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HCV remodels lipid metabolism in infected cells

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Fri, 01/18/2019 - 17:46

 

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.

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

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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.

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.

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

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FROM BBA: MOLECULAR AND CELL BIOLOGY OF LIPIDS

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Cigarette smoking epidemic among HCV-infected individuals

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Fri, 01/18/2019 - 17:46

 

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).

Cigarette butts
©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.

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

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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).

Cigarette butts
©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.

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).

Cigarette butts
©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.

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

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FROM THE AMERICAN JOURNAL OF MEDICINE

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HCV incidence is elevated in HIV-positive MSM

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Sat, 12/08/2018 - 15:07

 

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.

Hepatitis C
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.

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

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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.

Hepatitis C
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.

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.

Hepatitis C
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.

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

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Alcohol abuse untreated in HCV patients, including HIV coinfected

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Sat, 12/08/2018 - 15:04

 

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.

A photo of a man with a drink in his hand, head resting on his arms
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.

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

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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.

A photo of a man with a drink in his hand, head resting on his arms
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.

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.

A photo of a man with a drink in his hand, head resting on his arms
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.

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

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Key clinical point: Alcohol-use disorder therapy is underdelivered to patients with HCV who would benefit.

Major finding: Only 27% of patients with HCV plus alcohol-abuse disorder received AUD therapy.

Study details: National VA health care system database of 830,825 patients who screened positive for unhealthy alcohol use.

Disclosures: 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.

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

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Very few infants born to HCV-infected mothers receive testing

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Fri, 01/18/2019 - 17:37

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.

A test for heptatits C.
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Of the 1,026 infants born to HCV-infected women for whom data was available, only 323 received well child care, and only 96 infants in this subgroup received HCV testing.

Infants born to HCV-infected women are significantly more likely to be preterm and of low birth weight.

An additional 32 infants who did not receive well child care did receive HCV testing. A total of nine infants, seven in the well child group and two in the non-well child group, tested positive for HCV.

“Of the infants tested with conclusive results, the HCV transmission rate was 8.4%, with 7.2% having chronic HCV infection,” which is in line with previous reports, according to the researchers.

“Because of the poor rates of pediatric HCV screening described, future researchers should focus on interventions to increase screening in infants who are at risk for perinatal HCV acquisition by including technology to improve the transfer of maternal HCV status to the pediatric record and increase pediatric provider awareness regarding HCV screening guidelines,” the investigators concluded.

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

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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.

A test for heptatits C.
Jarun011/Thinkstock
Of the 1,026 infants born to HCV-infected women for whom data was available, only 323 received well child care, and only 96 infants in this subgroup received HCV testing.

Infants born to HCV-infected women are significantly more likely to be preterm and of low birth weight.

An additional 32 infants who did not receive well child care did receive HCV testing. A total of nine infants, seven in the well child group and two in the non-well child group, tested positive for HCV.

“Of the infants tested with conclusive results, the HCV transmission rate was 8.4%, with 7.2% having chronic HCV infection,” which is in line with previous reports, according to the researchers.

“Because of the poor rates of pediatric HCV screening described, future researchers should focus on interventions to increase screening in infants who are at risk for perinatal HCV acquisition by including technology to improve the transfer of maternal HCV status to the pediatric record and increase pediatric provider awareness regarding HCV screening guidelines,” the investigators concluded.

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.

A test for heptatits C.
Jarun011/Thinkstock
Of the 1,026 infants born to HCV-infected women for whom data was available, only 323 received well child care, and only 96 infants in this subgroup received HCV testing.

Infants born to HCV-infected women are significantly more likely to be preterm and of low birth weight.

An additional 32 infants who did not receive well child care did receive HCV testing. A total of nine infants, seven in the well child group and two in the non-well child group, tested positive for HCV.

“Of the infants tested with conclusive results, the HCV transmission rate was 8.4%, with 7.2% having chronic HCV infection,” which is in line with previous reports, according to the researchers.

