HCV Hub

Hepatitis C virus infection often is associated with the accumulation of fat in hepatocytes, which shows a connection between the virus and the lipid metabolism of the liver, according to Sarah Hoffman, MD, of the Leibniz Institute for Experimental Virology, Hamburg, Germany, and her colleagues. “Our study provides a detailed analysis of the changes in the lipid composition in HCV-infected cells that revealed dependency on FA [fatty acid] elongation and desaturation for effective viral replication and virion production,” they reported.

Dr. Hoffman and her colleagues assessed lipid composition of infected cells in an in vitro study of cell lines, which were assessed 8-11 days post infection, according to the report published in BBA: Molecular and Cell Biology of Lipids. They determined the abundance of each major lipid class and compared the pattern of HCV-infected cells with that of controls.

The researchers found that HCV caused an accumulation of membrane phosopholipids but not neutral lipids and that cholesterol accumulated in the perinuclear region of HCV-infected cells. In addition, lipid species with longer fatty acyl chains were more abundant in HCV-infected cells and free polyunsaturated fatty acid (PUFA) levels were greatly increased.

In further confirmation of the critical role of lipid metabolism in HCV replication, they found that knockdown of fatty acid elongases and desaturases disrupted HCV replication, while overexpression of these enzymes showed a proviral effect.

“We identified several lipid-remodeling pathways that are required for distinct steps in viral infection. Future studies have to address the molecular function of longer fatty acyl chains in HCV RNA replication and why PUFAs are needed for HCV particle production,” the researchers concluded.

The authors reported government and institutional-only funding and no personal disclosures.

[email protected]

SOURCE: Hoffman S et al. Biochim Biophys Acta. 2018 Jun 6;1863(9):1041-56.

Hepatitis C virus infection often is associated with the accumulation of fat in hepatocytes, which shows a connection between the virus and the lipid metabolism of the liver, according to Sarah Hoffman, MD, of the Leibniz Institute for Experimental Virology, Hamburg, Germany, and her colleagues. “Our study provides a detailed analysis of the changes in the lipid composition in HCV-infected cells that revealed dependency on FA [fatty acid] elongation and desaturation for effective viral replication and virion production,” they reported.

Dr. Hoffman and her colleagues assessed lipid composition of infected cells in an in vitro study of cell lines, which were assessed 8-11 days post infection, according to the report published in BBA: Molecular and Cell Biology of Lipids. They determined the abundance of each major lipid class and compared the pattern of HCV-infected cells with that of controls.

The researchers found that HCV caused an accumulation of membrane phosopholipids but not neutral lipids and that cholesterol accumulated in the perinuclear region of HCV-infected cells. In addition, lipid species with longer fatty acyl chains were more abundant in HCV-infected cells and free polyunsaturated fatty acid (PUFA) levels were greatly increased.

In further confirmation of the critical role of lipid metabolism in HCV replication, they found that knockdown of fatty acid elongases and desaturases disrupted HCV replication, while overexpression of these enzymes showed a proviral effect.

“We identified several lipid-remodeling pathways that are required for distinct steps in viral infection. Future studies have to address the molecular function of longer fatty acyl chains in HCV RNA replication and why PUFAs are needed for HCV particle production,” the researchers concluded.

The authors reported government and institutional-only funding and no personal disclosures.

[email protected]

SOURCE: Hoffman S et al. Biochim Biophys Acta. 2018 Jun 6;1863(9):1041-56.

Hepatitis C virus infection often is associated with the accumulation of fat in hepatocytes, which shows a connection between the virus and the lipid metabolism of the liver, according to Sarah Hoffman, MD, of the Leibniz Institute for Experimental Virology, Hamburg, Germany, and her colleagues. “Our study provides a detailed analysis of the changes in the lipid composition in HCV-infected cells that revealed dependency on FA [fatty acid] elongation and desaturation for effective viral replication and virion production,” they reported.

Dr. Hoffman and her colleagues assessed lipid composition of infected cells in an in vitro study of cell lines, which were assessed 8-11 days post infection, according to the report published in BBA: Molecular and Cell Biology of Lipids. They determined the abundance of each major lipid class and compared the pattern of HCV-infected cells with that of controls.

The researchers found that HCV caused an accumulation of membrane phosopholipids but not neutral lipids and that cholesterol accumulated in the perinuclear region of HCV-infected cells. In addition, lipid species with longer fatty acyl chains were more abundant in HCV-infected cells and free polyunsaturated fatty acid (PUFA) levels were greatly increased.

In further confirmation of the critical role of lipid metabolism in HCV replication, they found that knockdown of fatty acid elongases and desaturases disrupted HCV replication, while overexpression of these enzymes showed a proviral effect.

“We identified several lipid-remodeling pathways that are required for distinct steps in viral infection. Future studies have to address the molecular function of longer fatty acyl chains in HCV RNA replication and why PUFAs are needed for HCV particle production,” the researchers concluded.

The authors reported government and institutional-only funding and no personal disclosures.

[email protected]

SOURCE: Hoffman S et al. Biochim Biophys Acta. 2018 Jun 6;1863(9):1041-56.

There is a cigarette smoking epidemic embedded within the hepatitis C virus epidemic in the United States, according to the results of an analysis of data between 1999 and 2014 from the National Health and Nutrition Examination Survey (NHANES).

©siwaporn999/Thinkstock

Smoking and hepatitis C information were available for 90.1% of the NHANES adult population. Of the 39,472 individuals evaluated, 1.3% were hepatitis C+ and 22.3% were current smokers. Hepatitis C+ individuals were almost three times as likely to be smokers as were those who were hepatitis C– (62.4% vs. 22.9%, respectively), according to the report, published in The American Journal of Medicine (Am J Med. 2018 Jun;131[6]:699-75).

