Liver Disease

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Several editorials were published concurrently with the recommendation.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Several editorials were published concurrently with the recommendation.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Several editorials were published concurrently with the recommendation.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

More treatment options

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

This article first appeared on Medscape.com.

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

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

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

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

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

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

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

More treatment options

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

This article first appeared on Medscape.com.

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

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

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

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

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

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

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

More treatment options

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

This article first appeared on Medscape.com.

MAUI, HAWAII – There might well be a cure for hepatitis B in coming years, just like there is now for hepatitis C, according to Norah Terrault, MD, chief of the division of GI and liver at the University of Southern California, Los Angeles.

M. Alexander Otto/MDedge News

“We are going to have a laundry list of new drugs” that are in the pipeline now. Phase 2 results “look encouraging. You will hear much more about this in the years ahead,” said Dr. Terrault, lead author of the 2018 American Association for the Study of Liver Diseases (AASLD) hepatitis B guidance.

For now, though, the field is largely limited to the nucleoside analogues tenofovir and entecavir. Treatment is often indefinite because, although hepatitis B virus (HBV) e-antigen is cleared, it usually doesn’t clear the HBV surface antigen, which is linked to liver cancer. “Even with e-antigen–negative patients, we feel that indefinite therapy is really the way to go,” Dr. Terrault said at the Gastroenterology Updates, IBD, Liver Disease Conference.

One of the biggest problems with that strategy is what to do when HBV does not seem to be much of a problem for carriers. Such patients are referred to as immune tolerant.
 

A newly recognized cancer risk

Immune tolerant patients tend to be young and have extremely high viral loads but no apparent ill effects, with normal ALT levels, normal histology, and no sign of cirrhosis. Although the AASLD recommends not treating these patients until they are 40 years old, waiting makes people nervous. “You have a hammer, you want to hit a nail,” Dr. Terrault said.

A recent review (Gut. 2018 May;67[5]:945-52) suggests that hitting the nail might be the way to go. South Korean investigators found that 413 untreated immune tolerate patients with a mean age of 38 years had more than twice the risk of liver cancer over 10 years than did almost 1,500 treated patients with active disease.

The study investigators concluded that “unnecessary deaths could be prevented through earlier antiviral intervention in select [immune tolerate] patients.”

This finding is one reason “we [AASLD] are rethinking the mantra of not treating the immune tolerant. There is a group that is transitioning” to active disease. “I’m thinking we should really [lower] the age cutoff” to 30 years, as some other groups [European Association for the Study of the Liver and Asian Pacific Association for the Study of the Liver] have done, plus “patients feel really good when they know the virus is controlled, and so do physicians,” Dr. Terrault said.
 

Entecavir versus tenofovir

Meanwhile, recent studies have raised the question of whether tenofovir is better than entecavir at preventing liver cancer.

A JAMA Oncology (JAMA Oncol. 2019 Jan 1;5[1]:30-6) study of some 25,000 patients in South Korea found a 32% lower risk of liver cancer when they were treated with tenofovir instead of entecavir. “This led to a lot of concern that maybe we should be moving all our patients to tenofovir,” she said.

Another study, a meta-analysis published earlier this year (Hepatol Int. 2020 Jan;14[1]:105-14), confirmed the difference in cancer risk when it combined those findings with other research. After adjustment for potential confounders, including disease stage and length of follow-up, “the difference disappeared” (hazard ration, 0.87; 95% confidence interval, 0.73-1.04), authors of the meta-analysis reported.

Study patients who received entecavir tended to be “treated many years ago and tended to have more severe [baseline] disease,” Dr. Terrault said.

So “while we see this difference, there’s not enough data yet for us to make a recommendation for our patients to switch from” entecavir to tenofovir. “Until a randomized controlled trial is done, this may remain an issue,” she said.
 

A drug holiday?

Dr. Terrault also reviewed research that suggests nucleoside analogue treatment can be stopped in e-antigen–negative patients after at least 3 years.

“The evidence is increasing that a finite NA [nucleoside analogue] treatment approach leads to higher HBsAg [hepatitis B surface antigen] loss rates, compared with the current long-term NA strategy, and can be considered a rational strategy to induce a functional cure in selected HBeAg-negative patients without cirrhosis who are willing to comply with close follow-up monitoring. ... The current observed functional cure rates” – perhaps about 40% – “would be well worth the effort,” editorialists commenting on the research concluded (Hepatology. 2018 Aug;68[2]:397-400).

It’s an interesting idea, Dr. Terrault said, but the virus will flare 8-12 weeks after treatment withdrawal, which is why it shouldn’t be considered in patients with cirrhosis.

Dr. Terrault is a consultant for AbbVie, Merck, Gilead, and other companies and disclosed grants from those companies and others.

[email protected]

MAUI, HAWAII – There might well be a cure for hepatitis B in coming years, just like there is now for hepatitis C, according to Norah Terrault, MD, chief of the division of GI and liver at the University of Southern California, Los Angeles.

M. Alexander Otto/MDedge News

“We are going to have a laundry list of new drugs” that are in the pipeline now. Phase 2 results “look encouraging. You will hear much more about this in the years ahead,” said Dr. Terrault, lead author of the 2018 American Association for the Study of Liver Diseases (AASLD) hepatitis B guidance.

For now, though, the field is largely limited to the nucleoside analogues tenofovir and entecavir. Treatment is often indefinite because, although hepatitis B virus (HBV) e-antigen is cleared, it usually doesn’t clear the HBV surface antigen, which is linked to liver cancer. “Even with e-antigen–negative patients, we feel that indefinite therapy is really the way to go,” Dr. Terrault said at the Gastroenterology Updates, IBD, Liver Disease Conference.

One of the biggest problems with that strategy is what to do when HBV does not seem to be much of a problem for carriers. Such patients are referred to as immune tolerant.
 

A newly recognized cancer risk

Immune tolerant patients tend to be young and have extremely high viral loads but no apparent ill effects, with normal ALT levels, normal histology, and no sign of cirrhosis. Although the AASLD recommends not treating these patients until they are 40 years old, waiting makes people nervous. “You have a hammer, you want to hit a nail,” Dr. Terrault said.

A recent review (Gut. 2018 May;67[5]:945-52) suggests that hitting the nail might be the way to go. South Korean investigators found that 413 untreated immune tolerate patients with a mean age of 38 years had more than twice the risk of liver cancer over 10 years than did almost 1,500 treated patients with active disease.

The study investigators concluded that “unnecessary deaths could be prevented through earlier antiviral intervention in select [immune tolerate] patients.”

This finding is one reason “we [AASLD] are rethinking the mantra of not treating the immune tolerant. There is a group that is transitioning” to active disease. “I’m thinking we should really [lower] the age cutoff” to 30 years, as some other groups [European Association for the Study of the Liver and Asian Pacific Association for the Study of the Liver] have done, plus “patients feel really good when they know the virus is controlled, and so do physicians,” Dr. Terrault said.
 

Entecavir versus tenofovir

Meanwhile, recent studies have raised the question of whether tenofovir is better than entecavir at preventing liver cancer.

A JAMA Oncology (JAMA Oncol. 2019 Jan 1;5[1]:30-6) study of some 25,000 patients in South Korea found a 32% lower risk of liver cancer when they were treated with tenofovir instead of entecavir. “This led to a lot of concern that maybe we should be moving all our patients to tenofovir,” she said.

Another study, a meta-analysis published earlier this year (Hepatol Int. 2020 Jan;14[1]:105-14), confirmed the difference in cancer risk when it combined those findings with other research. After adjustment for potential confounders, including disease stage and length of follow-up, “the difference disappeared” (hazard ration, 0.87; 95% confidence interval, 0.73-1.04), authors of the meta-analysis reported.

Study patients who received entecavir tended to be “treated many years ago and tended to have more severe [baseline] disease,” Dr. Terrault said.

So “while we see this difference, there’s not enough data yet for us to make a recommendation for our patients to switch from” entecavir to tenofovir. “Until a randomized controlled trial is done, this may remain an issue,” she said.
 

A drug holiday?

Dr. Terrault also reviewed research that suggests nucleoside analogue treatment can be stopped in e-antigen–negative patients after at least 3 years.

