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Host stress response may be a factor in early-stage HCV clearance
The cellular stress response in hepatocytes may play a major role in controlling hepatitis C virus (HCV). This response may be an important host factor for virus clearance during the early stages of HCV infection, according to a review of acute and chronic HCV infection by W. Alfredo Ríos-Ocampo, MD, and his colleagues (Virus Res. 2019. doi: 10.1016/j.virusres.2018.12.013).
The reviewers examined the mechanisms of induction and modulation of oxidative stress and endoplasmic-reticular stress with regard to viral persistence and cell survival. The accumulated research indicates that the activation of the eIF2-alpha/ATF4 pathway and selective autophagy induction are involved in the elimination of harmful viral proteins after oxidative stress induction. This all suggests a negative role of autophagy upon HCV infection or a negative regulation of viral replication.
“We conclude from published studies and our own research that viral protein synthesis activates adaptive responses, including autophagy pathways, that act to limit viral protein load and thereby reduce oxidative stress and cell death. Exploitation of these pathways to reduce viral replication will be the next goal and might be a valuable addition to antiviral therapy,” the reviewers concluded.
The authors reported that they had no conflicts of interest.
SOURCE: Ríos-Ocampo, WA, et al. Virus Res. 2019. doi: 10.1016/j.virusres.2018.12.013).
The cellular stress response in hepatocytes may play a major role in controlling hepatitis C virus (HCV). This response may be an important host factor for virus clearance during the early stages of HCV infection, according to a review of acute and chronic HCV infection by W. Alfredo Ríos-Ocampo, MD, and his colleagues (Virus Res. 2019. doi: 10.1016/j.virusres.2018.12.013).
The reviewers examined the mechanisms of induction and modulation of oxidative stress and endoplasmic-reticular stress with regard to viral persistence and cell survival. The accumulated research indicates that the activation of the eIF2-alpha/ATF4 pathway and selective autophagy induction are involved in the elimination of harmful viral proteins after oxidative stress induction. This all suggests a negative role of autophagy upon HCV infection or a negative regulation of viral replication.
“We conclude from published studies and our own research that viral protein synthesis activates adaptive responses, including autophagy pathways, that act to limit viral protein load and thereby reduce oxidative stress and cell death. Exploitation of these pathways to reduce viral replication will be the next goal and might be a valuable addition to antiviral therapy,” the reviewers concluded.
The authors reported that they had no conflicts of interest.
SOURCE: Ríos-Ocampo, WA, et al. Virus Res. 2019. doi: 10.1016/j.virusres.2018.12.013).
The cellular stress response in hepatocytes may play a major role in controlling hepatitis C virus (HCV). This response may be an important host factor for virus clearance during the early stages of HCV infection, according to a review of acute and chronic HCV infection by W. Alfredo Ríos-Ocampo, MD, and his colleagues (Virus Res. 2019. doi: 10.1016/j.virusres.2018.12.013).
The reviewers examined the mechanisms of induction and modulation of oxidative stress and endoplasmic-reticular stress with regard to viral persistence and cell survival. The accumulated research indicates that the activation of the eIF2-alpha/ATF4 pathway and selective autophagy induction are involved in the elimination of harmful viral proteins after oxidative stress induction. This all suggests a negative role of autophagy upon HCV infection or a negative regulation of viral replication.
“We conclude from published studies and our own research that viral protein synthesis activates adaptive responses, including autophagy pathways, that act to limit viral protein load and thereby reduce oxidative stress and cell death. Exploitation of these pathways to reduce viral replication will be the next goal and might be a valuable addition to antiviral therapy,” the reviewers concluded.
The authors reported that they had no conflicts of interest.
SOURCE: Ríos-Ocampo, WA, et al. Virus Res. 2019. doi: 10.1016/j.virusres.2018.12.013).
FROM VIRUS RESEARCH
Chronic infections such as HCV, HIV, and TB cause unique problems for psoriasis patients
In a review of therapeutic issues for psoriasis patients who have such chronic infections as hepatitis, HIV, or latent tuberculosis infection (LTBI) or those who fall into the category of special populations (pregnant women or children), significant concerns were directly tied to the mode of action of the drugs involved.
In particular, “Most systemic agents for psoriasis are immunosuppressive, which poses a unique treatment challenge in patients with psoriasis with chronic infections because they are already immunosuppressed,” according to Shivani B. Kaushik, MD, a resident in the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York, and her colleague Mark G. Lebwohl, MD, professor and system chair of the department.
For example, the reviewers detailed a report of hepatitis B virus (HBV) and hepatitis C virus (HCV) reactivation in patients with psoriasis who were taking biologics. Virus reactivation was noted in 2/175 patients who were positive for anti-HBc antibody, 3/97 patients with HCV infection, and 8/40 patients who were positive for HBsAg (the surface antigen of HBV). From this, they concluded that “biologics pose minimal risk for viral reactivation in patients with anti-HCV or anti-HBc antibodies, but they are of considerable risk in HBsAg-positive patients.” (J Amer Acad Derm. 2019 Jan;80:43-53).
Giving a specific example, Dr. Kaushik and her colleague pointed out that the safety of ustekinumab in patients with psoriasis with concurrent HCV and HBV infection was not clear. Viral reactivation and hepatocellular cancer were reported in one of four patients with HCV and in two of seven HBsAg-positive patients; and yet, another study showed that the successful use of ustekinumab for psoriasis had no impact on liver function or viral load in a patient with coexisting HCV.
Overall, “Patients should not be treated with immunosuppressive therapies during the acute stage. However, biologic treatment can be initiated in patients with chronic or resolved hepatitis under close monitoring and collaboration with a gastroenterologist,” the researchers stated.
In addition, they pointed out that methotrexate, another commonly prescribed drug for psoriasis, is absolutely contraindicated, although the use of cyclosporine remains controversial for those patients who are HCV-antibody positive.
“Most systemic agents used in psoriasis are immunosuppressive and require appropriate screening, monitoring, and prophylaxis when used in [psoriasis] patients with chronic infections, such as hepatitis, HIV, and LTBI,” the authors concluded.
The authors reported receiving funding from a number of pharmaceutical companies.
SOURCE: Kaushik BS et al. J Amer Acad Derm. 2019;80:43-53.
In a review of therapeutic issues for psoriasis patients who have such chronic infections as hepatitis, HIV, or latent tuberculosis infection (LTBI) or those who fall into the category of special populations (pregnant women or children), significant concerns were directly tied to the mode of action of the drugs involved.
In particular, “Most systemic agents for psoriasis are immunosuppressive, which poses a unique treatment challenge in patients with psoriasis with chronic infections because they are already immunosuppressed,” according to Shivani B. Kaushik, MD, a resident in the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York, and her colleague Mark G. Lebwohl, MD, professor and system chair of the department.
For example, the reviewers detailed a report of hepatitis B virus (HBV) and hepatitis C virus (HCV) reactivation in patients with psoriasis who were taking biologics. Virus reactivation was noted in 2/175 patients who were positive for anti-HBc antibody, 3/97 patients with HCV infection, and 8/40 patients who were positive for HBsAg (the surface antigen of HBV). From this, they concluded that “biologics pose minimal risk for viral reactivation in patients with anti-HCV or anti-HBc antibodies, but they are of considerable risk in HBsAg-positive patients.” (J Amer Acad Derm. 2019 Jan;80:43-53).
Giving a specific example, Dr. Kaushik and her colleague pointed out that the safety of ustekinumab in patients with psoriasis with concurrent HCV and HBV infection was not clear. Viral reactivation and hepatocellular cancer were reported in one of four patients with HCV and in two of seven HBsAg-positive patients; and yet, another study showed that the successful use of ustekinumab for psoriasis had no impact on liver function or viral load in a patient with coexisting HCV.
Overall, “Patients should not be treated with immunosuppressive therapies during the acute stage. However, biologic treatment can be initiated in patients with chronic or resolved hepatitis under close monitoring and collaboration with a gastroenterologist,” the researchers stated.
In addition, they pointed out that methotrexate, another commonly prescribed drug for psoriasis, is absolutely contraindicated, although the use of cyclosporine remains controversial for those patients who are HCV-antibody positive.
“Most systemic agents used in psoriasis are immunosuppressive and require appropriate screening, monitoring, and prophylaxis when used in [psoriasis] patients with chronic infections, such as hepatitis, HIV, and LTBI,” the authors concluded.
The authors reported receiving funding from a number of pharmaceutical companies.
SOURCE: Kaushik BS et al. J Amer Acad Derm. 2019;80:43-53.
In a review of therapeutic issues for psoriasis patients who have such chronic infections as hepatitis, HIV, or latent tuberculosis infection (LTBI) or those who fall into the category of special populations (pregnant women or children), significant concerns were directly tied to the mode of action of the drugs involved.
In particular, “Most systemic agents for psoriasis are immunosuppressive, which poses a unique treatment challenge in patients with psoriasis with chronic infections because they are already immunosuppressed,” according to Shivani B. Kaushik, MD, a resident in the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York, and her colleague Mark G. Lebwohl, MD, professor and system chair of the department.
For example, the reviewers detailed a report of hepatitis B virus (HBV) and hepatitis C virus (HCV) reactivation in patients with psoriasis who were taking biologics. Virus reactivation was noted in 2/175 patients who were positive for anti-HBc antibody, 3/97 patients with HCV infection, and 8/40 patients who were positive for HBsAg (the surface antigen of HBV). From this, they concluded that “biologics pose minimal risk for viral reactivation in patients with anti-HCV or anti-HBc antibodies, but they are of considerable risk in HBsAg-positive patients.” (J Amer Acad Derm. 2019 Jan;80:43-53).
Giving a specific example, Dr. Kaushik and her colleague pointed out that the safety of ustekinumab in patients with psoriasis with concurrent HCV and HBV infection was not clear. Viral reactivation and hepatocellular cancer were reported in one of four patients with HCV and in two of seven HBsAg-positive patients; and yet, another study showed that the successful use of ustekinumab for psoriasis had no impact on liver function or viral load in a patient with coexisting HCV.
Overall, “Patients should not be treated with immunosuppressive therapies during the acute stage. However, biologic treatment can be initiated in patients with chronic or resolved hepatitis under close monitoring and collaboration with a gastroenterologist,” the researchers stated.
In addition, they pointed out that methotrexate, another commonly prescribed drug for psoriasis, is absolutely contraindicated, although the use of cyclosporine remains controversial for those patients who are HCV-antibody positive.
