Gender Differences in Hepatitis C Virus (HCV) Treatment Outcomes With Peginterferon (pegIFN) Plus Ribavirin (RBV): An Analysis of the IDEAL Study

Abstract Background The introduction of direct-acting antivirals (DAAs) created a major paradigm shift in the treatment of chronic hepatitis C. Currently, there is little “real-world” data regarding hepatitis C virus (HCV) treatment outcomes in the human immunodeficiency virus (HIV)/HCV-coinfected population. Methods This retrospective cohort study examined HCV treatment outcomes of HIV/HCV-coinfected patients at a large, urban, Ryan White-funded clinic caring for an underserved population. All HIV patients initiating HCV treatment from January 1, 2013 to November 30, 2015 were included in the analysis. The primary end point was sustained virologic response 12 weeks after the end of therapy (SVR12). Results A total of 172 patients initiated HCV treatment within the study period: 79% were male, 83% were black, 95% were HCV genotype 1, 79% were HCV treatment naive, and 16% had cirrhosis. At baseline, median CD4 was 494 cells/μL (interquartile range, 316–722) and 92% had HIV ribonucleic acid less than 40 copies/mL. The most common DAA initiated was ledipasvir/sofosbuvir (LDV/SOF) (85%), with 92% receiving 12 weeks of treatment. Overall, SVR12 was 93% by intention-to-treat analysis and 98% by per-protocol analysis. The majority of patients on LDV/SOF did not report any adverse effect. One patient in the ribavirin plus SOF group discontinued treatment due to adverse effect. Conclusions In a cohort of mainly black, male, HIV/HCV-coinfected patients at a large, urban, Ryan White clinic, HCV treatment with DAAs resulted in high SVR12 rates and was well tolerated despite real-world challenges including medication access barriers and drug interaction concerns.

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Hepatitis C Virus Glycan-Dependent Interactions and the Potential for Novel Preventative Strategies

Pathogens ◽

10.3390/pathogens10060685 ◽

2021 ◽

Vol 10 (6) ◽

pp. 685

Author(s):

Emmanuelle V. LeBlanc ◽

Youjin Kim ◽

Chantelle J. Capicciotti ◽

Che C. Colpitts

Keyword(s):

Chronic Hepatitis ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Immune Evasion ◽

Hcv Infection ◽

Major Contributor ◽

Effective Management ◽

Hcv Treatment ◽

Entry Inhibitors ◽

Chronic Hepatitis C Virus

Chronic hepatitis C virus (HCV) infections continue to be a major contributor to liver disease worldwide. HCV treatment has become highly effective, yet there are still no vaccines or prophylactic strategies available to prevent infection and allow effective management of the global HCV burden. Glycan-dependent interactions are crucial to many aspects of the highly complex HCV entry process, and also modulate immune evasion. This review provides an overview of the roles of viral and cellular glycans in HCV infection and highlights glycan-focused advances in the development of entry inhibitors and vaccines to effectively prevent HCV infection.

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Integrated, Co-located, Telemedicine-based Treatment Approaches for Hepatitis C Virus Management in Opioid Use Disorder Patients on Methadone

Clinical Infectious Diseases ◽

10.1093/cid/ciy899 ◽

2018 ◽

Vol 69 (2) ◽

pp. 323-331 ◽

Cited By ~ 15

Author(s):

Andrew H Talal ◽

Phyllis Andrews ◽

Anthony Mcleod ◽

Yang Chen ◽

Clewert Sylvester ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Multiple Correspondence Analysis ◽