“The evidence is increasing that a finite NA [nucleoside analogue] treatment approach leads to higher HBsAg [hepatitis B surface antigen] loss rates, compared with the current long-term NA strategy, and can be considered a rational strategy to induce a functional cure in selected HBeAg-negative patients without cirrhosis who are willing to comply with close follow-up monitoring. ... The current observed functional cure rates” – perhaps about 40% – “would be well worth the effort,” editorialists commenting on the research concluded (Hepatology. 2018 Aug;68[2]:397-400).

It’s an interesting idea, Dr. Terrault said, but the virus will flare 8-12 weeks after treatment withdrawal, which is why it shouldn’t be considered in patients with cirrhosis.

Dr. Terrault is a consultant for AbbVie, Merck, Gilead, and other companies and disclosed grants from those companies and others.

[email protected]

MAUI, HAWAII – There might well be a cure for hepatitis B in coming years, just like there is now for hepatitis C, according to Norah Terrault, MD, chief of the division of GI and liver at the University of Southern California, Los Angeles.

M. Alexander Otto/MDedge News

“We are going to have a laundry list of new drugs” that are in the pipeline now. Phase 2 results “look encouraging. You will hear much more about this in the years ahead,” said Dr. Terrault, lead author of the 2018 American Association for the Study of Liver Diseases (AASLD) hepatitis B guidance.

For now, though, the field is largely limited to the nucleoside analogues tenofovir and entecavir. Treatment is often indefinite because, although hepatitis B virus (HBV) e-antigen is cleared, it usually doesn’t clear the HBV surface antigen, which is linked to liver cancer. “Even with e-antigen–negative patients, we feel that indefinite therapy is really the way to go,” Dr. Terrault said at the Gastroenterology Updates, IBD, Liver Disease Conference.

One of the biggest problems with that strategy is what to do when HBV does not seem to be much of a problem for carriers. Such patients are referred to as immune tolerant.
 

A newly recognized cancer risk

Immune tolerant patients tend to be young and have extremely high viral loads but no apparent ill effects, with normal ALT levels, normal histology, and no sign of cirrhosis. Although the AASLD recommends not treating these patients until they are 40 years old, waiting makes people nervous. “You have a hammer, you want to hit a nail,” Dr. Terrault said.

A recent review (Gut. 2018 May;67[5]:945-52) suggests that hitting the nail might be the way to go. South Korean investigators found that 413 untreated immune tolerate patients with a mean age of 38 years had more than twice the risk of liver cancer over 10 years than did almost 1,500 treated patients with active disease.

The study investigators concluded that “unnecessary deaths could be prevented through earlier antiviral intervention in select [immune tolerate] patients.”

This finding is one reason “we [AASLD] are rethinking the mantra of not treating the immune tolerant. There is a group that is transitioning” to active disease. “I’m thinking we should really [lower] the age cutoff” to 30 years, as some other groups [European Association for the Study of the Liver and Asian Pacific Association for the Study of the Liver] have done, plus “patients feel really good when they know the virus is controlled, and so do physicians,” Dr. Terrault said.
 

Entecavir versus tenofovir

Meanwhile, recent studies have raised the question of whether tenofovir is better than entecavir at preventing liver cancer.

A JAMA Oncology (JAMA Oncol. 2019 Jan 1;5[1]:30-6) study of some 25,000 patients in South Korea found a 32% lower risk of liver cancer when they were treated with tenofovir instead of entecavir. “This led to a lot of concern that maybe we should be moving all our patients to tenofovir,” she said.

Another study, a meta-analysis published earlier this year (Hepatol Int. 2020 Jan;14[1]:105-14), confirmed the difference in cancer risk when it combined those findings with other research. After adjustment for potential confounders, including disease stage and length of follow-up, “the difference disappeared” (hazard ration, 0.87; 95% confidence interval, 0.73-1.04), authors of the meta-analysis reported.

Study patients who received entecavir tended to be “treated many years ago and tended to have more severe [baseline] disease,” Dr. Terrault said.

So “while we see this difference, there’s not enough data yet for us to make a recommendation for our patients to switch from” entecavir to tenofovir. “Until a randomized controlled trial is done, this may remain an issue,” she said.
 

A drug holiday?

Dr. Terrault also reviewed research that suggests nucleoside analogue treatment can be stopped in e-antigen–negative patients after at least 3 years.

“The evidence is increasing that a finite NA [nucleoside analogue] treatment approach leads to higher HBsAg [hepatitis B surface antigen] loss rates, compared with the current long-term NA strategy, and can be considered a rational strategy to induce a functional cure in selected HBeAg-negative patients without cirrhosis who are willing to comply with close follow-up monitoring. ... The current observed functional cure rates” – perhaps about 40% – “would be well worth the effort,” editorialists commenting on the research concluded (Hepatology. 2018 Aug;68[2]:397-400).

It’s an interesting idea, Dr. Terrault said, but the virus will flare 8-12 weeks after treatment withdrawal, which is why it shouldn’t be considered in patients with cirrhosis.

Dr. Terrault is a consultant for AbbVie, Merck, Gilead, and other companies and disclosed grants from those companies and others.

[email protected]

Alcohol use is associated with hepatic steatosis, even after exclusion of heavy drinkers. Binge drinking was associated with a particularly high risk. The results are drawn from a retrospective analysis of the Framingham Heart Study and indicate a possible connection between alcohol use and nonalcoholic fatty liver disease (NAFLD). If confirmed prospectively, the results suggest that alcohol use could be a target for prevention and treatment of presumed NAFLD.

The study was led by Michelle Long, MD, of Boston University, and was published in Clinical Gastroenterology and Hepatology.

Previous studies have produced mixed results with respect to alcohol consumption and NAFLD, with some reporting increased risk with alcohol consumption, and some a beneficial effect of moderate alcohol consumption. Most such studies focused on average daily or weekly alcohol intake, without examining individual differences in alcohol use behavior.

The current work included 2,475 participants from the Offspring and Third Generation Cohorts of the multidetector CT (MDCT) substudy of the Framingham Heart Study. The researchers excluded heavy drinkers, defined as those who had more than 21 drinks (men) or 14 drinks (women) per week.

Of the sample, 17.3% had hepatic steatosis as measured by MDCT. The risk of hepatic steatosis increased from 15.3% to 54.3% along increasing categories of alcohol use.

With each standard deviation increase in the number of alcohol drinks per week, the risk of hepatic steatosis increased by 15% (adjusted odds ratio, 1.15; 95% CI, 1.02-1.29). Of subjects with presumed NAFLD, 25.4% were binge drinkers, defined as four or more drinks per day in women and five or more in men.

A pattern of risky weekly drinking – defined as 8 or more drinks for women or 15 or more for men – was associated with a 45% increase in odds of hepatic steatosis (aOR, 1.45; 95% CI, 1.06-1.98).

An analysis of only current drinkers showed stronger associations between hepatic steatosis and the number of alcoholic drinks per week, risky weekly drinking, and maximum number of drinks in 24 hours.

When the researchers broke down the analysis by beer, wine, or spirit drinkers, they only found a statistically significant association between alcohol consumption and hepatic steatosis in beer drinkers.

The study authors received funding from a range of nonindustry sources. They reported having no relevant financial disclosures.

SOURCE: Long M et al. Clin Gastroenterol Hepatol. 2019 Nov 14. doi: 10.1016/j.cgh.2019.11.022

Alcohol use is associated with hepatic steatosis, even after exclusion of heavy drinkers. Binge drinking was associated with a particularly high risk. The results are drawn from a retrospective analysis of the Framingham Heart Study and indicate a possible connection between alcohol use and nonalcoholic fatty liver disease (NAFLD). If confirmed prospectively, the results suggest that alcohol use could be a target for prevention and treatment of presumed NAFLD.

The study was led by Michelle Long, MD, of Boston University, and was published in Clinical Gastroenterology and Hepatology.

Previous studies have produced mixed results with respect to alcohol consumption and NAFLD, with some reporting increased risk with alcohol consumption, and some a beneficial effect of moderate alcohol consumption. Most such studies focused on average daily or weekly alcohol intake, without examining individual differences in alcohol use behavior.