“Most systemic agents used in psoriasis are immunosuppressive and require appropriate screening, monitoring, and prophylaxis when used in [psoriasis] patients with chronic infections, such as hepatitis, HIV, and LTBI,” the authors concluded.
The authors reported receiving funding from a number of pharmaceutical companies.
SOURCE: Kaushik BS et al. J Amer Acad Derm. 2019;80:43-53.
FROM THE JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
Opioid clinic physicians report lack of competency in managing patients with HCV
A survey of clinicians who provide opioid agonist therapy (OAT) to people who inject drugs (PWID), showed several areas where self-reported competency in the management and treatment of hepatitis C virus (HCV) could be improved.
The C-SCOPE study consisted of a self-administered survey among physicians practicing at clinics providing OAT in Australia, Canada, Europe, and the United States during April-May of 2017. Among 203 physicians – 40% in the United States, 45% in Europe, and 14% in Australia/Canada – 21% were addiction medicine specialists, and 29% were psychiatrists.
The majority reported that HCV testing (86%) and treatment (82%) among PWID were important.
The minority reported less than average competence with respect to regular screening (12%) and interpretation of HCV test results (14%), while greater proportions reported less than average competence in advising patients about new HCV therapies (28%), knowledge of new treatments (37%), and treatment/management of HCV (40%). Although a minority of participants self-reported average or less competency related to the ability to ensure regular screening for HCV (34%) and in the ability to interpret HCV test results (39%), more than half of the participants self-reported average or less competency in other areas. These areas included the ability to assess liver disease (52%), the ability to treat HCV and manage side effects (65%), and knowledge of new HCV treatments (64%). This trend was consistent with findings from previous studies among competency related to HCV infection among primary care providers, according to the authors (Int J Drug Policy. 2019;63:29-38).
“These low levels of reported competency in HCV management and treatment highlight a critical need for improved HCV education and training in how to manage and treat HCV among PWID,” the researchers concluded.
The authors reported grant funding and consultancy with a number of pharmaceutical companies. Funding was provided by Merck Sharp & Dohme and the Australian government.
SOURCE: Grebely J et al. Int J Drug Policy. 2019;63:29-38.
A survey of clinicians who provide opioid agonist therapy (OAT) to people who inject drugs (PWID), showed several areas where self-reported competency in the management and treatment of hepatitis C virus (HCV) could be improved.
The C-SCOPE study consisted of a self-administered survey among physicians practicing at clinics providing OAT in Australia, Canada, Europe, and the United States during April-May of 2017. Among 203 physicians – 40% in the United States, 45% in Europe, and 14% in Australia/Canada – 21% were addiction medicine specialists, and 29% were psychiatrists.
The majority reported that HCV testing (86%) and treatment (82%) among PWID were important.
The minority reported less than average competence with respect to regular screening (12%) and interpretation of HCV test results (14%), while greater proportions reported less than average competence in advising patients about new HCV therapies (28%), knowledge of new treatments (37%), and treatment/management of HCV (40%). Although a minority of participants self-reported average or less competency related to the ability to ensure regular screening for HCV (34%) and in the ability to interpret HCV test results (39%), more than half of the participants self-reported average or less competency in other areas. These areas included the ability to assess liver disease (52%), the ability to treat HCV and manage side effects (65%), and knowledge of new HCV treatments (64%). This trend was consistent with findings from previous studies among competency related to HCV infection among primary care providers, according to the authors (Int J Drug Policy. 2019;63:29-38).
“These low levels of reported competency in HCV management and treatment highlight a critical need for improved HCV education and training in how to manage and treat HCV among PWID,” the researchers concluded.
The authors reported grant funding and consultancy with a number of pharmaceutical companies. Funding was provided by Merck Sharp & Dohme and the Australian government.
SOURCE: Grebely J et al. Int J Drug Policy. 2019;63:29-38.
A survey of clinicians who provide opioid agonist therapy (OAT) to people who inject drugs (PWID), showed several areas where self-reported competency in the management and treatment of hepatitis C virus (HCV) could be improved.
The C-SCOPE study consisted of a self-administered survey among physicians practicing at clinics providing OAT in Australia, Canada, Europe, and the United States during April-May of 2017. Among 203 physicians – 40% in the United States, 45% in Europe, and 14% in Australia/Canada – 21% were addiction medicine specialists, and 29% were psychiatrists.
The majority reported that HCV testing (86%) and treatment (82%) among PWID were important.
The minority reported less than average competence with respect to regular screening (12%) and interpretation of HCV test results (14%), while greater proportions reported less than average competence in advising patients about new HCV therapies (28%), knowledge of new treatments (37%), and treatment/management of HCV (40%). Although a minority of participants self-reported average or less competency related to the ability to ensure regular screening for HCV (34%) and in the ability to interpret HCV test results (39%), more than half of the participants self-reported average or less competency in other areas. These areas included the ability to assess liver disease (52%), the ability to treat HCV and manage side effects (65%), and knowledge of new HCV treatments (64%). This trend was consistent with findings from previous studies among competency related to HCV infection among primary care providers, according to the authors (Int J Drug Policy. 2019;63:29-38).
“These low levels of reported competency in HCV management and treatment highlight a critical need for improved HCV education and training in how to manage and treat HCV among PWID,” the researchers concluded.
The authors reported grant funding and consultancy with a number of pharmaceutical companies. Funding was provided by Merck Sharp & Dohme and the Australian government.
SOURCE: Grebely J et al. Int J Drug Policy. 2019;63:29-38.
FROM THE INTERNATIONAL JOURNAL OF DRUG POLICY
Risk-based testing missed 35% of HCV-positive prison inmates
Routine testing for hepatitis C virus at inmate entry should be considered by U.S. state prisons, according to Sabrina A. Assoumou, MD, of the Boston Medical Center and her colleagues.
The researchers performed a retrospective analysis of individuals entering the Washington state prison system, which routinely offers hepatitis C virus (HCV) testing, in order to compare routine opt-out testing with current risk-based and one-time testing for individuals born between 1945 and 1965. Additionally, liver fibrosis stage was characterized in blood samples from HCV-positive individuals, the investigators wrote in the American Journal of Preventative Medicine.
Between 2012 and 2016, 24,567 (83%) individuals were tested for HCV antibody, and of these, 4,921 (20%) tested positive. A total of 2,403 (49%) of those testing positive had subsequent hepatitis HCV RNA testing, with 1,727 (72%) of these showing chronic infection.
As expected, Dr. Assoumou and her colleagues found that reactive antibodies was more prevalent in individuals born between 1945 and 1965, compared with other years (44% vs. 17%). However, in actual case numbers, most (72%) were outside of this age bracket. Overall, they calculated that up to 35% of positive HCV tests would be missed using testing targeted by birth cohort and risk behavior alone. Among the chronically infected individuals, 23% had showed at least moderate liver fibrosis.
“Routine opt-out testing identified a substantial number of HCV cases that would have been missed by targeted testing. Almost one-quarter of individuals with chronic HCV had significant liver fibrosis and thus a more urgent need for treatment to prevent complications,” Dr Assoumou and her colleagues concluded.
The researchers reported that they had no conflicts of interest.
SOURCE: Assoumou SA et al, Am J Prev Med. 2019;56:8-16.
Routine testing for hepatitis C virus at inmate entry should be considered by U.S. state prisons, according to Sabrina A. Assoumou, MD, of the Boston Medical Center and her colleagues.
The researchers performed a retrospective analysis of individuals entering the Washington state prison system, which routinely offers hepatitis C virus (HCV) testing, in order to compare routine opt-out testing with current risk-based and one-time testing for individuals born between 1945 and 1965. Additionally, liver fibrosis stage was characterized in blood samples from HCV-positive individuals, the investigators wrote in the American Journal of Preventative Medicine.
Between 2012 and 2016, 24,567 (83%) individuals were tested for HCV antibody, and of these, 4,921 (20%) tested positive. A total of 2,403 (49%) of those testing positive had subsequent hepatitis HCV RNA testing, with 1,727 (72%) of these showing chronic infection.
As expected, Dr. Assoumou and her colleagues found that reactive antibodies was more prevalent in individuals born between 1945 and 1965, compared with other years (44% vs. 17%). However, in actual case numbers, most (72%) were outside of this age bracket. Overall, they calculated that up to 35% of positive HCV tests would be missed using testing targeted by birth cohort and risk behavior alone. Among the chronically infected individuals, 23% had showed at least moderate liver fibrosis.
“Routine opt-out testing identified a substantial number of HCV cases that would have been missed by targeted testing. Almost one-quarter of individuals with chronic HCV had significant liver fibrosis and thus a more urgent need for treatment to prevent complications,” Dr Assoumou and her colleagues concluded.
The researchers reported that they had no conflicts of interest.
SOURCE: Assoumou SA et al, Am J Prev Med. 2019;56:8-16.
Routine testing for hepatitis C virus at inmate entry should be considered by U.S. state prisons, according to Sabrina A. Assoumou, MD, of the Boston Medical Center and her colleagues.
The researchers performed a retrospective analysis of individuals entering the Washington state prison system, which routinely offers hepatitis C virus (HCV) testing, in order to compare routine opt-out testing with current risk-based and one-time testing for individuals born between 1945 and 1965. Additionally, liver fibrosis stage was characterized in blood samples from HCV-positive individuals, the investigators wrote in the American Journal of Preventative Medicine.
Between 2012 and 2016, 24,567 (83%) individuals were tested for HCV antibody, and of these, 4,921 (20%) tested positive. A total of 2,403 (49%) of those testing positive had subsequent hepatitis HCV RNA testing, with 1,727 (72%) of these showing chronic infection.
As expected, Dr. Assoumou and her colleagues found that reactive antibodies was more prevalent in individuals born between 1945 and 1965, compared with other years (44% vs. 17%). However, in actual case numbers, most (72%) were outside of this age bracket. Overall, they calculated that up to 35% of positive HCV tests would be missed using testing targeted by birth cohort and risk behavior alone. Among the chronically infected individuals, 23% had showed at least moderate liver fibrosis.
“Routine opt-out testing identified a substantial number of HCV cases that would have been missed by targeted testing. Almost one-quarter of individuals with chronic HCV had significant liver fibrosis and thus a more urgent need for treatment to prevent complications,” Dr Assoumou and her colleagues concluded.