Ryung S. Kim, PhD, of Albert Einstein College of Medicine, New York, and his colleagues also found that hepatitis C+ smokers were more likely to be older, male, black, less educated, poor, and uninsured compared with their hepatitis C– smoking counterparts. They also were more likely to use drugs, including heroin, and to be depressed.

Multivariate analysis showed a significant association of both hepatitis C infection and smoking with current depression and hypertension, Dr. Kim and his colleagues wrote.

“It is public health folly to spend tens of millions of dollars annually” on treatment of hepatitis C patients, “and ignore the lethal addiction affecting more than 60% of them. As we enter a new era of hepatitis C treatment, it is a public health imperative to research, develop, and implement tobacco treatments for the hepatitis C+ community,” Dr. Kim and his colleagues concluded.

The authors reported that they had no conflicts of interest.

[email protected]

SOURCE: Kim RS et al. Am J Med. 2018Jun;131[6]:669-75).

There is a cigarette smoking epidemic embedded within the hepatitis C virus epidemic in the United States, according to the results of an analysis of data between 1999 and 2014 from the National Health and Nutrition Examination Survey (NHANES).

©siwaporn999/Thinkstock

Smoking and hepatitis C information were available for 90.1% of the NHANES adult population. Of the 39,472 individuals evaluated, 1.3% were hepatitis C+ and 22.3% were current smokers. Hepatitis C+ individuals were almost three times as likely to be smokers as were those who were hepatitis C– (62.4% vs. 22.9%, respectively), according to the report, published in The American Journal of Medicine (Am J Med. 2018 Jun;131[6]:699-75).

Ryung S. Kim, PhD, of Albert Einstein College of Medicine, New York, and his colleagues also found that hepatitis C+ smokers were more likely to be older, male, black, less educated, poor, and uninsured compared with their hepatitis C– smoking counterparts. They also were more likely to use drugs, including heroin, and to be depressed.

Multivariate analysis showed a significant association of both hepatitis C infection and smoking with current depression and hypertension, Dr. Kim and his colleagues wrote.

“It is public health folly to spend tens of millions of dollars annually” on treatment of hepatitis C patients, “and ignore the lethal addiction affecting more than 60% of them. As we enter a new era of hepatitis C treatment, it is a public health imperative to research, develop, and implement tobacco treatments for the hepatitis C+ community,” Dr. Kim and his colleagues concluded.

The authors reported that they had no conflicts of interest.

[email protected]

SOURCE: Kim RS et al. Am J Med. 2018Jun;131[6]:669-75).

There is a cigarette smoking epidemic embedded within the hepatitis C virus epidemic in the United States, according to the results of an analysis of data between 1999 and 2014 from the National Health and Nutrition Examination Survey (NHANES).

©siwaporn999/Thinkstock

Smoking and hepatitis C information were available for 90.1% of the NHANES adult population. Of the 39,472 individuals evaluated, 1.3% were hepatitis C+ and 22.3% were current smokers. Hepatitis C+ individuals were almost three times as likely to be smokers as were those who were hepatitis C– (62.4% vs. 22.9%, respectively), according to the report, published in The American Journal of Medicine (Am J Med. 2018 Jun;131[6]:699-75).

Ryung S. Kim, PhD, of Albert Einstein College of Medicine, New York, and his colleagues also found that hepatitis C+ smokers were more likely to be older, male, black, less educated, poor, and uninsured compared with their hepatitis C– smoking counterparts. They also were more likely to use drugs, including heroin, and to be depressed.

Multivariate analysis showed a significant association of both hepatitis C infection and smoking with current depression and hypertension, Dr. Kim and his colleagues wrote.

“It is public health folly to spend tens of millions of dollars annually” on treatment of hepatitis C patients, “and ignore the lethal addiction affecting more than 60% of them. As we enter a new era of hepatitis C treatment, it is a public health imperative to research, develop, and implement tobacco treatments for the hepatitis C+ community,” Dr. Kim and his colleagues concluded.

The authors reported that they had no conflicts of interest.

[email protected]

SOURCE: Kim RS et al. Am J Med. 2018Jun;131[6]:669-75).

The incidence rate of HCV among HIV-positive men who have sex with men (MSM) was significantly higher than that found in HIV-negative MSM and the general population, according to a study published in Digestive and Liver Disease.

Sexual transmission of hepatitis C virus (HCV) is uncommon in the general population, but evidence indicates that its rate is higher in people living with HIV and that HIV-positive MSM who practice condomless sex have been shown to be at increased risk for sexually-acquired HCV, according to Gianluca Cuomo, MD, and his colleagues at the Azienda Ospedaliero-Universitaria di Modena (Italy), Infectious Diseases Clinic.

Courtesy U.S. Department of Veterans Affairs

Dr. Cuomo and his colleagues assessed 442 HIV-positive MSM outpatients who were antibody negative to HCV-Ab at first observation who were entered into a Kaplan-Meier model in order to assess the HCV infection incidence rate. Prevalence analysis was performed with HIV-positive MSM who were on follow-up at 2016. An HIV-negative MSM population served as a control.

“Our study indicates an incidence rate of HCV among MSM living with HIV of 0.44 cases per 100 patient-years with a global prevalence of 9%, both of which are significantly higher than that of non-HIV MSM and the general population,” Dr. Cuomo and his colleagues found (Digestive and Liver Disease; 2018, [doi.org/10.1016/j.dld.2018.05.021]).

“Early management and treatment of HCV infection and behavioral interventions could reduce HCV transmission. Annual screenings for HCV and other sexually transmitted diseases should be performed for HIV MSM patients,” the researchers concluded.

Dr. Cuomo and his colleagues reported that they had no disclosures.

[email protected]

SOURCE: Cuomo, G., et al. Digestive and Liver Disease (2018), [doi.org/10.1016/j.dld.2018.05.021].

