Hepatology

BOSTON – For almost half of patients with nonalcoholic steatohepatitis (NASH), bariatric surgery does not resolve severe fibrosis, even after significant weight loss and resolution of multiple metabolic comorbidities, according to investigators.

Still, bariatric surgery was highly effective at improving liver histology in patients without severe fibrosis, reported lead author Raluca Pais, MD, of Sorbonne University, Paris, and colleagues.

“There are many targeted agents for NASH at this time, but their response rate is limited to less than 30%,” Dr. Pais said in a presentation at the annual meeting of the American Association for the Study of Liver Diseases. “In very selective patients, bariatric surgery is a very attractive therapeutic option, as it promotes massive weight loss and sustained improvement in metabolic comorbidities, which are concomitant with very high rates of hepatic histological improvement in most but not all patients.” Despite the known benefits of bariatric surgery, histologic outcomes have been minimally studied, Dr. Pais said, which prompted the present trial.

The investigators began by analyzing data from 868 patients with NASH who underwent bariatric surgery with perioperative liver biopsy between 2004 and 2014. Of these patients, 181 had advanced NASH, a diagnosis that was subclassified by severe fibrosis (F3 or F4) or high activity (steatosis, activity, and fibrosis score of 3-4 with F0-2). Out of the 181 patients with advanced NASH, 65 consented to follow-up liver biopsy, which was conducted a mean of 6 years after surgery. Among these patients, 53 had undergone gastric bypass surgery, while 12 had undergone sleeve gastrectomy.

Almost one-third (29%) of the 65 patients who underwent bariatric surgery had normal livers at follow-up biopsy. Among the 35 patients who had severe fibrosis at baseline, slightly more than half (54%) had resolution of severe fibrosis. In contrast, resolution of high activity occurred in almost all affected patients (97%).

While the findings highlighted some of the benefits associated with bariatric surgery, Dr. Pais emphasized the other side of the coin; many patients did not have resolution of severe fibrosis, even years after surgery. Specifically, 45% of patients had persistent severe fibrosis at follow-up biopsy, despite improvements in comorbidities. On average, these patients lost 23% of their baseline body weight, and two-thirds of the group achieved normal ALT and resolution of NASH. Many also had improvements in insulin resistance and nonalcoholic fatty liver disease activity scores. These findings suggest that changes in severe fibrosis occur independently of many other improvements, Dr. Pais said.

Although multiple comorbidities were not correlated with changes in severe fibrosis, several other predictors were identified. Compared with patients who had resolution of severe fibrosis, nonresponders were typically older (56 vs. 49 years), more often had persistent diabetes (79% vs. 50%), and generally had shorter time between surgery and follow-up biopsy (4.2 vs. 7.5 years). Compared with nonresponders, responders were more likely to have undergone gastric bypass surgery (100% vs. 69%), suggesting that this procedure was more effective at resolving severe fibrosis than sleeve gastrectomy.

During the question-and-answer session following the presentation, multiple conference attendees suggested that the title of the study, “Persistence of severe liver fibrosis despite substantial weight loss with bariatric surgery,” was unnecessarily negative, when in fact the study offered strong support for bariatric surgery.

“This is wonderful data that shows surgery is very effective,” one attendee said.

“This is really positive data,” said another. “I mean, you’ve got reversal of advanced fibrosis in half of the population by the time you follow up for several years, so I would say this is really, very positive data.”

The investigators disclosed relationships with Allergan, Boehringer Ingelheim, Novo Nordisk, and others.

*This story was updated on November 15, 2019.

SOURCE: Pais R et al. The Liver Meeting 2019, Abstract 66.

BOSTON – For almost half of patients with nonalcoholic steatohepatitis (NASH), bariatric surgery does not resolve severe fibrosis, even after significant weight loss and resolution of multiple metabolic comorbidities, according to investigators.

Still, bariatric surgery was highly effective at improving liver histology in patients without severe fibrosis, reported lead author Raluca Pais, MD, of Sorbonne University, Paris, and colleagues.

“There are many targeted agents for NASH at this time, but their response rate is limited to less than 30%,” Dr. Pais said in a presentation at the annual meeting of the American Association for the Study of Liver Diseases. “In very selective patients, bariatric surgery is a very attractive therapeutic option, as it promotes massive weight loss and sustained improvement in metabolic comorbidities, which are concomitant with very high rates of hepatic histological improvement in most but not all patients.” Despite the known benefits of bariatric surgery, histologic outcomes have been minimally studied, Dr. Pais said, which prompted the present trial.

The investigators began by analyzing data from 868 patients with NASH who underwent bariatric surgery with perioperative liver biopsy between 2004 and 2014. Of these patients, 181 had advanced NASH, a diagnosis that was subclassified by severe fibrosis (F3 or F4) or high activity (steatosis, activity, and fibrosis score of 3-4 with F0-2). Out of the 181 patients with advanced NASH, 65 consented to follow-up liver biopsy, which was conducted a mean of 6 years after surgery. Among these patients, 53 had undergone gastric bypass surgery, while 12 had undergone sleeve gastrectomy.

Almost one-third (29%) of the 65 patients who underwent bariatric surgery had normal livers at follow-up biopsy. Among the 35 patients who had severe fibrosis at baseline, slightly more than half (54%) had resolution of severe fibrosis. In contrast, resolution of high activity occurred in almost all affected patients (97%).

While the findings highlighted some of the benefits associated with bariatric surgery, Dr. Pais emphasized the other side of the coin; many patients did not have resolution of severe fibrosis, even years after surgery. Specifically, 45% of patients had persistent severe fibrosis at follow-up biopsy, despite improvements in comorbidities. On average, these patients lost 23% of their baseline body weight, and two-thirds of the group achieved normal ALT and resolution of NASH. Many also had improvements in insulin resistance and nonalcoholic fatty liver disease activity scores. These findings suggest that changes in severe fibrosis occur independently of many other improvements, Dr. Pais said.

Although multiple comorbidities were not correlated with changes in severe fibrosis, several other predictors were identified. Compared with patients who had resolution of severe fibrosis, nonresponders were typically older (56 vs. 49 years), more often had persistent diabetes (79% vs. 50%), and generally had shorter time between surgery and follow-up biopsy (4.2 vs. 7.5 years). Compared with nonresponders, responders were more likely to have undergone gastric bypass surgery (100% vs. 69%), suggesting that this procedure was more effective at resolving severe fibrosis than sleeve gastrectomy.

During the question-and-answer session following the presentation, multiple conference attendees suggested that the title of the study, “Persistence of severe liver fibrosis despite substantial weight loss with bariatric surgery,” was unnecessarily negative, when in fact the study offered strong support for bariatric surgery.

“This is wonderful data that shows surgery is very effective,” one attendee said.

“This is really positive data,” said another. “I mean, you’ve got reversal of advanced fibrosis in half of the population by the time you follow up for several years, so I would say this is really, very positive data.”

The investigators disclosed relationships with Allergan, Boehringer Ingelheim, Novo Nordisk, and others.

*This story was updated on November 15, 2019.

SOURCE: Pais R et al. The Liver Meeting 2019, Abstract 66.

BOSTON – For almost half of patients with nonalcoholic steatohepatitis (NASH), bariatric surgery does not resolve severe fibrosis, even after significant weight loss and resolution of multiple metabolic comorbidities, according to investigators.

Still, bariatric surgery was highly effective at improving liver histology in patients without severe fibrosis, reported lead author Raluca Pais, MD, of Sorbonne University, Paris, and colleagues.

“There are many targeted agents for NASH at this time, but their response rate is limited to less than 30%,” Dr. Pais said in a presentation at the annual meeting of the American Association for the Study of Liver Diseases. “In very selective patients, bariatric surgery is a very attractive therapeutic option, as it promotes massive weight loss and sustained improvement in metabolic comorbidities, which are concomitant with very high rates of hepatic histological improvement in most but not all patients.” Despite the known benefits of bariatric surgery, histologic outcomes have been minimally studied, Dr. Pais said, which prompted the present trial.

The investigators began by analyzing data from 868 patients with NASH who underwent bariatric surgery with perioperative liver biopsy between 2004 and 2014. Of these patients, 181 had advanced NASH, a diagnosis that was subclassified by severe fibrosis (F3 or F4) or high activity (steatosis, activity, and fibrosis score of 3-4 with F0-2). Out of the 181 patients with advanced NASH, 65 consented to follow-up liver biopsy, which was conducted a mean of 6 years after surgery. Among these patients, 53 had undergone gastric bypass surgery, while 12 had undergone sleeve gastrectomy.

Almost one-third (29%) of the 65 patients who underwent bariatric surgery had normal livers at follow-up biopsy. Among the 35 patients who had severe fibrosis at baseline, slightly more than half (54%) had resolution of severe fibrosis. In contrast, resolution of high activity occurred in almost all affected patients (97%).

While the findings highlighted some of the benefits associated with bariatric surgery, Dr. Pais emphasized the other side of the coin; many patients did not have resolution of severe fibrosis, even years after surgery. Specifically, 45% of patients had persistent severe fibrosis at follow-up biopsy, despite improvements in comorbidities. On average, these patients lost 23% of their baseline body weight, and two-thirds of the group achieved normal ALT and resolution of NASH. Many also had improvements in insulin resistance and nonalcoholic fatty liver disease activity scores. These findings suggest that changes in severe fibrosis occur independently of many other improvements, Dr. Pais said.

Although multiple comorbidities were not correlated with changes in severe fibrosis, several other predictors were identified. Compared with patients who had resolution of severe fibrosis, nonresponders were typically older (56 vs. 49 years), more often had persistent diabetes (79% vs. 50%), and generally had shorter time between surgery and follow-up biopsy (4.2 vs. 7.5 years). Compared with nonresponders, responders were more likely to have undergone gastric bypass surgery (100% vs. 69%), suggesting that this procedure was more effective at resolving severe fibrosis than sleeve gastrectomy.

During the question-and-answer session following the presentation, multiple conference attendees suggested that the title of the study, “Persistence of severe liver fibrosis despite substantial weight loss with bariatric surgery,” was unnecessarily negative, when in fact the study offered strong support for bariatric surgery.

“This is wonderful data that shows surgery is very effective,” one attendee said.

“This is really positive data,” said another. “I mean, you’ve got reversal of advanced fibrosis in half of the population by the time you follow up for several years, so I would say this is really, very positive data.”

The investigators disclosed relationships with Allergan, Boehringer Ingelheim, Novo Nordisk, and others.

*This story was updated on November 15, 2019.

SOURCE: Pais R et al. The Liver Meeting 2019, Abstract 66.

BOSTON – For patients with a complete response following treatment for hepatitis C virus (HCV)–related hepatocellular carcinoma (HCC), treatment with direct-acting antiviral therapy was linked to significantly reduced mortality compared with no such treatment, according to results of a large cohort study.

UT Southwestern Medical Center

The mortality benefit associated with direct-acting antiviral (DAA) therapy was consistent across most subgroups, suggesting that the association was driven by achieving sustained virological response (SVR), according to Amit G. Singal, MD, associate professor of medicine at UT Southwestern Medical Center, Dallas.

