and Jan. 25, 2016, medication prices in Organisation for Economic Co-operation and Development (OECD) member countries and certain low- and middle-income countries were converted to U.S. dollars using period average exchange rates and were adjusted for purchasing power parity (PPP). “We analyzed prices compared to national economic performance and estimated market size and the cost of these drugs in terms of countries’ annual total pharmaceutical expenditure (TPE) and in terms of the duration of time an individual would need to work to pay for treatment out of pocket,” the researchers explained. “Patient affordability was calculated using 2014 OECD average annual wages, supplemented International Labour Organization median wages where necessary.”
Dr. Sullivan and her associates found that HCV medication prices varied significantly across countries, especially when adjusted for national wealth. For example, the median price of a 12-week course of sofosbuvir across 26 OECD countries was $42,017 in U.S. dollars, ranging from $37,729 in Japan to $64,680 in the United States. At the same time, countries in central and eastern Europe had higher PPP-adjusted prices, compared with other countries. For example, the PPP-adjusted prices of sofosbuvir in Poland and Turkey were $101,063 and $70,331, respectively, compared with a price of $64,680 in the Unite States. At the same time, the PPP-adjusted price of ledipasvir/sofosbuvir in Poland was $118,754, compared with a price of $72,765 in the United States.
The researchers also found that the PPP-adjusted price of a full course of sofosbuvir alone would be equivalent to at least 1 year of the PPP-adjusted average earnings for individuals in 12 of the 30 countries analyzed. In Poland, Slovakia, Portugal, and Turkey, a course of sofosbuvir alone would cost at least 2 years’ of average annual wages. “This analysis is conservative because prices were ex-factory prices with an assumed 23% price reduction, and did not include supply chain mark-ups and other costs such as the cost of diagnosis, daclatasvir, ribavirin, and health service costs,” they wrote.
They characterized the costs of sofosbuvir and ledipasvir/sofosbuvir as “not ‘affordable’ for most OECD countries at the nominal and PPP-adjusted prices, with Central and Eastern European countries being the most affected. While determining what is affordable or not is a value judgment, funding these treatments in these national health systems would consume large proportions of their TPE and increase pressure on existing budgets.”
They acknowledged certain limitations of the analysis, including the accuracy of the estimates of the numbers of people infected and of the price information that was accessible. “We have also not included all likely costs, such as the costs of combination treatment with ribavirin, other health care services, and increases in the duration of treatment in patients with cirrhosis; thus, our budget impact estimates are underestimates of the cost of treatment. We are also aware that in some countries, the prices are probably lower than the publicly accessible prices because of confidential discounts or rebates negotiated with the manufacturer.”
Dr. Hill disclosed that she is a member of the PLoS Medicine editorial board.
The savings to the medical system in averted future costs of liver complications were excluded from the assessment developed by Suzanne Hill, PhD, and her colleagues. However, studies of the cost-effectiveness of HCV therapies in the United States suggest that these benefits are substantial and can help finance HCV treatment.
Despite the discounts offered in both LMICs (low- and middle-income countries) and OECD (Organisation for Economic Cooperation and Development) countries, the short-term impact of HCV treatment on budgets of health care payers and individuals may limit access. However, there are two mitigating factors. First, once the backlog of prevalent cases is treated, the budgetary impact drops dramatically, as only the relatively few incident cases need be treated. Thus, while fiscally disruptive if all HCV-infected persons were immediately put on treatment, that disruption would last only 1 year. Second, treating everyone in year 1 is implausible. The process of identifying cases, limits to health care system capacity, and patient preferences all suggest a multi-year catch-up process. For those reasons, the fiscal burden expressed as a percent of TPE (total pharmaceutical expenditure) or as a portion of the average annual wage would be much less than the maximum burden as presented in Dr. Hill’s article.
One solution, then, is to spread the upfront cost of treatment over several years. Not everyone is eager to be treated, especially the asymptomatic for whom delay may be less harmful. Beyond this, there are options for phasing in treatment gradually by equity concerns, i.e., treating those with lower access to care first, or by disease stage. Our U.S.-based analysis found that while treating all patients in fibrosis stages 1–4 was cost-effective, initiating treatment in stages 3 and 4 was more cost-effective and would reduce total net treatment costs in the United States by about one-third per individual with chronic hepatitis C. A combination of equity and disease stage criteria can match phase-in plans to different countries’ budgets and political will.