The current work included 2,475 participants from the Offspring and Third Generation Cohorts of the multidetector CT (MDCT) substudy of the Framingham Heart Study. The researchers excluded heavy drinkers, defined as those who had more than 21 drinks (men) or 14 drinks (women) per week.

Of the sample, 17.3% had hepatic steatosis as measured by MDCT. The risk of hepatic steatosis increased from 15.3% to 54.3% along increasing categories of alcohol use.

With each standard deviation increase in the number of alcohol drinks per week, the risk of hepatic steatosis increased by 15% (adjusted odds ratio, 1.15; 95% CI, 1.02-1.29). Of subjects with presumed NAFLD, 25.4% were binge drinkers, defined as four or more drinks per day in women and five or more in men.

A pattern of risky weekly drinking – defined as 8 or more drinks for women or 15 or more for men – was associated with a 45% increase in odds of hepatic steatosis (aOR, 1.45; 95% CI, 1.06-1.98).

An analysis of only current drinkers showed stronger associations between hepatic steatosis and the number of alcoholic drinks per week, risky weekly drinking, and maximum number of drinks in 24 hours.

When the researchers broke down the analysis by beer, wine, or spirit drinkers, they only found a statistically significant association between alcohol consumption and hepatic steatosis in beer drinkers.

The study authors received funding from a range of nonindustry sources. They reported having no relevant financial disclosures.

SOURCE: Long M et al. Clin Gastroenterol Hepatol. 2019 Nov 14. doi: 10.1016/j.cgh.2019.11.022

Alcohol use is associated with hepatic steatosis, even after exclusion of heavy drinkers. Binge drinking was associated with a particularly high risk. The results are drawn from a retrospective analysis of the Framingham Heart Study and indicate a possible connection between alcohol use and nonalcoholic fatty liver disease (NAFLD). If confirmed prospectively, the results suggest that alcohol use could be a target for prevention and treatment of presumed NAFLD.

The study was led by Michelle Long, MD, of Boston University, and was published in Clinical Gastroenterology and Hepatology.

Previous studies have produced mixed results with respect to alcohol consumption and NAFLD, with some reporting increased risk with alcohol consumption, and some a beneficial effect of moderate alcohol consumption. Most such studies focused on average daily or weekly alcohol intake, without examining individual differences in alcohol use behavior.

The current work included 2,475 participants from the Offspring and Third Generation Cohorts of the multidetector CT (MDCT) substudy of the Framingham Heart Study. The researchers excluded heavy drinkers, defined as those who had more than 21 drinks (men) or 14 drinks (women) per week.

Of the sample, 17.3% had hepatic steatosis as measured by MDCT. The risk of hepatic steatosis increased from 15.3% to 54.3% along increasing categories of alcohol use.

With each standard deviation increase in the number of alcohol drinks per week, the risk of hepatic steatosis increased by 15% (adjusted odds ratio, 1.15; 95% CI, 1.02-1.29). Of subjects with presumed NAFLD, 25.4% were binge drinkers, defined as four or more drinks per day in women and five or more in men.

A pattern of risky weekly drinking – defined as 8 or more drinks for women or 15 or more for men – was associated with a 45% increase in odds of hepatic steatosis (aOR, 1.45; 95% CI, 1.06-1.98).

An analysis of only current drinkers showed stronger associations between hepatic steatosis and the number of alcoholic drinks per week, risky weekly drinking, and maximum number of drinks in 24 hours.

When the researchers broke down the analysis by beer, wine, or spirit drinkers, they only found a statistically significant association between alcohol consumption and hepatic steatosis in beer drinkers.

The study authors received funding from a range of nonindustry sources. They reported having no relevant financial disclosures.

SOURCE: Long M et al. Clin Gastroenterol Hepatol. 2019 Nov 14. doi: 10.1016/j.cgh.2019.11.022

Among patients with hepatitis B virus (HBV) infection who are not receiving antiviral therapy, surface antigen titers and alanine aminotransferase (ALT) levels may independently predict spontaneous seroconversion, based on a recent case-control study.

Patients with hepatitis B surface antigen (HBsAg) titers less than 1,000 IU/mL were significantly more likely to spontaneously seroconvert, reported principal author Sammy Saab, MD, of the University of California, Los Angeles, and colleagues.

While the predictive value of HBsAg titers has been demonstrated for patients undergoing antiviral therapy, data are limited for spontaneous seroconversion, the investigators wrote in Journal of Clinical Gastroenterology.

To learn more about this scenario, the investigators reviewed medical records from 2,126 patients who visited a large community practice in the Los Angeles area between 2014 and 2019. Cases were defined by HBV infection with seroconversion, whereas matched controls were defined by HBV without seroconversion. A variety of demographic and clinical data were also evaluated, including age, ethnicity, sex, HBsAg titer, ALT, HBV DNA, total cholesterol, presence of fatty liver, and other factors.

The investigators identified 167 patients with HBV who were not on antiviral therapy. Of these, 14 underwent seroconversion, and were matched with 70 patients who did not seroconvert. All patients were of Asian descent, most were women, and none had cirrhosis.

Across all demographic and clinical parameters, the two factors that significantly differed between cases and controls were ALT and HBsAg titer. The mean ALT for patients who seroconverted was 17.6 U/L, versus 25.1 U/L in those who did not undergo seroconversion (P less than .01). Similarly, mean titer was lower in the seroconversion group (459.8 vs. 782.0 IU/mL; P = .01).

The investigators noted that seroconversion was more common among patients with an HBsAg titer level less than 1,000 IU/mL. Specifically, 79% of patients who seroconverted had a titer less than 1,000 IU/mL, compared with just 16% of patients who did not seroconvert (P = .001).

HBV DNA levels were not predictive of seroconversion, the investigators noted, which aligns with most, but not all, previous research.

The investigators reported no disclosures.

SOURCE: Wu CF et al. J Clin Gastroenterol. 2020 Feb 11. doi: 10.1097/MCG.0000000000001324.

Among patients with hepatitis B virus (HBV) infection who are not receiving antiviral therapy, surface antigen titers and alanine aminotransferase (ALT) levels may independently predict spontaneous seroconversion, based on a recent case-control study.

Patients with hepatitis B surface antigen (HBsAg) titers less than 1,000 IU/mL were significantly more likely to spontaneously seroconvert, reported principal author Sammy Saab, MD, of the University of California, Los Angeles, and colleagues.

While the predictive value of HBsAg titers has been demonstrated for patients undergoing antiviral therapy, data are limited for spontaneous seroconversion, the investigators wrote in Journal of Clinical Gastroenterology.

To learn more about this scenario, the investigators reviewed medical records from 2,126 patients who visited a large community practice in the Los Angeles area between 2014 and 2019. Cases were defined by HBV infection with seroconversion, whereas matched controls were defined by HBV without seroconversion. A variety of demographic and clinical data were also evaluated, including age, ethnicity, sex, HBsAg titer, ALT, HBV DNA, total cholesterol, presence of fatty liver, and other factors.

The investigators identified 167 patients with HBV who were not on antiviral therapy. Of these, 14 underwent seroconversion, and were matched with 70 patients who did not seroconvert. All patients were of Asian descent, most were women, and none had cirrhosis.

Across all demographic and clinical parameters, the two factors that significantly differed between cases and controls were ALT and HBsAg titer. The mean ALT for patients who seroconverted was 17.6 U/L, versus 25.1 U/L in those who did not undergo seroconversion (P less than .01). Similarly, mean titer was lower in the seroconversion group (459.8 vs. 782.0 IU/mL; P = .01).

The investigators noted that seroconversion was more common among patients with an HBsAg titer level less than 1,000 IU/mL. Specifically, 79% of patients who seroconverted had a titer less than 1,000 IU/mL, compared with just 16% of patients who did not seroconvert (P = .001).

HBV DNA levels were not predictive of seroconversion, the investigators noted, which aligns with most, but not all, previous research.

The investigators reported no disclosures.

SOURCE: Wu CF et al. J Clin Gastroenterol. 2020 Feb 11. doi: 10.1097/MCG.0000000000001324.