Those results suggest that DAA therapy in patients with a history of HCC is not only safe, but is also beneficial, Dr. Singal said at the annual meeting of the American Association for the Study of Liver Diseases.

“To be slightly controversial, I think that this changes the paradigm in this subgroup of patients from ‘can be treated’ for their hepatitis C to ‘should be treated,’ ” he concluded in an oral presentation of the results.

While DAA treatment is proven to reduce risk of incident HCC in patients with cirrhosis, the risk-benefit ratio is “less clear” in patients with a history of HCC following complete response, according to Dr. Singal.

Moreover, concerns were raised about the safety of DAA therapy in patients with an HCC history, after early data suggested a potentially higher recurrence risk, he added.

In the current multicenter, retrospective North American cohort study, Dr. Singal and colleagues reviewed data for 797 patients with HCV–related HCC who achieved complete response following ablation, resection, radiotherapy, transarterial chemoembolization, or transarterial radioembolization.

Treatment with DAA therapy was associated with improved overall survival, according to results of multivariable analysis, with a hazard ratio of 0.54 (95% confidence interval, 0.33-0.90). Median time from HCC complete response to death was 25.7 months for the DAA treatment group, versus 11.5 months for the untreated group.

The association between DAA treatment and death was apparently driven by SVR, as reduced mortality was seen in the DAA-treated patients who did achieve SVR, but not in those without SVR, Dr. Singal reported.

While these findings together suggest that DAA treatment is linked to reduced mortality after HCC complete response, prospective studies are needed to confirm this association, Dr. Singal said.

Dr. Singal reported disclosures related to AbbVie, Bayer, BMS, Eisai, Exact Sciences, Exelixis, Genentech, Gilead FOCUS, Glycotest, GRAIL, Merck, Roche, TARGET Pharmasolutions, and Wako Diagnostics.
 

SOURCE: Singal AG et al. The Liver Meeting 2019, Abstract 199.

BOSTON – For patients with a complete response following treatment for hepatitis C virus (HCV)–related hepatocellular carcinoma (HCC), treatment with direct-acting antiviral therapy was linked to significantly reduced mortality compared with no such treatment, according to results of a large cohort study.

UT Southwestern Medical Center

The mortality benefit associated with direct-acting antiviral (DAA) therapy was consistent across most subgroups, suggesting that the association was driven by achieving sustained virological response (SVR), according to Amit G. Singal, MD, associate professor of medicine at UT Southwestern Medical Center, Dallas.

Those results suggest that DAA therapy in patients with a history of HCC is not only safe, but is also beneficial, Dr. Singal said at the annual meeting of the American Association for the Study of Liver Diseases.

“To be slightly controversial, I think that this changes the paradigm in this subgroup of patients from ‘can be treated’ for their hepatitis C to ‘should be treated,’ ” he concluded in an oral presentation of the results.

While DAA treatment is proven to reduce risk of incident HCC in patients with cirrhosis, the risk-benefit ratio is “less clear” in patients with a history of HCC following complete response, according to Dr. Singal.

Moreover, concerns were raised about the safety of DAA therapy in patients with an HCC history, after early data suggested a potentially higher recurrence risk, he added.

In the current multicenter, retrospective North American cohort study, Dr. Singal and colleagues reviewed data for 797 patients with HCV–related HCC who achieved complete response following ablation, resection, radiotherapy, transarterial chemoembolization, or transarterial radioembolization.

Treatment with DAA therapy was associated with improved overall survival, according to results of multivariable analysis, with a hazard ratio of 0.54 (95% confidence interval, 0.33-0.90). Median time from HCC complete response to death was 25.7 months for the DAA treatment group, versus 11.5 months for the untreated group.

The association between DAA treatment and death was apparently driven by SVR, as reduced mortality was seen in the DAA-treated patients who did achieve SVR, but not in those without SVR, Dr. Singal reported.

While these findings together suggest that DAA treatment is linked to reduced mortality after HCC complete response, prospective studies are needed to confirm this association, Dr. Singal said.

Dr. Singal reported disclosures related to AbbVie, Bayer, BMS, Eisai, Exact Sciences, Exelixis, Genentech, Gilead FOCUS, Glycotest, GRAIL, Merck, Roche, TARGET Pharmasolutions, and Wako Diagnostics.
 

SOURCE: Singal AG et al. The Liver Meeting 2019, Abstract 199.

BOSTON – For patients with a complete response following treatment for hepatitis C virus (HCV)–related hepatocellular carcinoma (HCC), treatment with direct-acting antiviral therapy was linked to significantly reduced mortality compared with no such treatment, according to results of a large cohort study.

UT Southwestern Medical Center

The mortality benefit associated with direct-acting antiviral (DAA) therapy was consistent across most subgroups, suggesting that the association was driven by achieving sustained virological response (SVR), according to Amit G. Singal, MD, associate professor of medicine at UT Southwestern Medical Center, Dallas.

Those results suggest that DAA therapy in patients with a history of HCC is not only safe, but is also beneficial, Dr. Singal said at the annual meeting of the American Association for the Study of Liver Diseases.

“To be slightly controversial, I think that this changes the paradigm in this subgroup of patients from ‘can be treated’ for their hepatitis C to ‘should be treated,’ ” he concluded in an oral presentation of the results.

While DAA treatment is proven to reduce risk of incident HCC in patients with cirrhosis, the risk-benefit ratio is “less clear” in patients with a history of HCC following complete response, according to Dr. Singal.

Moreover, concerns were raised about the safety of DAA therapy in patients with an HCC history, after early data suggested a potentially higher recurrence risk, he added.

In the current multicenter, retrospective North American cohort study, Dr. Singal and colleagues reviewed data for 797 patients with HCV–related HCC who achieved complete response following ablation, resection, radiotherapy, transarterial chemoembolization, or transarterial radioembolization.

Treatment with DAA therapy was associated with improved overall survival, according to results of multivariable analysis, with a hazard ratio of 0.54 (95% confidence interval, 0.33-0.90). Median time from HCC complete response to death was 25.7 months for the DAA treatment group, versus 11.5 months for the untreated group.

The association between DAA treatment and death was apparently driven by SVR, as reduced mortality was seen in the DAA-treated patients who did achieve SVR, but not in those without SVR, Dr. Singal reported.

While these findings together suggest that DAA treatment is linked to reduced mortality after HCC complete response, prospective studies are needed to confirm this association, Dr. Singal said.

Dr. Singal reported disclosures related to AbbVie, Bayer, BMS, Eisai, Exact Sciences, Exelixis, Genentech, Gilead FOCUS, Glycotest, GRAIL, Merck, Roche, TARGET Pharmasolutions, and Wako Diagnostics.
 

SOURCE: Singal AG et al. The Liver Meeting 2019, Abstract 199.

BOSTON – Kratom, a botanical product with opioid-like activity, is increasingly responsible for cases of liver injury in the United States, according to investigators.

Will Pass/MDedge News

Kratom-associated liver damage involves a mixed pattern of hepatocellular and cholestatic injury that typically occurs after about 2-6 weeks of use, reported lead author Victor J. Navarro, MD, division head of gastroenterology at Einstein Healthcare Network in Philadelphia, and colleagues.

“I think it’s important for clinicians to have heightened awareness of the abuse potential [of kratom], because it is an opioid agonist and [because of] its capacity to cause liver injury,” Dr. Navarro said.

Kratom acts as a stimulant at low doses, while higher doses have sedating and narcotic properties. These effects are attributed to several alkaloids found in kratom’s source plant, Mitragyna speciose, of which mitragynine, a suspected opioid agonist, is most common.

Presenting at the annual meeting of the American Association for the Study of Liver Diseases, Dr. Navarro cited figures from the National Poison Data System that suggest an upward trend in kratom usage in the United States, from very little use in 2011 to 1 exposure per million people in 2014 and more recently to slightly more than 2.5 exposures per million people in 2017, predominantly among individuals aged 20 years and older. According to the Centers for Disease Control and Prevention, more than 90 kratom-associated deaths occurred between July 2016 and December 2017. Because of growing concerns, the Food and Drug Administration has issued multiple public warnings about kratom, ranging from products contaminated with Salmonella and heavy metals, to adverse effects such as seizures and liver toxicity.

The present study aimed to characterize kratom-associated liver injury through a case series analysis. First, the investigators reviewed 404 cases of herbal and dietary supplement-associated liver injury from the Drug-Induced Liver Injury Network prospective study. They found 11 suspected cases of kratom-related liver injury, with an upward trend in recent years. At this time, seven of the cases have been adjudicated by an expert panel and confirmed to be highly likely or probably associated with kratom.

Of these seven cases, all patients were hospitalized, although all recovered without need for liver transplant. Patients presented after a median of 15 days of kratom use, with a 28-day symptom latency period. However, Dr. Navarro noted that some cases presented after just 5 days of use. The most common presenting symptom was itching (86%), followed by jaundice (71%), abdominal pain (71%), nausea (57%), and fever (43%). Blood work revealed a mixed hepatocellular and cholestatic pattern. Median peak ALT was 362 U/L, peak alkaline phosphatase was 294 U/L, and peak total bilirubin was 20.1 mg/dL. Despite these changes, patients did not have significant liver dysfunction, such as coagulopathy.

Following this clinical characterization, Dr. Navarro reviewed existing toxicity data. Rat studies suggest that kratom is safe at doses between 1-10 mg/kg, while toxicity occurs after prolonged exposure to more than 100 mg/kg. A cross-sectional human study reported that kratom was safe at doses up to 75 mg/day. However, in the present case series, some patients presented after ingesting as little as 0.66 mg/day, and Dr. Navarro pointed out wide variations in product concentrations of mitragynine.

“Certainly, we need more human toxicity studies to determine what a safe dose really is, because this product is not going away,” Dr. Navarro said.

The investigators disclosed relationships with Gilead, Bristol-Myers Squibb, Sanofi, and others.

SOURCE: Navarro VJ et al. The Liver Meeting 2019, Abstract 212.

BOSTON – Kratom, a botanical product with opioid-like activity, is increasingly responsible for cases of liver injury in the United States, according to investigators.

Will Pass/MDedge News

Kratom-associated liver damage involves a mixed pattern of hepatocellular and cholestatic injury that typically occurs after about 2-6 weeks of use, reported lead author Victor J. Navarro, MD, division head of gastroenterology at Einstein Healthcare Network in Philadelphia, and colleagues.

“I think it’s important for clinicians to have heightened awareness of the abuse potential [of kratom], because it is an opioid agonist and [because of] its capacity to cause liver injury,” Dr. Navarro said.

Kratom acts as a stimulant at low doses, while higher doses have sedating and narcotic properties. These effects are attributed to several alkaloids found in kratom’s source plant, Mitragyna speciose, of which mitragynine, a suspected opioid agonist, is most common.

