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Direct Acting Antiviral Agents in Korean Patients with Chronic Hepatitis C and Hemophilia Who Are Treatment-Naive or Treatment-Experienced.

ABSTRACT: Chronic hepatitis C (CHC) is a major comorbidity in patients with hemophilia.Patients (n=30) were enrolled between September 2015 and April 2016. Twenty-six patients were genotype 1 (1b, n=21; 1a, n=5) and four patients were genotype 2a/2b. Among 21 patients with genotype 1b, Y93H resistance-associated variants (RAVs) were detected in three patients (14.3%). We evaluated sustained virologic response (SVRs) at 12 weeks, as well as relapse and safety.Five patients with genotype 1a and three patients with genotype 1b (RAV positive) received ledipasvir/sofosbuvir for 12 weeks. SVR12 rate was 100% (8/8). Eleven patients with genotype 1b were treatment-naïve and received daclatasvir plus asunaprevir for 24 weeks. SVR12 rate was 91% (10/11). One patient experienced viral breakthrough without RAV at 12 weeks. Seven treatment-experienced patients with genotype 1b received daclatasvir plus asunaprevir for 24 weeks. SVR12 rate was 85.7% (6/7). One patient experienced viral breakthrough with RAV (L31M, Y93H) at 12 weeks. Four patients with genotype 2a/2b received sofosbuvir plus ribavirin for 12 weeks. SVR12 rate was 100% (4/4). No serious adverse event-related discontinuations were noted.New direct acting antiviral treatment achieved high SVRs rates at 12 weeks in CHC patients with hemophilia without serious adverse events.

SUBMITTER: Lee HW

PROVIDER: S-EPMC5593335 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Direct Acting Antiviral Agents in Korean Patients with Chronic Hepatitis C and Hemophilia Who Are Treatment-Naïve or Treatment-Experienced.

Lee Hyun Woong HW Yoo Ki Young KY Won Joung Won JW Kim Hyung Joon HJ

Gut and liver 20170901 5

<h4>Background/aims</h4>Chronic hepatitis C (CHC) is a major comorbidity in patients with hemophilia.<h4>Methods</h4>Patients (n=30) were enrolled between September 2015 and April 2016. Twenty-six patients were genotype 1 (1b, n=21; 1a, n=5) and four patients were genotype 2a/2b. Among 21 patients with genotype 1b, Y93H resistance-associated variants (RAVs) were detected in three patients (14.3%). We evaluated sustained virologic response (SVRs) at 12 weeks, as well as relapse and safety.<h4>Res ...[more]

PMID: 28874040

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Project description:UnlabelledHepatitis C virus (HCV) is the most common cause of mixed cryoglobulinemia syndrome (MCS). The efficacy and safety of all-oral direct-acting antiviral (DAA) therapy in HCV-associated MCS (HCV-MCS) is largely unknown. The authors studied case series of patients with HCV-MCS who were treated with sofosbuvir-based regimens and historical controls treated with pegylated interferon and ribavirin in a single health care network. HCV-MCS was defined by circulating cryoglobulin associated with systemic vasculitis symptoms. Renal involvement (n = 7) was established by kidney biopsy (n = 5) or by two or more of the following clinical findings: reduced kidney function, proteinuria, or hematuria with other causes excluded (n = 2). Twelve patients received DAA therapy between December 2013 and September 2014. Median age was 61 years, 58% were male, and 50% had cirrhosis. Median baseline serum creatinine was 0.97 mg/dL (range 0.7-2.47). Four patients received rituximab concurrent with DAA therapy. Sustained virological response rate at 12 weeks (SVR12) was 83% overall. Patients with glomerulonephritis who achieved SVR12 experienced an improvement in serum creatinine and a reduction in proteinuria. Cryoglobulin levels decreased in 89% of patients, with median percent decreasing from 1.5% to 0.5% and completely disappearing in four of nine cases who had cryoglobulins measured after treatment. Serious adverse events were infrequent (17%). In contrast, the historical cohort treated with pegylated interferon and ribavirin experienced only 10% SVR12, with 100% experiencing at least one adverse event and 50% experiencing premature discontinuation due to adverse events.ConclusionSVR12 rates for sofosbuvir-based DAA regimens in HCV-MCS were 83%, significantly higher than historical controls treated with pegylated interferon and ribavirin; patients with glomerulonephritis experienced improvement in renal function, including those not concomitantly treated with immunosuppression.