The researchers reported that they had no conflicts of interest.
SOURCE: Assoumou SA et al, Am J Prev Med. 2019;56:8-16.
FROM THE AMERICAN JOURNAL OF PREVENTIVE MEDICINE
Young opioid users in NYC savvy about HCV
Assessing patient knowledge about hepatitis C virus (HCV) transmission knowledge is difficult given the lack of psychometrically tested measures available, according to researchers who developed and validated an HCV injection–risk knowledge scale.
The 5-item, validated HCV Injection-Risk Knowledge Scale may provide educators, care providers, and researchers with critical information for reducing HCV among people who inject drugs (PWID), according to their report.
The researchers analyzed data from 539 New York City opioid users aged 18-29 years who were recruited via respondent-driven sampling in 2014-2016, according to the study published in Drug and Alcohol Dependence.
Principal components analysis (PCA) of nine knowledge items answered true, false, or don’t know identified useful scale items. These were then evaluated for internal consistency and assessed by comparing knowledge levels with those from a previously validated general HCV knowledge scale and by comparing key subgroup knowledge levels.
PCA identified one component with five items that explained 45% of the total variance and had high internal consistency (alpha, 0.91). All of the component items referred to transmission through drug-injection equipment and practices: sharing materials such as cookers, cottons, diluting water, water containers, and cleaning syringes with water.
The mean percent correct was 75%, and was moderately correlated with general HCV knowledge. Knowledge levels were highest for those previously tested for HCV, those with HCV antibody–positive status, PWID, and those who had received harm reduction information in various settings.
“The low percentage correct among those who had never injected [52% vs. 83% correct among injectors] is concerning given the possibility of their experimenting with drug injection as route of administration,” they added.
“These results suggest that primary care providers, drug treatment programs, and syringe exchange programs are important sources of HCV risk knowledge among at-risk populations, similar to other studies’ findings,” the researchers concluded.
The study was funded by the National Institutes of Health and the authors reported no conflicts of interest.
SOURCE: Quinn K et al. Drug Alcohol Depend. 2019;194:453-9.
Assessing patient knowledge about hepatitis C virus (HCV) transmission knowledge is difficult given the lack of psychometrically tested measures available, according to researchers who developed and validated an HCV injection–risk knowledge scale.
The 5-item, validated HCV Injection-Risk Knowledge Scale may provide educators, care providers, and researchers with critical information for reducing HCV among people who inject drugs (PWID), according to their report.
The researchers analyzed data from 539 New York City opioid users aged 18-29 years who were recruited via respondent-driven sampling in 2014-2016, according to the study published in Drug and Alcohol Dependence.
Principal components analysis (PCA) of nine knowledge items answered true, false, or don’t know identified useful scale items. These were then evaluated for internal consistency and assessed by comparing knowledge levels with those from a previously validated general HCV knowledge scale and by comparing key subgroup knowledge levels.
PCA identified one component with five items that explained 45% of the total variance and had high internal consistency (alpha, 0.91). All of the component items referred to transmission through drug-injection equipment and practices: sharing materials such as cookers, cottons, diluting water, water containers, and cleaning syringes with water.
The mean percent correct was 75%, and was moderately correlated with general HCV knowledge. Knowledge levels were highest for those previously tested for HCV, those with HCV antibody–positive status, PWID, and those who had received harm reduction information in various settings.
“The low percentage correct among those who had never injected [52% vs. 83% correct among injectors] is concerning given the possibility of their experimenting with drug injection as route of administration,” they added.
“These results suggest that primary care providers, drug treatment programs, and syringe exchange programs are important sources of HCV risk knowledge among at-risk populations, similar to other studies’ findings,” the researchers concluded.
The study was funded by the National Institutes of Health and the authors reported no conflicts of interest.
SOURCE: Quinn K et al. Drug Alcohol Depend. 2019;194:453-9.
Assessing patient knowledge about hepatitis C virus (HCV) transmission knowledge is difficult given the lack of psychometrically tested measures available, according to researchers who developed and validated an HCV injection–risk knowledge scale.
The 5-item, validated HCV Injection-Risk Knowledge Scale may provide educators, care providers, and researchers with critical information for reducing HCV among people who inject drugs (PWID), according to their report.
The researchers analyzed data from 539 New York City opioid users aged 18-29 years who were recruited via respondent-driven sampling in 2014-2016, according to the study published in Drug and Alcohol Dependence.
Principal components analysis (PCA) of nine knowledge items answered true, false, or don’t know identified useful scale items. These were then evaluated for internal consistency and assessed by comparing knowledge levels with those from a previously validated general HCV knowledge scale and by comparing key subgroup knowledge levels.
PCA identified one component with five items that explained 45% of the total variance and had high internal consistency (alpha, 0.91). All of the component items referred to transmission through drug-injection equipment and practices: sharing materials such as cookers, cottons, diluting water, water containers, and cleaning syringes with water.
The mean percent correct was 75%, and was moderately correlated with general HCV knowledge. Knowledge levels were highest for those previously tested for HCV, those with HCV antibody–positive status, PWID, and those who had received harm reduction information in various settings.
“The low percentage correct among those who had never injected [52% vs. 83% correct among injectors] is concerning given the possibility of their experimenting with drug injection as route of administration,” they added.
“These results suggest that primary care providers, drug treatment programs, and syringe exchange programs are important sources of HCV risk knowledge among at-risk populations, similar to other studies’ findings,” the researchers concluded.
The study was funded by the National Institutes of Health and the authors reported no conflicts of interest.
SOURCE: Quinn K et al. Drug Alcohol Depend. 2019;194:453-9.
FROM DRUG AND ALCOHOL DEPENDENCE
Vitamin D–binding protein polymorphisms affect HCV susceptibility
Two specific polymorphisms within the vitamin D–binding protein (VDBP) gene may contribute to susceptibility to hepatitis C virus (HCV) infection in a high-risk Chinese Han population, according to the results of a case-control study published in Gene.
Previous research has indicated that vitamin D deficiency may have an impact on the antiviral response in chronic HCV, and VDBP has been shown to transport vitamin D and its metabolites, thereby influencing vitamin D status. This made VDBP a valid candidate for study as to its effects on HCV infection.
The current study initially recruited around 2,500 Chinese subjects over the period October 2008 to January 2016. The majority were women, and the average age of the subjects was 49-50 years.
The researchers genotyped seven genetic variants in the VDBP gene in 886 patients with HCV persistent infection, 539 subjects with spontaneous clearance, and 1,081 uninfected controls, according to Chao-Nan Xie of the department of epidemiology and biostatistics, Nanjing (China) Medical University, and colleagues.
The researchers found that two variants (rs7041-G and rs3733359-T alleles) were significantly associated with an increased susceptibility of HCV infection. In addition, the combined effect of having the two unfavorable alleles was related to an elevated risk of HCV infection in a locus-dosage manner (P = .000816).
Haplotype analysis suggested that the GT haplotype showed an increased risk effect of HCV infection (odds ratio, 1.464), compared with the most frequent TC haplotype.
“Taken together, polymorphisms within the VDBP gene (rs4588 and rs3733359) may contribute to susceptibility to HCV infection in a high-risk Chinese Han population, which implicates a role of VDR genetic polymorphisms and vitamin D levels in the immune regulation and course of HCV infection,” the researchers concluded.
The authors reported that they had no conflicts of interest.
SOURCE: Xie C-N et al. Gene 2018;679:405-11.
Two specific polymorphisms within the vitamin D–binding protein (VDBP) gene may contribute to susceptibility to hepatitis C virus (HCV) infection in a high-risk Chinese Han population, according to the results of a case-control study published in Gene.
Previous research has indicated that vitamin D deficiency may have an impact on the antiviral response in chronic HCV, and VDBP has been shown to transport vitamin D and its metabolites, thereby influencing vitamin D status. This made VDBP a valid candidate for study as to its effects on HCV infection.
The current study initially recruited around 2,500 Chinese subjects over the period October 2008 to January 2016. The majority were women, and the average age of the subjects was 49-50 years.
The researchers genotyped seven genetic variants in the VDBP gene in 886 patients with HCV persistent infection, 539 subjects with spontaneous clearance, and 1,081 uninfected controls, according to Chao-Nan Xie of the department of epidemiology and biostatistics, Nanjing (China) Medical University, and colleagues.
The researchers found that two variants (rs7041-G and rs3733359-T alleles) were significantly associated with an increased susceptibility of HCV infection. In addition, the combined effect of having the two unfavorable alleles was related to an elevated risk of HCV infection in a locus-dosage manner (P = .000816).
Haplotype analysis suggested that the GT haplotype showed an increased risk effect of HCV infection (odds ratio, 1.464), compared with the most frequent TC haplotype.
“Taken together, polymorphisms within the VDBP gene (rs4588 and rs3733359) may contribute to susceptibility to HCV infection in a high-risk Chinese Han population, which implicates a role of VDR genetic polymorphisms and vitamin D levels in the immune regulation and course of HCV infection,” the researchers concluded.
The authors reported that they had no conflicts of interest.
SOURCE: Xie C-N et al. Gene 2018;679:405-11.
Two specific polymorphisms within the vitamin D–binding protein (VDBP) gene may contribute to susceptibility to hepatitis C virus (HCV) infection in a high-risk Chinese Han population, according to the results of a case-control study published in Gene.
Previous research has indicated that vitamin D deficiency may have an impact on the antiviral response in chronic HCV, and VDBP has been shown to transport vitamin D and its metabolites, thereby influencing vitamin D status. This made VDBP a valid candidate for study as to its effects on HCV infection.
The current study initially recruited around 2,500 Chinese subjects over the period October 2008 to January 2016. The majority were women, and the average age of the subjects was 49-50 years.
The researchers genotyped seven genetic variants in the VDBP gene in 886 patients with HCV persistent infection, 539 subjects with spontaneous clearance, and 1,081 uninfected controls, according to Chao-Nan Xie of the department of epidemiology and biostatistics, Nanjing (China) Medical University, and colleagues.
The researchers found that two variants (rs7041-G and rs3733359-T alleles) were significantly associated with an increased susceptibility of HCV infection. In addition, the combined effect of having the two unfavorable alleles was related to an elevated risk of HCV infection in a locus-dosage manner (P = .000816).
Haplotype analysis suggested that the GT haplotype showed an increased risk effect of HCV infection (odds ratio, 1.464), compared with the most frequent TC haplotype.
