Treatment of chronic hepatitis C genotype 3 with Sofosbuvir-based therpy: a real-life study.

BACKGROUND AND AIMS: Recently, Sofosbuvir was launched in India at affordable cost. We conducted a real-life study to determine the efficacy and safety of Sofosbuvir plus Ribavirin, with and without peginterferon-alfa 2a, in patients with chronic hepatitis C (CHC) genotype 3, the commonest genotype in South Asia. METHODS: This study included data of CHC patients from 11 sites in northern India between March 2015 and December 2015 (n = 1203). Patients with CHC genotype 3 (n = 931), who were treated with either Sofosbuvir 400 mg plus weight-based Ribavirin, daily ×24 weeks (n = 432) (dual therapy), or Peginterferon-α2a 180 mcg weekly, Sofosbuvir 400 mg plus weight-based Ribavirin, daily ×12 weeks (n = 499) (triple therapy) were included for analysis. Primary outcome was the proportion of patients achieving sustained viral response at 12 weeks post-therapy. RESULTS: The overall SVR rates were 91 and 92% in the dual and triple therapy arms, respectively. The SVR rates in treatment experienced were 67 and 74% versus 93 and 96% in naïve patients, on the dual and triple therapy arms, respectively. The SVR rates of cirrhotics were 73 and 75% on the dual and triple treatment arms, respectively. The SVR rates were low in the experienced cirrhotic patients: 44% (dual therapy) and 58% (triple therapy). Common adverse events were fatigue, headache, and myalgia. CONCLUSION: Both dual and triple therapy regimes resulted in SVR rates of >95% in CHC genotype 3 who were naive non-cirrhotics. However, the SVR rates were low in treatment-experienced cirrhotics.

Effect of lowering HBV DNA levels by initial antiviral therapy before adding immunomodulator on treatment of chronic hepatitis B.

BACKGROUND: Lower hepatitis B virus DNA (HBV DNA) levels are associated with better responses in chronic hepatitis B (CHB). It is unclear whether an initial phase of antiviral treatment to lower HBV DNA levels before adding immunomodulator therapy is more effective than the strategy of using immunomodulators from the beginning. AIM: The aim of the study was to compare the efficacy of lamivudine followed by pegylated-interferon (peg-IFN) therapy with placebo followed by peg-IFN therapy in HBeAg-positive CHB patients. PATIENTS AND METHODS: Sixty-three treatment-naive HBeAg-positive patients with histologically proven CHB and alanine aminotransferase (ALT) > 1.2 x upper limit of normal (ULN) received placebo for 4 wk followed by peg-IFN 1.0 mug/kg/wk for next 24 wk (group A, N = 27; age 32 +/- 11 yr; M:F = 25:2) or lamivudine 100 mg per day for 4 wk followed by peg-IFN 1.0 mug/kg/wk for next 24 wk (group B, N = 36; age 32.5 +/- 10.5 yr; M:F = 31:5). Patients were followed for next 24 wk after completion of treatment. Biochemical and virologic responses were assessed at weeks 4, 28, and 52 and analysis was done on intention-to-treat basis. RESULTS: At wk 4, mean +/- SD of log change in DNA from baseline was 0.2594 +/- 1.7873 in group A and 1.2186 +/- 1.6347 in group B, respectively (P = 0.032). At week 28, undetectable HBV DNA was seen in eight (29.6%) and 16 (44.4%) patients in groups A and B, respectively (P= 0.298). At week 28, HBeAg loss occurred in eight (29.6%) in group A and 15 (41.7%) in group B (P = 0.43). Six months posttherapy, at week 52, undetectable HBV DNA was seen in four (14.8%) and 18 (50%) in groups A and B, respectively (P = 0.028) and HBeAg loss was maintained in four (14.8%) and 14 (38.9%) (P = 0.05) patients. Normal ALT was seen in five (18.5%) and 10 (27.8%) at week 28 (P = 0.552) and five (18.5%) and 13 (36.1%) at week 52 (P = 0.159) in groups A and B, respectively. There was a significant correlation among achievement of HBeAg loss, anti-HBe appearance, and undetectable HBV DNA levels at week 28 (P = 0.008) and 52 (P < 0.001) and HBV DNA levels at week 4. CONCLUSIONS: The strategy of using an antiviral initially to decrease HBV DNA levels before adding an immunomodulatory agent leads to improved sustained virological response as compared with using immunomodulator from the start.