Daclatasvir plus peginterferon alfa and ribavirin for treatment-naive chronic hepatitis C genotype 1 or 4 infection: a randomised study.

OBJECTIVE: To evaluate the safety and efficacy of daclatasvir, an HCV NS5A inhibitor with pangenotypic activity, administered with peginterferon-alfa-2a/ribavirin. DESIGN: In this Phase 2b double-blind, placebo-controlled study, treatment-naive adults with HCV genotype 1 (N=365) or 4 (N=30) infection were randomly assigned (2:2:1) to daclatasvir 20 mg or 60 mg, or placebo once daily plus weekly peginterferon-alfa-2a and twice-daily ribavirin. Daclatasvir recipients achieving protocol-defined response (PDR; HCV-RNA

Optimal therapy in genotype 4 chronic hepatitis C: finally cured?

Optimal therapy for patients with hepatitis C virus (HCV) genotype 4 (HCV-4) infection is changing rapidly, and the possibility of a total cure is near. The standard of care has been combination pegylated interferon (PEG-IFN)-ribavirin (RBV), with modest response rates and considerable adverse events. Since the introduction of sofosbuvir (SOF), simeprevir (SIM), and daclatasvir (DCV), the duration of treatment has been significantly shortened and response rates have increased. The recommended treatment for IFN-eligible patients is PEG-IFN/RBV plus SOF, SIM or DCV. In IFN ineligible patients, the optimal regimen is a 24-week course of SOF/RBV, or a 12-week course of SOF-SIM or SOF-DCV with or without RBV. The pipeline for patients with chronic HCV is highly active. IFN-free combinations with paritaprevir-ombitasvir, SOF-ledipasvir, or DCV-asunaprevir (ASV)-beclabuvir (BMS-791325) for 12 weeks or less with close to 100% cure rates will soon become the optimal therapy.

Direct acting antivirals are associated with more liver stiffness regression than pegylated interferon therapy in chronic hepatitis C patients.

OBJECTIVES: Extent of post-treatment fibrosis change in patients with different stages of fibrosis not fully known. We aimed to study changes in liver fibrosis in chronic hepatitis C patients who were treated with pegylated interferon/ribavirin (PEG/RBV) or direct acting antivirals (DAAs). METHODS: Retrospective evaluation of results of transient elastography (TE) was done before and 1 year after end of treatment for patients treated with PEG/RBV (n = 268) and DAAs (n = 245). RESULTS: The average age was 45.54 ± 10.64 years; mainly males. All patients in the DAAs group achieved sustained virological response (SVR), unlike 56.3% of the patients in the PEG/RBV group. F3-F4 fibrosis was predominant in the PEG/RBV nonresponder patients (51.3%) and DAAs responders (57.1%). TE decreased 1 year after end of treatment (p = 0.001) in the viral responders of the PEG/RBV group (7.44 ± 4.02 vs. 10.24 ± 7.29 kPa) and DAAs group (12.12 ± 9.21 vs. 16.81 ± 12.84 kPa) respectively. The delta TE change in the DAAs responders was higher than the PEG/RBV responders (p = 0.001) and PEG/RBV nonresponders (p = 0.001). The percentage of patients with liver fibrosis regression was higher in DAAs responders (52.5%) than in PEG/RBV responders (23.3%). CONCLUSION: Treatment with DAAs is associated with fibrosis improvement more than treatment with PEG/RBV in chronic hepatitis C patients.

Simple Predictive Model for Identifying Patients with Chronic Hepatitis C and Hepatitis C Virus Genotype 4 Infection with a High Probability of Sustained Virologic Response with Peginterferon Alfa-2a/Ribavirin: Pooled Analysis of Data from Two Large, International Cohort Studies.

INTRODUCTION: Wherever access to direct-acting antiviral agents is restricted, dual peginterferon/ribavirin (PegIFN/RBV) therapy remains an option for treatment of hepatitis C virus (HCV) genotype 4 (GT4) infection, which predominates in the Middle East and Sub-Saharan Africa. Our goal was to develop a baseline scoring system to identify GT4-infected patients with a low or high probability of achieving a sustained virologic response (SVR) with PegIFN alfa-2a/RBV using data from two large cohort studies. METHODS: Associations between baseline characteristics and SVR were explored by generalized additive models and multiple logistic regression analysis to develop a predictive model, which was then checked by bootstrapping. The score comprised four factors with points assigned thus: age ≤40, 3 points; >40 but ≤55, 2 points; alanine aminotransferase ≤1 or >3× the upper limit of normal, 1 point; no cirrhosis, 1 point; HCV RNA <50,000 IU/mL, 2 points; 50,000 to <400,000 IU/mL, 1 point. The values for a given patient are summed to produce a score from 0 to 7 where higher scores indicate higher chances of SVR. RESULTS: Among the 459 patients, 28 (6%), 50 (11%), 92 (20%), 121 (26%), 103 (22%), and 65 (14%) patients had scores of 0-1, 2, 3, 4, 5, and 6-7, respectively, with respective SVR rates of 11%, 28%, 50%, 57%, 63%, and 83%. Relapse rates decreased with increasing prediction score (80%, 39%, 15%, 19%, 5%, and 7%, respectively). SVR rates were consistently higher in Caucasian than Black patients and in patients with a rapid virologic response HCV RNA <50 IU/mL at week 4); however, the trend toward higher SVR rates with increasing score remained apparent in each subgroup. CONCLUSION: In conclusion, a simple scoring system can be used to identify GT4-infected patients with a high probability of achieving an SVR with PegIFN alfa-2a/RBV. FUNDING: F. Hoffmann-La Roche Ltd.

A comparative study of variants of pegylated interferon alpha in treatment of chronic HCV patients.

HCV infection presents a vast burden in the regions of high prevalence such as Egypt, where most HCV isolates are genotype 4b. Combined treatment of three variants of pegylated interferon and ribavirin is still the standard of care in Egypt. However, no conclusive data confirming their efficacy are available. Here, 60 chronic HCV patients were randomized for ribavirin plus Peg Intron (PEG-IFNα-2b), Pegasys (PEG-IFNα-2a) or Reiveron Retard (PEG-IFNα-2a). Serum interferon and antibody (Ab) levels were measured, and responses and costs were compared. Serum interferon levels were higher in Pegasys group (1625.1 ng/mL) followed by Reiveron Retard (1076.5 ng/mL), and Peg Intron group (857.72 ng/mL). Moreover, Ab levels were the lowest in Reiveron Retard group (318.4 ng/mL), followed by Peg Intron (439.93 ng/mL), and Pegasys cases (610.83 ng/mL). The best 24-week response rates were detected in the Pegasys group (73.3%), followed by Peg Intron (66.67%), and Reiveron Retard (40%). Treatment with both Pegasys and Peg Intron were most cost-effective. Furthermore, Pegasys was superior in both 6-month response and serum interferon, despite having higher Ab levels (more antigenicity). Our data have notable clinical implications and suggest that Pegasys may be a superior choice of interferon therapy for chronic HCV under low socioeconomic conditions.