“Taken together, polymorphisms within the VDBP gene (rs4588 and rs3733359) may contribute to susceptibility to HCV infection in a high-risk Chinese Han population, which implicates a role of VDR genetic polymorphisms and vitamin D levels in the immune regulation and course of HCV infection,” the researchers concluded.
The authors reported that they had no conflicts of interest.
SOURCE: Xie C-N et al. Gene 2018;679:405-11.
FROM GENE
Key clinical point: VDBP alleles influence susceptibility to HCV infection in a Chinese population.
Major finding: The GT haplotype showed an increased risk effect of HCV infection (odds ratio 1.464) compared to the most frequent TC haplotype.
Study details: Case-control study of 886 HIV-infected, 539 spontaneously cleared, and 1,081 control patients.
Disclosures: The authors reported that they had no conflicts of interest.
Source: Xie C-N et al. Gene. 2018;679:405-11.
It’s time for universal HCV screening in the ED
SAN FRANCISCO – Emergency departments are the ideal place to screen for hepatitis C infection, according to investigators from Vanderbilt University, Nashville, Tenn.
Current recommendations call for screening baby boomers born from 1945 to 1965 and patients with risk factors, especially injection drug use. The problem is that the guidelines don’t say, exactly, how and where that should be done, so uptake has been spotty. Also, people aren’t exactly forthcoming when it comes to admitting IV drug use.
Enter universal screening in the ED. Vanderbilt is one of several academic centers that have adopted the approach, and others are following suit. Across the board, they’ve found that HCV infection is more common than projections based on baby boomer and risk factor demographics suggest, and, even more importantly, the boomer/risk factor strategy misses a large number of active cases, said Cody A. Chastain, MD, assistant professor of infectious diseases at Vanderbilt, who led the ED screening initiative.
In short, universal screening in the ED would keep people from falling through the cracks.
From April 2017 to March 2018, every adult who had blood drawn at Vanderbilt’s tertiary care ED was asked by a nurse if they’d also like to be checked for HCV, so long as they were alert enough for the conversation. If they agreed, an additional phlebotomy tube was added to the draw, and sent off for testing. Fewer than 5% of patients opted out.
Antibody positive samples were automatically screened for active disease by HCV RNA. Results were entered into the medical record and shared with patients at discharge. Active cases were counseled and offered linkage to care, regardless of insurance status.
The initiative screened 11,637 patients; 1,008 (8.7%) were antibody positive, of whom 488 (48%) were RNA positive. Thirty-seven percent of the active cases were in non–baby boomers – most born after 1965 – with no known injection drug use. The baby boomer/risk factor model would have missed most of them.
Also, spontaneous clearance – antibody positive, RNA negative without HCV treatment – “is dramatically higher” than what’s thought. “The historic estimate of 20% clearly is not reflected” in the Vanderbilt results, nor in similar universal screening studies; “spontaneous clearance is about 50% or so,” Dr. Chastain said.
Even so, “virtually every study published in this space finds more cases of infection than traditional screening would find. [Our work] is just one more piece of data” to indicate the usefulness of the approach. “Emergency departments [are] ideal for hepatitis C screening,” he said at IDWeek, an annual scientific meeting on infectious diseases, where he presented the findings.
“This is well trodden territory; we’ve already addressed it with HIV. We recognized that HIV screening had a stigma and was a challenge, [so we] moved to universal screening” of all adults, at least once. It “drastically improved screening rates. I don’t see a rational reason” not to do this for hepatitis C. “There are very well-meaning people who engage in the cost effectiveness side of this discussion, but I don’t think it helps us in our efforts to control this epidemic from a public health standpoint,” Dr. Chastain said.
Vanderbilt continues to screen for HCV in the ED; the next step is to see how well efforts to link active cases with care are working. Many times during the study, Dr. Chastain said positive patients eventually revealed that they already knew they had HCV, but had been told there was nothing they could do about it, so they didn’t get care. Maybe they were told that because they didn’t have insurance.
Vanderbilt has dropped screening ED patients born before 1945 because the odds of picking up an unknown HCV infection proved to be tiny, and, in any case, patients are generally too comorbid for treatment. It’s made screening more efficient.
Dr. Chastain reported that he had no personal disclosures. The study was funded by Vanderbilt, which receives grants from pharmaceutical companies.
SOURCE: Chastain C et al. 2018 ID Week, Abstract 932.
SAN FRANCISCO – Emergency departments are the ideal place to screen for hepatitis C infection, according to investigators from Vanderbilt University, Nashville, Tenn.
Current recommendations call for screening baby boomers born from 1945 to 1965 and patients with risk factors, especially injection drug use. The problem is that the guidelines don’t say, exactly, how and where that should be done, so uptake has been spotty. Also, people aren’t exactly forthcoming when it comes to admitting IV drug use.
Enter universal screening in the ED. Vanderbilt is one of several academic centers that have adopted the approach, and others are following suit. Across the board, they’ve found that HCV infection is more common than projections based on baby boomer and risk factor demographics suggest, and, even more importantly, the boomer/risk factor strategy misses a large number of active cases, said Cody A. Chastain, MD, assistant professor of infectious diseases at Vanderbilt, who led the ED screening initiative.
In short, universal screening in the ED would keep people from falling through the cracks.
From April 2017 to March 2018, every adult who had blood drawn at Vanderbilt’s tertiary care ED was asked by a nurse if they’d also like to be checked for HCV, so long as they were alert enough for the conversation. If they agreed, an additional phlebotomy tube was added to the draw, and sent off for testing. Fewer than 5% of patients opted out.
Antibody positive samples were automatically screened for active disease by HCV RNA. Results were entered into the medical record and shared with patients at discharge. Active cases were counseled and offered linkage to care, regardless of insurance status.
The initiative screened 11,637 patients; 1,008 (8.7%) were antibody positive, of whom 488 (48%) were RNA positive. Thirty-seven percent of the active cases were in non–baby boomers – most born after 1965 – with no known injection drug use. The baby boomer/risk factor model would have missed most of them.
Also, spontaneous clearance – antibody positive, RNA negative without HCV treatment – “is dramatically higher” than what’s thought. “The historic estimate of 20% clearly is not reflected” in the Vanderbilt results, nor in similar universal screening studies; “spontaneous clearance is about 50% or so,” Dr. Chastain said.
Even so, “virtually every study published in this space finds more cases of infection than traditional screening would find. [Our work] is just one more piece of data” to indicate the usefulness of the approach. “Emergency departments [are] ideal for hepatitis C screening,” he said at IDWeek, an annual scientific meeting on infectious diseases, where he presented the findings.
“This is well trodden territory; we’ve already addressed it with HIV. We recognized that HIV screening had a stigma and was a challenge, [so we] moved to universal screening” of all adults, at least once. It “drastically improved screening rates. I don’t see a rational reason” not to do this for hepatitis C. “There are very well-meaning people who engage in the cost effectiveness side of this discussion, but I don’t think it helps us in our efforts to control this epidemic from a public health standpoint,” Dr. Chastain said.
Vanderbilt continues to screen for HCV in the ED; the next step is to see how well efforts to link active cases with care are working. Many times during the study, Dr. Chastain said positive patients eventually revealed that they already knew they had HCV, but had been told there was nothing they could do about it, so they didn’t get care. Maybe they were told that because they didn’t have insurance.
Vanderbilt has dropped screening ED patients born before 1945 because the odds of picking up an unknown HCV infection proved to be tiny, and, in any case, patients are generally too comorbid for treatment. It’s made screening more efficient.
Dr. Chastain reported that he had no personal disclosures. The study was funded by Vanderbilt, which receives grants from pharmaceutical companies.
SOURCE: Chastain C et al. 2018 ID Week, Abstract 932.
SAN FRANCISCO – Emergency departments are the ideal place to screen for hepatitis C infection, according to investigators from Vanderbilt University, Nashville, Tenn.
Current recommendations call for screening baby boomers born from 1945 to 1965 and patients with risk factors, especially injection drug use. The problem is that the guidelines don’t say, exactly, how and where that should be done, so uptake has been spotty. Also, people aren’t exactly forthcoming when it comes to admitting IV drug use.
Enter universal screening in the ED. Vanderbilt is one of several academic centers that have adopted the approach, and others are following suit. Across the board, they’ve found that HCV infection is more common than projections based on baby boomer and risk factor demographics suggest, and, even more importantly, the boomer/risk factor strategy misses a large number of active cases, said Cody A. Chastain, MD, assistant professor of infectious diseases at Vanderbilt, who led the ED screening initiative.
In short, universal screening in the ED would keep people from falling through the cracks.
From April 2017 to March 2018, every adult who had blood drawn at Vanderbilt’s tertiary care ED was asked by a nurse if they’d also like to be checked for HCV, so long as they were alert enough for the conversation. If they agreed, an additional phlebotomy tube was added to the draw, and sent off for testing. Fewer than 5% of patients opted out.
Antibody positive samples were automatically screened for active disease by HCV RNA. Results were entered into the medical record and shared with patients at discharge. Active cases were counseled and offered linkage to care, regardless of insurance status.
The initiative screened 11,637 patients; 1,008 (8.7%) were antibody positive, of whom 488 (48%) were RNA positive. Thirty-seven percent of the active cases were in non–baby boomers – most born after 1965 – with no known injection drug use. The baby boomer/risk factor model would have missed most of them.
Also, spontaneous clearance – antibody positive, RNA negative without HCV treatment – “is dramatically higher” than what’s thought. “The historic estimate of 20% clearly is not reflected” in the Vanderbilt results, nor in similar universal screening studies; “spontaneous clearance is about 50% or so,” Dr. Chastain said.
Even so, “virtually every study published in this space finds more cases of infection than traditional screening would find. [Our work] is just one more piece of data” to indicate the usefulness of the approach. “Emergency departments [are] ideal for hepatitis C screening,” he said at IDWeek, an annual scientific meeting on infectious diseases, where he presented the findings.
“This is well trodden territory; we’ve already addressed it with HIV. We recognized that HIV screening had a stigma and was a challenge, [so we] moved to universal screening” of all adults, at least once. It “drastically improved screening rates. I don’t see a rational reason” not to do this for hepatitis C. “There are very well-meaning people who engage in the cost effectiveness side of this discussion, but I don’t think it helps us in our efforts to control this epidemic from a public health standpoint,” Dr. Chastain said.