Among patients with hepatitis B virus (HBV) infection who are not receiving antiviral therapy, surface antigen titers and alanine aminotransferase (ALT) levels may independently predict spontaneous seroconversion, based on a recent case-control study.

Patients with hepatitis B surface antigen (HBsAg) titers less than 1,000 IU/mL were significantly more likely to spontaneously seroconvert, reported principal author Sammy Saab, MD, of the University of California, Los Angeles, and colleagues.

While the predictive value of HBsAg titers has been demonstrated for patients undergoing antiviral therapy, data are limited for spontaneous seroconversion, the investigators wrote in Journal of Clinical Gastroenterology.

To learn more about this scenario, the investigators reviewed medical records from 2,126 patients who visited a large community practice in the Los Angeles area between 2014 and 2019. Cases were defined by HBV infection with seroconversion, whereas matched controls were defined by HBV without seroconversion. A variety of demographic and clinical data were also evaluated, including age, ethnicity, sex, HBsAg titer, ALT, HBV DNA, total cholesterol, presence of fatty liver, and other factors.

The investigators identified 167 patients with HBV who were not on antiviral therapy. Of these, 14 underwent seroconversion, and were matched with 70 patients who did not seroconvert. All patients were of Asian descent, most were women, and none had cirrhosis.

Across all demographic and clinical parameters, the two factors that significantly differed between cases and controls were ALT and HBsAg titer. The mean ALT for patients who seroconverted was 17.6 U/L, versus 25.1 U/L in those who did not undergo seroconversion (P less than .01). Similarly, mean titer was lower in the seroconversion group (459.8 vs. 782.0 IU/mL; P = .01).

The investigators noted that seroconversion was more common among patients with an HBsAg titer level less than 1,000 IU/mL. Specifically, 79% of patients who seroconverted had a titer less than 1,000 IU/mL, compared with just 16% of patients who did not seroconvert (P = .001).

HBV DNA levels were not predictive of seroconversion, the investigators noted, which aligns with most, but not all, previous research.

The investigators reported no disclosures.

SOURCE: Wu CF et al. J Clin Gastroenterol. 2020 Feb 11. doi: 10.1097/MCG.0000000000001324.

For patients with nonalcoholic steatohepatitis (NASH), the GALAD score may accurately predict hepatocellular carcinoma (HCC) as early as 560 days before diagnosis, according to investigators.

The GALAD score, which combines sex, age, alpha-fetoprotein-L3 (AFP-L3), alpha-fetoprotein, and des-gamma-carboxyprothrombin (DCP), could improve cancer surveillance among NASH patients whose obesity limits sensitivity of ultrasound, reported lead author Jan Best, MD, of the University Hospital Magdeburg in Germany, and colleagues.

“The limitations of ultrasound surveillance alone for early detection of HCC are particularly evident in patients with NASH,” the investigators wrote in Clinical Gastroenterology and Hepatology. “Serum-based biomarkers might be more effective, with or without ultrasound surveillance, for HCC surveillance in NASH patients, although data in this patient population are currently lacking. The current study assessed the performance of the GALAD score for early HCC detection in patients with NASH-related liver disease.”

The study consisted of two parts: first, a retrospective case-control analysis, and second, a phase 3 prospective trial that implemented the GALAD score in a real-world population.

The retrospective component of the study involved 126 NASH patients with HCC (cases) and 231 NASH patients without HCC (controls), all of whom were treated at eight centers in Germany. The median GALAD score was significantly higher among NASH patients with HCC than in those without (2.93 vs. –3.96; P less than .001). At an optimal cutoff of –1.334, the GALAD score predicted HCC with a sensitivity of 91.2% and a specificity of 95.2%. Each component of the GALAD score aligned with previously published findings, as patients with HCC were predominantly older men with elevated serum AFP-L3, AFP, and DCP. But a closer look at the data showed that the GALAD score more accurately predicted HCC than any of its constituent serum measurements in isolation. For any stage of HCC, GALAD had an area under the curve (AUC) of 0.96, compared with significantly lower values for AFP (0.88), AFP-L3 (0.86), and DCP (0.87). Similarly, for early-stage HCC, GALAD score AUC was 0.92, compared with significantly lower values for AFP (0.77), AFP-L3 (0.74), and DCP (0.87).

The accuracy of the GALAD score – for detection of both any-stage and early-stage HCC — remained high regardless of cirrhosis status. Among patients with cirrhosis, the AUC for any-stage HCC was 0.93, and 0.85 for early-stage HCC. For patients without cirrhosis, GALAD was slightly more predictive, based on AUC’s of 0.98 and 0.94 for detection of any-stage and early-stage HCC, respectively. Again, these accuracy values significantly outmatched each serum measurement in isolation.

“These data on NASH-HCC patients demonstrate that GALAD can detect HCC independent of cirrhosis or stage of HCC,” the investigators wrote. “Indeed, even early noncirrhotic NASH-HCC seems clearly separable from NASH controls, as even small groups resulted in robust performance.”

The prospective component of the study involved screening 392 patients with NASH at a single treatment center in Japan. From this cohort, 28 patients developed HCC after a median of 10.1 years. Many patients in this group had significantly higher GALAD scores for 5 or more years before being diagnosed with HCC, and scores rose sharply in the months preceding diagnosis. Depending on selected cutoff value, the GALAD score predicted HCC from 200 to 560 days prior to diagnosis.

“While this specific result has to be confirmed in further prospective studies, it is a promising observation for potential use of GALAD as a screening tool in NASH patients,” the investigators wrote.

“In conclusion, our data confirm that the GALAD score is superior to individual serum markers for detection of HCC in NASH, independent of tumor stage or cirrhosis,” the investigators wrote. “The findings suggest that GALAD should be investigated as a potential tool for screening of NASH individuals to detect HCC at a resectable stage in a sufficiently large prospective study to identify a cutoff.”

The study was funded by Deutsche Forschungsgemeinschaft, the Wilhelm-Laupitz Foundation, and the Werner Jackstaedt Foundation. The investigators declared no conflicts of interest.

SOURCE: Best J et al. Clin Gastro Hepatol. 2019 Nov 8. doi: 10.1016/j.cgh.2019.11.012.

For patients with nonalcoholic steatohepatitis (NASH), the GALAD score may accurately predict hepatocellular carcinoma (HCC) as early as 560 days before diagnosis, according to investigators.

The GALAD score, which combines sex, age, alpha-fetoprotein-L3 (AFP-L3), alpha-fetoprotein, and des-gamma-carboxyprothrombin (DCP), could improve cancer surveillance among NASH patients whose obesity limits sensitivity of ultrasound, reported lead author Jan Best, MD, of the University Hospital Magdeburg in Germany, and colleagues.

“The limitations of ultrasound surveillance alone for early detection of HCC are particularly evident in patients with NASH,” the investigators wrote in Clinical Gastroenterology and Hepatology. “Serum-based biomarkers might be more effective, with or without ultrasound surveillance, for HCC surveillance in NASH patients, although data in this patient population are currently lacking. The current study assessed the performance of the GALAD score for early HCC detection in patients with NASH-related liver disease.”

The study consisted of two parts: first, a retrospective case-control analysis, and second, a phase 3 prospective trial that implemented the GALAD score in a real-world population.

The retrospective component of the study involved 126 NASH patients with HCC (cases) and 231 NASH patients without HCC (controls), all of whom were treated at eight centers in Germany. The median GALAD score was significantly higher among NASH patients with HCC than in those without (2.93 vs. –3.96; P less than .001). At an optimal cutoff of –1.334, the GALAD score predicted HCC with a sensitivity of 91.2% and a specificity of 95.2%. Each component of the GALAD score aligned with previously published findings, as patients with HCC were predominantly older men with elevated serum AFP-L3, AFP, and DCP. But a closer look at the data showed that the GALAD score more accurately predicted HCC than any of its constituent serum measurements in isolation. For any stage of HCC, GALAD had an area under the curve (AUC) of 0.96, compared with significantly lower values for AFP (0.88), AFP-L3 (0.86), and DCP (0.87). Similarly, for early-stage HCC, GALAD score AUC was 0.92, compared with significantly lower values for AFP (0.77), AFP-L3 (0.74), and DCP (0.87).