Project description:BACKGROUND:The treatment of hepatitis C (HCV) infections has significantly changed in the past few years due to the introduction of direct-acting antiviral agents (DAAs). DAAs could improve the sustained virological response compared to pegylated interferon with ribavirin (PR). However, there has been no evidence from randomized controlled trials (RCTs) that directly compare the efficacy among the different regimens of DAAs. AIM:Therefore, we performed a systematic review and network meta-analysis aiming to compare the treatment efficacy between different DAA regimens for treatment naïve HCV genotype 1. METHODS:Medline and Scopus were searched up to 25th May 2015. RCTs investigating the efficacy of second generation DAA regimens for treatment naïve HCV genotype 1 were eligible for the review. Due to the lower efficacy and more side effects of first generation DAAs, this review included only second generation DAAs approved by the US or EU Food and Drug Administration, that comprised of simeprevir (SMV), sofosbuvir (SOF), daclatasvir (DCV), ledipasvir (LDV), and paritaprevir/ritonavir/ombitasvir plus dasabuvir (PrOD). Primary outcomes were sustained virological response at weeks 12 (SVR12) and 24 (SVR24) after the end of treatment and adverse drug events (i.e. serious adverse events, anemia, and fatigue). Efficacy of all treatment regimens were compared by applying a multivariate random effect meta-analysis. Incidence rates of SVR12 and SVR24, and adverse drug events of each treatment regimen were pooled using 'pmeta' command in STATA program. RESULTS:Overall, 869 studies were reviewed and 16 studies were eligible for this study. Compared with the PR regimen, SOF plus PR, SMV plus PR, and DVC plus PR regimens yielded significantly higher probability of having SVR24 with pooled risk ratios (RR) of 1.98 (95% CI 1.24, 3.14), 1.46 (95% CI: 1.22, 1.75), and 1.68 (95% CI: 1.14, 2.46), respectively. Pooled incidence rates of SVR12 and SVR24 in all treatment regimens without PR, i.e. SOF plus LDV with/without ribavirin, SOF plus SMV with/without ribavirin, SOF plus DCV with/without ribavirin, and PrOD with/without ribavirin, (pooled incidence of SVR12 ranging from 93% to 100%, and pooled incidence of SVR24 ranging from 89% to 96%) were much higher than the pooled incidence rates of SVR12 (51%) and SVR24 (48%) in PR alone. In comparing SOF plus LDV with ribavirin and SOF plus LDV without ribavirin, the chance of having SVR12 was not significantly different between these two regimens, with the pooled RR of 0.99 (95% CI: 0.97, 1.01). Regarding adverse drug events, risk of serious adverse drug events, anemia and fatigue were relatively higher in treatment regimens with PR than the treatment regimens without PR. The main limitation of our study is that a subgroup analysis according to dosages and duration of treatment could not be performed. Therefore, the dose and duration of recommended treatment have been suggested in range and not in definite value. CONCLUSIONS:Both DAA plus PR and dual DAA regimens should be included in the first line drug for treatment naïve HCV genotype 1 because of the significant clinical benefits over PR alone. However, due to high drug costs, an economic evaluation should be conducted in order to assess the value of the investment when making coverage decisions.

Project description:ImportanceRecent reports based on the US Food and Drug Administration's voluntary Adverse Events Reporting System raised questions about the safety of direct-acting antivirals (DAAs) for treatment of the hepatitis C virus (HCV).ObjectiveTo assess the rates of adverse events in patients with HCV infection exposed to DAAs compared with those not exposed.Design, setting, and participantsA retrospective cohort study calculated unadjusted adverse event rates for exposed vs unexposed time, using claims and clinical data from 3 health systems between January 1, 2012, and December 31, 2017. Of 82 419 eligible adults, a total of 33 808 who met eligibility criteria (age, 18-88 years; HCV quantitative result or genotype from 2012 or later; continuously enrolled; naive to DAA treatment at baseline) were included. Marginal structural modeling methods were used to adjust time-to-event analyses for characteristics that are associated with both outcomes and probability of treatment.Interventions or exposuresExposure to DAAs compared with no DAA exposure.Main outcomes and measuresDeath, multiple organ failure, liver cancer, hepatic decompensation, acute-on-chronic liver event, acute myocardial infarction, ischemic or hemorrhagic stroke, arrhythmia, acute kidney failure, nonliver cancer, hepatitis B reactivation, hospitalizations, and emergency department visits.ResultsOf the 33 808 patients who met all inclusion criteria, 20 899 (61.8%) were men; mean (SD) age was 57.2 (10.6) years. In unadjusted analyses, DAA exposure was associated with significantly lower rates of death (10.7 vs 33.7 events per 1000 person-years; rate ratio [RR], 0.32, 95% CI, 0.25-0.40). Seven other unadjusted adverse clinical events ratios were below 70% and statistically significant favoring the DAA group: multiple organ failure (RR, 0.56; 95% CI, 0.44-0.72), liver cancer (RR, 0.62; 95% CI, 0.48-0.80), hepatic decompensation (RR, 0.62; 95% CI, 0.52-0.73), acute-on-chronic liver event (RR, 0.68; 95% CI, 0.56-0.84), acute myocardial infarction (RR, 0.64; 95% CI, 0.42-0.97), ischemic stroke (RR, 0.63; 95% CI, 0.42-0.95), and hemorrhagic stroke (RR, 0.47; 95% CI, 0.25-0.89); none favored the non-DAA group. In the marginal structural modeling-adjusted analysis, DAA exposure was associated with statistically significant lower odds of adverse events than non-DAA exposure for death (adjusted odds ratio [aOR], 0.42; 95% CI, 0.30-0.59), multiple organ failure (aOR, 0.67; 95% CI, 0.49-0.90), hepatic decompensation (aOR, 0.61; 95% CI, 0.49-0.76), acute-on-chronic liver event (aOR, 0.71; 95% CI, 0.56-0.91), and arrhythmia (aOR, 0.47; 95% CI, 0.25-0.88).Conclusions and relevanceDirect-acting antiviral exposure may not be associated with higher rates of any serious adverse events, including those related to liver, kidney, and cardiovascular systems. Safety concerns based on previous reports did not appear to be supported in this study with more comprehensive data and rigorous statistical methods.

Dataset Information

Direct Acting Antiviral Agents in Korean Patients with Chronic Hepatitis C and Hemophilia Who Are Treatment-Naive or Treatment-Experienced.

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Direct Acting Antiviral Agents in Korean Patients with Chronic Hepatitis C and Hemophilia Who Are Treatment-Naïve or Treatment-Experienced.

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