Vanderbilt continues to screen for HCV in the ED; the next step is to see how well efforts to link active cases with care are working. Many times during the study, Dr. Chastain said positive patients eventually revealed that they already knew they had HCV, but had been told there was nothing they could do about it, so they didn’t get care. Maybe they were told that because they didn’t have insurance.
Vanderbilt has dropped screening ED patients born before 1945 because the odds of picking up an unknown HCV infection proved to be tiny, and, in any case, patients are generally too comorbid for treatment. It’s made screening more efficient.
Dr. Chastain reported that he had no personal disclosures. The study was funded by Vanderbilt, which receives grants from pharmaceutical companies.
SOURCE: Chastain C et al. 2018 ID Week, Abstract 932.
REPORTING FROM IDWEEK 2018
Key clinical point: HCV infection is more common than traditionally thought; screening in the ED will keep people from falling through the cracks.
Major finding: Of patients screened; 8.7% were antibody positive, with 48% of these RNA positive; 37% of active cases were in non–baby boomers with no known injection drug use. Spontaneous remission appeared to top 50%.
Study details: Quality improvement initiative in Vanderbilt University’s tertiary care ED.
Disclosures: Dr. Chastain reported that he had no disclosures. The study was funded by Vanderbilt, which receives grants from pharmaceutical companies.
Source: Chastain C et al. 2018 ID Week, Abstract 932.
Hepatitis C debrief: Therapy has matured, access issues remain
SAN FRANCISCO – Hepatitis C therapy has matured and now offers excellent sustained viral response (SVR) in the vast majority of cases, but key challenges remain in getting the therapy to those who need it.
“Unfortunately, we’re not making some of the progress we might have hoped to see, particularly in North America,” said Jordan Feld, MD, MPH, who gave a debrief of hepatitis C abstracts during a wrap-up session at the annual meeting of the American Association for the Study of Liver Diseases.
The problem is particularly acute in young adults aged 18-39 years – only about 9% of those who tested positive for HCV RNA saw a specialist, and about 23% of those who saw a specialist went on to receive treatment, according to an analysis of over 17 million patients in the United States (abstract 1567). The numbers were better for older adults but still far from optimal, with 23% who tested positive seeing a specialist, and just 32% of those patients getting treatment.
Another study (abstract 0147) looked state by state at the percentage of Medicaid patients who received a prescription for direct-acting antiviral (DAA) medication and then went on to fill the prescription. The rates ranged from 0% in Alaska to 96% in Connecticut. Eight states were higher than 70%, six were between 50% and 70%, and 15 states were below 50%.
“Despite our efforts, there continue to be major access barriers across the U.S., particularly for Medicaid individuals,” said Dr. Feld, who is a clinician-scientist at the Toronto Western Hospital Liver Clinic and the McLaughlin-Rotman Centre for Global Health.
A study examining the Chronic Hepatitis (CHeCS) cohort (abstract 0585) described a big spike in treatment uptake shortly after approvals of the new HCV regimens, but by 2016, only about one-third of individuals who required treatment actually began treatment. Factors associated with nontreatment largely reflected marginalization, including low income, being on Medicaid, and lack of long-term follow-up.
Even as health systems struggle to get treatment to those who need it, new studies are showing how to expand existing treatments into new populations.
Results from the EXPEDITION 8 study (abstract LB-7) showed efficacy of an 8-week regimen of the glecaprevir/pibrentasvir combination in patients with compensated cirrhosis. It looked at genotypes 1, 2, and 4-6. In an intention-to-treat analysis, 98% attained SVR and there were no viral failures or safety concerns. A follow-up trial is ongoing that includes patients with genotype 3. “This is exciting to be able to shorten therapy in patients with cirrhosis,” said Dr. Feld.
Although first-line DAAs are extremely effective, there are a few patients who do not achieve a cure. One study (abstract 0227) examined the combination of sofosbuvir, velpatasvir, and voxilaprevir in retreatment of these patients. The drugs resulted in SVR rates similar to those in registration trials, but the regimen was somewhat less effective in patients previously treated with sofosbuvir and velpatasvir. “I think we need to investigate that further,” said Dr. Feld.
The combination of glecaprevir and pibrentasvir also proved effective for retreatment in patients with genotype 1/1A who had failed treatment with an NS5A inhibitor plus sofosbuvir with or without ribavirin (abstract 226). SVR rates at 16 weeks were quite good, but lower in genotype 1a patients at 12 weeks (87% week 12 versus 94% week 16).”I think this is a really good regimen for genotype 1b. For 1a, serum definitely needs 16 weeks [to clear],” said Dr. Feld.
Other abstracts presented at the meeting detailed some of the benefits of SVR, not all of which are broadly appreciated. An analysis of the Hepatitis Testers Cohort in British Columbia (abstract 145), which includes over 7,000 patients who were followed for a median of 2 years (DAA) or 9.5 years (interferon-based), showed survival advantages to SVR in both cirrhotic (adjusted hazard ratio, 0.14) and noncirrhotic patients (aHR, 0.13). Other benefits include lower risk of diabetes (aHR, 0.53), chronic kidney disease/endstage renal disease (aHR, 0.48), stroke (aHR, 0.67), and mood and anxiety disorders (aHR, 0.53) (abstract 148).
As is generally accepted, SVR reduces the risk of hepatocellular cancer (HCC), according to analyses of VA and Gilead data (abstract 635), with a benefit in both cirrhotic and noncirrhotic patients. The risk almost disappears in patients without cirrhosis (incidence rate 0.07 per 100 person-years and is curbed in cirrhotic patients (incidence rate 1.30 in compensated, 4.05 in decompensated cirrhosis).
“There is really very significantly high incidence in cancer in decompensated cirrhosis, which just highlights that these patients continue to need ongoing surveillance. Although there have been efforts at developing strategies to risk stratify patients with cirrhosis, at least for now we’re stuck with surveillance, but I think for patients without cirrhosis there are now enough data showing a low enough incidence of primary HCC that we can probably avoid surveillance in that group,” said Dr. Feld.
Injectable drug users represent a special challenge in hepatitis C treatment, but new studies show cause for optimism in this population. These patients are harder to reach, and they may be less medication compliant, but one study (abstract 1632) found that imperfect adherence doesn’t necessarily undermine results – in a 12-week regimen, patients who didn’t finish until 14 weeks had no significant difference in SVR rates.
“So these therapies have a bit of forgiveness. We probably shouldn’t tell that to the patients, but it’s reassuring that we can use these therapies even in tough-to-reach populations,” said Dr. Feld.
SAN FRANCISCO – Hepatitis C therapy has matured and now offers excellent sustained viral response (SVR) in the vast majority of cases, but key challenges remain in getting the therapy to those who need it.
“Unfortunately, we’re not making some of the progress we might have hoped to see, particularly in North America,” said Jordan Feld, MD, MPH, who gave a debrief of hepatitis C abstracts during a wrap-up session at the annual meeting of the American Association for the Study of Liver Diseases.
The problem is particularly acute in young adults aged 18-39 years – only about 9% of those who tested positive for HCV RNA saw a specialist, and about 23% of those who saw a specialist went on to receive treatment, according to an analysis of over 17 million patients in the United States (abstract 1567). The numbers were better for older adults but still far from optimal, with 23% who tested positive seeing a specialist, and just 32% of those patients getting treatment.
Another study (abstract 0147) looked state by state at the percentage of Medicaid patients who received a prescription for direct-acting antiviral (DAA) medication and then went on to fill the prescription. The rates ranged from 0% in Alaska to 96% in Connecticut. Eight states were higher than 70%, six were between 50% and 70%, and 15 states were below 50%.
“Despite our efforts, there continue to be major access barriers across the U.S., particularly for Medicaid individuals,” said Dr. Feld, who is a clinician-scientist at the Toronto Western Hospital Liver Clinic and the McLaughlin-Rotman Centre for Global Health.
A study examining the Chronic Hepatitis (CHeCS) cohort (abstract 0585) described a big spike in treatment uptake shortly after approvals of the new HCV regimens, but by 2016, only about one-third of individuals who required treatment actually began treatment. Factors associated with nontreatment largely reflected marginalization, including low income, being on Medicaid, and lack of long-term follow-up.
Even as health systems struggle to get treatment to those who need it, new studies are showing how to expand existing treatments into new populations.
Results from the EXPEDITION 8 study (abstract LB-7) showed efficacy of an 8-week regimen of the glecaprevir/pibrentasvir combination in patients with compensated cirrhosis. It looked at genotypes 1, 2, and 4-6. In an intention-to-treat analysis, 98% attained SVR and there were no viral failures or safety concerns. A follow-up trial is ongoing that includes patients with genotype 3. “This is exciting to be able to shorten therapy in patients with cirrhosis,” said Dr. Feld.
Although first-line DAAs are extremely effective, there are a few patients who do not achieve a cure. One study (abstract 0227) examined the combination of sofosbuvir, velpatasvir, and voxilaprevir in retreatment of these patients. The drugs resulted in SVR rates similar to those in registration trials, but the regimen was somewhat less effective in patients previously treated with sofosbuvir and velpatasvir. “I think we need to investigate that further,” said Dr. Feld.
The combination of glecaprevir and pibrentasvir also proved effective for retreatment in patients with genotype 1/1A who had failed treatment with an NS5A inhibitor plus sofosbuvir with or without ribavirin (abstract 226). SVR rates at 16 weeks were quite good, but lower in genotype 1a patients at 12 weeks (87% week 12 versus 94% week 16).”I think this is a really good regimen for genotype 1b. For 1a, serum definitely needs 16 weeks [to clear],” said Dr. Feld.
Other abstracts presented at the meeting detailed some of the benefits of SVR, not all of which are broadly appreciated. An analysis of the Hepatitis Testers Cohort in British Columbia (abstract 145), which includes over 7,000 patients who were followed for a median of 2 years (DAA) or 9.5 years (interferon-based), showed survival advantages to SVR in both cirrhotic (adjusted hazard ratio, 0.14) and noncirrhotic patients (aHR, 0.13). Other benefits include lower risk of diabetes (aHR, 0.53), chronic kidney disease/endstage renal disease (aHR, 0.48), stroke (aHR, 0.67), and mood and anxiety disorders (aHR, 0.53) (abstract 148).