The accuracy of the GALAD score – for detection of both any-stage and early-stage HCC — remained high regardless of cirrhosis status. Among patients with cirrhosis, the AUC for any-stage HCC was 0.93, and 0.85 for early-stage HCC. For patients without cirrhosis, GALAD was slightly more predictive, based on AUC’s of 0.98 and 0.94 for detection of any-stage and early-stage HCC, respectively. Again, these accuracy values significantly outmatched each serum measurement in isolation.

“These data on NASH-HCC patients demonstrate that GALAD can detect HCC independent of cirrhosis or stage of HCC,” the investigators wrote. “Indeed, even early noncirrhotic NASH-HCC seems clearly separable from NASH controls, as even small groups resulted in robust performance.”

The prospective component of the study involved screening 392 patients with NASH at a single treatment center in Japan. From this cohort, 28 patients developed HCC after a median of 10.1 years. Many patients in this group had significantly higher GALAD scores for 5 or more years before being diagnosed with HCC, and scores rose sharply in the months preceding diagnosis. Depending on selected cutoff value, the GALAD score predicted HCC from 200 to 560 days prior to diagnosis.

“While this specific result has to be confirmed in further prospective studies, it is a promising observation for potential use of GALAD as a screening tool in NASH patients,” the investigators wrote.

“In conclusion, our data confirm that the GALAD score is superior to individual serum markers for detection of HCC in NASH, independent of tumor stage or cirrhosis,” the investigators wrote. “The findings suggest that GALAD should be investigated as a potential tool for screening of NASH individuals to detect HCC at a resectable stage in a sufficiently large prospective study to identify a cutoff.”

The study was funded by Deutsche Forschungsgemeinschaft, the Wilhelm-Laupitz Foundation, and the Werner Jackstaedt Foundation. The investigators declared no conflicts of interest.

SOURCE: Best J et al. Clin Gastro Hepatol. 2019 Nov 8. doi: 10.1016/j.cgh.2019.11.012.

For patients with nonalcoholic steatohepatitis (NASH), the GALAD score may accurately predict hepatocellular carcinoma (HCC) as early as 560 days before diagnosis, according to investigators.

The GALAD score, which combines sex, age, alpha-fetoprotein-L3 (AFP-L3), alpha-fetoprotein, and des-gamma-carboxyprothrombin (DCP), could improve cancer surveillance among NASH patients whose obesity limits sensitivity of ultrasound, reported lead author Jan Best, MD, of the University Hospital Magdeburg in Germany, and colleagues.

“The limitations of ultrasound surveillance alone for early detection of HCC are particularly evident in patients with NASH,” the investigators wrote in Clinical Gastroenterology and Hepatology. “Serum-based biomarkers might be more effective, with or without ultrasound surveillance, for HCC surveillance in NASH patients, although data in this patient population are currently lacking. The current study assessed the performance of the GALAD score for early HCC detection in patients with NASH-related liver disease.”

The study consisted of two parts: first, a retrospective case-control analysis, and second, a phase 3 prospective trial that implemented the GALAD score in a real-world population.

The retrospective component of the study involved 126 NASH patients with HCC (cases) and 231 NASH patients without HCC (controls), all of whom were treated at eight centers in Germany. The median GALAD score was significantly higher among NASH patients with HCC than in those without (2.93 vs. –3.96; P less than .001). At an optimal cutoff of –1.334, the GALAD score predicted HCC with a sensitivity of 91.2% and a specificity of 95.2%. Each component of the GALAD score aligned with previously published findings, as patients with HCC were predominantly older men with elevated serum AFP-L3, AFP, and DCP. But a closer look at the data showed that the GALAD score more accurately predicted HCC than any of its constituent serum measurements in isolation. For any stage of HCC, GALAD had an area under the curve (AUC) of 0.96, compared with significantly lower values for AFP (0.88), AFP-L3 (0.86), and DCP (0.87). Similarly, for early-stage HCC, GALAD score AUC was 0.92, compared with significantly lower values for AFP (0.77), AFP-L3 (0.74), and DCP (0.87).

The accuracy of the GALAD score – for detection of both any-stage and early-stage HCC — remained high regardless of cirrhosis status. Among patients with cirrhosis, the AUC for any-stage HCC was 0.93, and 0.85 for early-stage HCC. For patients without cirrhosis, GALAD was slightly more predictive, based on AUC’s of 0.98 and 0.94 for detection of any-stage and early-stage HCC, respectively. Again, these accuracy values significantly outmatched each serum measurement in isolation.

“These data on NASH-HCC patients demonstrate that GALAD can detect HCC independent of cirrhosis or stage of HCC,” the investigators wrote. “Indeed, even early noncirrhotic NASH-HCC seems clearly separable from NASH controls, as even small groups resulted in robust performance.”

The prospective component of the study involved screening 392 patients with NASH at a single treatment center in Japan. From this cohort, 28 patients developed HCC after a median of 10.1 years. Many patients in this group had significantly higher GALAD scores for 5 or more years before being diagnosed with HCC, and scores rose sharply in the months preceding diagnosis. Depending on selected cutoff value, the GALAD score predicted HCC from 200 to 560 days prior to diagnosis.

“While this specific result has to be confirmed in further prospective studies, it is a promising observation for potential use of GALAD as a screening tool in NASH patients,” the investigators wrote.

“In conclusion, our data confirm that the GALAD score is superior to individual serum markers for detection of HCC in NASH, independent of tumor stage or cirrhosis,” the investigators wrote. “The findings suggest that GALAD should be investigated as a potential tool for screening of NASH individuals to detect HCC at a resectable stage in a sufficiently large prospective study to identify a cutoff.”

The study was funded by Deutsche Forschungsgemeinschaft, the Wilhelm-Laupitz Foundation, and the Werner Jackstaedt Foundation. The investigators declared no conflicts of interest.

SOURCE: Best J et al. Clin Gastro Hepatol. 2019 Nov 8. doi: 10.1016/j.cgh.2019.11.012.

Serum keratin 18, an epithelial protein released from dying hepatocytes, identifies patients with severe acute alcoholic hepatitis (AAH) at high risk for death, according to an investigation of 173 subjects.

Standard biomarker scores – Model for End-stage Liver Disease (MELD), age, serum bilirubin, International Normalized Ratio, and serum creatinine (ABIC), as well as others – predict prognosis and severity of alcoholic liver disease, but they don’t reflect “the magnitude of cell death nor the form of cell death (apoptosis/necrosis), which may be important in distinguishing various forms of liver injury” and guiding therapy, explained investigators led by Vatsalya Vatsalya, MD, of the division of gastroenterology, hepatology, and nutrition at the University of Louisville (Ky.).

It’s important, for instance, to identify people with alcoholic cirrhosis but not active hepatitis, as they “would likely not benefit from anti-inflammatory agents such as steroids or [interleukin]-1 receptor antagonists, but would incur their side effects.” For those and other reasons, “new biomarkers are needed for diagnosing AAH, assessing the degree of hepatocyte death, and predicting mortality,” they said (Clin Gastroenterol Hepatol. 2019 Dec 4. doi: 10.1016/j.cgh.2019.11.050).

Keratin 18 – both the cleaved form (K18M30) and the uncleaved protein (K18M65) – have been suggested before as a marker for AAH, so the investigators took a closer look.

They analyzed serum from 57 people with severe AAH (MELD score above 20), 27 people with moderate AAH (MELD score 12-19), 34 with nonalcoholic steatohepatitis, 17 healthy controls, and 38 people with alcohol use disorder and either mild or no liver injury.

Overall, 51.9% of moderate AAH cases and 38.9% of severe cases had K18M65 levels between 641 and 2,000 IU/L; 25.9% of moderate and 61.1% of severe cases had K18M65 levels greater than 2,000 IU/L. All severe cases had levels above 641 IU/L. Serum levels of K18 also identified patients who died within 90 days with greater accuracy than did MELD, ABIC, and other scores, the investigators said.