Opioid Use Disorder ◽

Hcv Rna ◽

Directly Observed Therapy ◽

Opioid Use ◽

Hcv Treatment ◽

Opioid Substitution Therapy ◽

Direct Acting

Abstract Background Despite high hepatitis C virus (HCV) prevalence, opioid use disorder (OUD) patients on methadone rarely engage in HCV treatment. We investigated the effectiveness of HCV management via telemedicine in an opioid substitution therapy (OST) program. Methods OUD patients on methadone underwent biweekly telemedicine sessions between a hepatologist and physician assistant during the entire HCV treatment course. All pretreatment labs (HCV RNA, genotype, and noninvasive fibrosis assessments) were obtained onsite and direct-acting antivirals were coadministered with methadone using modified directly observed therapy. We used multiple correspondence analysis, least absolute shrinkage and selection operator, and logistic regression to identify variables associated with pursuit of HCV care. Results Sixty-two HCV RNA–positive patients (24% human immunodeficiency virus [HIV] infected, 61% male, 61% African American, 25.8% Hispanic) were evaluated. All patients were stabilized on methadone and all except 4 were HCV genotype 1 infected. Advanced fibrosis/cirrhosis was present in 34.5% of patients. Of the 45 treated patients, 42 (93.3%) achieved viral eradication. Of 17 evaluated patients who were not treated, 5 were discontinued from the drug treatment program or did not follow up after the evaluation, 2 had HIV adherence issues, and 10 had insurance authorization issues. Marriage and a mental health diagnosis other than depression were the strongest positive predictors of treatment pursuit, whereas being divorced, separated, or widowed was the strongest negative predictor. Conclusions HCV management via telemedicine integrated into an OST program is a feasible model with excellent virologic effectiveness. Psychosocial and demographic variables can assist in identification of subgroups with a propensity or aversion to pursue HCV treatment.

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Chronic hepatitis C virus (HCV) increases the risk of chronic kidney disease (CKD) while effective HCV treatment decreases the incidence of CKD

Hepatology ◽

10.1002/hep.29505 ◽

2017 ◽

Vol 67 (2) ◽

pp. 492-504 ◽

Cited By ~ 31

Author(s):

Haesuk Park ◽

Chao Chen ◽

Wei Wang ◽

Linda Henry ◽

Robert L. Cook ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Chronic Hepatitis ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Kidney Disease ◽

Chronic Hepatitis C ◽

Hcv Treatment ◽

Chronic Hepatitis C Virus ◽

Incidence Of Ckd

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Hepatitis C Virus Treatment Access Among Human Immunodeficiency Virus and Hepatitis C Virus (HCV)-Coinfected People Who Inject Drugs in Guangzhou, China: Implications for HCV Treatment Expansion

Open Forum Infectious Diseases ◽

10.1093/ofid/ofw065 ◽

2016 ◽

Vol 3 (2) ◽

Cited By ~ 6

Author(s):

Carissa E. Chu ◽

Feng Wu ◽

Xi He ◽

Kali Zhou ◽

Yu Cheng ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Social Workers ◽

People Who Inject Drugs ◽

Hiv Treatment ◽

Direct Acting Antivirals ◽

Hcv Treatment ◽

Treatment Access ◽

Immunodeficiency Virus ◽

Direct Acting

Abstract Background. Hepatitis C virus (HCV) treatment access among human immunodeficiency virus (HIV)/HCV-coinfected people who inject drugs is poor, despite a high burden of disease in this population. Understanding barriers and facilitators to HCV treatment uptake is critical to the implementation of new direct-acting antivirals. Methods. We conducted in-depth interviews with patients, physicians, and social workers at an HIV treatment facility and methadone maintenance treatment centers in Guangzhou, China to identify barriers and facilitators to HCV treatment. We included patients who were in various stages of HCV treatment and those who were not treated. We used standard qualitative methods and organized data into themes. Results. Interview data from 29 patients, 8 physicians, and 3 social workers were analyzed. Facilitators and barriers were organized according to a modified Consolidated Framework for Implementation Research schematic. Facilitators included patient trust in physicians, hope for a cure, peer networks, and social support. Barriers included ongoing drug use, low HCV disease knowledge, fragmented reimbursement systems, HIV exceptionalism, and stigma. Conclusions. Expanding existing harm reduction programs, HIV treatment programs, and social services may facilitate scale-up of direct-acting antivirals globally. Improving integration of ancillary social and mental health services within existing HIV care systems may facilitate HCV treatment access.