As is generally accepted, SVR reduces the risk of hepatocellular cancer (HCC), according to analyses of VA and Gilead data (abstract 635), with a benefit in both cirrhotic and noncirrhotic patients. The risk almost disappears in patients without cirrhosis (incidence rate 0.07 per 100 person-years and is curbed in cirrhotic patients (incidence rate 1.30 in compensated, 4.05 in decompensated cirrhosis).
“There is really very significantly high incidence in cancer in decompensated cirrhosis, which just highlights that these patients continue to need ongoing surveillance. Although there have been efforts at developing strategies to risk stratify patients with cirrhosis, at least for now we’re stuck with surveillance, but I think for patients without cirrhosis there are now enough data showing a low enough incidence of primary HCC that we can probably avoid surveillance in that group,” said Dr. Feld.
Injectable drug users represent a special challenge in hepatitis C treatment, but new studies show cause for optimism in this population. These patients are harder to reach, and they may be less medication compliant, but one study (abstract 1632) found that imperfect adherence doesn’t necessarily undermine results – in a 12-week regimen, patients who didn’t finish until 14 weeks had no significant difference in SVR rates.
“So these therapies have a bit of forgiveness. We probably shouldn’t tell that to the patients, but it’s reassuring that we can use these therapies even in tough-to-reach populations,” said Dr. Feld.
SAN FRANCISCO – Hepatitis C therapy has matured and now offers excellent sustained viral response (SVR) in the vast majority of cases, but key challenges remain in getting the therapy to those who need it.
“Unfortunately, we’re not making some of the progress we might have hoped to see, particularly in North America,” said Jordan Feld, MD, MPH, who gave a debrief of hepatitis C abstracts during a wrap-up session at the annual meeting of the American Association for the Study of Liver Diseases.
The problem is particularly acute in young adults aged 18-39 years – only about 9% of those who tested positive for HCV RNA saw a specialist, and about 23% of those who saw a specialist went on to receive treatment, according to an analysis of over 17 million patients in the United States (abstract 1567). The numbers were better for older adults but still far from optimal, with 23% who tested positive seeing a specialist, and just 32% of those patients getting treatment.
Another study (abstract 0147) looked state by state at the percentage of Medicaid patients who received a prescription for direct-acting antiviral (DAA) medication and then went on to fill the prescription. The rates ranged from 0% in Alaska to 96% in Connecticut. Eight states were higher than 70%, six were between 50% and 70%, and 15 states were below 50%.
“Despite our efforts, there continue to be major access barriers across the U.S., particularly for Medicaid individuals,” said Dr. Feld, who is a clinician-scientist at the Toronto Western Hospital Liver Clinic and the McLaughlin-Rotman Centre for Global Health.
A study examining the Chronic Hepatitis (CHeCS) cohort (abstract 0585) described a big spike in treatment uptake shortly after approvals of the new HCV regimens, but by 2016, only about one-third of individuals who required treatment actually began treatment. Factors associated with nontreatment largely reflected marginalization, including low income, being on Medicaid, and lack of long-term follow-up.
Even as health systems struggle to get treatment to those who need it, new studies are showing how to expand existing treatments into new populations.
Results from the EXPEDITION 8 study (abstract LB-7) showed efficacy of an 8-week regimen of the glecaprevir/pibrentasvir combination in patients with compensated cirrhosis. It looked at genotypes 1, 2, and 4-6. In an intention-to-treat analysis, 98% attained SVR and there were no viral failures or safety concerns. A follow-up trial is ongoing that includes patients with genotype 3. “This is exciting to be able to shorten therapy in patients with cirrhosis,” said Dr. Feld.
Although first-line DAAs are extremely effective, there are a few patients who do not achieve a cure. One study (abstract 0227) examined the combination of sofosbuvir, velpatasvir, and voxilaprevir in retreatment of these patients. The drugs resulted in SVR rates similar to those in registration trials, but the regimen was somewhat less effective in patients previously treated with sofosbuvir and velpatasvir. “I think we need to investigate that further,” said Dr. Feld.
The combination of glecaprevir and pibrentasvir also proved effective for retreatment in patients with genotype 1/1A who had failed treatment with an NS5A inhibitor plus sofosbuvir with or without ribavirin (abstract 226). SVR rates at 16 weeks were quite good, but lower in genotype 1a patients at 12 weeks (87% week 12 versus 94% week 16).”I think this is a really good regimen for genotype 1b. For 1a, serum definitely needs 16 weeks [to clear],” said Dr. Feld.
Other abstracts presented at the meeting detailed some of the benefits of SVR, not all of which are broadly appreciated. An analysis of the Hepatitis Testers Cohort in British Columbia (abstract 145), which includes over 7,000 patients who were followed for a median of 2 years (DAA) or 9.5 years (interferon-based), showed survival advantages to SVR in both cirrhotic (adjusted hazard ratio, 0.14) and noncirrhotic patients (aHR, 0.13). Other benefits include lower risk of diabetes (aHR, 0.53), chronic kidney disease/endstage renal disease (aHR, 0.48), stroke (aHR, 0.67), and mood and anxiety disorders (aHR, 0.53) (abstract 148).
As is generally accepted, SVR reduces the risk of hepatocellular cancer (HCC), according to analyses of VA and Gilead data (abstract 635), with a benefit in both cirrhotic and noncirrhotic patients. The risk almost disappears in patients without cirrhosis (incidence rate 0.07 per 100 person-years and is curbed in cirrhotic patients (incidence rate 1.30 in compensated, 4.05 in decompensated cirrhosis).
“There is really very significantly high incidence in cancer in decompensated cirrhosis, which just highlights that these patients continue to need ongoing surveillance. Although there have been efforts at developing strategies to risk stratify patients with cirrhosis, at least for now we’re stuck with surveillance, but I think for patients without cirrhosis there are now enough data showing a low enough incidence of primary HCC that we can probably avoid surveillance in that group,” said Dr. Feld.
Injectable drug users represent a special challenge in hepatitis C treatment, but new studies show cause for optimism in this population. These patients are harder to reach, and they may be less medication compliant, but one study (abstract 1632) found that imperfect adherence doesn’t necessarily undermine results – in a 12-week regimen, patients who didn’t finish until 14 weeks had no significant difference in SVR rates.
“So these therapies have a bit of forgiveness. We probably shouldn’t tell that to the patients, but it’s reassuring that we can use these therapies even in tough-to-reach populations,” said Dr. Feld.
REPORTING FROM THE LIVER MEETING 2018
The Liver Meeting 2018: Hepatitis B novel therapies debrief – key abstracts
SAN FRANCISCO – Most years, when it comes to research to treat hepatitis viral infections, hepatitis C has been front and center at the annual meeting of the American Association for the Study of Liver Diseases. But things have changed in the past couple of years, with hepatitis C curative treatment maturing and altering the therapeutic landscape.
“Hepatitis C has been where all the action is, but that’s clearly changed in the last few years,” said Jordan Feld, MD, MPH, who summed up the hepatitis B findings during a wrap-up session on the final day of the conference. Dr. Feld is a clinician-scientist at the Toronto Western Hospital Liver Clinic and the McLaughlin-Rotman Centre for Global Health.
An analysis (Abstract 212) of a mixed North American and Asian cohort of more than 10,000 untreated patients showed just a 1.3% annual clearance rate of surface antigen, with little guidance for risk stratification. “This leaves us really needing new therapies,” said Dr. Feld.
Fortunately, the hepatitis B virus (HBV) life cycle offers various opportunities for therapeutic intervention, including blocking entry, targeting assembly and export of the virus, targeting HBV RNA, and targeting the capsid protein and viral packaging.
One study (Abstract 16) examined a hepatitis B entry inhibitor’s effect on hepatitis D virus (HDV), which requires coinfection with HBV to replicate. A phase 2 clinical trial found that treatment with Myrcludex B alone or in combination with interferon led to a decline in HDV RNA, but the result was most pronounced in patients who received the combination therapy. The combination was also associated with a greater probability of surface antigen decline. “I think that’s really important, that we see this synergistic effect. This is really promising phase 2 data that raises the possibility of curative therapy for this troubling infection,” said Dr. Feld.
Another study (Abstract LB-25) looked at an RNA inhibitor that targets both integrated and covalently closed circular DNA (cccDNA)–derived HBV RNA. The drug was given to 11 HBV patients who were positive for HBeAg (hepatitis B e-antigen) and 13 HBV patients who were HBeAg negative. It had similar effects in reducing HBV surface antigens and other correlated antigens in both groups of patients, and no evidence of a dose-response relationship. “Seeing a similar effect is quite important and suggests that it’s targeting both cccDNA-derived and integrated HBV DNA, and although there were some mild injection reactions, it generally seemed to be safe and pretty well tolerated,” said Dr. Feld.
Further down the life cycle, capsid assembly modulators (CAMs) have the potential to counter HBV by two mechanisms; blocking encapsulation of pregenomic RNA, and degrading capsids, which could prevent the replenishment of cccDNA. The latter effect could be important for achieving a cure, according to Dr. Feld.
A novel CAM, JNJ-6379 (Abstract 74), was tested at three different doses, and was well tolerated at higher doses, but it had limited dose response at the higher dose with respect to HBV DNA suppression. However, it could be that the two CAM mechanisms may require different doses. “These two things are hard to tease apart, and hopefully, we’ll see more data to separate them in the future,” said Dr. Feld.
Another CAM, ABI-HO731 (Abstract 73), had a potent effect on HBV DNA and HBV RNA, showing that it blocks encapsulation of both pregenomic RNA related to reverse transcription and pregenomic RNAs within the capsid. Stopping the medication led to some HBV DNA rebound, though no alanine aminotransferase flares, which Dr. Feld found reassuring. One patient had baseline resistance but was nevertheless able to achieve some suppression on the drug.
Another therapeutic approach used a nucleic acid polymer to block subviral particle release (Abstract 393). The study treated immunosuppressed patients with the polymer alone or in combination with interferon or tenofovir disoproxil, and led to “striking reductions in hepatitis B surface antigen quantities during therapy,” said Dr. Feld. An alanine aminotransferase flair did occur, which may signify an immune response, and it will be important to determine if this is indeed the case, he said. After stopping therapy there was a gain of anti–hepatitis B antibodies, which suggests that functional clearance of surface antigen is occurring.