Presenting at the annual meeting of the American Association for the Study of Liver Diseases, Dr. Navarro cited figures from the National Poison Data System that suggest an upward trend in kratom usage in the United States, from very little use in 2011 to 1 exposure per million people in 2014 and more recently to slightly more than 2.5 exposures per million people in 2017, predominantly among individuals aged 20 years and older. According to the Centers for Disease Control and Prevention, more than 90 kratom-associated deaths occurred between July 2016 and December 2017. Because of growing concerns, the Food and Drug Administration has issued multiple public warnings about kratom, ranging from products contaminated with Salmonella and heavy metals, to adverse effects such as seizures and liver toxicity.

The present study aimed to characterize kratom-associated liver injury through a case series analysis. First, the investigators reviewed 404 cases of herbal and dietary supplement-associated liver injury from the Drug-Induced Liver Injury Network prospective study. They found 11 suspected cases of kratom-related liver injury, with an upward trend in recent years. At this time, seven of the cases have been adjudicated by an expert panel and confirmed to be highly likely or probably associated with kratom.

Of these seven cases, all patients were hospitalized, although all recovered without need for liver transplant. Patients presented after a median of 15 days of kratom use, with a 28-day symptom latency period. However, Dr. Navarro noted that some cases presented after just 5 days of use. The most common presenting symptom was itching (86%), followed by jaundice (71%), abdominal pain (71%), nausea (57%), and fever (43%). Blood work revealed a mixed hepatocellular and cholestatic pattern. Median peak ALT was 362 U/L, peak alkaline phosphatase was 294 U/L, and peak total bilirubin was 20.1 mg/dL. Despite these changes, patients did not have significant liver dysfunction, such as coagulopathy.

Following this clinical characterization, Dr. Navarro reviewed existing toxicity data. Rat studies suggest that kratom is safe at doses between 1-10 mg/kg, while toxicity occurs after prolonged exposure to more than 100 mg/kg. A cross-sectional human study reported that kratom was safe at doses up to 75 mg/day. However, in the present case series, some patients presented after ingesting as little as 0.66 mg/day, and Dr. Navarro pointed out wide variations in product concentrations of mitragynine.

“Certainly, we need more human toxicity studies to determine what a safe dose really is, because this product is not going away,” Dr. Navarro said.

The investigators disclosed relationships with Gilead, Bristol-Myers Squibb, Sanofi, and others.

SOURCE: Navarro VJ et al. The Liver Meeting 2019, Abstract 212.

BOSTON – Kratom, a botanical product with opioid-like activity, is increasingly responsible for cases of liver injury in the United States, according to investigators.

Will Pass/MDedge News

Kratom-associated liver damage involves a mixed pattern of hepatocellular and cholestatic injury that typically occurs after about 2-6 weeks of use, reported lead author Victor J. Navarro, MD, division head of gastroenterology at Einstein Healthcare Network in Philadelphia, and colleagues.

“I think it’s important for clinicians to have heightened awareness of the abuse potential [of kratom], because it is an opioid agonist and [because of] its capacity to cause liver injury,” Dr. Navarro said.

Kratom acts as a stimulant at low doses, while higher doses have sedating and narcotic properties. These effects are attributed to several alkaloids found in kratom’s source plant, Mitragyna speciose, of which mitragynine, a suspected opioid agonist, is most common.

Presenting at the annual meeting of the American Association for the Study of Liver Diseases, Dr. Navarro cited figures from the National Poison Data System that suggest an upward trend in kratom usage in the United States, from very little use in 2011 to 1 exposure per million people in 2014 and more recently to slightly more than 2.5 exposures per million people in 2017, predominantly among individuals aged 20 years and older. According to the Centers for Disease Control and Prevention, more than 90 kratom-associated deaths occurred between July 2016 and December 2017. Because of growing concerns, the Food and Drug Administration has issued multiple public warnings about kratom, ranging from products contaminated with Salmonella and heavy metals, to adverse effects such as seizures and liver toxicity.

The present study aimed to characterize kratom-associated liver injury through a case series analysis. First, the investigators reviewed 404 cases of herbal and dietary supplement-associated liver injury from the Drug-Induced Liver Injury Network prospective study. They found 11 suspected cases of kratom-related liver injury, with an upward trend in recent years. At this time, seven of the cases have been adjudicated by an expert panel and confirmed to be highly likely or probably associated with kratom.

Of these seven cases, all patients were hospitalized, although all recovered without need for liver transplant. Patients presented after a median of 15 days of kratom use, with a 28-day symptom latency period. However, Dr. Navarro noted that some cases presented after just 5 days of use. The most common presenting symptom was itching (86%), followed by jaundice (71%), abdominal pain (71%), nausea (57%), and fever (43%). Blood work revealed a mixed hepatocellular and cholestatic pattern. Median peak ALT was 362 U/L, peak alkaline phosphatase was 294 U/L, and peak total bilirubin was 20.1 mg/dL. Despite these changes, patients did not have significant liver dysfunction, such as coagulopathy.

Following this clinical characterization, Dr. Navarro reviewed existing toxicity data. Rat studies suggest that kratom is safe at doses between 1-10 mg/kg, while toxicity occurs after prolonged exposure to more than 100 mg/kg. A cross-sectional human study reported that kratom was safe at doses up to 75 mg/day. However, in the present case series, some patients presented after ingesting as little as 0.66 mg/day, and Dr. Navarro pointed out wide variations in product concentrations of mitragynine.

“Certainly, we need more human toxicity studies to determine what a safe dose really is, because this product is not going away,” Dr. Navarro said.

The investigators disclosed relationships with Gilead, Bristol-Myers Squibb, Sanofi, and others.

SOURCE: Navarro VJ et al. The Liver Meeting 2019, Abstract 212.

BOSTON – A short course of direct-acting antiviral therapy combined with ezetimibe prevented or rapidly cured hepatitis C virus infection in transplant recipients receiving organs from infected donors, results of a recent study show.

The regimen, given right before transplantation and for 7 days afterward, reduced the cost of direct-acting antiviral (DAA) therapy and allowed patients to complete hepatitis C virus (HCV) therapy before hospital discharge, according to authors of the study, which was presented at the annual meeting of the American Association for the Study of Liver Diseases.

If confirmed in subsequent studies, this regimen could become the standard of care for donor-positive, recipient-negative transplantation, said lead study author Jordan J. Feld, MD, R. Phelan Chair in translational liver disease research at the University of Toronto and research director at the Toronto Centre for Liver Disease.

“Transplant recipients are understandably nervous about accepting organs from people with HCV infection,” said Dr. Feld in a press release. “This very short therapy allows them to leave hospital free of HCV, which is a huge benefit. Not only is it cheaper and likely safer, but the patients really prefer not having to worry about HCV with all of the other challenges after a transplant.”

Results of this study come at a time when the proportion of overdose death organ donors is on the rise, from just 1% in 2000 to 15% in 2016, according to Dr. Feld. Overdose deaths account for the largest percentage of HCV-infected donors, most of whom are young and often otherwise healthy, he added.

Recipients of HCV-infected organs can be cured after transplant as a number of studies have previously shown. However, preventing transmission would be better than cure, Dr. Feld said, in part because of issues with drug-drug interactions, potential for relapse, and issues with procuring the drugs after transplant.

Accordingly, Dr. Feld and colleagues sought to evaluate “preemptive” treatment with DAA therapy combined with ezetimibe, which they said has been shown to inhibit HCV entry blockers. The recipients, who were listed for heart, lung, kidney, or kidney-pancreas transplant, were given glecaprevir/pibrentasvir plus ezetimibe starting 6-12 hours prior to transplantation, and then daily for 7 days.

The median age was 36 years for the 16 donors reported, and 61 years for the 25 recipients. Most recipients (12 patients) had a lung transplant, while 8 had a heart transplant, 4 had a kidney transplant, and 1 had a kidney-pancreas transplant.

There were no virologic failures, according to the investigators, with sustained virologic response (SVR) after 6 weeks in 7 patients, and SVR after 12 weeks in the remaining 18. Three recipients did have detectable HCV RNA, though all cleared and had SVR at 6 weeks in one case, and SVR at 12 weeks in the other two, according to the investigators’ report.

Of 22 serious adverse events noted in the study, 1 was considered treatment related, according to the report, and there were 2 deaths among lung transplant patients, caused by sepsis in 1 case to sepsis and subarachnoid hemorrhage in another.

It’s not clear whether ezetimibe is needed in this short-duration regimen, but in any case, it is well tolerated and inexpensive, and so there is “minimal downside” to include it, Dr. Feld and coinvestigators wrote in their report.

Dr. Feld reported disclosures related to Abbvie, Abbott, Enanta Pharmaceuticals, Gilead, Janssen, Merck, and Roche.

SOURCE: Feld JJ et al. The Liver Meeting 2019, Abstract 38.

BOSTON – A short course of direct-acting antiviral therapy combined with ezetimibe prevented or rapidly cured hepatitis C virus infection in transplant recipients receiving organs from infected donors, results of a recent study show.

The regimen, given right before transplantation and for 7 days afterward, reduced the cost of direct-acting antiviral (DAA) therapy and allowed patients to complete hepatitis C virus (HCV) therapy before hospital discharge, according to authors of the study, which was presented at the annual meeting of the American Association for the Study of Liver Diseases.

If confirmed in subsequent studies, this regimen could become the standard of care for donor-positive, recipient-negative transplantation, said lead study author Jordan J. Feld, MD, R. Phelan Chair in translational liver disease research at the University of Toronto and research director at the Toronto Centre for Liver Disease.

“Transplant recipients are understandably nervous about accepting organs from people with HCV infection,” said Dr. Feld in a press release. “This very short therapy allows them to leave hospital free of HCV, which is a huge benefit. Not only is it cheaper and likely safer, but the patients really prefer not having to worry about HCV with all of the other challenges after a transplant.”

Results of this study come at a time when the proportion of overdose death organ donors is on the rise, from just 1% in 2000 to 15% in 2016, according to Dr. Feld. Overdose deaths account for the largest percentage of HCV-infected donors, most of whom are young and often otherwise healthy, he added.

Recipients of HCV-infected organs can be cured after transplant as a number of studies have previously shown. However, preventing transmission would be better than cure, Dr. Feld said, in part because of issues with drug-drug interactions, potential for relapse, and issues with procuring the drugs after transplant.

Accordingly, Dr. Feld and colleagues sought to evaluate “preemptive” treatment with DAA therapy combined with ezetimibe, which they said has been shown to inhibit HCV entry blockers. The recipients, who were listed for heart, lung, kidney, or kidney-pancreas transplant, were given glecaprevir/pibrentasvir plus ezetimibe starting 6-12 hours prior to transplantation, and then daily for 7 days.

The median age was 36 years for the 16 donors reported, and 61 years for the 25 recipients. Most recipients (12 patients) had a lung transplant, while 8 had a heart transplant, 4 had a kidney transplant, and 1 had a kidney-pancreas transplant.

There were no virologic failures, according to the investigators, with sustained virologic response (SVR) after 6 weeks in 7 patients, and SVR after 12 weeks in the remaining 18. Three recipients did have detectable HCV RNA, though all cleared and had SVR at 6 weeks in one case, and SVR at 12 weeks in the other two, according to the investigators’ report.