The K18M65:ALT [alanine aminotransferase] ratio distinguished AAH from nonalcoholic steatohepatitis with a sensitivity of 0.971 and specificity of 0.829. Findings were similar for the K18M30:ALT ratio.

Levels of K18M65 and K18M30 increased significantly as liver disease worsened, as did the degree of necrosis as indicated by the K18M65:K18M30 ratio. Meanwhile, although k18 levels correlated with MELD scores, levels of ALT, aspartate aminotransferase (AST), and the ratio of AST:ALT did not.

“There is a stronger association between serum level of keratin 18 and amount of hepatocyte death and liver disease severity than for other biomarkers,” the team concluded.

Patients were in their mid 40s, on average, and there were more men than women.

The National Institutes of Health supported the work, and the investigators had no disclosures.

[email protected]

Serum keratin 18, an epithelial protein released from dying hepatocytes, identifies patients with severe acute alcoholic hepatitis (AAH) at high risk for death, according to an investigation of 173 subjects.

Standard biomarker scores – Model for End-stage Liver Disease (MELD), age, serum bilirubin, International Normalized Ratio, and serum creatinine (ABIC), as well as others – predict prognosis and severity of alcoholic liver disease, but they don’t reflect “the magnitude of cell death nor the form of cell death (apoptosis/necrosis), which may be important in distinguishing various forms of liver injury” and guiding therapy, explained investigators led by Vatsalya Vatsalya, MD, of the division of gastroenterology, hepatology, and nutrition at the University of Louisville (Ky.).

It’s important, for instance, to identify people with alcoholic cirrhosis but not active hepatitis, as they “would likely not benefit from anti-inflammatory agents such as steroids or [interleukin]-1 receptor antagonists, but would incur their side effects.” For those and other reasons, “new biomarkers are needed for diagnosing AAH, assessing the degree of hepatocyte death, and predicting mortality,” they said (Clin Gastroenterol Hepatol. 2019 Dec 4. doi: 10.1016/j.cgh.2019.11.050).

Keratin 18 – both the cleaved form (K18M30) and the uncleaved protein (K18M65) – have been suggested before as a marker for AAH, so the investigators took a closer look.

They analyzed serum from 57 people with severe AAH (MELD score above 20), 27 people with moderate AAH (MELD score 12-19), 34 with nonalcoholic steatohepatitis, 17 healthy controls, and 38 people with alcohol use disorder and either mild or no liver injury.

Overall, 51.9% of moderate AAH cases and 38.9% of severe cases had K18M65 levels between 641 and 2,000 IU/L; 25.9% of moderate and 61.1% of severe cases had K18M65 levels greater than 2,000 IU/L. All severe cases had levels above 641 IU/L. Serum levels of K18 also identified patients who died within 90 days with greater accuracy than did MELD, ABIC, and other scores, the investigators said.

The K18M65:ALT [alanine aminotransferase] ratio distinguished AAH from nonalcoholic steatohepatitis with a sensitivity of 0.971 and specificity of 0.829. Findings were similar for the K18M30:ALT ratio.

Levels of K18M65 and K18M30 increased significantly as liver disease worsened, as did the degree of necrosis as indicated by the K18M65:K18M30 ratio. Meanwhile, although k18 levels correlated with MELD scores, levels of ALT, aspartate aminotransferase (AST), and the ratio of AST:ALT did not.

“There is a stronger association between serum level of keratin 18 and amount of hepatocyte death and liver disease severity than for other biomarkers,” the team concluded.

Patients were in their mid 40s, on average, and there were more men than women.

The National Institutes of Health supported the work, and the investigators had no disclosures.

[email protected]

Serum keratin 18, an epithelial protein released from dying hepatocytes, identifies patients with severe acute alcoholic hepatitis (AAH) at high risk for death, according to an investigation of 173 subjects.

Standard biomarker scores – Model for End-stage Liver Disease (MELD), age, serum bilirubin, International Normalized Ratio, and serum creatinine (ABIC), as well as others – predict prognosis and severity of alcoholic liver disease, but they don’t reflect “the magnitude of cell death nor the form of cell death (apoptosis/necrosis), which may be important in distinguishing various forms of liver injury” and guiding therapy, explained investigators led by Vatsalya Vatsalya, MD, of the division of gastroenterology, hepatology, and nutrition at the University of Louisville (Ky.).

It’s important, for instance, to identify people with alcoholic cirrhosis but not active hepatitis, as they “would likely not benefit from anti-inflammatory agents such as steroids or [interleukin]-1 receptor antagonists, but would incur their side effects.” For those and other reasons, “new biomarkers are needed for diagnosing AAH, assessing the degree of hepatocyte death, and predicting mortality,” they said (Clin Gastroenterol Hepatol. 2019 Dec 4. doi: 10.1016/j.cgh.2019.11.050).

Keratin 18 – both the cleaved form (K18M30) and the uncleaved protein (K18M65) – have been suggested before as a marker for AAH, so the investigators took a closer look.

They analyzed serum from 57 people with severe AAH (MELD score above 20), 27 people with moderate AAH (MELD score 12-19), 34 with nonalcoholic steatohepatitis, 17 healthy controls, and 38 people with alcohol use disorder and either mild or no liver injury.

Overall, 51.9% of moderate AAH cases and 38.9% of severe cases had K18M65 levels between 641 and 2,000 IU/L; 25.9% of moderate and 61.1% of severe cases had K18M65 levels greater than 2,000 IU/L. All severe cases had levels above 641 IU/L. Serum levels of K18 also identified patients who died within 90 days with greater accuracy than did MELD, ABIC, and other scores, the investigators said.

The K18M65:ALT [alanine aminotransferase] ratio distinguished AAH from nonalcoholic steatohepatitis with a sensitivity of 0.971 and specificity of 0.829. Findings were similar for the K18M30:ALT ratio.

Levels of K18M65 and K18M30 increased significantly as liver disease worsened, as did the degree of necrosis as indicated by the K18M65:K18M30 ratio. Meanwhile, although k18 levels correlated with MELD scores, levels of ALT, aspartate aminotransferase (AST), and the ratio of AST:ALT did not.

“There is a stronger association between serum level of keratin 18 and amount of hepatocyte death and liver disease severity than for other biomarkers,” the team concluded.

Patients were in their mid 40s, on average, and there were more men than women.

The National Institutes of Health supported the work, and the investigators had no disclosures.

[email protected]

The incorporation of telehealth in the liver transplantation process is demonstrating the potential to expedite the evaluation of patients and get them listed on the transplant wait list.

kgtoh/Thinkstock

New research shows “a transplant hepatologist evaluation using telehealth was associated with significantly reduced time to evaluation and listing without adversely affecting pretransplant mortality compared to the current standard of care of in-person evaluation at a transplant center,” Binu V. John, MD, of McGuire VA Medical Center, Richmond, and colleagues wrote in a report published in Clinical Gastroenterology and Hepatology (2019 Dec 27. doi: 10.1016/j.cgh.2019.12.021).

Researchers looked at 465 patients who had evaluations for liver transplants at the Richmond Veterans Affairs Medical Center from 2005 through 2017. Nearly half (232 patients) were evaluated via telehealth, with the remaining 233 evaluated with traditional in-person evaluations.

“Patients in the telehealth group were evaluated significantly faster than patients in the usual care group (22 vs. 54 days, P less than .001),” Dr. John and colleagues wrote, adding that, after conducting a propensity-matched analysis, “telehealth was associated with an 85% reduction in time from referral to evaluation.”

Additionally, patients “who underwent the initial evaluation by telehealth were listed significantly earlier than the usual care group (95 vs. 149 days; P less than .001),” the authors stated, adding that “telehealth was associated with a 74% reduction in time to listing” after conducting a propensity-matched analysis.

However, while speeding up time to referral and listing, “the median time to transplant was not significantly different between the two groups on unadjusted (218 vs. 244 days; P = .084) or adjusted analysis (325 vs. 409 days; P = .08),” they added.

Additionally, “there was no difference in pretransplant mortality between [those] evaluated by telehealth or usual care in unadjusted analysis,” Dr. John and colleagues observed, noting that 169 of 465 patients (51 on the waiting list for a transplant and 118 who were not listed) who were referred died without receiving a liver transplant.