The incidence rate of HCV among HIV-positive men who have sex with men (MSM) was significantly higher than that found in HIV-negative MSM and the general population, according to a study published in Digestive and Liver Disease.

Sexual transmission of hepatitis C virus (HCV) is uncommon in the general population, but evidence indicates that its rate is higher in people living with HIV and that HIV-positive MSM who practice condomless sex have been shown to be at increased risk for sexually-acquired HCV, according to Gianluca Cuomo, MD, and his colleagues at the Azienda Ospedaliero-Universitaria di Modena (Italy), Infectious Diseases Clinic.

Courtesy U.S. Department of Veterans Affairs

Dr. Cuomo and his colleagues assessed 442 HIV-positive MSM outpatients who were antibody negative to HCV-Ab at first observation who were entered into a Kaplan-Meier model in order to assess the HCV infection incidence rate. Prevalence analysis was performed with HIV-positive MSM who were on follow-up at 2016. An HIV-negative MSM population served as a control.

“Our study indicates an incidence rate of HCV among MSM living with HIV of 0.44 cases per 100 patient-years with a global prevalence of 9%, both of which are significantly higher than that of non-HIV MSM and the general population,” Dr. Cuomo and his colleagues found (Digestive and Liver Disease; 2018, [doi.org/10.1016/j.dld.2018.05.021]).

“Early management and treatment of HCV infection and behavioral interventions could reduce HCV transmission. Annual screenings for HCV and other sexually transmitted diseases should be performed for HIV MSM patients,” the researchers concluded.

Dr. Cuomo and his colleagues reported that they had no disclosures.

[email protected]

SOURCE: Cuomo, G., et al. Digestive and Liver Disease (2018), [doi.org/10.1016/j.dld.2018.05.021].

The incidence rate of HCV among HIV-positive men who have sex with men (MSM) was significantly higher than that found in HIV-negative MSM and the general population, according to a study published in Digestive and Liver Disease.

Sexual transmission of hepatitis C virus (HCV) is uncommon in the general population, but evidence indicates that its rate is higher in people living with HIV and that HIV-positive MSM who practice condomless sex have been shown to be at increased risk for sexually-acquired HCV, according to Gianluca Cuomo, MD, and his colleagues at the Azienda Ospedaliero-Universitaria di Modena (Italy), Infectious Diseases Clinic.

Courtesy U.S. Department of Veterans Affairs

Dr. Cuomo and his colleagues assessed 442 HIV-positive MSM outpatients who were antibody negative to HCV-Ab at first observation who were entered into a Kaplan-Meier model in order to assess the HCV infection incidence rate. Prevalence analysis was performed with HIV-positive MSM who were on follow-up at 2016. An HIV-negative MSM population served as a control.

“Our study indicates an incidence rate of HCV among MSM living with HIV of 0.44 cases per 100 patient-years with a global prevalence of 9%, both of which are significantly higher than that of non-HIV MSM and the general population,” Dr. Cuomo and his colleagues found (Digestive and Liver Disease; 2018, [doi.org/10.1016/j.dld.2018.05.021]).

“Early management and treatment of HCV infection and behavioral interventions could reduce HCV transmission. Annual screenings for HCV and other sexually transmitted diseases should be performed for HIV MSM patients,” the researchers concluded.

Dr. Cuomo and his colleagues reported that they had no disclosures.

[email protected]

SOURCE: Cuomo, G., et al. Digestive and Liver Disease (2018), [doi.org/10.1016/j.dld.2018.05.021].

Nearly 4% of Veterans Affairs patients who screened positive for unhealthy alcohol use were infected with hepatitis C virus, and 64% of these patients were diagnosed with alcohol use disorder, according to the results of a large database analysis.

Despite the fact that alcohol use at all levels can compound the adverse effects of HCV and lead to heightened risks of mortality, particularly among those coinfected with HIV, the majority of these patients did not receive specialty addiction treatment, according to Mandy D. Owens, PhD, and her colleagues at the VA Puget Sound Health Care System, Seattle.

Katarzyna Bialasiewicz/ThinkStock

In their study, published in Drug and Alcohol Dependence, the researchers queried the national VA health care system database, which is made up of 139 large facilities and more than 900 clinics throughout the United States, for all patients with a documented outpatient appointment between October 2009 and May 2013 to identify those with one or more with positive screens on the AUDIT-C (Alcohol Use Disorders Identification Test-Consumption) questionnaire. Those with AUDIT-C scores greater than or equal to 5 were considered positive, and each positive screen was tracked for up to 1 year to assess alcohol-related care outcomes. The four alcohol-related care outcomes measured were: receipt of brief intervention, specialty addiction treatment, alcohol use disorder (AUD) pharmacotherapy, and a composite measure of receiving any of these services.

Patients also were compared across HCV status in the entire sample of patients with positive screening as well as in the subsample with a clinically documented AUD.

During the study period, 830,825 VA patients screened positive for unhealthy alcohol use. Among those, 31,841 (3.8%) patients had a documented diagnosis for HCV, and of these 20,320 (64%) had an AUD. Two-thirds of these AUD patients did not receive specialty addiction treatment, and more than 90% did not receive pharmacotherapy that is approved by the Food and Drug Administration to treat AUD, according to the researchers. “These rates are concerning given the negative impact alcohol use can have on HCV,” they wrote.

They reiterated the importance of the 2016 change in policy adopted by the VA Health System, which updated its treatment guidelines to recommend that all patients with HCV be considered for treatment, regardless of substance use, and explicitly stated that alcohol use and length of abstinence should not be disqualifiers for receiving HCV treatment.

“All patients with HCV should be receiving evidence-based alcohol-related care given the risks of alcohol use in this population, particularly among those coinfected with HIV,” the researchers concluded.