Of 22 serious adverse events noted in the study, 1 was considered treatment related, according to the report, and there were 2 deaths among lung transplant patients, caused by sepsis in 1 case to sepsis and subarachnoid hemorrhage in another.

It’s not clear whether ezetimibe is needed in this short-duration regimen, but in any case, it is well tolerated and inexpensive, and so there is “minimal downside” to include it, Dr. Feld and coinvestigators wrote in their report.

Dr. Feld reported disclosures related to Abbvie, Abbott, Enanta Pharmaceuticals, Gilead, Janssen, Merck, and Roche.

SOURCE: Feld JJ et al. The Liver Meeting 2019, Abstract 38.

BOSTON – A short course of direct-acting antiviral therapy combined with ezetimibe prevented or rapidly cured hepatitis C virus infection in transplant recipients receiving organs from infected donors, results of a recent study show.

The regimen, given right before transplantation and for 7 days afterward, reduced the cost of direct-acting antiviral (DAA) therapy and allowed patients to complete hepatitis C virus (HCV) therapy before hospital discharge, according to authors of the study, which was presented at the annual meeting of the American Association for the Study of Liver Diseases.

If confirmed in subsequent studies, this regimen could become the standard of care for donor-positive, recipient-negative transplantation, said lead study author Jordan J. Feld, MD, R. Phelan Chair in translational liver disease research at the University of Toronto and research director at the Toronto Centre for Liver Disease.

“Transplant recipients are understandably nervous about accepting organs from people with HCV infection,” said Dr. Feld in a press release. “This very short therapy allows them to leave hospital free of HCV, which is a huge benefit. Not only is it cheaper and likely safer, but the patients really prefer not having to worry about HCV with all of the other challenges after a transplant.”

Results of this study come at a time when the proportion of overdose death organ donors is on the rise, from just 1% in 2000 to 15% in 2016, according to Dr. Feld. Overdose deaths account for the largest percentage of HCV-infected donors, most of whom are young and often otherwise healthy, he added.

Recipients of HCV-infected organs can be cured after transplant as a number of studies have previously shown. However, preventing transmission would be better than cure, Dr. Feld said, in part because of issues with drug-drug interactions, potential for relapse, and issues with procuring the drugs after transplant.

Accordingly, Dr. Feld and colleagues sought to evaluate “preemptive” treatment with DAA therapy combined with ezetimibe, which they said has been shown to inhibit HCV entry blockers. The recipients, who were listed for heart, lung, kidney, or kidney-pancreas transplant, were given glecaprevir/pibrentasvir plus ezetimibe starting 6-12 hours prior to transplantation, and then daily for 7 days.

The median age was 36 years for the 16 donors reported, and 61 years for the 25 recipients. Most recipients (12 patients) had a lung transplant, while 8 had a heart transplant, 4 had a kidney transplant, and 1 had a kidney-pancreas transplant.

There were no virologic failures, according to the investigators, with sustained virologic response (SVR) after 6 weeks in 7 patients, and SVR after 12 weeks in the remaining 18. Three recipients did have detectable HCV RNA, though all cleared and had SVR at 6 weeks in one case, and SVR at 12 weeks in the other two, according to the investigators’ report.

Of 22 serious adverse events noted in the study, 1 was considered treatment related, according to the report, and there were 2 deaths among lung transplant patients, caused by sepsis in 1 case to sepsis and subarachnoid hemorrhage in another.

It’s not clear whether ezetimibe is needed in this short-duration regimen, but in any case, it is well tolerated and inexpensive, and so there is “minimal downside” to include it, Dr. Feld and coinvestigators wrote in their report.

Dr. Feld reported disclosures related to Abbvie, Abbott, Enanta Pharmaceuticals, Gilead, Janssen, Merck, and Roche.

SOURCE: Feld JJ et al. The Liver Meeting 2019, Abstract 38.

A high level of hepatitis B core–related antigen (HBcrAg) was a complementary risk factor for hepatocellular carcinoma, according to the results of a retrospective cohort study of more than 2,600 noncirrhotic adults with untreated hepatitis B virus (HBV) infection with a median of 16 years of follow-up.

SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION

“Patients with an intermediate viral load and high levels of HBcrAg had a risk for hepatocellular carcinoma that did not differ significantly from that of patients with a high viral load. [An] HBcrAg of 10 KU/mL may serve as a novel biomarker for the management of patients with intermediate viral load in our clinical practice,” wrote Tai-Chung Tseng, MD, PhD, of National Taiwan University Hospital in Taipei and associates in Gastroenterology.

Deciding whether to start antiviral therapy is controversial for some patients with HBV infection. Typically, monitoring without treatment is recommended for patients who have both low hepatitis B surface antigen levels (less than 1,000 IU/mL) and low levels of HBV DNA (less than 2,000 IU/mL), and early antiviral therapy is recommended for patients who have high levels of HBV DNA (20,000 IU/mL or more). However, there is no clear evidence that early antiviral therapy benefits patients who have intermediate levels of HBV DNA (2,000-19,999 IU/mL) and are negative for hepatitis B e antigen. Biomarkers for risk-stratifying these patients also are lacking, the researchers noted.

Therefore, they studied a cohort of 2,666 adults who had tested positive for hepatitis B surface antigen and were followed at National Taiwan University Hospital from 1985 through 2000. No patient had cirrhosis at baseline. In all, 209 patients developed hepatocellular carcinoma, yielding an incidence rate of 4.91 cases per 1,000 person-years.

Hepatitis B core–related antigen level remained an independent risk factor for hepatocellular carcinoma after accounting for age, sex, serum alanine aminotransferase (ALT) level, FIB-4 index, hepatitis B e antigen status, hepatitis B genotype (B, C, or undetermined), and HBV DNA level. Compared with patients whose HBcrAg level was less than 10 KU, a level of 10-99 KU/mL was associated with a nearly threefold increase in risk for hepatocellular carcinoma (HR, 2.93; 95% CI, 1.67-4.80), and this risk rose even further as HBcrAg levels increased.

In the subgroup of patients who tested negative for hepatitis B e antigen, had an intermediate HBV DNA load (2,000-19,999 IU/mL), and had a normal baseline ALT level (less than 40 U/L), a high HBcrAg level (10 KU/mL or more) was tied to a nearly fivefold greater risk for hepatocellular carcinoma (HR, 4.89; 95% CI, 2.18-10.93). This approximated the risk that is observed with high viral load (20,000 IU/mL), the researchers noted. In contrast, a low HBcrAg level was associated with a risk similar to that of minimal risk carriers (annual incidence rate, 0.10%; 95% CI, 0.04%-0.24%).

“To the best of our knowledge, this is the first study to report HBcrAg level as an independent viral biomarker to stratify hepatocellular risks in a large number of patients with intermediate viral load,” the researchers commented. Among the study limitations, 412 patients received antiviral therapy during follow-up. “This is a retrospective cohort study including Asian HBV patients with genotype B or C infection,” the investigators added. “It is unclear whether this finding could be extrapolated to populations with other HBV genotype infections. Nonetheless, we had a sound cohort, as several HBsAg-related clinical findings based on our cohort have already been validated by other prospective cohort studies, implying that our data were unlikely to be biased by the study design.”

Funders included National Taiwan University Hospital, the Ministry of Science and Technology, Executive Yuan in Taiwan, and National Health Research Institutes. The researchers reported having no conflicts of interest.

SOURCE: Tseng T-C et al. Gastroenterology. 2019 Aug 27. doi: 10.1053/j.gastro.2019.08.028.

A high level of hepatitis B core–related antigen (HBcrAg) was a complementary risk factor for hepatocellular carcinoma, according to the results of a retrospective cohort study of more than 2,600 noncirrhotic adults with untreated hepatitis B virus (HBV) infection with a median of 16 years of follow-up.

SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION

“Patients with an intermediate viral load and high levels of HBcrAg had a risk for hepatocellular carcinoma that did not differ significantly from that of patients with a high viral load. [An] HBcrAg of 10 KU/mL may serve as a novel biomarker for the management of patients with intermediate viral load in our clinical practice,” wrote Tai-Chung Tseng, MD, PhD, of National Taiwan University Hospital in Taipei and associates in Gastroenterology.

Deciding whether to start antiviral therapy is controversial for some patients with HBV infection. Typically, monitoring without treatment is recommended for patients who have both low hepatitis B surface antigen levels (less than 1,000 IU/mL) and low levels of HBV DNA (less than 2,000 IU/mL), and early antiviral therapy is recommended for patients who have high levels of HBV DNA (20,000 IU/mL or more). However, there is no clear evidence that early antiviral therapy benefits patients who have intermediate levels of HBV DNA (2,000-19,999 IU/mL) and are negative for hepatitis B e antigen. Biomarkers for risk-stratifying these patients also are lacking, the researchers noted.

Therefore, they studied a cohort of 2,666 adults who had tested positive for hepatitis B surface antigen and were followed at National Taiwan University Hospital from 1985 through 2000. No patient had cirrhosis at baseline. In all, 209 patients developed hepatocellular carcinoma, yielding an incidence rate of 4.91 cases per 1,000 person-years.

Hepatitis B core–related antigen level remained an independent risk factor for hepatocellular carcinoma after accounting for age, sex, serum alanine aminotransferase (ALT) level, FIB-4 index, hepatitis B e antigen status, hepatitis B genotype (B, C, or undetermined), and HBV DNA level. Compared with patients whose HBcrAg level was less than 10 KU, a level of 10-99 KU/mL was associated with a nearly threefold increase in risk for hepatocellular carcinoma (HR, 2.93; 95% CI, 1.67-4.80), and this risk rose even further as HBcrAg levels increased.

In the subgroup of patients who tested negative for hepatitis B e antigen, had an intermediate HBV DNA load (2,000-19,999 IU/mL), and had a normal baseline ALT level (less than 40 U/L), a high HBcrAg level (10 KU/mL or more) was tied to a nearly fivefold greater risk for hepatocellular carcinoma (HR, 4.89; 95% CI, 2.18-10.93). This approximated the risk that is observed with high viral load (20,000 IU/mL), the researchers noted. In contrast, a low HBcrAg level was associated with a risk similar to that of minimal risk carriers (annual incidence rate, 0.10%; 95% CI, 0.04%-0.24%).

“To the best of our knowledge, this is the first study to report HBcrAg level as an independent viral biomarker to stratify hepatocellular risks in a large number of patients with intermediate viral load,” the researchers commented. Among the study limitations, 412 patients received antiviral therapy during follow-up. “This is a retrospective cohort study including Asian HBV patients with genotype B or C infection,” the investigators added. “It is unclear whether this finding could be extrapolated to populations with other HBV genotype infections. Nonetheless, we had a sound cohort, as several HBsAg-related clinical findings based on our cohort have already been validated by other prospective cohort studies, implying that our data were unlikely to be biased by the study design.”

