Efficacy and safety of elbasvir/grazoprevir for 8 or 12 weeks for hepatitis C virus genotype 4 infection: A randomized study.

BACKGROUND & AIMS: Hepatitis C virus (HCV) genotype (GT) 4 infection is prevalent in sub-Saharan Africa and the Middle East, particularly in Egypt. This study evaluated the safety and efficacy of elbasvir/grazoprevir administered for 8 and 12 weeks in participants with HCV GT4 infection. METHODS: In this partially randomized, open-label multicentre study conducted in France (NCT03111108; Protocol MK5172-096), treatment-naive participants with GT4 infection and F0-F2 fibrosis were randomized 2:1 to elbasvir (50 mg)/grazoprevir (100 mg) for 8 or 12 weeks. Treatment-naive participants with F3-F4 fibrosis and all treatment-experienced participants (F0-F4) were assigned to elbasvir/grazoprevir for 12 weeks. The primary endpoint was sustained virologic response (SVR) 12 weeks after the end of therapy. RESULTS: One hundred and seventeen participants were enrolled. Among treatment-naive participants with F0-F2 fibrosis, SVR was achieved by 94% (50/53) and 96% (26/27) of those receiving elbasvir/grazoprevir for 8 or 12 weeks, respectively, and four participants relapsed. In the 12-week arm, 95% (35/37) achieved SVR and two participants relapsed. NS5A resistance-associated substitutions were present at baseline and virologic failure in five of the participants with relapse. Drug-related adverse events occurred in 42% (n = 22) and 50% (n = 32) of participants receiving 8 and 12 weeks of treatment, respectively. No participant discontinued treatment owing to an adverse event. CONCLUSION: These data confirm the efficacy of elbasvir/grazoprevir administered for 12 weeks in treatment-experienced individuals with HCV GT4 infection and those with advanced fibrosis. Treatment-naive individuals with mild fibrosis can be treated effectively with an 8-week regimen.

End points of therapy in chronic hepatitis B.

This review assesses the relevance of the clinical, histological, biochemical and virological end points in the course and outcome of chronic hepatitis B. The pathway and the impact of the variation in these end points are presented, as well as their definitions. The treatment goals are discussed in terms of quality of life and survival. Prevention of the progression of the disease to cirrhosis, decompensated cirrhosis, end-stage liver disease and hepatocellular carcinoma seems to be the best approach to improve survival. As these criteria are long-term end points, easier to use end points assessed in clinical trials as efficacy objectives were also analyzed to determine whether they can be used as accurate surrogate criteria. Results of therapy were then analyzed according to the approved end points and in terms of management of chronic hepatitis B. Finally, an attempt to define new clinical end points is discussed in view of the development of more potent antiviral strategies.

Management of nonresponsive hepatitis C.

More than 50% of hepatitis C virus (HCV)-infected patients do not respond to the classical pegylated interferon (PEG-IFN)/ribavirin combination therapy. However, failing to respond to one course of treatment is not synonymous of therapy failure and retreatment is often beneficial. Alternative retreatment strategies include repeating the classical standard of care with an optimized drug regimen and adherence, including ribavirin serum concentration adjustment, correcting, if at all possible, comorbidities, and the addition of new specific anti-HCV molecules to the backbone of pegylated interferon/ribavirin. Options of retreatment should include consensus and natural interferons. For patients with advanced disease exposed to a high risk of lethal complications, customized maintenance therapy could be an effective option since it may slow down complications in some patients. Since low-dose interferon monotherapy is not sufficient, such a maintenance therapy remains to be verified via clinical trials. New possibilities of noninvasive assessment of fibrosis and the use of genetic tests to predict fibrosis progression and responsiveness to interferon are major emerging opportunities that run parallel to the revolution of the pharmacologic armentarium.

Interferon-alpha 2b plus ribavirin in patients with chronic hepatitis C after liver transplantation: a randomized study.

BACKGROUND AND AIMS: Hepatitis C virus (HCV) reinfection after liver transplantation is frequent and leads to chronic hepatitis and cirrhosis. The use of antiviral therapy in this situation remains controversial. This study aimed to assess the safety and efficacy of interferon alfa-2b plus ribavirin for recurrent hepatitis C following liver transplantation. METHODS: Transplant recipients with recurrent chronic hepatitis C were randomized to receive either no treatment or therapy with interferon alfa-2b (3 MU 3 times a week) plus 1000-1200 mg/day ribavirin for 1 year. Patients were followed up for 6 months after the end of treatment. The primary end point was loss of HCV RNA 6 months after the end of treatment. RESULTS: Fifty-two patients were randomized (treatment, 28; placebo, 24). Sixteen patients were withdrawn from the study; 12 (43%) were from the treated group (mainly for anemia [7 patients]) and 4 (17%) from the control group. In the treated group, serum HCV RNA was undetectable in 9 patients (32%) at the end of treatment and 6 (21.4%) at the end of the follow-up period, whereas no patient in the control group lost HCV RNA at any point (P = 0.036 at the end of follow-up). However, there was no significant histologic improvement. CONCLUSIONS: The combination of interferon alfa-2b plus ribavirin induced a sustained virologic response in 21% of transplant recipients with recurrent hepatitis C. However, 43% discontinued therapy due to adverse events (primarily severe anemia). Strategies to enable treatment with lower doses of ribavirin need to be explored.