It is in each country’s capacity, and without disruptive budgetary impact, to start treating many of those most in need of care now and to extend coverage to all over the succeeding few years.
These comments were extracted from an accompanying editorial (PLoS Med. 2016 May 31;[5]:e1002031. doi:10.1371/journal.pmed.1002031) by Elliot Marseille, DrPH, and James G. Kahn, MD, MPH. Dr. Marseille is with the Oakland, Calif.-based Health Strategies International. Dr. Kahn is with the Philip R. Lee Institute for Health Policy Studies at the University of California, San Francisco. The authors reported having no relevant financial disclosures.
The savings to the medical system in averted future costs of liver complications were excluded from the assessment developed by Suzanne Hill, PhD, and her colleagues. However, studies of the cost-effectiveness of HCV therapies in the United States suggest that these benefits are substantial and can help finance HCV treatment.
Despite the discounts offered in both LMICs (low- and middle-income countries) and OECD (Organisation for Economic Cooperation and Development) countries, the short-term impact of HCV treatment on budgets of health care payers and individuals may limit access. However, there are two mitigating factors. First, once the backlog of prevalent cases is treated, the budgetary impact drops dramatically, as only the relatively few incident cases need be treated. Thus, while fiscally disruptive if all HCV-infected persons were immediately put on treatment, that disruption would last only 1 year. Second, treating everyone in year 1 is implausible. The process of identifying cases, limits to health care system capacity, and patient preferences all suggest a multi-year catch-up process. For those reasons, the fiscal burden expressed as a percent of TPE (total pharmaceutical expenditure) or as a portion of the average annual wage would be much less than the maximum burden as presented in Dr. Hill’s article.
One solution, then, is to spread the upfront cost of treatment over several years. Not everyone is eager to be treated, especially the asymptomatic for whom delay may be less harmful. Beyond this, there are options for phasing in treatment gradually by equity concerns, i.e., treating those with lower access to care first, or by disease stage. Our U.S.-based analysis found that while treating all patients in fibrosis stages 1–4 was cost-effective, initiating treatment in stages 3 and 4 was more cost-effective and would reduce total net treatment costs in the United States by about one-third per individual with chronic hepatitis C. A combination of equity and disease stage criteria can match phase-in plans to different countries’ budgets and political will.
It is in each country’s capacity, and without disruptive budgetary impact, to start treating many of those most in need of care now and to extend coverage to all over the succeeding few years.
These comments were extracted from an accompanying editorial (PLoS Med. 2016 May 31;[5]:e1002031. doi:10.1371/journal.pmed.1002031) by Elliot Marseille, DrPH, and James G. Kahn, MD, MPH. Dr. Marseille is with the Oakland, Calif.-based Health Strategies International. Dr. Kahn is with the Philip R. Lee Institute for Health Policy Studies at the University of California, San Francisco. The authors reported having no relevant financial disclosures.
The savings to the medical system in averted future costs of liver complications were excluded from the assessment developed by Suzanne Hill, PhD, and her colleagues. However, studies of the cost-effectiveness of HCV therapies in the United States suggest that these benefits are substantial and can help finance HCV treatment.
Despite the discounts offered in both LMICs (low- and middle-income countries) and OECD (Organisation for Economic Cooperation and Development) countries, the short-term impact of HCV treatment on budgets of health care payers and individuals may limit access. However, there are two mitigating factors. First, once the backlog of prevalent cases is treated, the budgetary impact drops dramatically, as only the relatively few incident cases need be treated. Thus, while fiscally disruptive if all HCV-infected persons were immediately put on treatment, that disruption would last only 1 year. Second, treating everyone in year 1 is implausible. The process of identifying cases, limits to health care system capacity, and patient preferences all suggest a multi-year catch-up process. For those reasons, the fiscal burden expressed as a percent of TPE (total pharmaceutical expenditure) or as a portion of the average annual wage would be much less than the maximum burden as presented in Dr. Hill’s article.
One solution, then, is to spread the upfront cost of treatment over several years. Not everyone is eager to be treated, especially the asymptomatic for whom delay may be less harmful. Beyond this, there are options for phasing in treatment gradually by equity concerns, i.e., treating those with lower access to care first, or by disease stage. Our U.S.-based analysis found that while treating all patients in fibrosis stages 1–4 was cost-effective, initiating treatment in stages 3 and 4 was more cost-effective and would reduce total net treatment costs in the United States by about one-third per individual with chronic hepatitis C. A combination of equity and disease stage criteria can match phase-in plans to different countries’ budgets and political will.