“Because of the poor rates of pediatric HCV screening described, future researchers should focus on interventions to increase screening in infants who are at risk for perinatal HCV acquisition by including technology to improve the transfer of maternal HCV status to the pediatric record and increase pediatric provider awareness regarding HCV screening guidelines,” the investigators concluded.

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

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New drugs provide new options in HCC

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– 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.

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– 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.

 

– 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.

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REPORTING FROM DIGESTIVE DISEASES: NEW ADVANCES

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DAAs open up organ donation from HCV patients

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– 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
Dr. Christine Durand
Until now, organs from HCV-infected donors were usually discarded if they were retrieved at all. Around 500 hepatitis C–positive kidneys are thrown out in the United States every year.

The number of organs from HCV–infected people is on the rise because of the opioid epidemic. Organ donations from drug overdoses used to be rare, but about 10% of transplanted organs are now from an overdose death, and about 30% of people who overdose have HCV. “These are young people who could donate hearts, lungs, and kidneys, and their parents and families want them to be able to make that gift of life,” said lead investigator Christine Durand, MD, of Johns Hopkins University, Baltimore.

DAAs make that possible because they cure HCV. “If the success of these transplants continues, it could pave the way for other hepatitis C–positive organs, including hearts and livers, to be transplanted as well,” Dr. Durand and her colleagues said in a press release from Johns Hopkins.

The 10 patients were over age 50 years, with a mean age of 71 years, and had been on the kidney transplant list for an average of 4 months. The HCV-positive donors were 13-50 years old with no evidence of kidney disease (Ann Intern Med. 2018 Mar 6. doi: 10.7326/M17-2871)..

Each recipient received a dose of grazoprevir/elbasvir (Zepatier) before transplant and stayed on the medication daily for 12 weeks postop. Three patients also took a daily dose of sofosbuvir (Sovaldi) because of the strain of HCV in the donor kidney. Maybe 8 weeks of treatment, or even 4, is enough, Dr. Durand said at the Conference on Retroviruses and Opportunistic Infections.

 

 


“I am thrilled to report that at 1 year post transplant 10 out of 10 of these recipients are HCV free, and they are doing very well. Prophylactic treatment may mean that more individuals can receive transplants from hepatitis C–infected donors without transmission of infection. The use of organs from infected donors can help everyone on the transplant list by shortening wait times and shortening the wait list,” she said.

“I’m not surprised by the results of the study because these DAAs are highly effective, but I was surprised by how willing patients were to sign up for the study. They said it was a no-brainer. In our region, if you need a kidney, you are going to wait for up to 5 years, and you may die while you are waiting. If you can accept a hepatitis C–positive donor organ, you will get transplanted in a matter of weeks,” she said.

“I hope providers tell their patients with HCV that they can register as organ donors,” she said.

The work is being supported primarily by Merck Sharp & Dohme. Dr. Durand is an advisor to Bristol-Meyers Squibb, Gilead Sciences, and Merck Pharmaceuticals and has research funding from the companies.

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

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– 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
Dr. Christine Durand
Until now, organs from HCV-infected donors were usually discarded if they were retrieved at all. Around 500 hepatitis C–positive kidneys are thrown out in the United States every year.

The number of organs from HCV–infected people is on the rise because of the opioid epidemic. Organ donations from drug overdoses used to be rare, but about 10% of transplanted organs are now from an overdose death, and about 30% of people who overdose have HCV. “These are young people who could donate hearts, lungs, and kidneys, and their parents and families want them to be able to make that gift of life,” said lead investigator Christine Durand, MD, of Johns Hopkins University, Baltimore.

DAAs make that possible because they cure HCV. “If the success of these transplants continues, it could pave the way for other hepatitis C–positive organs, including hearts and livers, to be transplanted as well,” Dr. Durand and her colleagues said in a press release from Johns Hopkins.