Researchers also are recruiting the immune system to combat HBV. The novel agent inarigivir is a retinoic acid-inducible gene-1 agonist, which has both a direct antiviral effect and an indirect effect via the intrahepatic innate immune response, which it accomplishes by activating the interferon signaling pathway. It also directly interferes with the interaction between pregenomic RNA and the HBV polymerase, preventing replication. In the ACHIEVE trial, the researchers noted greater reduction in HBV RNA and DNA at higher doses (Abstract 75). “This is certainly an interesting molecule and an interesting proof of concept that you can potentially target HBV using two different pathways, and we’ll be interested to see more data with this approach,” said Dr. Feld.
Dr. Feld wrapped up the discussion of novel therapies with an animal model study (Abstract 77) that suggests future strategies for a cure. In it, the researchers combined a therapeutic vaccine with a stabilized, liver-targeted small interfering RNA to suppress surface antigen. Animals that received only the vaccine saw little benefit, but the combined approach led to viral clearance. The treatment also restored the immune response. “It gives us an inkling that we may need to both reduce the antigen load and stimulate immunity,” said Dr. Feld.
Dr. Feld has consulted for AbbVie, Gilead, ContraVir, MedImmune, and Merck. He has received funding from AbbVie, Gilead, Merck, and Janssen.
SAN FRANCISCO – Most years, when it comes to research to treat hepatitis viral infections, hepatitis C has been front and center at the annual meeting of the American Association for the Study of Liver Diseases. But things have changed in the past couple of years, with hepatitis C curative treatment maturing and altering the therapeutic landscape.
“Hepatitis C has been where all the action is, but that’s clearly changed in the last few years,” said Jordan Feld, MD, MPH, who summed up the hepatitis B findings during a wrap-up session on the final day of the conference. Dr. Feld is a clinician-scientist at the Toronto Western Hospital Liver Clinic and the McLaughlin-Rotman Centre for Global Health.
An analysis (Abstract 212) of a mixed North American and Asian cohort of more than 10,000 untreated patients showed just a 1.3% annual clearance rate of surface antigen, with little guidance for risk stratification. “This leaves us really needing new therapies,” said Dr. Feld.
Fortunately, the hepatitis B virus (HBV) life cycle offers various opportunities for therapeutic intervention, including blocking entry, targeting assembly and export of the virus, targeting HBV RNA, and targeting the capsid protein and viral packaging.
One study (Abstract 16) examined a hepatitis B entry inhibitor’s effect on hepatitis D virus (HDV), which requires coinfection with HBV to replicate. A phase 2 clinical trial found that treatment with Myrcludex B alone or in combination with interferon led to a decline in HDV RNA, but the result was most pronounced in patients who received the combination therapy. The combination was also associated with a greater probability of surface antigen decline. “I think that’s really important, that we see this synergistic effect. This is really promising phase 2 data that raises the possibility of curative therapy for this troubling infection,” said Dr. Feld.
Another study (Abstract LB-25) looked at an RNA inhibitor that targets both integrated and covalently closed circular DNA (cccDNA)–derived HBV RNA. The drug was given to 11 HBV patients who were positive for HBeAg (hepatitis B e-antigen) and 13 HBV patients who were HBeAg negative. It had similar effects in reducing HBV surface antigens and other correlated antigens in both groups of patients, and no evidence of a dose-response relationship. “Seeing a similar effect is quite important and suggests that it’s targeting both cccDNA-derived and integrated HBV DNA, and although there were some mild injection reactions, it generally seemed to be safe and pretty well tolerated,” said Dr. Feld.
Further down the life cycle, capsid assembly modulators (CAMs) have the potential to counter HBV by two mechanisms; blocking encapsulation of pregenomic RNA, and degrading capsids, which could prevent the replenishment of cccDNA. The latter effect could be important for achieving a cure, according to Dr. Feld.
A novel CAM, JNJ-6379 (Abstract 74), was tested at three different doses, and was well tolerated at higher doses, but it had limited dose response at the higher dose with respect to HBV DNA suppression. However, it could be that the two CAM mechanisms may require different doses. “These two things are hard to tease apart, and hopefully, we’ll see more data to separate them in the future,” said Dr. Feld.
Another CAM, ABI-HO731 (Abstract 73), had a potent effect on HBV DNA and HBV RNA, showing that it blocks encapsulation of both pregenomic RNA related to reverse transcription and pregenomic RNAs within the capsid. Stopping the medication led to some HBV DNA rebound, though no alanine aminotransferase flares, which Dr. Feld found reassuring. One patient had baseline resistance but was nevertheless able to achieve some suppression on the drug.
Another therapeutic approach used a nucleic acid polymer to block subviral particle release (Abstract 393). The study treated immunosuppressed patients with the polymer alone or in combination with interferon or tenofovir disoproxil, and led to “striking reductions in hepatitis B surface antigen quantities during therapy,” said Dr. Feld. An alanine aminotransferase flair did occur, which may signify an immune response, and it will be important to determine if this is indeed the case, he said. After stopping therapy there was a gain of anti–hepatitis B antibodies, which suggests that functional clearance of surface antigen is occurring.
Researchers also are recruiting the immune system to combat HBV. The novel agent inarigivir is a retinoic acid-inducible gene-1 agonist, which has both a direct antiviral effect and an indirect effect via the intrahepatic innate immune response, which it accomplishes by activating the interferon signaling pathway. It also directly interferes with the interaction between pregenomic RNA and the HBV polymerase, preventing replication. In the ACHIEVE trial, the researchers noted greater reduction in HBV RNA and DNA at higher doses (Abstract 75). “This is certainly an interesting molecule and an interesting proof of concept that you can potentially target HBV using two different pathways, and we’ll be interested to see more data with this approach,” said Dr. Feld.
Dr. Feld wrapped up the discussion of novel therapies with an animal model study (Abstract 77) that suggests future strategies for a cure. In it, the researchers combined a therapeutic vaccine with a stabilized, liver-targeted small interfering RNA to suppress surface antigen. Animals that received only the vaccine saw little benefit, but the combined approach led to viral clearance. The treatment also restored the immune response. “It gives us an inkling that we may need to both reduce the antigen load and stimulate immunity,” said Dr. Feld.
Dr. Feld has consulted for AbbVie, Gilead, ContraVir, MedImmune, and Merck. He has received funding from AbbVie, Gilead, Merck, and Janssen.
SAN FRANCISCO – Most years, when it comes to research to treat hepatitis viral infections, hepatitis C has been front and center at the annual meeting of the American Association for the Study of Liver Diseases. But things have changed in the past couple of years, with hepatitis C curative treatment maturing and altering the therapeutic landscape.
“Hepatitis C has been where all the action is, but that’s clearly changed in the last few years,” said Jordan Feld, MD, MPH, who summed up the hepatitis B findings during a wrap-up session on the final day of the conference. Dr. Feld is a clinician-scientist at the Toronto Western Hospital Liver Clinic and the McLaughlin-Rotman Centre for Global Health.
An analysis (Abstract 212) of a mixed North American and Asian cohort of more than 10,000 untreated patients showed just a 1.3% annual clearance rate of surface antigen, with little guidance for risk stratification. “This leaves us really needing new therapies,” said Dr. Feld.
Fortunately, the hepatitis B virus (HBV) life cycle offers various opportunities for therapeutic intervention, including blocking entry, targeting assembly and export of the virus, targeting HBV RNA, and targeting the capsid protein and viral packaging.
One study (Abstract 16) examined a hepatitis B entry inhibitor’s effect on hepatitis D virus (HDV), which requires coinfection with HBV to replicate. A phase 2 clinical trial found that treatment with Myrcludex B alone or in combination with interferon led to a decline in HDV RNA, but the result was most pronounced in patients who received the combination therapy. The combination was also associated with a greater probability of surface antigen decline. “I think that’s really important, that we see this synergistic effect. This is really promising phase 2 data that raises the possibility of curative therapy for this troubling infection,” said Dr. Feld.
Another study (Abstract LB-25) looked at an RNA inhibitor that targets both integrated and covalently closed circular DNA (cccDNA)–derived HBV RNA. The drug was given to 11 HBV patients who were positive for HBeAg (hepatitis B e-antigen) and 13 HBV patients who were HBeAg negative. It had similar effects in reducing HBV surface antigens and other correlated antigens in both groups of patients, and no evidence of a dose-response relationship. “Seeing a similar effect is quite important and suggests that it’s targeting both cccDNA-derived and integrated HBV DNA, and although there were some mild injection reactions, it generally seemed to be safe and pretty well tolerated,” said Dr. Feld.
Further down the life cycle, capsid assembly modulators (CAMs) have the potential to counter HBV by two mechanisms; blocking encapsulation of pregenomic RNA, and degrading capsids, which could prevent the replenishment of cccDNA. The latter effect could be important for achieving a cure, according to Dr. Feld.
A novel CAM, JNJ-6379 (Abstract 74), was tested at three different doses, and was well tolerated at higher doses, but it had limited dose response at the higher dose with respect to HBV DNA suppression. However, it could be that the two CAM mechanisms may require different doses. “These two things are hard to tease apart, and hopefully, we’ll see more data to separate them in the future,” said Dr. Feld.
Another CAM, ABI-HO731 (Abstract 73), had a potent effect on HBV DNA and HBV RNA, showing that it blocks encapsulation of both pregenomic RNA related to reverse transcription and pregenomic RNAs within the capsid. Stopping the medication led to some HBV DNA rebound, though no alanine aminotransferase flares, which Dr. Feld found reassuring. One patient had baseline resistance but was nevertheless able to achieve some suppression on the drug.
Another therapeutic approach used a nucleic acid polymer to block subviral particle release (Abstract 393). The study treated immunosuppressed patients with the polymer alone or in combination with interferon or tenofovir disoproxil, and led to “striking reductions in hepatitis B surface antigen quantities during therapy,” said Dr. Feld. An alanine aminotransferase flair did occur, which may signify an immune response, and it will be important to determine if this is indeed the case, he said. After stopping therapy there was a gain of anti–hepatitis B antibodies, which suggests that functional clearance of surface antigen is occurring.
Researchers also are recruiting the immune system to combat HBV. The novel agent inarigivir is a retinoic acid-inducible gene-1 agonist, which has both a direct antiviral effect and an indirect effect via the intrahepatic innate immune response, which it accomplishes by activating the interferon signaling pathway. It also directly interferes with the interaction between pregenomic RNA and the HBV polymerase, preventing replication. In the ACHIEVE trial, the researchers noted greater reduction in HBV RNA and DNA at higher doses (Abstract 75). “This is certainly an interesting molecule and an interesting proof of concept that you can potentially target HBV using two different pathways, and we’ll be interested to see more data with this approach,” said Dr. Feld.