It is in each country’s capacity, and without disruptive budgetary impact, to start treating many of those most in need of care now and to extend coverage to all over the succeeding few years.
These comments were extracted from an accompanying editorial (PLoS Med. 2016 May 31;[5]:e1002031. doi:10.1371/journal.pmed.1002031) by Elliot Marseille, DrPH, and James G. Kahn, MD, MPH. Dr. Marseille is with the Oakland, Calif.-based Health Strategies International. Dr. Kahn is with the Philip R. Lee Institute for Health Policy Studies at the University of California, San Francisco. The authors reported having no relevant financial disclosures.
The cost of new medicines for patients infected with hepatitis C virus vary widely around the globe, especially when adjusted for national wealth, results from an economic analysis led by World Health Organization officials suggest.
“These prices threaten the sustainability of health systems in many countries and prevent large-scale provision of treatment,” Suzanne Hill, PhD, of the World Health Organization, Geneva, and her associates wrote (PLoS Med. 2016 May 31;[5]:e1002032. doi:10.1371/journal.pmed.1002032).
“Stakeholders should implement a fairer pricing framework to deliver lower prices that take account of affordability. Without lower prices, countries are unlikely to be able to increase investment to minimize the burden of hepatitis C.”
In an effort to calculate the potential total cost of sofosbuvir and ledipasvir/sofosbuvir for different national health systems and individual patients in 30 countries, the researchers obtained 2015 prices for a 12-week course of treatment with the medications for as many countries as possible. Sources of reference were the Pharma Price Information service of the Austrian public health institute Gesundheit Österreich GmbH, national government and drug reimbursement authority website, and press releases.
Using data compiled between July 17, 2015, and Jan. 25, 2016, medication prices in Organisation for Economic Co-operation and Development (OECD) member countries and certain low- and middle-income countries were converted to U.S. dollars using period average exchange rates and were adjusted for purchasing power parity (PPP). “We analyzed prices compared to national economic performance and estimated market size and the cost of these drugs in terms of countries’ annual total pharmaceutical expenditure (TPE) and in terms of the duration of time an individual would need to work to pay for treatment out of pocket,” the researchers explained. “Patient affordability was calculated using 2014 OECD average annual wages, supplemented International Labour Organization median wages where necessary.”
Dr. Sullivan and her associates found that HCV medication prices varied significantly across countries, especially when adjusted for national wealth. For example, the median price of a 12-week course of sofosbuvir across 26 OECD countries was $42,017 in U.S. dollars, ranging from $37,729 in Japan to $64,680 in the United States. At the same time, countries in central and eastern Europe had higher PPP-adjusted prices, compared with other countries. For example, the PPP-adjusted prices of sofosbuvir in Poland and Turkey were $101,063 and $70,331, respectively, compared with a price of $64,680 in the Unite States. At the same time, the PPP-adjusted price of ledipasvir/sofosbuvir in Poland was $118,754, compared with a price of $72,765 in the United States.
The researchers also found that the PPP-adjusted price of a full course of sofosbuvir alone would be equivalent to at least 1 year of the PPP-adjusted average earnings for individuals in 12 of the 30 countries analyzed. In Poland, Slovakia, Portugal, and Turkey, a course of sofosbuvir alone would cost at least 2 years’ of average annual wages. “This analysis is conservative because prices were ex-factory prices with an assumed 23% price reduction, and did not include supply chain mark-ups and other costs such as the cost of diagnosis, daclatasvir, ribavirin, and health service costs,” they wrote.
They characterized the costs of sofosbuvir and ledipasvir/sofosbuvir as “not ‘affordable’ for most OECD countries at the nominal and PPP-adjusted prices, with Central and Eastern European countries being the most affected. While determining what is affordable or not is a value judgment, funding these treatments in these national health systems would consume large proportions of their TPE and increase pressure on existing budgets.”
They acknowledged certain limitations of the analysis, including the accuracy of the estimates of the numbers of people infected and of the price information that was accessible. “We have also not included all likely costs, such as the costs of combination treatment with ribavirin, other health care services, and increases in the duration of treatment in patients with cirrhosis; thus, our budget impact estimates are underestimates of the cost of treatment. We are also aware that in some countries, the prices are probably lower than the publicly accessible prices because of confidential discounts or rebates negotiated with the manufacturer.”