The 10 patients were over age 50 years, with a mean age of 71 years, and had been on the kidney transplant list for an average of 4 months. The HCV-positive donors were 13-50 years old with no evidence of kidney disease (Ann Intern Med. 2018 Mar 6. doi: 10.7326/M17-2871)..

Each recipient received a dose of grazoprevir/elbasvir (Zepatier) before transplant and stayed on the medication daily for 12 weeks postop. Three patients also took a daily dose of sofosbuvir (Sovaldi) because of the strain of HCV in the donor kidney. Maybe 8 weeks of treatment, or even 4, is enough, Dr. Durand said at the Conference on Retroviruses and Opportunistic Infections.

 

 


“I am thrilled to report that at 1 year post transplant 10 out of 10 of these recipients are HCV free, and they are doing very well. Prophylactic treatment may mean that more individuals can receive transplants from hepatitis C–infected donors without transmission of infection. The use of organs from infected donors can help everyone on the transplant list by shortening wait times and shortening the wait list,” she said.

“I’m not surprised by the results of the study because these DAAs are highly effective, but I was surprised by how willing patients were to sign up for the study. They said it was a no-brainer. In our region, if you need a kidney, you are going to wait for up to 5 years, and you may die while you are waiting. If you can accept a hepatitis C–positive donor organ, you will get transplanted in a matter of weeks,” she said.

“I hope providers tell their patients with HCV that they can register as organ donors,” she said.

The work is being supported primarily by Merck Sharp & Dohme. Dr. Durand is an advisor to Bristol-Meyers Squibb, Gilead Sciences, and Merck Pharmaceuticals and has research funding from the companies.

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

 

– 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
Dr. Christine Durand
Until now, organs from HCV-infected donors were usually discarded if they were retrieved at all. Around 500 hepatitis C–positive kidneys are thrown out in the United States every year.

The number of organs from HCV–infected people is on the rise because of the opioid epidemic. Organ donations from drug overdoses used to be rare, but about 10% of transplanted organs are now from an overdose death, and about 30% of people who overdose have HCV. “These are young people who could donate hearts, lungs, and kidneys, and their parents and families want them to be able to make that gift of life,” said lead investigator Christine Durand, MD, of Johns Hopkins University, Baltimore.

DAAs make that possible because they cure HCV. “If the success of these transplants continues, it could pave the way for other hepatitis C–positive organs, including hearts and livers, to be transplanted as well,” Dr. Durand and her colleagues said in a press release from Johns Hopkins.

The 10 patients were over age 50 years, with a mean age of 71 years, and had been on the kidney transplant list for an average of 4 months. The HCV-positive donors were 13-50 years old with no evidence of kidney disease (Ann Intern Med. 2018 Mar 6. doi: 10.7326/M17-2871)..

Each recipient received a dose of grazoprevir/elbasvir (Zepatier) before transplant and stayed on the medication daily for 12 weeks postop. Three patients also took a daily dose of sofosbuvir (Sovaldi) because of the strain of HCV in the donor kidney. Maybe 8 weeks of treatment, or even 4, is enough, Dr. Durand said at the Conference on Retroviruses and Opportunistic Infections.

 

 


“I am thrilled to report that at 1 year post transplant 10 out of 10 of these recipients are HCV free, and they are doing very well. Prophylactic treatment may mean that more individuals can receive transplants from hepatitis C–infected donors without transmission of infection. The use of organs from infected donors can help everyone on the transplant list by shortening wait times and shortening the wait list,” she said.

“I’m not surprised by the results of the study because these DAAs are highly effective, but I was surprised by how willing patients were to sign up for the study. They said it was a no-brainer. In our region, if you need a kidney, you are going to wait for up to 5 years, and you may die while you are waiting. If you can accept a hepatitis C–positive donor organ, you will get transplanted in a matter of weeks,” she said.

“I hope providers tell their patients with HCV that they can register as organ donors,” she said.

The work is being supported primarily by Merck Sharp & Dohme. Dr. Durand is an advisor to Bristol-Meyers Squibb, Gilead Sciences, and Merck Pharmaceuticals and has research funding from the companies.