Funders included National Taiwan University Hospital, the Ministry of Science and Technology, Executive Yuan in Taiwan, and National Health Research Institutes. The researchers reported having no conflicts of interest.

SOURCE: Tseng T-C et al. Gastroenterology. 2019 Aug 27. doi: 10.1053/j.gastro.2019.08.028.

A high level of hepatitis B core–related antigen (HBcrAg) was a complementary risk factor for hepatocellular carcinoma, according to the results of a retrospective cohort study of more than 2,600 noncirrhotic adults with untreated hepatitis B virus (HBV) infection with a median of 16 years of follow-up.

SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION

“Patients with an intermediate viral load and high levels of HBcrAg had a risk for hepatocellular carcinoma that did not differ significantly from that of patients with a high viral load. [An] HBcrAg of 10 KU/mL may serve as a novel biomarker for the management of patients with intermediate viral load in our clinical practice,” wrote Tai-Chung Tseng, MD, PhD, of National Taiwan University Hospital in Taipei and associates in Gastroenterology.

Deciding whether to start antiviral therapy is controversial for some patients with HBV infection. Typically, monitoring without treatment is recommended for patients who have both low hepatitis B surface antigen levels (less than 1,000 IU/mL) and low levels of HBV DNA (less than 2,000 IU/mL), and early antiviral therapy is recommended for patients who have high levels of HBV DNA (20,000 IU/mL or more). However, there is no clear evidence that early antiviral therapy benefits patients who have intermediate levels of HBV DNA (2,000-19,999 IU/mL) and are negative for hepatitis B e antigen. Biomarkers for risk-stratifying these patients also are lacking, the researchers noted.

Therefore, they studied a cohort of 2,666 adults who had tested positive for hepatitis B surface antigen and were followed at National Taiwan University Hospital from 1985 through 2000. No patient had cirrhosis at baseline. In all, 209 patients developed hepatocellular carcinoma, yielding an incidence rate of 4.91 cases per 1,000 person-years.

Hepatitis B core–related antigen level remained an independent risk factor for hepatocellular carcinoma after accounting for age, sex, serum alanine aminotransferase (ALT) level, FIB-4 index, hepatitis B e antigen status, hepatitis B genotype (B, C, or undetermined), and HBV DNA level. Compared with patients whose HBcrAg level was less than 10 KU, a level of 10-99 KU/mL was associated with a nearly threefold increase in risk for hepatocellular carcinoma (HR, 2.93; 95% CI, 1.67-4.80), and this risk rose even further as HBcrAg levels increased.

In the subgroup of patients who tested negative for hepatitis B e antigen, had an intermediate HBV DNA load (2,000-19,999 IU/mL), and had a normal baseline ALT level (less than 40 U/L), a high HBcrAg level (10 KU/mL or more) was tied to a nearly fivefold greater risk for hepatocellular carcinoma (HR, 4.89; 95% CI, 2.18-10.93). This approximated the risk that is observed with high viral load (20,000 IU/mL), the researchers noted. In contrast, a low HBcrAg level was associated with a risk similar to that of minimal risk carriers (annual incidence rate, 0.10%; 95% CI, 0.04%-0.24%).

“To the best of our knowledge, this is the first study to report HBcrAg level as an independent viral biomarker to stratify hepatocellular risks in a large number of patients with intermediate viral load,” the researchers commented. Among the study limitations, 412 patients received antiviral therapy during follow-up. “This is a retrospective cohort study including Asian HBV patients with genotype B or C infection,” the investigators added. “It is unclear whether this finding could be extrapolated to populations with other HBV genotype infections. Nonetheless, we had a sound cohort, as several HBsAg-related clinical findings based on our cohort have already been validated by other prospective cohort studies, implying that our data were unlikely to be biased by the study design.”

Funders included National Taiwan University Hospital, the Ministry of Science and Technology, Executive Yuan in Taiwan, and National Health Research Institutes. The researchers reported having no conflicts of interest.

SOURCE: Tseng T-C et al. Gastroenterology. 2019 Aug 27. doi: 10.1053/j.gastro.2019.08.028.

Taking daily aspirin may help keep nonalcoholic fatty liver disease (NAFLD) from progressing to liver fibrosis and nonalcoholic steatohepatitis (NASH), suggest the results of a prospective study of 361 adults.

Previously, preclinical evidence had linked aspirin to fibrogenesis prevention in fatty liver disease, but this is the first report of a prospective study to do so. Daily aspirin use “was associated with less severe histologic features of NAFLD (nonalcoholic fatty liver disease) at study enrollment and with significantly lower risk for advanced fibrosis over time in a duration-dependent manner,” wrote Tracey G. Simon, MD, MPH, and her associates. Their report is in Clinical Gastroenterology and Hepatology.

The study comprised 361 adults with biopsy-confirmed NAFLD who were enrolled in the Massachusetts General Hospital NAFLD Repository between 2006 and 2015. At baseline, 151 individuals were already on daily aspirin, usually to reduce the primary (54%) or secondary (30%) risk of cardiovascular disease. Median duration of aspirin use was 2.5 years. After a median 7.4 years of follow-up (which was similar between aspirin users and nonusers), daily aspirin use was associated with significantly lower odds of NASH (adjusted odds ratio, 0.68; 95% confidence interval, 0.37-0.89) and fibrosis (aOR, 0.54; 95% CI, 0.31-0.82).

The researchers did not find a similar protective effect for nonsteroidal anti-inflammatory drugs (NSAIDs) other than aspirin (adjusted hazard ratio for advanced fibrosis, 0.93; 95% CI, 0.81–1.05). This might be because of differences between how aspirin and nonaspirin NSAIDs affect COX isoforms – aspirin does so irreversibly, while other NSAIDs have a reversible effect, they added. “Nonaspirin NSAIDs also disrupt the intestinal barrier, increasing delivery of proinflammatory cytokines to the liver,” they wrote. “Finally, aspirin uniquely modulates bioactive lipids by stimulating the biosynthesis of pro-resolving mediators and inhibiting proinflammatory lipids, which in turn may prevent progressive liver damage.”

In this study, a single blinded hepatopathologist interpreted baseline liver biopsy specimens, and patients were followed every 3-6 months with clinical examinations and serial calculations of FIB-4, NFS, and APRI scores. All patients were followed for at least a year. Patients were classified as users of nonaspirin NSAIDs if they reported using an NSAID besides aspirin at least twice weekly, or if they had been prescribed drugs such as ibuprofen, naproxen, ketoprofen, diclofenac, or indomethacin.

In a longitudinal analysis of the 317 patients who had early-stage (F0-2) fibrosis at baseline, 86 developed new-onset advanced fibrosis over a median of 3,692 person-years, the researchers said. In all, 26 individuals developed hepatic decompensation and 18 patients died, including eight from liver-related causes. Importantly, the link between aspirin and decreased risk of fibrosis progression seemed to depend on duration of use (adjusted P trend = .026), with the greatest benefit seen with 4 years or more of use (aHR, 0.50; 95% CI, 0.35-0.73). Although subgroup analyses were limited by lack of power, daily aspirin use was associated with a 36% lower odds of incident advanced fibrosis among the 72 study participants who had paired biopsy samples, even after accounting for the effect of age, sex, baseline fibrosis stage, and time between biopsies (aOR, 0.64; 95% CI, 0.50-0.80).

“Our findings add to the growing literature supporting the potential hepatoprotective effects of aspirin in NAFLD,” the researchers concluded. “Research to uncover the mechanisms by which aspirin might prevent fibrogenesis could help develop urgently needed antifibrotic therapies for NAFLD.”

Funders included the National Institutes of Health and the AASLD Foundation. The investigators reported having no conflicts of interest.

SOURCE: Simon TG et al. Clin Gastroenterol Hepatol. 2019 May 8.

Taking daily aspirin may help keep nonalcoholic fatty liver disease (NAFLD) from progressing to liver fibrosis and nonalcoholic steatohepatitis (NASH), suggest the results of a prospective study of 361 adults.

Previously, preclinical evidence had linked aspirin to fibrogenesis prevention in fatty liver disease, but this is the first report of a prospective study to do so. Daily aspirin use “was associated with less severe histologic features of NAFLD (nonalcoholic fatty liver disease) at study enrollment and with significantly lower risk for advanced fibrosis over time in a duration-dependent manner,” wrote Tracey G. Simon, MD, MPH, and her associates. Their report is in Clinical Gastroenterology and Hepatology.

The study comprised 361 adults with biopsy-confirmed NAFLD who were enrolled in the Massachusetts General Hospital NAFLD Repository between 2006 and 2015. At baseline, 151 individuals were already on daily aspirin, usually to reduce the primary (54%) or secondary (30%) risk of cardiovascular disease. Median duration of aspirin use was 2.5 years. After a median 7.4 years of follow-up (which was similar between aspirin users and nonusers), daily aspirin use was associated with significantly lower odds of NASH (adjusted odds ratio, 0.68; 95% confidence interval, 0.37-0.89) and fibrosis (aOR, 0.54; 95% CI, 0.31-0.82).

The researchers did not find a similar protective effect for nonsteroidal anti-inflammatory drugs (NSAIDs) other than aspirin (adjusted hazard ratio for advanced fibrosis, 0.93; 95% CI, 0.81–1.05). This might be because of differences between how aspirin and nonaspirin NSAIDs affect COX isoforms – aspirin does so irreversibly, while other NSAIDs have a reversible effect, they added. “Nonaspirin NSAIDs also disrupt the intestinal barrier, increasing delivery of proinflammatory cytokines to the liver,” they wrote. “Finally, aspirin uniquely modulates bioactive lipids by stimulating the biosynthesis of pro-resolving mediators and inhibiting proinflammatory lipids, which in turn may prevent progressive liver damage.”

In this study, a single blinded hepatopathologist interpreted baseline liver biopsy specimens, and patients were followed every 3-6 months with clinical examinations and serial calculations of FIB-4, NFS, and APRI scores. All patients were followed for at least a year. Patients were classified as users of nonaspirin NSAIDs if they reported using an NSAID besides aspirin at least twice weekly, or if they had been prescribed drugs such as ibuprofen, naproxen, ketoprofen, diclofenac, or indomethacin.

In a longitudinal analysis of the 317 patients who had early-stage (F0-2) fibrosis at baseline, 86 developed new-onset advanced fibrosis over a median of 3,692 person-years, the researchers said. In all, 26 individuals developed hepatic decompensation and 18 patients died, including eight from liver-related causes. Importantly, the link between aspirin and decreased risk of fibrosis progression seemed to depend on duration of use (adjusted P trend = .026), with the greatest benefit seen with 4 years or more of use (aHR, 0.50; 95% CI, 0.35-0.73). Although subgroup analyses were limited by lack of power, daily aspirin use was associated with a 36% lower odds of incident advanced fibrosis among the 72 study participants who had paired biopsy samples, even after accounting for the effect of age, sex, baseline fibrosis stage, and time between biopsies (aOR, 0.64; 95% CI, 0.50-0.80).