Researchers suggested that while evaluation times may have been shorter with the use of telehealth, they did not translate to shorter transplantation times “likely because the latter is a complex metric that is driven primarily by organ availability.”

Dr. John and colleagues cautioned that the centralized nature of the VA medical system could make the results of this study not generalizable across private care settings, particularly when care needs to cross state lines, which does not present an issue within the VA medical system.

That being said, the “ability to successfully evaluate and list patients via telehealth and obtain the same outcomes in terms of time to transplant and pretransplant mortality is significant because of the numerous advantages that telehealth offers to improve overall access to transplantation,” they stated, adding that more studies are needed, both in and out of the VA system, “to confirm that telehealth is a safe and effective way to expand access for patients undergoing evaluation for liver transplantation.”

Lead author Dr. Binu John serves on medical advisory boards for Gilead and Eisai and received research funding from a number of pharmaceutical manufacturers. No conflicts of interest were reported by the other authors.

[email protected]

SOURCE: John BV et al. Clin Gastroenterol Hepatol. doi: 10.1016/j.cgh.2019.12.021.

The incorporation of telehealth in the liver transplantation process is demonstrating the potential to expedite the evaluation of patients and get them listed on the transplant wait list.

kgtoh/Thinkstock

New research shows “a transplant hepatologist evaluation using telehealth was associated with significantly reduced time to evaluation and listing without adversely affecting pretransplant mortality compared to the current standard of care of in-person evaluation at a transplant center,” Binu V. John, MD, of McGuire VA Medical Center, Richmond, and colleagues wrote in a report published in Clinical Gastroenterology and Hepatology (2019 Dec 27. doi: 10.1016/j.cgh.2019.12.021).

Researchers looked at 465 patients who had evaluations for liver transplants at the Richmond Veterans Affairs Medical Center from 2005 through 2017. Nearly half (232 patients) were evaluated via telehealth, with the remaining 233 evaluated with traditional in-person evaluations.

“Patients in the telehealth group were evaluated significantly faster than patients in the usual care group (22 vs. 54 days, P less than .001),” Dr. John and colleagues wrote, adding that, after conducting a propensity-matched analysis, “telehealth was associated with an 85% reduction in time from referral to evaluation.”

Additionally, patients “who underwent the initial evaluation by telehealth were listed significantly earlier than the usual care group (95 vs. 149 days; P less than .001),” the authors stated, adding that “telehealth was associated with a 74% reduction in time to listing” after conducting a propensity-matched analysis.

However, while speeding up time to referral and listing, “the median time to transplant was not significantly different between the two groups on unadjusted (218 vs. 244 days; P = .084) or adjusted analysis (325 vs. 409 days; P = .08),” they added.

Additionally, “there was no difference in pretransplant mortality between [those] evaluated by telehealth or usual care in unadjusted analysis,” Dr. John and colleagues observed, noting that 169 of 465 patients (51 on the waiting list for a transplant and 118 who were not listed) who were referred died without receiving a liver transplant.

Researchers suggested that while evaluation times may have been shorter with the use of telehealth, they did not translate to shorter transplantation times “likely because the latter is a complex metric that is driven primarily by organ availability.”

Dr. John and colleagues cautioned that the centralized nature of the VA medical system could make the results of this study not generalizable across private care settings, particularly when care needs to cross state lines, which does not present an issue within the VA medical system.

That being said, the “ability to successfully evaluate and list patients via telehealth and obtain the same outcomes in terms of time to transplant and pretransplant mortality is significant because of the numerous advantages that telehealth offers to improve overall access to transplantation,” they stated, adding that more studies are needed, both in and out of the VA system, “to confirm that telehealth is a safe and effective way to expand access for patients undergoing evaluation for liver transplantation.”

Lead author Dr. Binu John serves on medical advisory boards for Gilead and Eisai and received research funding from a number of pharmaceutical manufacturers. No conflicts of interest were reported by the other authors.

[email protected]

SOURCE: John BV et al. Clin Gastroenterol Hepatol. doi: 10.1016/j.cgh.2019.12.021.

The incorporation of telehealth in the liver transplantation process is demonstrating the potential to expedite the evaluation of patients and get them listed on the transplant wait list.

kgtoh/Thinkstock

New research shows “a transplant hepatologist evaluation using telehealth was associated with significantly reduced time to evaluation and listing without adversely affecting pretransplant mortality compared to the current standard of care of in-person evaluation at a transplant center,” Binu V. John, MD, of McGuire VA Medical Center, Richmond, and colleagues wrote in a report published in Clinical Gastroenterology and Hepatology (2019 Dec 27. doi: 10.1016/j.cgh.2019.12.021).

Researchers looked at 465 patients who had evaluations for liver transplants at the Richmond Veterans Affairs Medical Center from 2005 through 2017. Nearly half (232 patients) were evaluated via telehealth, with the remaining 233 evaluated with traditional in-person evaluations.

“Patients in the telehealth group were evaluated significantly faster than patients in the usual care group (22 vs. 54 days, P less than .001),” Dr. John and colleagues wrote, adding that, after conducting a propensity-matched analysis, “telehealth was associated with an 85% reduction in time from referral to evaluation.”

Additionally, patients “who underwent the initial evaluation by telehealth were listed significantly earlier than the usual care group (95 vs. 149 days; P less than .001),” the authors stated, adding that “telehealth was associated with a 74% reduction in time to listing” after conducting a propensity-matched analysis.

However, while speeding up time to referral and listing, “the median time to transplant was not significantly different between the two groups on unadjusted (218 vs. 244 days; P = .084) or adjusted analysis (325 vs. 409 days; P = .08),” they added.

Additionally, “there was no difference in pretransplant mortality between [those] evaluated by telehealth or usual care in unadjusted analysis,” Dr. John and colleagues observed, noting that 169 of 465 patients (51 on the waiting list for a transplant and 118 who were not listed) who were referred died without receiving a liver transplant.

Researchers suggested that while evaluation times may have been shorter with the use of telehealth, they did not translate to shorter transplantation times “likely because the latter is a complex metric that is driven primarily by organ availability.”

Dr. John and colleagues cautioned that the centralized nature of the VA medical system could make the results of this study not generalizable across private care settings, particularly when care needs to cross state lines, which does not present an issue within the VA medical system.

That being said, the “ability to successfully evaluate and list patients via telehealth and obtain the same outcomes in terms of time to transplant and pretransplant mortality is significant because of the numerous advantages that telehealth offers to improve overall access to transplantation,” they stated, adding that more studies are needed, both in and out of the VA system, “to confirm that telehealth is a safe and effective way to expand access for patients undergoing evaluation for liver transplantation.”

Lead author Dr. Binu John serves on medical advisory boards for Gilead and Eisai and received research funding from a number of pharmaceutical manufacturers. No conflicts of interest were reported by the other authors.

[email protected]

SOURCE: John BV et al. Clin Gastroenterol Hepatol. doi: 10.1016/j.cgh.2019.12.021.

Patients with nonalcoholic fatty liver disease (NAFLD) in a prospective observational study had a twofold increase in cardiovascular events, NAFLD patients with liver fibrosis had a fourfold increase in risk, and liver fibrosis scores predicted risk.

At median follow-up of 41.4 months representing 3,044.4 person-years of observation in the Progression of Liver Damage and Cardiometabolic Disorders in NAFLD (PLINIO) study, 58 cardiovascular events (CVEs) were reported in 898 consecutive outpatients who were screened for liver steatosis by ultrasound. The annual rate of CVEs among 643 patients with NAFLD was 2.1%, compared with 1.0% among 255 patients without NAFLD, according to Francesco Baratta, MD, of Clinica Medica, Sapienza University of Rome, and colleagues. Their report is in Clinical Gastroenterology and Hepatology.

The difference did not meet a priori thresholds for statistical significance (P = .066), but became significant after exclusion of new-onset atrial fibrillation events (annual CVE rates of 1.9% vs. 0.7%; P = .034), and on multivariate analysis, age, male sex, and NAFLD were found to be independently associated with CVE occurrence (hazard ratios, 1.07, 3.20, and 2.73, respectively), the investigators found.