The research was funded by a grant from the National Institute on Alcohol Abuse and Alcoholism. The authors reported that they had no conflicts of interest.

[email protected]

SOURCE: Owens MD et al. Drug Alcohol Depend. 2018;188:79-85.

Nearly 4% of Veterans Affairs patients who screened positive for unhealthy alcohol use were infected with hepatitis C virus, and 64% of these patients were diagnosed with alcohol use disorder, according to the results of a large database analysis.

Despite the fact that alcohol use at all levels can compound the adverse effects of HCV and lead to heightened risks of mortality, particularly among those coinfected with HIV, the majority of these patients did not receive specialty addiction treatment, according to Mandy D. Owens, PhD, and her colleagues at the VA Puget Sound Health Care System, Seattle.

Katarzyna Bialasiewicz/ThinkStock

In their study, published in Drug and Alcohol Dependence, the researchers queried the national VA health care system database, which is made up of 139 large facilities and more than 900 clinics throughout the United States, for all patients with a documented outpatient appointment between October 2009 and May 2013 to identify those with one or more with positive screens on the AUDIT-C (Alcohol Use Disorders Identification Test-Consumption) questionnaire. Those with AUDIT-C scores greater than or equal to 5 were considered positive, and each positive screen was tracked for up to 1 year to assess alcohol-related care outcomes. The four alcohol-related care outcomes measured were: receipt of brief intervention, specialty addiction treatment, alcohol use disorder (AUD) pharmacotherapy, and a composite measure of receiving any of these services.

Patients also were compared across HCV status in the entire sample of patients with positive screening as well as in the subsample with a clinically documented AUD.

During the study period, 830,825 VA patients screened positive for unhealthy alcohol use. Among those, 31,841 (3.8%) patients had a documented diagnosis for HCV, and of these 20,320 (64%) had an AUD. Two-thirds of these AUD patients did not receive specialty addiction treatment, and more than 90% did not receive pharmacotherapy that is approved by the Food and Drug Administration to treat AUD, according to the researchers. “These rates are concerning given the negative impact alcohol use can have on HCV,” they wrote.

They reiterated the importance of the 2016 change in policy adopted by the VA Health System, which updated its treatment guidelines to recommend that all patients with HCV be considered for treatment, regardless of substance use, and explicitly stated that alcohol use and length of abstinence should not be disqualifiers for receiving HCV treatment.

“All patients with HCV should be receiving evidence-based alcohol-related care given the risks of alcohol use in this population, particularly among those coinfected with HIV,” the researchers concluded.

The research was funded by a grant from the National Institute on Alcohol Abuse and Alcoholism. The authors reported that they had no conflicts of interest.

[email protected]

SOURCE: Owens MD et al. Drug Alcohol Depend. 2018;188:79-85.

Nearly 4% of Veterans Affairs patients who screened positive for unhealthy alcohol use were infected with hepatitis C virus, and 64% of these patients were diagnosed with alcohol use disorder, according to the results of a large database analysis.

Despite the fact that alcohol use at all levels can compound the adverse effects of HCV and lead to heightened risks of mortality, particularly among those coinfected with HIV, the majority of these patients did not receive specialty addiction treatment, according to Mandy D. Owens, PhD, and her colleagues at the VA Puget Sound Health Care System, Seattle.

Katarzyna Bialasiewicz/ThinkStock

In their study, published in Drug and Alcohol Dependence, the researchers queried the national VA health care system database, which is made up of 139 large facilities and more than 900 clinics throughout the United States, for all patients with a documented outpatient appointment between October 2009 and May 2013 to identify those with one or more with positive screens on the AUDIT-C (Alcohol Use Disorders Identification Test-Consumption) questionnaire. Those with AUDIT-C scores greater than or equal to 5 were considered positive, and each positive screen was tracked for up to 1 year to assess alcohol-related care outcomes. The four alcohol-related care outcomes measured were: receipt of brief intervention, specialty addiction treatment, alcohol use disorder (AUD) pharmacotherapy, and a composite measure of receiving any of these services.

Patients also were compared across HCV status in the entire sample of patients with positive screening as well as in the subsample with a clinically documented AUD.

During the study period, 830,825 VA patients screened positive for unhealthy alcohol use. Among those, 31,841 (3.8%) patients had a documented diagnosis for HCV, and of these 20,320 (64%) had an AUD. Two-thirds of these AUD patients did not receive specialty addiction treatment, and more than 90% did not receive pharmacotherapy that is approved by the Food and Drug Administration to treat AUD, according to the researchers. “These rates are concerning given the negative impact alcohol use can have on HCV,” they wrote.

They reiterated the importance of the 2016 change in policy adopted by the VA Health System, which updated its treatment guidelines to recommend that all patients with HCV be considered for treatment, regardless of substance use, and explicitly stated that alcohol use and length of abstinence should not be disqualifiers for receiving HCV treatment.

“All patients with HCV should be receiving evidence-based alcohol-related care given the risks of alcohol use in this population, particularly among those coinfected with HIV,” the researchers concluded.

The research was funded by a grant from the National Institute on Alcohol Abuse and Alcoholism. The authors reported that they had no conflicts of interest.

[email protected]

SOURCE: Owens MD et al. Drug Alcohol Depend. 2018;188:79-85.

Despite the increasing prevalence of hepatitis C virus (HCV) infection in pregnant women, infants exposed to the disease are screened at a very low rate, Catherine A. Chappell, MD, and her associates wrote in Pediatrics.

During 2006-2014, 87,924 women gave birth at the Magee-Womens Hospital at the University of Pittsburgh Medical Center, of whom 1,043 had HCV. Over this time, the HCV prevalence rate increased 60%, from 1,026 cases per 100,000 women to 1,637 cases per 100,000 women. Women with HCV were more likely to be white, have Medicaid, have opiate use disorder, have other substance use disorders, and be under the age of 30 years.