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

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Key clinical point: HCV may soon no longer bar organ donation.

Major finding: 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.

Study details: Open-label nonrandomized trial.

Disclosures: The work is being supported primarily by Merck Sharp & Dohme. The study lead is an advisor to Bristol-Meyers Squibb, Gilead Sciences, and Merck Pharmaceuticals, and has research funding from the companies.

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

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Fibrosis-related genes are dysregulated in HCV-induced liver disease

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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.

Hepatitis C
Courtesy U.S. Department of Veterans Affairs
Hepatic stellate cell activators (i.e., TGF-beta pathway genes) were considerably overexpressed at transcriptional levels early on in HCV patients compared with controls, whereas expression of their inhibitor TGIF1 was simultaneously downregulated. Extracellular matrix proteins (ECMs) including collagen were upregulated in early fibrosis whereas tissue inhibitors TIMPs 1 and 2 began overexpression in late fibrosis.

The researchers found that the expression at protein levels confirmed the RNA data, thereby excluding dysregulation at posttranscriptional levels.

“We assume that the overall expression pattern of ECM molecules described in the present study may be utilized for a prognostic transcriptomic or proteomic signatures for staging of liver fibrosis,” the authors concluded.
 

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

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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.

Hepatitis C
Courtesy U.S. Department of Veterans Affairs
Hepatic stellate cell activators (i.e., TGF-beta pathway genes) were considerably overexpressed at transcriptional levels early on in HCV patients compared with controls, whereas expression of their inhibitor TGIF1 was simultaneously downregulated. Extracellular matrix proteins (ECMs) including collagen were upregulated in early fibrosis whereas tissue inhibitors TIMPs 1 and 2 began overexpression in late fibrosis.

The researchers found that the expression at protein levels confirmed the RNA data, thereby excluding dysregulation at posttranscriptional levels.

“We assume that the overall expression pattern of ECM molecules described in the present study may be utilized for a prognostic transcriptomic or proteomic signatures for staging of liver fibrosis,” the authors concluded.
 

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.

Hepatitis C
Courtesy U.S. Department of Veterans Affairs
Hepatic stellate cell activators (i.e., TGF-beta pathway genes) were considerably overexpressed at transcriptional levels early on in HCV patients compared with controls, whereas expression of their inhibitor TGIF1 was simultaneously downregulated. Extracellular matrix proteins (ECMs) including collagen were upregulated in early fibrosis whereas tissue inhibitors TIMPs 1 and 2 began overexpression in late fibrosis.

The researchers found that the expression at protein levels confirmed the RNA data, thereby excluding dysregulation at posttranscriptional levels.

“We assume that the overall expression pattern of ECM molecules described in the present study may be utilized for a prognostic transcriptomic or proteomic signatures for staging of liver fibrosis,” the authors concluded.
 

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

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New point-of-care HCV assay shows promise for developing world

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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.

A binder label reads "Diagnosis: hepatitis"
©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.

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

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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.

A binder label reads "Diagnosis: hepatitis"
©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.

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.

A binder label reads "Diagnosis: hepatitis"
©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.

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

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NASH rapidly overtaking hepatitis C as cause of liver cancer

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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.

 

 


In terms of the effect on the prevalence of hepatocellular carcinoma (HCC), the modeling suggested cases of HCV-related liver cancer were predicted to peak at around 29,000 cases in 2015 then decline to fewer than 18,000 cases by 2025. In contrast, the prevalence of HCC from NASH is forecast to increase from between 5000 and 6000 cases in 2005 to 45,000 in 2025 by the conservative linear model or even as high as 106,000 cases according to the exponential model. It overtook HCV infection as a cause of liver cancer by around 2015.

“Despite the lack of existing data off of which to work, the general trends of our prediction models are consistent with the documented trends of liver transplant etiology, as well as 2010 insurance data indicating nonalcoholic fatty liver disease/NASH as the leading etiology associated with HCC,” wrote Osmanuddin Ahmed, MD, from the Rush University Medical Center in Chicago and his coauthors.

