Effectiveness Of Treatment For Hepatitis Research Articles

Planning a clinical trial programme for direct-acting antivirals for chronic viral hepatitis C

Scientific relevance. Direct-acting antivirals have significantly improved the effectiveness of treatment for hepatitis C. However, Russia and the Eurasian Economic Union lack recommendations for the clinical development of medicinal products from this pharmacotherapeutic group.Aim. The study aimed to analyse the requirements and recommendations for planning safety and efficacy clinical trials of direct-acting antivirals for chronic viral hepatitis C, outlined in the regulatory documents of the European Union and the United States.Discussion. Upon analysing the requirements and recommendations, the authors explained the reasons behind choosing the target population and the design for the efficacy and confirmatory studies. The article covers the clinical development of direct-acting antivirals in special populations, including patients with hepatitis C and HIV co-infection, a liver transplant, and prior treatment experience. According to the authors, patients who achieved a sustained virological response should be followed up for a full year after the end of treatment in order to confirm the durability of their response. A dose-finding study should first identify a suitable dose range for monotherapy and, subsequently, for combined therapy. Current treatment regimens should be optimised, and studies should be conducted to reduce treatment duration.Conclusions. The authors outlined the main approaches and a methodology for clinical trial programmes that should take into account the degree of correlation between the efficacy of direct-acting antivirals and the genotype/subtype of hepatitis C virus.

Effectiveness of treatment for hepatitis C virus reinfection following direct acting antiviral therapy in the REACH-C cohort.

Direct acting antiviral (DAA) therapy is highly effective for hepatitis C virus (HCV) infection, but reinfection following treatment may compromise benefits of cure. This study assessed the real-world effectiveness of treatment for reinfection. Real-world effectiveness of antiviral therapy in chronic hepatitis C (REACH-C) is an observational study evaluating treatment outcomes following sequential DAA initiations across 33 health services in Australia between March 2016-June 2019. Reinfection was defined by post-treatment genotype switch or HCV viraemia after sustained virologic response (SVR12). Of the 10,843 individuals initiating DAA therapy post-treatment viraemia was reported in 526 of whom 99 were reinfections. Treatment for reinfection occurred in 88 individuals. In those with available treatment outcomes, SVR12 was similar to initial treatment in the overall REACH-C cohort (95% vs 95%; p=0.745) and comparable across primary, tertiary, and prison settings. Classifying unknown treatment outcomes as failures, SVR12 for treatment of reinfection was lower than initial treatment in REACH-C (67% vs 81%; p=0.002), due to higher lost to follow-up. Treatment of reinfection is highly effective and can be delivered in non-specialist settings. Access to treatment for reinfection in high-risk populations is crucial to HCV elimination.

Chronic hepatitis C treatment outcomes in low- and middle-income countries: a systematic review and meta-analysis

To assess the effectiveness of treatment for hepatitis C virus (HCV) infection in low- and middle-income countries and identify factors associated with successful outcomes. We performed a systematic review and meta-analysis of studies of HCV treatment programmes in low- and middle-income countries. The primary outcome was a sustained virological response (SVR). Factors associated with treatment outcomes were identified by random-effects meta-regression analysis. The analysis involved data on 12 213 patients included in 93 studies from 17 countries. The overall SVR rate was 52% (95% confidence interval, CI: 48-56). For studies in which patients were predominantly infected with genotype 1 or 4 HCV, the pooled SVR rate was 49% (95% CI: 43-55). This was significantly lower than the rate of 59% (95% CI: 54-64) found in studies in which patients were predominantly infected with other genotypes (P = 0.012). Factors associated with successful outcomes included treatment with pegylated interferon and ribavirin, infection with an HCV genotype other than genotype 1 or 4 and the absence of liver damage or human immunodeficiency virus infection at baseline. No significant difference in the SVR rate was observed between weight-adjusted and fixed-dose ribavirin treatment. Overall, 17% (95% CI: 13-23) of adverse events resulted in treatment interruption or dose modification, but only 4% (95% CI: 3-5) resulted in treatment discontinuation. The outcomes of treatment for HCV infection in low- and middle-income countries were similar to those reported in high-income countries.

Falsely Low Hemoglobin A1c Levels in a Patient Receiving Ribavirin and Peginterferon alfa‐2b for Hepatitis C

The effect of treatment for hepatitis C viral infection on hemoglobin A(1c) (A1C) levels is not well described in the literature. We describe a 59-year-old man with type 2 diabetes mellitus whose A1C level became falsely low when ribavirin and peginterferon alfa-2b therapy were started for treatment of hepatitis C. After treatment was discontinued, the patient's A1C returned to its previous baseline value. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 7) between the patient's low AIC level and his ribavirin-peginterferon alfa-2b therapy. Clinicians should be aware that combination therapy for hepatitis C may affect A1C values. To maintain accurate glucose control in patients with diabetes who are receiving treatment for hepatitis C, it is important that they self-monitor their blood glucose levels in conjunction with A1C data, especially when A1C values become falsely low.

Adverse event management

The Brazilian Journal of Infectious Diseases 2007;11 (5) Suppl. 1:66-70. © 2007 by The Brazilian Journal of Infectious Diseases and Contexto Publishing. All rights reserved. The treatment of hepatitis C involves combining conventional interferon (IFN) or pegylated IFN (PEG-IFN) with ribavirin (RBV). These therapeutic regimens are associated with numerous adverse events, among which constitutional and neuropsychiatric symptoms, as well as hematological abnormalities, stand out [1,2]. The adverse events observed with the use of PEG-IFN or conventional IFN are similar, and the frequencies of those events are shown in Table 1 [3-5]. Adverse events resulting from the treatment of hepatitis C can jeopardize the quality of life of patients and their response to treatment. The control of those events involves medicinal and non-medicinal interventions. The latter include a reduction in the dosage of IFN or RBV and discontinuation of the treatment. A temporary or permanent reduction in the dosage of PEGIFN, conventional IFN or RBV as a result of an adverse event is necessary in approximately 30% of patients. In 10% of patients it is necessary to discontinue the treatment [4]. Hematological abnormalities (neutropenia, anemia and thrombocytopenia) and depression are the most common causes of dose reduction. The maintenance of the dosages of medications used in the treatment of hepatitis C and of the recommended course of treatment are important for the effectiveness of the therapy, as shown in Figure 1 [6]. Dose reduction is associated with lowering the rate at which a sustained viral response (SVR) is achieved. Early identification and strategies for controlling adverse events are important in the prevention of moderate and severe complications. These practices also attenuate the deleterious effects on the quality of life of patients and maximize the effectiveness of treatment for hepatitis C. Constitutional Symptoms Constitutional symptoms such as fatigue, headache and myalgia are the most common adverse events in patients