“Our findings add to the growing literature supporting the potential hepatoprotective effects of aspirin in NAFLD,” the researchers concluded. “Research to uncover the mechanisms by which aspirin might prevent fibrogenesis could help develop urgently needed antifibrotic therapies for NAFLD.”

Funders included the National Institutes of Health and the AASLD Foundation. The investigators reported having no conflicts of interest.

SOURCE: Simon TG et al. Clin Gastroenterol Hepatol. 2019 May 8.

Taking daily aspirin may help keep nonalcoholic fatty liver disease (NAFLD) from progressing to liver fibrosis and nonalcoholic steatohepatitis (NASH), suggest the results of a prospective study of 361 adults.

Previously, preclinical evidence had linked aspirin to fibrogenesis prevention in fatty liver disease, but this is the first report of a prospective study to do so. Daily aspirin use “was associated with less severe histologic features of NAFLD (nonalcoholic fatty liver disease) at study enrollment and with significantly lower risk for advanced fibrosis over time in a duration-dependent manner,” wrote Tracey G. Simon, MD, MPH, and her associates. Their report is in Clinical Gastroenterology and Hepatology.

The study comprised 361 adults with biopsy-confirmed NAFLD who were enrolled in the Massachusetts General Hospital NAFLD Repository between 2006 and 2015. At baseline, 151 individuals were already on daily aspirin, usually to reduce the primary (54%) or secondary (30%) risk of cardiovascular disease. Median duration of aspirin use was 2.5 years. After a median 7.4 years of follow-up (which was similar between aspirin users and nonusers), daily aspirin use was associated with significantly lower odds of NASH (adjusted odds ratio, 0.68; 95% confidence interval, 0.37-0.89) and fibrosis (aOR, 0.54; 95% CI, 0.31-0.82).

The researchers did not find a similar protective effect for nonsteroidal anti-inflammatory drugs (NSAIDs) other than aspirin (adjusted hazard ratio for advanced fibrosis, 0.93; 95% CI, 0.81–1.05). This might be because of differences between how aspirin and nonaspirin NSAIDs affect COX isoforms – aspirin does so irreversibly, while other NSAIDs have a reversible effect, they added. “Nonaspirin NSAIDs also disrupt the intestinal barrier, increasing delivery of proinflammatory cytokines to the liver,” they wrote. “Finally, aspirin uniquely modulates bioactive lipids by stimulating the biosynthesis of pro-resolving mediators and inhibiting proinflammatory lipids, which in turn may prevent progressive liver damage.”

In this study, a single blinded hepatopathologist interpreted baseline liver biopsy specimens, and patients were followed every 3-6 months with clinical examinations and serial calculations of FIB-4, NFS, and APRI scores. All patients were followed for at least a year. Patients were classified as users of nonaspirin NSAIDs if they reported using an NSAID besides aspirin at least twice weekly, or if they had been prescribed drugs such as ibuprofen, naproxen, ketoprofen, diclofenac, or indomethacin.

In a longitudinal analysis of the 317 patients who had early-stage (F0-2) fibrosis at baseline, 86 developed new-onset advanced fibrosis over a median of 3,692 person-years, the researchers said. In all, 26 individuals developed hepatic decompensation and 18 patients died, including eight from liver-related causes. Importantly, the link between aspirin and decreased risk of fibrosis progression seemed to depend on duration of use (adjusted P trend = .026), with the greatest benefit seen with 4 years or more of use (aHR, 0.50; 95% CI, 0.35-0.73). Although subgroup analyses were limited by lack of power, daily aspirin use was associated with a 36% lower odds of incident advanced fibrosis among the 72 study participants who had paired biopsy samples, even after accounting for the effect of age, sex, baseline fibrosis stage, and time between biopsies (aOR, 0.64; 95% CI, 0.50-0.80).

“Our findings add to the growing literature supporting the potential hepatoprotective effects of aspirin in NAFLD,” the researchers concluded. “Research to uncover the mechanisms by which aspirin might prevent fibrogenesis could help develop urgently needed antifibrotic therapies for NAFLD.”

Funders included the National Institutes of Health and the AASLD Foundation. The investigators reported having no conflicts of interest.

SOURCE: Simon TG et al. Clin Gastroenterol Hepatol. 2019 May 8.

BOSTON – For most patients with chronic hepatitis D virus (HDV) infection, combination therapy with lonafarnib, ritonavir, and peginterferon may significantly decrease viral loads, based on interim results from the phase IIa LIFT trial.

After 6 months of therapy, more than one-third of evaluable patients (37%) achieved undetectable levels of HDV RNA in serum, according to lead author Christopher Koh, MD, of the National Institute of Diabetes, Digestive and Kidney Diseases at the National Institutes of Health and colleagues.

The open-label LIFT trial, which is ongoing, initially recruited 26 patients with HDV RNA who had serum levels of at least 40 IU/mL (lower limit of quantification). After starting tenofovir or entecavir, patients began a combination regimen of twice-daily oral lonafarnib (50 mg) and ritonavir (100 mg) plus weekly subcutaneous injections of Peginterferon Lambda-1a (180 mcg).

The median patient age was 40 years, with a slightly higher proportion of male participants (60%). Approximately half of the patients were of Asian descent (52%), followed by patients who were white (32%), or African (16%). The investigators reported median baseline measurements of modified histology activity index (9) and Ishak fibrosis stage (3), as well as serum levels of alanine aminotransferase (64 IU/mL), aspartate aminotransferase (47 IU/mL), hepatitis B virus DNA (less than 21 IU/mL), and log HDV RNA (4.74 IU/mL), with this latter measurement serving as a key determinant of efficacy.

After 12 weeks of therapy, the median decrease in HDV RNA among 21 evaluable patients was 3.6 log IU/mL with an interquartile range from 2.6 to 4.2 (P less than .0001). Of these patients, 5 (24%) achieved undetectable levels of HDV RNA, while another 5 tested below the lower limit of quantification.

Following an additional 12 weeks of therapy, 19 patients remained evaluable, among whom the median decrease in HDV RNA was 3.4 log IU/mL with an interquartile range from 2.9 to 4.5 (P less than .0001). Seven of these patients (37%) achieved undetectable HDV RNA, whereas 3 others fell below the lower limit of quantification. Furthermore, 18 out of 19 of these patients (95%) experienced a decline in HDV RNA of more than 2 log IU/mL.

According to the investigators, the trial regimen was safe and well tolerated. Adverse events were mild to moderate; most common were anemia, hyperbilirubinemia, weight loss, and gastrointestinal issues. Doses were reduced in three patients while four others discontinued therapy prematurely.

“These interim results support continued exploration of this therapeutic combination in HDV,” the investigators concluded.

The above findings will be presented in an oral abstract session at the annual meeting of the American Association for the Study of Liver Diseases.

The investigators disclosed relationships with I-Cubed Therapeutics, Eiger BioPharmaceuticals, Riboscience, and others.

SOURCE: Koh C et al. The Liver Meeting 2019. Abstract LO8.

BOSTON – For most patients with chronic hepatitis D virus (HDV) infection, combination therapy with lonafarnib, ritonavir, and peginterferon may significantly decrease viral loads, based on interim results from the phase IIa LIFT trial.

After 6 months of therapy, more than one-third of evaluable patients (37%) achieved undetectable levels of HDV RNA in serum, according to lead author Christopher Koh, MD, of the National Institute of Diabetes, Digestive and Kidney Diseases at the National Institutes of Health and colleagues.

The open-label LIFT trial, which is ongoing, initially recruited 26 patients with HDV RNA who had serum levels of at least 40 IU/mL (lower limit of quantification). After starting tenofovir or entecavir, patients began a combination regimen of twice-daily oral lonafarnib (50 mg) and ritonavir (100 mg) plus weekly subcutaneous injections of Peginterferon Lambda-1a (180 mcg).

The median patient age was 40 years, with a slightly higher proportion of male participants (60%). Approximately half of the patients were of Asian descent (52%), followed by patients who were white (32%), or African (16%). The investigators reported median baseline measurements of modified histology activity index (9) and Ishak fibrosis stage (3), as well as serum levels of alanine aminotransferase (64 IU/mL), aspartate aminotransferase (47 IU/mL), hepatitis B virus DNA (less than 21 IU/mL), and log HDV RNA (4.74 IU/mL), with this latter measurement serving as a key determinant of efficacy.

After 12 weeks of therapy, the median decrease in HDV RNA among 21 evaluable patients was 3.6 log IU/mL with an interquartile range from 2.6 to 4.2 (P less than .0001). Of these patients, 5 (24%) achieved undetectable levels of HDV RNA, while another 5 tested below the lower limit of quantification.

Following an additional 12 weeks of therapy, 19 patients remained evaluable, among whom the median decrease in HDV RNA was 3.4 log IU/mL with an interquartile range from 2.9 to 4.5 (P less than .0001). Seven of these patients (37%) achieved undetectable HDV RNA, whereas 3 others fell below the lower limit of quantification. Furthermore, 18 out of 19 of these patients (95%) experienced a decline in HDV RNA of more than 2 log IU/mL.

According to the investigators, the trial regimen was safe and well tolerated. Adverse events were mild to moderate; most common were anemia, hyperbilirubinemia, weight loss, and gastrointestinal issues. Doses were reduced in three patients while four others discontinued therapy prematurely.

“These interim results support continued exploration of this therapeutic combination in HDV,” the investigators concluded.

The above findings will be presented in an oral abstract session at the annual meeting of the American Association for the Study of Liver Diseases.

The investigators disclosed relationships with I-Cubed Therapeutics, Eiger BioPharmaceuticals, Riboscience, and others.

SOURCE: Koh C et al. The Liver Meeting 2019. Abstract LO8.

BOSTON – For most patients with chronic hepatitis D virus (HDV) infection, combination therapy with lonafarnib, ritonavir, and peginterferon may significantly decrease viral loads, based on interim results from the phase IIa LIFT trial.

After 6 months of therapy, more than one-third of evaluable patients (37%) achieved undetectable levels of HDV RNA in serum, according to lead author Christopher Koh, MD, of the National Institute of Diabetes, Digestive and Kidney Diseases at the National Institutes of Health and colleagues.

The open-label LIFT trial, which is ongoing, initially recruited 26 patients with HDV RNA who had serum levels of at least 40 IU/mL (lower limit of quantification). After starting tenofovir or entecavir, patients began a combination regimen of twice-daily oral lonafarnib (50 mg) and ritonavir (100 mg) plus weekly subcutaneous injections of Peginterferon Lambda-1a (180 mcg).

The median patient age was 40 years, with a slightly higher proportion of male participants (60%). Approximately half of the patients were of Asian descent (52%), followed by patients who were white (32%), or African (16%). The investigators reported median baseline measurements of modified histology activity index (9) and Ishak fibrosis stage (3), as well as serum levels of alanine aminotransferase (64 IU/mL), aspartate aminotransferase (47 IU/mL), hepatitis B virus DNA (less than 21 IU/mL), and log HDV RNA (4.74 IU/mL), with this latter measurement serving as a key determinant of efficacy.