Jarun011/Thinkstock

[email protected]

SOURCE: Chappell CA et al. Pediatrics. 2018 May 2. doi: 10.1542/peds.2017-3273.

Despite the increasing prevalence of hepatitis C virus (HCV) infection in pregnant women, infants exposed to the disease are screened at a very low rate, Catherine A. Chappell, MD, and her associates wrote in Pediatrics.

During 2006-2014, 87,924 women gave birth at the Magee-Womens Hospital at the University of Pittsburgh Medical Center, of whom 1,043 had HCV. Over this time, the HCV prevalence rate increased 60%, from 1,026 cases per 100,000 women to 1,637 cases per 100,000 women. Women with HCV were more likely to be white, have Medicaid, have opiate use disorder, have other substance use disorders, and be under the age of 30 years.

Jarun011/Thinkstock

[email protected]

SOURCE: Chappell CA et al. Pediatrics. 2018 May 2. doi: 10.1542/peds.2017-3273.

Despite the increasing prevalence of hepatitis C virus (HCV) infection in pregnant women, infants exposed to the disease are screened at a very low rate, Catherine A. Chappell, MD, and her associates wrote in Pediatrics.

During 2006-2014, 87,924 women gave birth at the Magee-Womens Hospital at the University of Pittsburgh Medical Center, of whom 1,043 had HCV. Over this time, the HCV prevalence rate increased 60%, from 1,026 cases per 100,000 women to 1,637 cases per 100,000 women. Women with HCV were more likely to be white, have Medicaid, have opiate use disorder, have other substance use disorders, and be under the age of 30 years.

Jarun011/Thinkstock

[email protected]

SOURCE: Chappell CA et al. Pediatrics. 2018 May 2. doi: 10.1542/peds.2017-3273.

PHILADELPHIA – Recent approvals and investigations of targeted and immune treatments for advanced hepatocellular carcinoma (HCC) are encouraging, Nikolaos Pyrsopoulos, MD, MBA, said at Digestive Diseases: New Advances, jointly provided by Rutgers and Global Academy for Medical Education.

“I am excited, because a few years ago, there was only one [Food and Drug Administration] approved medication,” Dr. Pyrsopoulos, division director for gastroenterology and hepatology at Rutgers New Jersey Medical School, Newark, said in an interview. “We are on the cusp where new compounds not only are being tested, but they are being approved.”

In one of the most recent developments, the multikinase inhibitor cabozantinib significantly improved the primary endpoint of overall survival versus placebo in HCC patients in the randomized phase 3 CELESTIAL trial.

Median overall survival in CELESTIAL was 10.2 months for cabozantinib versus 8.0 for placebo (P = .0049), according to the published report, and investigators also reported significant improvements in progression-free survival and response versus placebo.

“It is very encouraging,” Dr. Pyrsopoulos said of the cabozantinib results in a presentation on advances in HCC that he gave at the conference.

For years, the only FDA-approved treatment for advanced HCC was sorafenib. In the randomized phase 3 SHARP trial, published in the New England Journal of Medicine in 2008, patients receiving the multikinase inhibitor had a median survival of 10.7 months, versus 7.9 months for placebo (P less than .001).

In April 2017, the FDA approved regorafenib for patients with HCC previously treated with sorafenib. In the randomized phase 3 RESORCE trial, published in The Lancet in 2017, median overall survival was 10.6 months for regorafenib-treated patients versus 7.8 months in the placebo group. Investigators reported that regorafenib improved overall survival with a hazard ratio of 0.63 (P less than .0001).

Dr. Pyrsopoulos noted that a strategy of sorafenib followed by regorafenib would combine two treatments, each of which in clinical trials had a median overall survival approaching 11 months.

“In essence, you have an approximate 2-year survival,” he said.

More agents are under investigation, including lenvatinib, another multikinase inhibitor. In results of a phase 3 randomized trial presented at the 2017 meeting of the American Society of Clinical Oncology, lenvatinib was noninferior to sorafenib in overall survival, with treatment-related adverse effects such as hypertension and diarrhea that were expected based on previous experience with the drug, investigators said.

Cancer immunotherapy is making inroads into HCC. Just a few months after approving regorafenib, the FDA granted approval to nivolumab, a PD-1 inhibitor, for patients with HCC previously treated with sorafenib. The September 2017 approval of this checkpoint inhibitor was based in part on data from the CheckMate-040 trial that included a 14.3% response rate in the 154-patient subgroup of patients who had progressive disease on sorafenib or were intolerant of the treatment.

Dr. Pyrsopoulos highlighted another checkpoint inhibitor, known as BGB-A317, or tislelizumab. In January, BeiGene announced the initiation of a global phase 3 trial of this anti-PD-1 antibody versus sorafenib as first-line treatment of patients with unresectable HCC.

Although cancer immunotherapy holds great promise for HCC and other cancers, the treatments are associated with unique immune-related adverse events (irAEs) including immune-related hepatitis that may require corticosteroid treatment, according to Dr. Pyrsopoulos.

Dr. Pyrsopoulos reported disclosures related to AbbVie, Bayer, Genfit, Gilead Sciences, Hologic, Merck, Prometheus, Shire, and Vital Therapies.

Global Academy for Medical Education and this news organization are owned by the same company.

PHILADELPHIA – Recent approvals and investigations of targeted and immune treatments for advanced hepatocellular carcinoma (HCC) are encouraging, Nikolaos Pyrsopoulos, MD, MBA, said at Digestive Diseases: New Advances, jointly provided by Rutgers and Global Academy for Medical Education.