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Hepatitis C Virus (HCV) Treatment With Directly Acting Agents Reduces the Risk of Incident Diabetes: Results From Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES)

Clinical Infectious Diseases ◽

10.1093/cid/ciz304 ◽

2019 ◽

Cited By ~ 4

Author(s):

Adeel A Butt ◽

Peng Yan ◽

Samia Aslam ◽

Obaid S Shaikh ◽

Abdul-Badi Abou-Samra

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Survival Rates ◽

Pegylated Interferon ◽

Incidence Rates ◽

Absolute Difference ◽

Diabetes Incidence ◽

Hcv Treatment ◽

Free Survival ◽

Significant Difference

Abstract Background The effects of interferon-based therapies for hepatitis C virus (HCV) upon the risk of diabetes are controversial. The effects of newer, directly acting antiviral agents (DAA) upon this risk are unknown. We sought to determine the effects of HCV treatment upon the risk and incidence of diabetes. Methods Using the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES) database for persons with chronic HCV infection (n = 242 680), we identified those treated with a pegylated interferon and ribavirin regimen (PEG/RBV, n = 4764) or a DAA-containing regimen (n = 21 279), after excluding those with diabetes at baseline, those with a human immunodeficiency virus or hepatitis B virus coinfection, and those treated with both PEG/RBV and DAA regimens. Age-, race-, sex-, and propensity score–matched controls (1:1) were also identified. Results Diabetes incidence rates per 1000 person-years were 20.6 (95% confidence interval [CI] 19.6–21.6) among untreated persons, 19.8 (95% CI 18.3–21.4) among those treated with PEG/RBV, and 9.89 (95% CI 8.7–11.1) among DAA-treated persons (P < .001). Among the treated, rates were 13.3 (95% CI 12.2–14.5) for those with a sustained virologic response (SVR) and 19.2 (95% CI 17.4–21.1) for those without an SVR (P < .0001). A larger reduction was observed in persons with more advanced fibrosis/cirrhosis (absolute difference 2.9 for fibrosis severity score [FIB-4] < 1.25; 5.7 for FIB-4 1.26–3.25; 9.8 for FIB-4 >3.25). DAA treatment (hazard ratio [HR] 0.53, 95% CI .46–.63) and SVR (HR 0.81, 95% CI .70–.93) were associated with a significantly reduced risk of diabetes. DAA-treated persons had longer diabetes-free survival rates, compared to untreated and PEG/RBV-treated persons. There was no significant difference in diabetes-free survival rates between untreated and PEG/RBV-treated persons. The results were similar in inverse probability of treatment and censoring weight models. Conclusions DAA therapy significantly reduces the incidence and risk of subsequent diabetes. Treatment benefits are more pronounced in persons with more advanced liver fibrosis.

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Interplay of Amino Acid Residues at Positions 28 and 31 in NS5A Defines Resistance Pathways in Hepatitis C Virus Genotype 2

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01269-19 ◽

2019 ◽

Vol 63 (12) ◽

Cited By ~ 1

Author(s):