After 12 weeks of therapy, the median decrease in HDV RNA among 21 evaluable patients was 3.6 log IU/mL with an interquartile range from 2.6 to 4.2 (P less than .0001). Of these patients, 5 (24%) achieved undetectable levels of HDV RNA, while another 5 tested below the lower limit of quantification.

Following an additional 12 weeks of therapy, 19 patients remained evaluable, among whom the median decrease in HDV RNA was 3.4 log IU/mL with an interquartile range from 2.9 to 4.5 (P less than .0001). Seven of these patients (37%) achieved undetectable HDV RNA, whereas 3 others fell below the lower limit of quantification. Furthermore, 18 out of 19 of these patients (95%) experienced a decline in HDV RNA of more than 2 log IU/mL.

According to the investigators, the trial regimen was safe and well tolerated. Adverse events were mild to moderate; most common were anemia, hyperbilirubinemia, weight loss, and gastrointestinal issues. Doses were reduced in three patients while four others discontinued therapy prematurely.

“These interim results support continued exploration of this therapeutic combination in HDV,” the investigators concluded.

The above findings will be presented in an oral abstract session at the annual meeting of the American Association for the Study of Liver Diseases.

The investigators disclosed relationships with I-Cubed Therapeutics, Eiger BioPharmaceuticals, Riboscience, and others.

SOURCE: Koh C et al. The Liver Meeting 2019. Abstract LO8.

BOSTON – Treatment with novel agent DUR-928 may be able to reduce mortality rates among patients with severe alcoholic hepatitis, investigators predicted.

In an open-label, phase IIa trial, 89% of patients with alcoholic hepatitis responded to treatment with the new therapy, reported lead author Tarek Hassanein, MD, of Southern California Research Center in Coronado, Calif., and colleagues.

In an abstract that will be presented at the annual meeting of the American Association for the Study of Liver Diseases, the investigators explained the urgent need for an agent such as DUR-928: “The mortality of severe alcoholic hepatitis remains high in the absence of effective treatment,” they wrote, noting that corticosteroids are only suitable for select patients. According to the investigators, DUR-928 is an endogenous sulfated oxysterol that has been shown to control lipotoxicity and inflammation while increasing hepatic regeneration and cell survival.

The agent was tested among 19 patients with alcoholic hepatitis, many of whom had severe disease; at baseline, 15 had Maddrey’s discriminant function (DF) scores of 32 or less, 12 had Model for End-stage Liver Disease (MELD) scores between 12 and 30, and 11 had serum bilirubin levels higher than 8 mg/dL.

Via intravenous infusion, three dose levels were given: 30 mg, 90 mg, or 150 mg. All patients received at least one dose on day 1, and if still hospitalized, a second dose on day 4, with a total follow-up of 28 days. Treatment response was defined by a Lille score of less than 0.45.

DUR-928 was well tolerated; no serious drug-related adverse events occurred and all patients survived the 28-day follow-up period. Across the population, the response rate was 89%. This figure fell slightly to 87% when considering only patients with severe disease (DF scores of 32 or less), and marginally further still to 83% for those with MELD scores between 21 and 30. Among patients with severe disease, MELD scores decreased by a median of 17.5% (P = .01) over the 28-day period, and in cases with bilirubin starting higher than 8 mg/dL, levels dropped by a median of 25.1% (P = .02) within the first week.

A comparison of these results with historical data revealed that treatment with DUR-928 led to significantly better Lille scores than previously reported (P less than .0001).

“These initial findings are encouraging for further development of DUR-928 in patients with alcoholic hepatitis, including severe alcoholic hepatitis,” the investigators concluded.

The investigators disclosed relationships with DURECT Corporation, Assembly Biosciences, Gilead, and others.

SOURCE: Hassanein T et al. The Liver Meeting 2019, Abstract LO9.

BOSTON – Treatment with novel agent DUR-928 may be able to reduce mortality rates among patients with severe alcoholic hepatitis, investigators predicted.

In an open-label, phase IIa trial, 89% of patients with alcoholic hepatitis responded to treatment with the new therapy, reported lead author Tarek Hassanein, MD, of Southern California Research Center in Coronado, Calif., and colleagues.

In an abstract that will be presented at the annual meeting of the American Association for the Study of Liver Diseases, the investigators explained the urgent need for an agent such as DUR-928: “The mortality of severe alcoholic hepatitis remains high in the absence of effective treatment,” they wrote, noting that corticosteroids are only suitable for select patients. According to the investigators, DUR-928 is an endogenous sulfated oxysterol that has been shown to control lipotoxicity and inflammation while increasing hepatic regeneration and cell survival.

The agent was tested among 19 patients with alcoholic hepatitis, many of whom had severe disease; at baseline, 15 had Maddrey’s discriminant function (DF) scores of 32 or less, 12 had Model for End-stage Liver Disease (MELD) scores between 12 and 30, and 11 had serum bilirubin levels higher than 8 mg/dL.

Via intravenous infusion, three dose levels were given: 30 mg, 90 mg, or 150 mg. All patients received at least one dose on day 1, and if still hospitalized, a second dose on day 4, with a total follow-up of 28 days. Treatment response was defined by a Lille score of less than 0.45.

DUR-928 was well tolerated; no serious drug-related adverse events occurred and all patients survived the 28-day follow-up period. Across the population, the response rate was 89%. This figure fell slightly to 87% when considering only patients with severe disease (DF scores of 32 or less), and marginally further still to 83% for those with MELD scores between 21 and 30. Among patients with severe disease, MELD scores decreased by a median of 17.5% (P = .01) over the 28-day period, and in cases with bilirubin starting higher than 8 mg/dL, levels dropped by a median of 25.1% (P = .02) within the first week.

A comparison of these results with historical data revealed that treatment with DUR-928 led to significantly better Lille scores than previously reported (P less than .0001).

“These initial findings are encouraging for further development of DUR-928 in patients with alcoholic hepatitis, including severe alcoholic hepatitis,” the investigators concluded.

The investigators disclosed relationships with DURECT Corporation, Assembly Biosciences, Gilead, and others.

SOURCE: Hassanein T et al. The Liver Meeting 2019, Abstract LO9.

BOSTON – Treatment with novel agent DUR-928 may be able to reduce mortality rates among patients with severe alcoholic hepatitis, investigators predicted.

In an open-label, phase IIa trial, 89% of patients with alcoholic hepatitis responded to treatment with the new therapy, reported lead author Tarek Hassanein, MD, of Southern California Research Center in Coronado, Calif., and colleagues.

In an abstract that will be presented at the annual meeting of the American Association for the Study of Liver Diseases, the investigators explained the urgent need for an agent such as DUR-928: “The mortality of severe alcoholic hepatitis remains high in the absence of effective treatment,” they wrote, noting that corticosteroids are only suitable for select patients. According to the investigators, DUR-928 is an endogenous sulfated oxysterol that has been shown to control lipotoxicity and inflammation while increasing hepatic regeneration and cell survival.

The agent was tested among 19 patients with alcoholic hepatitis, many of whom had severe disease; at baseline, 15 had Maddrey’s discriminant function (DF) scores of 32 or less, 12 had Model for End-stage Liver Disease (MELD) scores between 12 and 30, and 11 had serum bilirubin levels higher than 8 mg/dL.

Via intravenous infusion, three dose levels were given: 30 mg, 90 mg, or 150 mg. All patients received at least one dose on day 1, and if still hospitalized, a second dose on day 4, with a total follow-up of 28 days. Treatment response was defined by a Lille score of less than 0.45.

DUR-928 was well tolerated; no serious drug-related adverse events occurred and all patients survived the 28-day follow-up period. Across the population, the response rate was 89%. This figure fell slightly to 87% when considering only patients with severe disease (DF scores of 32 or less), and marginally further still to 83% for those with MELD scores between 21 and 30. Among patients with severe disease, MELD scores decreased by a median of 17.5% (P = .01) over the 28-day period, and in cases with bilirubin starting higher than 8 mg/dL, levels dropped by a median of 25.1% (P = .02) within the first week.

A comparison of these results with historical data revealed that treatment with DUR-928 led to significantly better Lille scores than previously reported (P less than .0001).

“These initial findings are encouraging for further development of DUR-928 in patients with alcoholic hepatitis, including severe alcoholic hepatitis,” the investigators concluded.

The investigators disclosed relationships with DURECT Corporation, Assembly Biosciences, Gilead, and others.

SOURCE: Hassanein T et al. The Liver Meeting 2019, Abstract LO9.

BOSTON – Specifically in patients with hepatitis C virus (HCV) genotype 3 infection and compensated cirrhosis, glecaprevir/pibrentasvir (Mavyret) was safe and had high efficacy in a phase 3 clinical trial, echoing an earlier report describing clinical results for the fixed-dose combination in multiple other genotypes.

Treatment with glecaprevir/pibrentasvir was safe and produced high rates of sustained virologic response 12 weeks after treatment (SVR12) for the genotype 3 patients and compensated cirrhosis in the recent results from the EXPEDITION-8 study, which will be presented at the annual meeting of the American Association for the Study of Liver Diseases.

In a previous report from EXPEDITION-8, investigators said that the treatment was well tolerated and effective in patients with HCV genotypes 1, 2, 4, 5, and 6.

“The availability of an 8-week, pangenotypic regimen for all treatment-naive HCV-infected patients regardless of cirrhosis status may simplify the HCV care pathway, furthering progress towards HCV elimination,” said investigator Robert S. Brown Jr., MD, MPH, and coinvestigators in a late-breaking abstract of the latest study results.

The nonrandomized, multicenter, phase 3b study included 343 adults with HCV genotypes 1-6 who received glecaprevir 300 mg and pibrentasvir 120 mg once daily for 8 weeks. A total of 63% of patients were male, 83% were white; 18% had HCV genotype 3, while the majority (67%) had HCV genotype 1.

For the genotype 3 patients, SVR12 rates were 95.2% in the intention-to-treat population, and 98.4% in the per-protocol population, Dr. Brown and coauthors said in their report on the study. For genotype 1, 2, 4, 5, and 6 patients, the intention-to-treat and per-protocol SVR12 rates were 98.2% and 100%.

Taken together, the SVR12 rates for all genotypes were 97.7% and 99.7%, respectively, for the intention-to-treat and per-protocol populations, according to the investigators.

There were no virologic failures on treatment, and one patients with genotype 3 relapsed in week 4 posttreatment, while one genotype 1 patient discontinued treatment though not because of adverse events, they said.

Most adverse events were grade 1 in severity, and included fatigue, pruritus, headache, and nausea. There were no liver-related toxicities, and no serious adverse events that were related to the study treatment, according to the investigators.

Glecaprevir/pibrentasvir is indicated for patients aged 12 years and older with treatment-naive HCV genotype 1-6 infection without cirrhosis or with compensated cirrhosis, and in patients with HCV genotype 1 infection previously treated with an HCV NS5A inhibitor or an NS3/4A protease inhibitor.

Dr. Brown reported disclosures related to pharmaceutical companies including AbbVie, which markets Mavyret.