“I am excited, because a few years ago, there was only one [Food and Drug Administration] approved medication,” Dr. Pyrsopoulos, division director for gastroenterology and hepatology at Rutgers New Jersey Medical School, Newark, said in an interview. “We are on the cusp where new compounds not only are being tested, but they are being approved.”

In one of the most recent developments, the multikinase inhibitor cabozantinib significantly improved the primary endpoint of overall survival versus placebo in HCC patients in the randomized phase 3 CELESTIAL trial.

Median overall survival in CELESTIAL was 10.2 months for cabozantinib versus 8.0 for placebo (P = .0049), according to the published report, and investigators also reported significant improvements in progression-free survival and response versus placebo.

“It is very encouraging,” Dr. Pyrsopoulos said of the cabozantinib results in a presentation on advances in HCC that he gave at the conference.

For years, the only FDA-approved treatment for advanced HCC was sorafenib. In the randomized phase 3 SHARP trial, published in the New England Journal of Medicine in 2008, patients receiving the multikinase inhibitor had a median survival of 10.7 months, versus 7.9 months for placebo (P less than .001).

In April 2017, the FDA approved regorafenib for patients with HCC previously treated with sorafenib. In the randomized phase 3 RESORCE trial, published in The Lancet in 2017, median overall survival was 10.6 months for regorafenib-treated patients versus 7.8 months in the placebo group. Investigators reported that regorafenib improved overall survival with a hazard ratio of 0.63 (P less than .0001).

Dr. Pyrsopoulos noted that a strategy of sorafenib followed by regorafenib would combine two treatments, each of which in clinical trials had a median overall survival approaching 11 months.

“In essence, you have an approximate 2-year survival,” he said.

More agents are under investigation, including lenvatinib, another multikinase inhibitor. In results of a phase 3 randomized trial presented at the 2017 meeting of the American Society of Clinical Oncology, lenvatinib was noninferior to sorafenib in overall survival, with treatment-related adverse effects such as hypertension and diarrhea that were expected based on previous experience with the drug, investigators said.

Cancer immunotherapy is making inroads into HCC. Just a few months after approving regorafenib, the FDA granted approval to nivolumab, a PD-1 inhibitor, for patients with HCC previously treated with sorafenib. The September 2017 approval of this checkpoint inhibitor was based in part on data from the CheckMate-040 trial that included a 14.3% response rate in the 154-patient subgroup of patients who had progressive disease on sorafenib or were intolerant of the treatment.

Dr. Pyrsopoulos highlighted another checkpoint inhibitor, known as BGB-A317, or tislelizumab. In January, BeiGene announced the initiation of a global phase 3 trial of this anti-PD-1 antibody versus sorafenib as first-line treatment of patients with unresectable HCC.

Although cancer immunotherapy holds great promise for HCC and other cancers, the treatments are associated with unique immune-related adverse events (irAEs) including immune-related hepatitis that may require corticosteroid treatment, according to Dr. Pyrsopoulos.

Dr. Pyrsopoulos reported disclosures related to AbbVie, Bayer, Genfit, Gilead Sciences, Hologic, Merck, Prometheus, Shire, and Vital Therapies.

Global Academy for Medical Education and this news organization are owned by the same company.

PHILADELPHIA – Recent approvals and investigations of targeted and immune treatments for advanced hepatocellular carcinoma (HCC) are encouraging, Nikolaos Pyrsopoulos, MD, MBA, said at Digestive Diseases: New Advances, jointly provided by Rutgers and Global Academy for Medical Education.

“I am excited, because a few years ago, there was only one [Food and Drug Administration] approved medication,” Dr. Pyrsopoulos, division director for gastroenterology and hepatology at Rutgers New Jersey Medical School, Newark, said in an interview. “We are on the cusp where new compounds not only are being tested, but they are being approved.”

In one of the most recent developments, the multikinase inhibitor cabozantinib significantly improved the primary endpoint of overall survival versus placebo in HCC patients in the randomized phase 3 CELESTIAL trial.

Median overall survival in CELESTIAL was 10.2 months for cabozantinib versus 8.0 for placebo (P = .0049), according to the published report, and investigators also reported significant improvements in progression-free survival and response versus placebo.

“It is very encouraging,” Dr. Pyrsopoulos said of the cabozantinib results in a presentation on advances in HCC that he gave at the conference.

For years, the only FDA-approved treatment for advanced HCC was sorafenib. In the randomized phase 3 SHARP trial, published in the New England Journal of Medicine in 2008, patients receiving the multikinase inhibitor had a median survival of 10.7 months, versus 7.9 months for placebo (P less than .001).

In April 2017, the FDA approved regorafenib for patients with HCC previously treated with sorafenib. In the randomized phase 3 RESORCE trial, published in The Lancet in 2017, median overall survival was 10.6 months for regorafenib-treated patients versus 7.8 months in the placebo group. Investigators reported that regorafenib improved overall survival with a hazard ratio of 0.63 (P less than .0001).

Dr. Pyrsopoulos noted that a strategy of sorafenib followed by regorafenib would combine two treatments, each of which in clinical trials had a median overall survival approaching 11 months.

“In essence, you have an approximate 2-year survival,” he said.

More agents are under investigation, including lenvatinib, another multikinase inhibitor. In results of a phase 3 randomized trial presented at the 2017 meeting of the American Society of Clinical Oncology, lenvatinib was noninferior to sorafenib in overall survival, with treatment-related adverse effects such as hypertension and diarrhea that were expected based on previous experience with the drug, investigators said.

Cancer immunotherapy is making inroads into HCC. Just a few months after approving regorafenib, the FDA granted approval to nivolumab, a PD-1 inhibitor, for patients with HCC previously treated with sorafenib. The September 2017 approval of this checkpoint inhibitor was based in part on data from the CheckMate-040 trial that included a 14.3% response rate in the 154-patient subgroup of patients who had progressive disease on sorafenib or were intolerant of the treatment.