In NAFLD patients, a NAFLD fibrosis score (NFS) greater than 0.676 was significantly associated with CVEs after adjustment for comorbidities (HR, 2.29), and a Fibrosis-4 (FIB-4) score greater than 2.67, a history of cardiovascular disease, and metabolic syndrome predicted incident CVEs (HRs, 4.57, 2.95, and 2.30, respectively). The findings were similar after exclusion of new-onset atrial fibrillation from the composite endpoint (HRs, 2.42 and 4.00, respectively).

“Furthermore, when we analyzed only patients without CVEs at baseline, we found a similar association between liver fibrosis and CVEs,” the researchers wrote, noting that the adjusted HRs for NFS were 2.50 and 4.28, respectively.

In addition to liver-related complications, patients with NAFLD are known to have an increased CVE risk, and while liver fibrosis severity is used to determine prognosis, not all patients can undergo a liver biopsy to assess fibrosis. Therefore, there is a need to identify and validate noninvasive markers of liver fibrosis, but few data exist with respect to the predictive role of noninvasive scoring on CVEs, they said.

The findings of this study suggest the use of the NFS and FIB-4 score may reduce the need for liver biopsy by identifying NAFLD patients at higher risk of having advanced liver fibrosis. They further suggest that liver fibrosis development in patients with NAFLD “may be the result of a long-term exposure to cardiometabolic risk factors such as diabetes,” and that “the concomitant presence of multiple cardiometabolic conditions may induce a chronic low-grade proinflammatory and pro-oxidant status leading to liver inflammation (i.e., macrophage activation) and collagen deposition.”

The findings may also have clinical implications: “The association between liver fibrosis and cardiovascular risk supports a potential role for statin treatment in patients with NAFLD,” they explained.

The authors reported having no disclosures.
 

[email protected]

SOURCE: Baratta F et al. Clin Gastroenterol Hepatol. doi: 10.1016/j.cgh.2019.12.026.

Patients with nonalcoholic fatty liver disease (NAFLD) in a prospective observational study had a twofold increase in cardiovascular events, NAFLD patients with liver fibrosis had a fourfold increase in risk, and liver fibrosis scores predicted risk.

At median follow-up of 41.4 months representing 3,044.4 person-years of observation in the Progression of Liver Damage and Cardiometabolic Disorders in NAFLD (PLINIO) study, 58 cardiovascular events (CVEs) were reported in 898 consecutive outpatients who were screened for liver steatosis by ultrasound. The annual rate of CVEs among 643 patients with NAFLD was 2.1%, compared with 1.0% among 255 patients without NAFLD, according to Francesco Baratta, MD, of Clinica Medica, Sapienza University of Rome, and colleagues. Their report is in Clinical Gastroenterology and Hepatology.

The difference did not meet a priori thresholds for statistical significance (P = .066), but became significant after exclusion of new-onset atrial fibrillation events (annual CVE rates of 1.9% vs. 0.7%; P = .034), and on multivariate analysis, age, male sex, and NAFLD were found to be independently associated with CVE occurrence (hazard ratios, 1.07, 3.20, and 2.73, respectively), the investigators found.

In NAFLD patients, a NAFLD fibrosis score (NFS) greater than 0.676 was significantly associated with CVEs after adjustment for comorbidities (HR, 2.29), and a Fibrosis-4 (FIB-4) score greater than 2.67, a history of cardiovascular disease, and metabolic syndrome predicted incident CVEs (HRs, 4.57, 2.95, and 2.30, respectively). The findings were similar after exclusion of new-onset atrial fibrillation from the composite endpoint (HRs, 2.42 and 4.00, respectively).

“Furthermore, when we analyzed only patients without CVEs at baseline, we found a similar association between liver fibrosis and CVEs,” the researchers wrote, noting that the adjusted HRs for NFS were 2.50 and 4.28, respectively.

In addition to liver-related complications, patients with NAFLD are known to have an increased CVE risk, and while liver fibrosis severity is used to determine prognosis, not all patients can undergo a liver biopsy to assess fibrosis. Therefore, there is a need to identify and validate noninvasive markers of liver fibrosis, but few data exist with respect to the predictive role of noninvasive scoring on CVEs, they said.

The findings of this study suggest the use of the NFS and FIB-4 score may reduce the need for liver biopsy by identifying NAFLD patients at higher risk of having advanced liver fibrosis. They further suggest that liver fibrosis development in patients with NAFLD “may be the result of a long-term exposure to cardiometabolic risk factors such as diabetes,” and that “the concomitant presence of multiple cardiometabolic conditions may induce a chronic low-grade proinflammatory and pro-oxidant status leading to liver inflammation (i.e., macrophage activation) and collagen deposition.”

The findings may also have clinical implications: “The association between liver fibrosis and cardiovascular risk supports a potential role for statin treatment in patients with NAFLD,” they explained.

The authors reported having no disclosures.
 

[email protected]

SOURCE: Baratta F et al. Clin Gastroenterol Hepatol. doi: 10.1016/j.cgh.2019.12.026.

Patients with nonalcoholic fatty liver disease (NAFLD) in a prospective observational study had a twofold increase in cardiovascular events, NAFLD patients with liver fibrosis had a fourfold increase in risk, and liver fibrosis scores predicted risk.

At median follow-up of 41.4 months representing 3,044.4 person-years of observation in the Progression of Liver Damage and Cardiometabolic Disorders in NAFLD (PLINIO) study, 58 cardiovascular events (CVEs) were reported in 898 consecutive outpatients who were screened for liver steatosis by ultrasound. The annual rate of CVEs among 643 patients with NAFLD was 2.1%, compared with 1.0% among 255 patients without NAFLD, according to Francesco Baratta, MD, of Clinica Medica, Sapienza University of Rome, and colleagues. Their report is in Clinical Gastroenterology and Hepatology.

The difference did not meet a priori thresholds for statistical significance (P = .066), but became significant after exclusion of new-onset atrial fibrillation events (annual CVE rates of 1.9% vs. 0.7%; P = .034), and on multivariate analysis, age, male sex, and NAFLD were found to be independently associated with CVE occurrence (hazard ratios, 1.07, 3.20, and 2.73, respectively), the investigators found.

In NAFLD patients, a NAFLD fibrosis score (NFS) greater than 0.676 was significantly associated with CVEs after adjustment for comorbidities (HR, 2.29), and a Fibrosis-4 (FIB-4) score greater than 2.67, a history of cardiovascular disease, and metabolic syndrome predicted incident CVEs (HRs, 4.57, 2.95, and 2.30, respectively). The findings were similar after exclusion of new-onset atrial fibrillation from the composite endpoint (HRs, 2.42 and 4.00, respectively).

“Furthermore, when we analyzed only patients without CVEs at baseline, we found a similar association between liver fibrosis and CVEs,” the researchers wrote, noting that the adjusted HRs for NFS were 2.50 and 4.28, respectively.

In addition to liver-related complications, patients with NAFLD are known to have an increased CVE risk, and while liver fibrosis severity is used to determine prognosis, not all patients can undergo a liver biopsy to assess fibrosis. Therefore, there is a need to identify and validate noninvasive markers of liver fibrosis, but few data exist with respect to the predictive role of noninvasive scoring on CVEs, they said.

The findings of this study suggest the use of the NFS and FIB-4 score may reduce the need for liver biopsy by identifying NAFLD patients at higher risk of having advanced liver fibrosis. They further suggest that liver fibrosis development in patients with NAFLD “may be the result of a long-term exposure to cardiometabolic risk factors such as diabetes,” and that “the concomitant presence of multiple cardiometabolic conditions may induce a chronic low-grade proinflammatory and pro-oxidant status leading to liver inflammation (i.e., macrophage activation) and collagen deposition.”

The findings may also have clinical implications: “The association between liver fibrosis and cardiovascular risk supports a potential role for statin treatment in patients with NAFLD,” they explained.

The authors reported having no disclosures.
 

[email protected]

SOURCE: Baratta F et al. Clin Gastroenterol Hepatol. doi: 10.1016/j.cgh.2019.12.026.