The study used liver transplant data as a proxy for the prevalence of hepatocellular carcinoma and also took into account the natural history of the disease. Between 5% and 20% of untreated HCV infections will go on to develop into cirrhosis, and of patients with HCV-related cirrhosis, around 15% will develop HCC within 10 years. In the case of NASH, the authors cited research suggesting that around 35% of patients go on to develop progressive fibrosis, that progression to cirrhosis takes around 29 years, and that the risk of progression to HCC ranged from 2.4% over 7 years to 12.8% over 3 years.

“A higher proportion of patients with NASH develop cirrhosis, but of those who develop cirrhosis, the probability of developing HCC is higher in patients with HCV,” the authors wrote. “In contrast, HCV progression to HCC rarely occurs in noncirrhotic patients.”

The authors wrote that it was important to explore projected trends in the etiology of hepatocellular carcinoma to inform the development of screening, diagnostic, and treatment approaches, particularly given potential differences in the pathology, natural history, and treatment options for NASH-related and HCV-related liver cancer.
 

 


“Histologically, NASH shares characteristics with alcoholic liver disease, primarily proinflammatory fat accumulation in parenchymal cells, [and] key players in NASH progression to HCC are suggested to include genetic modifications, proinflammatory high-fat and/or high-fructose diets, and oxidative and endoplasmic cellular stresses,” they wrote. “In HCV progression to HCC, the presence of the HCV core protein may induce HCC without the prerequisite load of genetic errors normally required for cancer development, skipping or accelerating some of the classic steps of cancer induction.”

The authors did note that their model represented a base scenario that assumed the environmental and genetic factors driving NASH would continue along the path of current trends.

“Therefore, the possibility exists that our models underestimate the response of the medical community in addressing the rising nonalcoholic fatty liver disease/NASH epidemic.”

No funding sources or conflicts of interest were declared.
 

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

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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.

 

 


In terms of the effect on the prevalence of hepatocellular carcinoma (HCC), the modeling suggested cases of HCV-related liver cancer were predicted to peak at around 29,000 cases in 2015 then decline to fewer than 18,000 cases by 2025. In contrast, the prevalence of HCC from NASH is forecast to increase from between 5000 and 6000 cases in 2005 to 45,000 in 2025 by the conservative linear model or even as high as 106,000 cases according to the exponential model. It overtook HCV infection as a cause of liver cancer by around 2015.

“Despite the lack of existing data off of which to work, the general trends of our prediction models are consistent with the documented trends of liver transplant etiology, as well as 2010 insurance data indicating nonalcoholic fatty liver disease/NASH as the leading etiology associated with HCC,” wrote Osmanuddin Ahmed, MD, from the Rush University Medical Center in Chicago and his coauthors.

The study used liver transplant data as a proxy for the prevalence of hepatocellular carcinoma and also took into account the natural history of the disease. Between 5% and 20% of untreated HCV infections will go on to develop into cirrhosis, and of patients with HCV-related cirrhosis, around 15% will develop HCC within 10 years. In the case of NASH, the authors cited research suggesting that around 35% of patients go on to develop progressive fibrosis, that progression to cirrhosis takes around 29 years, and that the risk of progression to HCC ranged from 2.4% over 7 years to 12.8% over 3 years.

“A higher proportion of patients with NASH develop cirrhosis, but of those who develop cirrhosis, the probability of developing HCC is higher in patients with HCV,” the authors wrote. “In contrast, HCV progression to HCC rarely occurs in noncirrhotic patients.”

The authors wrote that it was important to explore projected trends in the etiology of hepatocellular carcinoma to inform the development of screening, diagnostic, and treatment approaches, particularly given potential differences in the pathology, natural history, and treatment options for NASH-related and HCV-related liver cancer.
 