Dr. Pyrsopoulos highlighted another checkpoint inhibitor, known as BGB-A317, or tislelizumab. In January, BeiGene announced the initiation of a global phase 3 trial of this anti-PD-1 antibody versus sorafenib as first-line treatment of patients with unresectable HCC.

Although cancer immunotherapy holds great promise for HCC and other cancers, the treatments are associated with unique immune-related adverse events (irAEs) including immune-related hepatitis that may require corticosteroid treatment, according to Dr. Pyrsopoulos.

Dr. Pyrsopoulos reported disclosures related to AbbVie, Bayer, Genfit, Gilead Sciences, Hologic, Merck, Prometheus, Shire, and Vital Therapies.

Global Academy for Medical Education and this news organization are owned by the same company.

BOSTON – There was no sign of HCV infection more than a year after 10 patients at Johns Hopkins University, Baltimore, received kidneys from HCV-infected donors.

The patients were treated with prophylactic direct-acting antivirals (DAAs) before and after the procedure. Low levels of hepatitis C RNA were detected shortly after transplant in five patients, but it became undetectable within a week. None of the patients developed any clinical signs of chronic hepatitis C infection, and the transplanted kidneys functioned well.

Alex Otto/MDedge News

[email protected]

SOURCE: Durand CM et al. Ann Intern Med. 2018 Mar 6. doi: 10.7326/M17-2871.

BOSTON – There was no sign of HCV infection more than a year after 10 patients at Johns Hopkins University, Baltimore, received kidneys from HCV-infected donors.

The patients were treated with prophylactic direct-acting antivirals (DAAs) before and after the procedure. Low levels of hepatitis C RNA were detected shortly after transplant in five patients, but it became undetectable within a week. None of the patients developed any clinical signs of chronic hepatitis C infection, and the transplanted kidneys functioned well.

Alex Otto/MDedge News

[email protected]

SOURCE: Durand CM et al. Ann Intern Med. 2018 Mar 6. doi: 10.7326/M17-2871.

BOSTON – There was no sign of HCV infection more than a year after 10 patients at Johns Hopkins University, Baltimore, received kidneys from HCV-infected donors.

The patients were treated with prophylactic direct-acting antivirals (DAAs) before and after the procedure. Low levels of hepatitis C RNA were detected shortly after transplant in five patients, but it became undetectable within a week. None of the patients developed any clinical signs of chronic hepatitis C infection, and the transplanted kidneys functioned well.

Alex Otto/MDedge News

[email protected]

SOURCE: Durand CM et al. Ann Intern Med. 2018 Mar 6. doi: 10.7326/M17-2871.

Two major pathways exhibited high dysregulation in early liver fibrosis compared with controls or compared with late liver fibrosis – the transforming growth factor beta (TGF-beta)–related pathway genes and Matrix deposition–associated genes, according to an online report in the journal Gene.

The study examined 105 treatment naive HCV genotype 4–infected patients and 16 healthy subjects. The gene-regulation assays were done via PCR arrays on 84 fibrosis-related genes followed by customization of a smaller array consisting of 11 genes that were designed on the bases of results obtained from the larger array. Genes that displayed significant dysregulation at mRNA levels were validated at protein levels, according to the authors.

Courtesy U.S. Department of Veterans Affairs

[email protected]

SOURCE: Dawood RM et al. Gene 2018 Apr 21. doi: 10.1016/j.gene.2018.04.032.

Two major pathways exhibited high dysregulation in early liver fibrosis compared with controls or compared with late liver fibrosis – the transforming growth factor beta (TGF-beta)–related pathway genes and Matrix deposition–associated genes, according to an online report in the journal Gene.

The study examined 105 treatment naive HCV genotype 4–infected patients and 16 healthy subjects. The gene-regulation assays were done via PCR arrays on 84 fibrosis-related genes followed by customization of a smaller array consisting of 11 genes that were designed on the bases of results obtained from the larger array. Genes that displayed significant dysregulation at mRNA levels were validated at protein levels, according to the authors.

Courtesy U.S. Department of Veterans Affairs

[email protected]

SOURCE: Dawood RM et al. Gene 2018 Apr 21. doi: 10.1016/j.gene.2018.04.032.

Two major pathways exhibited high dysregulation in early liver fibrosis compared with controls or compared with late liver fibrosis – the transforming growth factor beta (TGF-beta)–related pathway genes and Matrix deposition–associated genes, according to an online report in the journal Gene.

The study examined 105 treatment naive HCV genotype 4–infected patients and 16 healthy subjects. The gene-regulation assays were done via PCR arrays on 84 fibrosis-related genes followed by customization of a smaller array consisting of 11 genes that were designed on the bases of results obtained from the larger array. Genes that displayed significant dysregulation at mRNA levels were validated at protein levels, according to the authors.

Courtesy U.S. Department of Veterans Affairs

[email protected]

SOURCE: Dawood RM et al. Gene 2018 Apr 21. doi: 10.1016/j.gene.2018.04.032.

Researchers have developed a new portable point-of-care (PoC) molecular test for hepatitis C virus (HCV), with sensitivity and specificity that fulfills the recent FIND/WHO Target Product Profile for HCV decentralized testing in low- and middle-income countries, according to an online report in the journal Gut.

©vchal/Thinkstock

The new assay identified all major HCV genotypes, with a limit of detection of 2,362 IU/mL. In the PoC-HCV Genedrive Viral Detection Assay Validation Study (NCT02992184), 422 patients chronically infected with HCV and 503 controls negative for anti-HCV and HCV RNA were assayed with the device. The Genedrive HCV assay showed 98.6% sensitivity and 100% specificity to detect HCV, the researchers reported. The test was further validated in a small clinical setting in a resource-limited country, they added.