Dr. Hill disclosed that she is a member of the PLoS Medicine editorial board.
The cost of new medicines for patients infected with hepatitis C virus vary widely around the globe, especially when adjusted for national wealth, results from an economic analysis led by World Health Organization officials suggest.
“These prices threaten the sustainability of health systems in many countries and prevent large-scale provision of treatment,” Suzanne Hill, PhD, of the World Health Organization, Geneva, and her associates wrote (PLoS Med. 2016 May 31;[5]:e1002032. doi:10.1371/journal.pmed.1002032).
“Stakeholders should implement a fairer pricing framework to deliver lower prices that take account of affordability. Without lower prices, countries are unlikely to be able to increase investment to minimize the burden of hepatitis C.”
In an effort to calculate the potential total cost of sofosbuvir and ledipasvir/sofosbuvir for different national health systems and individual patients in 30 countries, the researchers obtained 2015 prices for a 12-week course of treatment with the medications for as many countries as possible. Sources of reference were the Pharma Price Information service of the Austrian public health institute Gesundheit Österreich GmbH, national government and drug reimbursement authority website, and press releases.
Using data compiled between July 17, 2015, and Jan. 25, 2016, medication prices in Organisation for Economic Co-operation and Development (OECD) member countries and certain low- and middle-income countries were converted to U.S. dollars using period average exchange rates and were adjusted for purchasing power parity (PPP). “We analyzed prices compared to national economic performance and estimated market size and the cost of these drugs in terms of countries’ annual total pharmaceutical expenditure (TPE) and in terms of the duration of time an individual would need to work to pay for treatment out of pocket,” the researchers explained. “Patient affordability was calculated using 2014 OECD average annual wages, supplemented International Labour Organization median wages where necessary.”
Dr. Sullivan and her associates found that HCV medication prices varied significantly across countries, especially when adjusted for national wealth. For example, the median price of a 12-week course of sofosbuvir across 26 OECD countries was $42,017 in U.S. dollars, ranging from $37,729 in Japan to $64,680 in the United States. At the same time, countries in central and eastern Europe had higher PPP-adjusted prices, compared with other countries. For example, the PPP-adjusted prices of sofosbuvir in Poland and Turkey were $101,063 and $70,331, respectively, compared with a price of $64,680 in the Unite States. At the same time, the PPP-adjusted price of ledipasvir/sofosbuvir in Poland was $118,754, compared with a price of $72,765 in the United States.
The researchers also found that the PPP-adjusted price of a full course of sofosbuvir alone would be equivalent to at least 1 year of the PPP-adjusted average earnings for individuals in 12 of the 30 countries analyzed. In Poland, Slovakia, Portugal, and Turkey, a course of sofosbuvir alone would cost at least 2 years’ of average annual wages. “This analysis is conservative because prices were ex-factory prices with an assumed 23% price reduction, and did not include supply chain mark-ups and other costs such as the cost of diagnosis, daclatasvir, ribavirin, and health service costs,” they wrote.
They characterized the costs of sofosbuvir and ledipasvir/sofosbuvir as “not ‘affordable’ for most OECD countries at the nominal and PPP-adjusted prices, with Central and Eastern European countries being the most affected. While determining what is affordable or not is a value judgment, funding these treatments in these national health systems would consume large proportions of their TPE and increase pressure on existing budgets.”
They acknowledged certain limitations of the analysis, including the accuracy of the estimates of the numbers of people infected and of the price information that was accessible. “We have also not included all likely costs, such as the costs of combination treatment with ribavirin, other health care services, and increases in the duration of treatment in patients with cirrhosis; thus, our budget impact estimates are underestimates of the cost of treatment. We are also aware that in some countries, the prices are probably lower than the publicly accessible prices because of confidential discounts or rebates negotiated with the manufacturer.”
Dr. Hill disclosed that she is a member of the PLoS Medicine editorial board.
FROM PLoS MEDICINE
Key clinical point: Current prices of new medicines for hepatitis C virus are variable and unaffordable globally.
Major finding: The median price of a 12-week course of sofosbuvir across 26 OECD countries was $42,017 in U.S. dollars, ranging from $37,729 in Japan to $64,680 in the United States.
Data source: An economic analysis of prices, costs, and affordability of new medicines for HCV in 30 countries .
Disclosures: Dr. Hill disclosed that she is a member of the PLoS Medicine editorial board.