Dr. Feld wrapped up the discussion of novel therapies with an animal model study (Abstract 77) that suggests future strategies for a cure. In it, the researchers combined a therapeutic vaccine with a stabilized, liver-targeted small interfering RNA to suppress surface antigen. Animals that received only the vaccine saw little benefit, but the combined approach led to viral clearance. The treatment also restored the immune response. “It gives us an inkling that we may need to both reduce the antigen load and stimulate immunity,” said Dr. Feld.
Dr. Feld has consulted for AbbVie, Gilead, ContraVir, MedImmune, and Merck. He has received funding from AbbVie, Gilead, Merck, and Janssen.
REPORTING FROM THE LIVER MEETING 2018
Hep C–infected livers are safe for transplant
SAN FRANCISCO – A new analysis shows that hepatitis C–infected livers can be safely transplanted into recipients with no effect on graft survival, retransplantation, or mortality. The work confirms that readily available direct-acting antiviral therapy can protect organ recipients and open a source of organs that is typically overlooked.
The work should encourage both physicians and patients to take a closer look at hepatitis C–infected organs, especially for sicker patients, according to Sonali Paul, MD, who presented the study at the annual meeting of the American Association for the Study of Liver Disease 2018.
“A lot of people have an ethical issue with it because we’re actively transplanting a virus into someone. We’re giving someone a disease. My take on it is that we give people Epstein Barr virus or cytomegalovirus all the time – we just [provide] prophylaxis against it, and we don’t even bat an eye. Hepatitis C can be devastating, but we have totally effective treatments for it,” said Dr. Paul, who is an assistant professor of medicine at the University of Chicago.
She cited one colleague at the University of Chicago who several years ago transplanted an organ that had been passed over 700 times, though times have changed since then. “I think people more and more are doing this practice because we know it’s so successful,” said Dr. Paul.
It’s also cost effective. Another study, presented during the same session by Jag Chhatwal, PhD, assistant professor at Harvard Medical School, Boston, showed that accepting a hepatitis C–positive liver is cost effective in patients with Model for End-Stage Liver Disease (MELD) scores ranging from 22 to 40.
“I think we’re going to find across all organ systems, if we can transplant patients rather than keep them on dialysis or keep them on wait lists, it’s got to be cost effective, especially if you think of the health care–associated costs – like a heart transplant patient waiting on the list in the ICU. That’s a huge health care cost,” said Dr. Paul.
Dr. Paul’s team performed an analysis of the Scientific Registry of Transplant Recipients, including single organ transplants from deceased donors, during 2014-2018. Over that period, the number of transplants from hepatitis C–positive donors to hepatitis C–positive recipients rose from 8 in 2014 to 269, and the number of transplants from hepatitis C–positive donors to hepatitis C–negative recipients rose from 0 to 46.
The researchers compared trends from hepatitis C–negative donors with hepatitis C–negative recipients (n = 11,270), negative donors with positive recipients (n = 4,748), positive donors with negative recipients (n = 87), and positive donors with positive recipients (n = 753). Donor status had no effect on graft survival times at 1 or 2 years, with values ranging from 92.6% (negative to negative) to 94.3% (positive to positive) at 1 year and between 85.7% (positive to negative) and 89.7% (positive to positive) at 2 years.
“For someone who has a MELD score of over 20, who has a declining quality of life and really can’t do anything, I think this is a great opportunity. And most patients are absolutely willing to take these organs. We haven’t had many people say no, especially if they feel poorly,” said Dr. Paul.
She also underscored the importance of ensuring that the patient is informed of the status of the donor liver and the need to complete treatment: “The patient has to know what’s happening, and the hospital has to have a safety net if the insurance doesn’t pay for hepatitis C treatment.”
SOURCE: AASLD 2018, Abstract 0249.
SAN FRANCISCO – A new analysis shows that hepatitis C–infected livers can be safely transplanted into recipients with no effect on graft survival, retransplantation, or mortality. The work confirms that readily available direct-acting antiviral therapy can protect organ recipients and open a source of organs that is typically overlooked.
The work should encourage both physicians and patients to take a closer look at hepatitis C–infected organs, especially for sicker patients, according to Sonali Paul, MD, who presented the study at the annual meeting of the American Association for the Study of Liver Disease 2018.
“A lot of people have an ethical issue with it because we’re actively transplanting a virus into someone. We’re giving someone a disease. My take on it is that we give people Epstein Barr virus or cytomegalovirus all the time – we just [provide] prophylaxis against it, and we don’t even bat an eye. Hepatitis C can be devastating, but we have totally effective treatments for it,” said Dr. Paul, who is an assistant professor of medicine at the University of Chicago.
She cited one colleague at the University of Chicago who several years ago transplanted an organ that had been passed over 700 times, though times have changed since then. “I think people more and more are doing this practice because we know it’s so successful,” said Dr. Paul.
It’s also cost effective. Another study, presented during the same session by Jag Chhatwal, PhD, assistant professor at Harvard Medical School, Boston, showed that accepting a hepatitis C–positive liver is cost effective in patients with Model for End-Stage Liver Disease (MELD) scores ranging from 22 to 40.
“I think we’re going to find across all organ systems, if we can transplant patients rather than keep them on dialysis or keep them on wait lists, it’s got to be cost effective, especially if you think of the health care–associated costs – like a heart transplant patient waiting on the list in the ICU. That’s a huge health care cost,” said Dr. Paul.
Dr. Paul’s team performed an analysis of the Scientific Registry of Transplant Recipients, including single organ transplants from deceased donors, during 2014-2018. Over that period, the number of transplants from hepatitis C–positive donors to hepatitis C–positive recipients rose from 8 in 2014 to 269, and the number of transplants from hepatitis C–positive donors to hepatitis C–negative recipients rose from 0 to 46.
The researchers compared trends from hepatitis C–negative donors with hepatitis C–negative recipients (n = 11,270), negative donors with positive recipients (n = 4,748), positive donors with negative recipients (n = 87), and positive donors with positive recipients (n = 753). Donor status had no effect on graft survival times at 1 or 2 years, with values ranging from 92.6% (negative to negative) to 94.3% (positive to positive) at 1 year and between 85.7% (positive to negative) and 89.7% (positive to positive) at 2 years.
“For someone who has a MELD score of over 20, who has a declining quality of life and really can’t do anything, I think this is a great opportunity. And most patients are absolutely willing to take these organs. We haven’t had many people say no, especially if they feel poorly,” said Dr. Paul.
She also underscored the importance of ensuring that the patient is informed of the status of the donor liver and the need to complete treatment: “The patient has to know what’s happening, and the hospital has to have a safety net if the insurance doesn’t pay for hepatitis C treatment.”
SOURCE: AASLD 2018, Abstract 0249.
SAN FRANCISCO – A new analysis shows that hepatitis C–infected livers can be safely transplanted into recipients with no effect on graft survival, retransplantation, or mortality. The work confirms that readily available direct-acting antiviral therapy can protect organ recipients and open a source of organs that is typically overlooked.
The work should encourage both physicians and patients to take a closer look at hepatitis C–infected organs, especially for sicker patients, according to Sonali Paul, MD, who presented the study at the annual meeting of the American Association for the Study of Liver Disease 2018.
“A lot of people have an ethical issue with it because we’re actively transplanting a virus into someone. We’re giving someone a disease. My take on it is that we give people Epstein Barr virus or cytomegalovirus all the time – we just [provide] prophylaxis against it, and we don’t even bat an eye. Hepatitis C can be devastating, but we have totally effective treatments for it,” said Dr. Paul, who is an assistant professor of medicine at the University of Chicago.
She cited one colleague at the University of Chicago who several years ago transplanted an organ that had been passed over 700 times, though times have changed since then. “I think people more and more are doing this practice because we know it’s so successful,” said Dr. Paul.
It’s also cost effective. Another study, presented during the same session by Jag Chhatwal, PhD, assistant professor at Harvard Medical School, Boston, showed that accepting a hepatitis C–positive liver is cost effective in patients with Model for End-Stage Liver Disease (MELD) scores ranging from 22 to 40.
“I think we’re going to find across all organ systems, if we can transplant patients rather than keep them on dialysis or keep them on wait lists, it’s got to be cost effective, especially if you think of the health care–associated costs – like a heart transplant patient waiting on the list in the ICU. That’s a huge health care cost,” said Dr. Paul.
Dr. Paul’s team performed an analysis of the Scientific Registry of Transplant Recipients, including single organ transplants from deceased donors, during 2014-2018. Over that period, the number of transplants from hepatitis C–positive donors to hepatitis C–positive recipients rose from 8 in 2014 to 269, and the number of transplants from hepatitis C–positive donors to hepatitis C–negative recipients rose from 0 to 46.
The researchers compared trends from hepatitis C–negative donors with hepatitis C–negative recipients (n = 11,270), negative donors with positive recipients (n = 4,748), positive donors with negative recipients (n = 87), and positive donors with positive recipients (n = 753). Donor status had no effect on graft survival times at 1 or 2 years, with values ranging from 92.6% (negative to negative) to 94.3% (positive to positive) at 1 year and between 85.7% (positive to negative) and 89.7% (positive to positive) at 2 years.
“For someone who has a MELD score of over 20, who has a declining quality of life and really can’t do anything, I think this is a great opportunity. And most patients are absolutely willing to take these organs. We haven’t had many people say no, especially if they feel poorly,” said Dr. Paul.
She also underscored the importance of ensuring that the patient is informed of the status of the donor liver and the need to complete treatment: “The patient has to know what’s happening, and the hospital has to have a safety net if the insurance doesn’t pay for hepatitis C treatment.”
SOURCE: AASLD 2018, Abstract 0249.
REPORTING FROM THE LIVER MEETING 2018
Key clinical point: Use of hepatitis C–positive livers can significantly increase the donor organ pool.
Major finding: Hepatitis C–infected livers can be safely transplanted into recipients with no effect on graft survival, retransplantation, or mortality.
Study details: Retrospective analysis of 16,858 liver transplants.
Disclosures: The study was funded internally. Dr. Paul has no financial disclosures.
Source: AASLD 2018, Abstract 0249.