“The next step with the Genedrive HCV assay requires prospective validation in real-life decentralized settings in low-income and middle-income countries,” the authors concluded.

[email protected]

SOURCE: Llibre A et al. Gut 2018 Apr 3. doi: 10.1136/gutjnl-2017-315783.

Researchers have developed a new portable point-of-care (PoC) molecular test for hepatitis C virus (HCV), with sensitivity and specificity that fulfills the recent FIND/WHO Target Product Profile for HCV decentralized testing in low- and middle-income countries, according to an online report in the journal Gut.

©vchal/Thinkstock

The new assay identified all major HCV genotypes, with a limit of detection of 2,362 IU/mL. In the PoC-HCV Genedrive Viral Detection Assay Validation Study (NCT02992184), 422 patients chronically infected with HCV and 503 controls negative for anti-HCV and HCV RNA were assayed with the device. The Genedrive HCV assay showed 98.6% sensitivity and 100% specificity to detect HCV, the researchers reported. The test was further validated in a small clinical setting in a resource-limited country, they added.

“The next step with the Genedrive HCV assay requires prospective validation in real-life decentralized settings in low-income and middle-income countries,” the authors concluded.

[email protected]

SOURCE: Llibre A et al. Gut 2018 Apr 3. doi: 10.1136/gutjnl-2017-315783.

Researchers have developed a new portable point-of-care (PoC) molecular test for hepatitis C virus (HCV), with sensitivity and specificity that fulfills the recent FIND/WHO Target Product Profile for HCV decentralized testing in low- and middle-income countries, according to an online report in the journal Gut.

©vchal/Thinkstock

The new assay identified all major HCV genotypes, with a limit of detection of 2,362 IU/mL. In the PoC-HCV Genedrive Viral Detection Assay Validation Study (NCT02992184), 422 patients chronically infected with HCV and 503 controls negative for anti-HCV and HCV RNA were assayed with the device. The Genedrive HCV assay showed 98.6% sensitivity and 100% specificity to detect HCV, the researchers reported. The test was further validated in a small clinical setting in a resource-limited country, they added.

“The next step with the Genedrive HCV assay requires prospective validation in real-life decentralized settings in low-income and middle-income countries,” the authors concluded.

[email protected]

SOURCE: Llibre A et al. Gut 2018 Apr 3. doi: 10.1136/gutjnl-2017-315783.

Nonalcoholic steatohepatitis (NASH) is rapidly eclipsing hepatitis C virus (HCV) infection as the leading contributor to liver cancer in the United States.

Researchers reported on their analysis of past prevalence of HCV, NASH, and alcoholic cirrhosis and prediction of future trends and their effect on hepatocellular carcinoma in the Feb. 24 online edition of the Journal of Clinical and Experimental Hepatology.

copyright Eraxion/Thinkstock

The analysis, based on data from the National Health and Nutrition Examination Survey and the Organ Procurement and Transplantation Network, shows that the prevalence of HCV has been in steady decline since 2005 and that decline is forecast to continue. From a prevalence of 3.22 million cases in 2005, researchers have forecasted a decline to 1.06 million cases by 2025.

At the same time, even a conservative linear model for the changing prevalence of NASH forecast a rapid increase from 1.37 million cases in 2005 to 17.95 million in 2025. The exponential model suggested an increase from 2.41 million in 2005 to 42.34 million in 2025.

SOURCE: Ahmed O et al. J Clin Exp Hepatology. 2018 Feb 24. doi: 10.1016/j.jceh.2018.02.006.

Nonalcoholic steatohepatitis (NASH) is rapidly eclipsing hepatitis C virus (HCV) infection as the leading contributor to liver cancer in the United States.

Researchers reported on their analysis of past prevalence of HCV, NASH, and alcoholic cirrhosis and prediction of future trends and their effect on hepatocellular carcinoma in the Feb. 24 online edition of the Journal of Clinical and Experimental Hepatology.

copyright Eraxion/Thinkstock

The analysis, based on data from the National Health and Nutrition Examination Survey and the Organ Procurement and Transplantation Network, shows that the prevalence of HCV has been in steady decline since 2005 and that decline is forecast to continue. From a prevalence of 3.22 million cases in 2005, researchers have forecasted a decline to 1.06 million cases by 2025.

At the same time, even a conservative linear model for the changing prevalence of NASH forecast a rapid increase from 1.37 million cases in 2005 to 17.95 million in 2025. The exponential model suggested an increase from 2.41 million in 2005 to 42.34 million in 2025.

SOURCE: Ahmed O et al. J Clin Exp Hepatology. 2018 Feb 24. doi: 10.1016/j.jceh.2018.02.006.

Nonalcoholic steatohepatitis (NASH) is rapidly eclipsing hepatitis C virus (HCV) infection as the leading contributor to liver cancer in the United States.

Researchers reported on their analysis of past prevalence of HCV, NASH, and alcoholic cirrhosis and prediction of future trends and their effect on hepatocellular carcinoma in the Feb. 24 online edition of the Journal of Clinical and Experimental Hepatology.

copyright Eraxion/Thinkstock

The analysis, based on data from the National Health and Nutrition Examination Survey and the Organ Procurement and Transplantation Network, shows that the prevalence of HCV has been in steady decline since 2005 and that decline is forecast to continue. From a prevalence of 3.22 million cases in 2005, researchers have forecasted a decline to 1.06 million cases by 2025.

At the same time, even a conservative linear model for the changing prevalence of NASH forecast a rapid increase from 1.37 million cases in 2005 to 17.95 million in 2025. The exponential model suggested an increase from 2.41 million in 2005 to 42.34 million in 2025.

SOURCE: Ahmed O et al. J Clin Exp Hepatology. 2018 Feb 24. doi: 10.1016/j.jceh.2018.02.006.