Ernest Asante-Appiah ◽

Paul Ingravallo ◽

Patricia McMonagle ◽

Karin Bystol ◽

Ellen Xia ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Amino Acid ◽

Treatment Outcomes ◽

Cross Talk ◽

Site Directed Mutagenesis ◽

Virus Genotype ◽

Ns5a Inhibitor ◽

Genotype 2 ◽

Antiviral Activities

ABSTRACT Hepatitis C virus (HCV) genotype 2 (GT2) represents approximately 9% of all viral infections globally. While treatment outcomes for GT2-infected patients have improved substantially with direct-acting antiviral agents (DAAs) compared to alpha interferon, the presence of polymorphisms in NS5A can impact the efficacy of NS5A inhibitor-containing regimens. Thus, pathways of NS5A resistance were explored in GT2 subtypes using elbasvir, an NS5A inhibitor with broad genotype activity. Resistance selection studies, resistance analysis in NS5A-inhibitor treated virologic failures, and analyses of antiviral activities in replicons bearing a panel of GT2 subtype sequences and amino acid substitutions introduced by site-directed mutagenesis were performed to define determinants of inhibitor susceptibility. Elbasvir showed differential antiviral activities in replicons bearing GT2 sequences. The 50% effective concentration (EC50) values for replicons bearing reference NS5A sequences for GT2a and GT2b were 0.003 and 3.4 nM, respectively. Studies performed with recombinant replicons demonstrated cross talk between amino acid positions 28 and 31. The combination of phenylalanine and methionine at positions 28 and 31, respectively, conferred the highest potency reduction for elbasvir in GT2a and GT2b. This combination was observed in failures seen in the C-SCAPE trial. Addition of grazoprevir, an NS3/4A protease inhibitor, to elbasvir more effectively suppressed the emergence of resistance in GT2 at modest inhibitor concentrations (3× EC90). Ruzasvir, a potent, pan-genotype NS5A inhibitor, successfully inhibited replicons bearing GT2 resistance-associated substitutions (RASs) at positions 28 and 31. The results demonstrate that cross talk between amino acids at positions 28 and 31 in NS5A modulated inhibitor potency and may impact treatment outcomes in some HCV GT2-infected patients.

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Evaluation of Oral Cannabinoid-Containing Medications for the Management of Interferon and Ribavirin-Induced Anorexia, Nausea and Weight Loss in Patients Treated for Chronic Hepatitis C Virus

Canadian Journal of Gastroenterology ◽

10.1155/2008/725702 ◽

2008 ◽

Vol 22 (4) ◽

pp. 376-380 ◽

Cited By ~ 17

Author(s):

Cecilia T Costiniuk ◽

Edward Mills ◽

Curtis L Cooper

Keyword(s):

Weight Loss ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Side Effects ◽

Cohort Analysis ◽

Smoking History ◽

Hcv Treatment ◽

Hcv Therapy ◽

Median Weight Loss ◽

Dose Reductions

OBJECTIVES: The systemic and cognitive side effects of hepatitis C virus (HCV) therapy may be incapacitating, necessitating dose reductions or abandonment of therapy. Oral cannabinoid-containing medications (OCs) ameliorate chemotherapy-induced nausea and vomiting, as well as AIDS wasting syndrome. The efficacy of OCs in managing HCV treatment-related side effects is unknown.METHODS: All patients who initiated interferon-ribavirin therapy at The Ottawa Hospital Viral Hepatitis Clinic (Ottawa, Ontario) between August 2003 and January 2007 were identified using a computerized clinical database. The baseline characteristics of OC recipients were compared with those of nonrecipients. The treatment-related side effect response to OC was assessed by χ2analysis. The key therapeutic outcomes related to weight, interferon dose reduction and treatment outcomes were assessed by Student’sttest and χ2analysis.RESULTS: Twenty-five of 191 patients (13%) initiated OC use. Recipients had similar characteristics to nonrecipients, aside from prior marijuana smoking history (24% versus 10%, respectively; P=0.04). The median time to OC initiation was seven weeks. The most common indications for initiation of OC were anorexia (72%) and nausea (32%). Sixty-four per cent of all patients who received OC experienced subjective improvement in symptoms. The median weight loss before OC initiation was 4.5 kg. A trend toward greater median weight loss was noted at week 4 in patients eventually initiating OC use (−1.4 kg), compared with those who did not (−1.0 kg). Weight loss stabilized one month after OC initiation (median 0.5 kg additional loss). Interferon dose reductions were rare and did not differ by OC use (8% of OC recipients versus 5% of nonrecipients). The proportions of patients completing a full course of HCV therapy and achieving a sustained virological response were greater in OC recipients.CONCLUSIONS: The present retrospective cohort analysis found that OC use is often effective in managing HCV treatment-related symptoms that contribute to weight loss, and may stabilize weight decline once initiated.

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