 


“Histologically, NASH shares characteristics with alcoholic liver disease, primarily proinflammatory fat accumulation in parenchymal cells, [and] key players in NASH progression to HCC are suggested to include genetic modifications, proinflammatory high-fat and/or high-fructose diets, and oxidative and endoplasmic cellular stresses,” they wrote. “In HCV progression to HCC, the presence of the HCV core protein may induce HCC without the prerequisite load of genetic errors normally required for cancer development, skipping or accelerating some of the classic steps of cancer induction.”

The authors did note that their model represented a base scenario that assumed the environmental and genetic factors driving NASH would continue along the path of current trends.

“Therefore, the possibility exists that our models underestimate the response of the medical community in addressing the rising nonalcoholic fatty liver disease/NASH epidemic.”

No funding sources or conflicts of interest were declared.
 

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.

 

 


In terms of the effect on the prevalence of hepatocellular carcinoma (HCC), the modeling suggested cases of HCV-related liver cancer were predicted to peak at around 29,000 cases in 2015 then decline to fewer than 18,000 cases by 2025. In contrast, the prevalence of HCC from NASH is forecast to increase from between 5000 and 6000 cases in 2005 to 45,000 in 2025 by the conservative linear model or even as high as 106,000 cases according to the exponential model. It overtook HCV infection as a cause of liver cancer by around 2015.

“Despite the lack of existing data off of which to work, the general trends of our prediction models are consistent with the documented trends of liver transplant etiology, as well as 2010 insurance data indicating nonalcoholic fatty liver disease/NASH as the leading etiology associated with HCC,” wrote Osmanuddin Ahmed, MD, from the Rush University Medical Center in Chicago and his coauthors.

The study used liver transplant data as a proxy for the prevalence of hepatocellular carcinoma and also took into account the natural history of the disease. Between 5% and 20% of untreated HCV infections will go on to develop into cirrhosis, and of patients with HCV-related cirrhosis, around 15% will develop HCC within 10 years. In the case of NASH, the authors cited research suggesting that around 35% of patients go on to develop progressive fibrosis, that progression to cirrhosis takes around 29 years, and that the risk of progression to HCC ranged from 2.4% over 7 years to 12.8% over 3 years.

“A higher proportion of patients with NASH develop cirrhosis, but of those who develop cirrhosis, the probability of developing HCC is higher in patients with HCV,” the authors wrote. “In contrast, HCV progression to HCC rarely occurs in noncirrhotic patients.”

The authors wrote that it was important to explore projected trends in the etiology of hepatocellular carcinoma to inform the development of screening, diagnostic, and treatment approaches, particularly given potential differences in the pathology, natural history, and treatment options for NASH-related and HCV-related liver cancer.
 

 


“Histologically, NASH shares characteristics with alcoholic liver disease, primarily proinflammatory fat accumulation in parenchymal cells, [and] key players in NASH progression to HCC are suggested to include genetic modifications, proinflammatory high-fat and/or high-fructose diets, and oxidative and endoplasmic cellular stresses,” they wrote. “In HCV progression to HCC, the presence of the HCV core protein may induce HCC without the prerequisite load of genetic errors normally required for cancer development, skipping or accelerating some of the classic steps of cancer induction.”

The authors did note that their model represented a base scenario that assumed the environmental and genetic factors driving NASH would continue along the path of current trends.

“Therefore, the possibility exists that our models underestimate the response of the medical community in addressing the rising nonalcoholic fatty liver disease/NASH epidemic.”

No funding sources or conflicts of interest were declared.
 

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

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Key clinical point: NASH is rapidly eclipsing HCV infection as the leading contributor to liver cancer in the United States.

Major finding: The prevalence of HCV infection is forecast to decline to 1.06 million cases by 2025 while the prevalence of NASH is projected to increase to as many as 42.34 million cases by 2025.

Data source: Analysis based on data from the National Health and Nutrition Examination Survey and the Organ Procurement and Transplantation Network.

Disclosures: No funding sources or conflicts of interest were declared.

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

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