SOURCE: Brown RS et al. The Liver Meeting 2019. Abstract LP9.

BOSTON – Specifically in patients with hepatitis C virus (HCV) genotype 3 infection and compensated cirrhosis, glecaprevir/pibrentasvir (Mavyret) was safe and had high efficacy in a phase 3 clinical trial, echoing an earlier report describing clinical results for the fixed-dose combination in multiple other genotypes.

Treatment with glecaprevir/pibrentasvir was safe and produced high rates of sustained virologic response 12 weeks after treatment (SVR12) for the genotype 3 patients and compensated cirrhosis in the recent results from the EXPEDITION-8 study, which will be presented at the annual meeting of the American Association for the Study of Liver Diseases.

In a previous report from EXPEDITION-8, investigators said that the treatment was well tolerated and effective in patients with HCV genotypes 1, 2, 4, 5, and 6.

“The availability of an 8-week, pangenotypic regimen for all treatment-naive HCV-infected patients regardless of cirrhosis status may simplify the HCV care pathway, furthering progress towards HCV elimination,” said investigator Robert S. Brown Jr., MD, MPH, and coinvestigators in a late-breaking abstract of the latest study results.

The nonrandomized, multicenter, phase 3b study included 343 adults with HCV genotypes 1-6 who received glecaprevir 300 mg and pibrentasvir 120 mg once daily for 8 weeks. A total of 63% of patients were male, 83% were white; 18% had HCV genotype 3, while the majority (67%) had HCV genotype 1.

For the genotype 3 patients, SVR12 rates were 95.2% in the intention-to-treat population, and 98.4% in the per-protocol population, Dr. Brown and coauthors said in their report on the study. For genotype 1, 2, 4, 5, and 6 patients, the intention-to-treat and per-protocol SVR12 rates were 98.2% and 100%.

Taken together, the SVR12 rates for all genotypes were 97.7% and 99.7%, respectively, for the intention-to-treat and per-protocol populations, according to the investigators.

There were no virologic failures on treatment, and one patients with genotype 3 relapsed in week 4 posttreatment, while one genotype 1 patient discontinued treatment though not because of adverse events, they said.

Most adverse events were grade 1 in severity, and included fatigue, pruritus, headache, and nausea. There were no liver-related toxicities, and no serious adverse events that were related to the study treatment, according to the investigators.

Glecaprevir/pibrentasvir is indicated for patients aged 12 years and older with treatment-naive HCV genotype 1-6 infection without cirrhosis or with compensated cirrhosis, and in patients with HCV genotype 1 infection previously treated with an HCV NS5A inhibitor or an NS3/4A protease inhibitor.

Dr. Brown reported disclosures related to pharmaceutical companies including AbbVie, which markets Mavyret.

SOURCE: Brown RS et al. The Liver Meeting 2019. Abstract LP9.

BOSTON – Specifically in patients with hepatitis C virus (HCV) genotype 3 infection and compensated cirrhosis, glecaprevir/pibrentasvir (Mavyret) was safe and had high efficacy in a phase 3 clinical trial, echoing an earlier report describing clinical results for the fixed-dose combination in multiple other genotypes.

Treatment with glecaprevir/pibrentasvir was safe and produced high rates of sustained virologic response 12 weeks after treatment (SVR12) for the genotype 3 patients and compensated cirrhosis in the recent results from the EXPEDITION-8 study, which will be presented at the annual meeting of the American Association for the Study of Liver Diseases.

In a previous report from EXPEDITION-8, investigators said that the treatment was well tolerated and effective in patients with HCV genotypes 1, 2, 4, 5, and 6.

“The availability of an 8-week, pangenotypic regimen for all treatment-naive HCV-infected patients regardless of cirrhosis status may simplify the HCV care pathway, furthering progress towards HCV elimination,” said investigator Robert S. Brown Jr., MD, MPH, and coinvestigators in a late-breaking abstract of the latest study results.

The nonrandomized, multicenter, phase 3b study included 343 adults with HCV genotypes 1-6 who received glecaprevir 300 mg and pibrentasvir 120 mg once daily for 8 weeks. A total of 63% of patients were male, 83% were white; 18% had HCV genotype 3, while the majority (67%) had HCV genotype 1.

For the genotype 3 patients, SVR12 rates were 95.2% in the intention-to-treat population, and 98.4% in the per-protocol population, Dr. Brown and coauthors said in their report on the study. For genotype 1, 2, 4, 5, and 6 patients, the intention-to-treat and per-protocol SVR12 rates were 98.2% and 100%.

Taken together, the SVR12 rates for all genotypes were 97.7% and 99.7%, respectively, for the intention-to-treat and per-protocol populations, according to the investigators.

There were no virologic failures on treatment, and one patients with genotype 3 relapsed in week 4 posttreatment, while one genotype 1 patient discontinued treatment though not because of adverse events, they said.

Most adverse events were grade 1 in severity, and included fatigue, pruritus, headache, and nausea. There were no liver-related toxicities, and no serious adverse events that were related to the study treatment, according to the investigators.

Glecaprevir/pibrentasvir is indicated for patients aged 12 years and older with treatment-naive HCV genotype 1-6 infection without cirrhosis or with compensated cirrhosis, and in patients with HCV genotype 1 infection previously treated with an HCV NS5A inhibitor or an NS3/4A protease inhibitor.

Dr. Brown reported disclosures related to pharmaceutical companies including AbbVie, which markets Mavyret.

SOURCE: Brown RS et al. The Liver Meeting 2019. Abstract LP9.

BOSTON – A prime-boost hepatitis C virus (HCV) vaccine regimen did not protect against chronic infection, but it did evoke immune responses and differences in viral trajectory, according to investigators in what is believed to be the first randomized, placebo-controlled efficacy trial in this setting.

copyright wildpixel/Thinkstock

There were no apparent safety concerns with the vaccine according to investigators, led by Kimberly Page, PhD, MPH, of the University of New Mexico, Albuquerque.

“A safe and effective vaccine to prevent chronic hepatitis C virus infection is essential to reduce transmission,” Dr. Page and coauthors said in a late-breaking abstract of the study results, which will be presented at the annual meeting of the American Association for the Study of Liver Diseases.

The phase 1/2 trial described by Dr. Page and colleagues included 455 adults at risk of HCV infection because of injection drug use. They were randomized to vaccine, which consisted of a recombinant chimpanzee adenovirus-3 vectored vaccine prime plus a recombinant Modified Vaccinia virus Ankara boost, or to two doses of placebo at days 0 and 56 of the study.

There was no difference in chronic HCV infection at 6 months, the primary endpoint of the study. There were 14 chronically infected participants in the vaccine group, as well as 14 in the placebo group, for an overall incidence of infection of 13.0/100 person-years, Dr. Page and coauthors reported in the abstract.

However, there were significant differences in HCV RNA geometric mean peak at 1 month, which was 193,795 IU/L in the vaccine group and 1,078,092 IU/L in the placebo group, according to investigators. Similarly, geometric mean fold rise after infection was 0.2 in the vaccine group and 13.5 in the placebo group.

A total of 78% of vaccinated individuals had T-cell responses to at least one vaccine antigen pool, investigators said, adding that the vaccine was safe, well tolerated, and not associated with any serious adverse events.

Dr. Page had no disclosures related to the abstract.

SOURCE: Page K et al. The Liver Meeting 2019. Abstract LP17.

BOSTON – A prime-boost hepatitis C virus (HCV) vaccine regimen did not protect against chronic infection, but it did evoke immune responses and differences in viral trajectory, according to investigators in what is believed to be the first randomized, placebo-controlled efficacy trial in this setting.

copyright wildpixel/Thinkstock

There were no apparent safety concerns with the vaccine according to investigators, led by Kimberly Page, PhD, MPH, of the University of New Mexico, Albuquerque.

“A safe and effective vaccine to prevent chronic hepatitis C virus infection is essential to reduce transmission,” Dr. Page and coauthors said in a late-breaking abstract of the study results, which will be presented at the annual meeting of the American Association for the Study of Liver Diseases.

The phase 1/2 trial described by Dr. Page and colleagues included 455 adults at risk of HCV infection because of injection drug use. They were randomized to vaccine, which consisted of a recombinant chimpanzee adenovirus-3 vectored vaccine prime plus a recombinant Modified Vaccinia virus Ankara boost, or to two doses of placebo at days 0 and 56 of the study.

There was no difference in chronic HCV infection at 6 months, the primary endpoint of the study. There were 14 chronically infected participants in the vaccine group, as well as 14 in the placebo group, for an overall incidence of infection of 13.0/100 person-years, Dr. Page and coauthors reported in the abstract.

However, there were significant differences in HCV RNA geometric mean peak at 1 month, which was 193,795 IU/L in the vaccine group and 1,078,092 IU/L in the placebo group, according to investigators. Similarly, geometric mean fold rise after infection was 0.2 in the vaccine group and 13.5 in the placebo group.

A total of 78% of vaccinated individuals had T-cell responses to at least one vaccine antigen pool, investigators said, adding that the vaccine was safe, well tolerated, and not associated with any serious adverse events.

Dr. Page had no disclosures related to the abstract.

SOURCE: Page K et al. The Liver Meeting 2019. Abstract LP17.

BOSTON – A prime-boost hepatitis C virus (HCV) vaccine regimen did not protect against chronic infection, but it did evoke immune responses and differences in viral trajectory, according to investigators in what is believed to be the first randomized, placebo-controlled efficacy trial in this setting.

copyright wildpixel/Thinkstock

There were no apparent safety concerns with the vaccine according to investigators, led by Kimberly Page, PhD, MPH, of the University of New Mexico, Albuquerque.

“A safe and effective vaccine to prevent chronic hepatitis C virus infection is essential to reduce transmission,” Dr. Page and coauthors said in a late-breaking abstract of the study results, which will be presented at the annual meeting of the American Association for the Study of Liver Diseases.

The phase 1/2 trial described by Dr. Page and colleagues included 455 adults at risk of HCV infection because of injection drug use. They were randomized to vaccine, which consisted of a recombinant chimpanzee adenovirus-3 vectored vaccine prime plus a recombinant Modified Vaccinia virus Ankara boost, or to two doses of placebo at days 0 and 56 of the study.

There was no difference in chronic HCV infection at 6 months, the primary endpoint of the study. There were 14 chronically infected participants in the vaccine group, as well as 14 in the placebo group, for an overall incidence of infection of 13.0/100 person-years, Dr. Page and coauthors reported in the abstract.

However, there were significant differences in HCV RNA geometric mean peak at 1 month, which was 193,795 IU/L in the vaccine group and 1,078,092 IU/L in the placebo group, according to investigators. Similarly, geometric mean fold rise after infection was 0.2 in the vaccine group and 13.5 in the placebo group.

A total of 78% of vaccinated individuals had T-cell responses to at least one vaccine antigen pool, investigators said, adding that the vaccine was safe, well tolerated, and not associated with any serious adverse events.

Dr. Page had no disclosures related to the abstract.

SOURCE: Page K et al. The Liver Meeting 2019. Abstract LP17.