Efficacy and safety of peginterferon α-2a (40 kD) plus ribavirin among patients with chronic hepatitis C and earlier treatment failure to interferon and ribavirin: an open-label study in central and Eastern Europe.
ABSTRACT To assess the safety and efficacy of 48 weeks of re-treatment with peginterferon α-2a (40 kD) plus ribavirin in previously treated hepatitis C virus (HCV) genotype 1 patients.
HCV genotype 1 patients previously treated with conventional interferon with or without ribavirin were assigned to 48 weeks of treatment with peginterferon α-2a (40 kD; 180 μg/week) plus ribavirin (recommended dose: 1000/1200 mg/day) in this open-label trial conducted in central and Eastern Europe. The primary efficacy endpoint was sustained virological response (SVR, HCV RNA <50 IU/ml) after 24 weeks of untreated follow-up. Early virological response (EVR) was defined as an undetectable HCV RNA or at least 2-log drop at week 12.
A total of 154 of the 203 (76%) treatment-experienced genotype 1 patients completed the treatment. Overall, 113 patients (56%) achieved an EVR, 107 (53%) had an end-of-treatment response and 63 patients (31%) achieved an SVR [including 38% (40/105) of those with an earlier breakthrough or relapse and 24% (21/88) of those with earlier nonresponse]. Among patients with an EVR, 47% (53/113) achieved an SVR (positive predictive value=47%), compared with 3% (1/34) of patients without an EVR (negative predictive value=97.1%). Rates of SVR were higher in patients without cirrhosis (54/169, 32%), with a baseline viral load of 800 000 IU/ml or less (29/68, 43%) and younger than 40 years of age (36/77, 47%).
The combination of peginterferon α-2a (40 kD) plus ribavirin produced an overall SVR rate of 31% in difficult-to-treat genotype 1 patients who had not responded to the previous treatment with conventional interferon plus ribavirin.
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ABSTRACT: To evaluate the impact of sociodemographic/clinical factors on early virological response (EVR) to peginterferon/ribavirin for chronic hepatitis C (CHC) in clinical practice. We conducted a multicenter, cross-sectional, observational study in Hepatology Units of 91 Spanish hospitals. CHC patients treated with peginterferon α-2a plus ribavirin were included. EVR was defined as undetectable hepatitis C virus (HCV)-ribonucleic acid (RNA) or ≥ 2 log HCV-RNA decrease after 12 wk of treatment. A bivariate analysis of sociodemographic and clinical variables associated with EVR was carried out. Independent factors associated with an EVR were analyzed using a multiple regression analysis that included the following baseline demographic and clinical variables: age (≤ 40 years vs > 40 years), gender, race, educational level, marital status and family status, weight, alcohol and tobacco consumption, source of HCV infection, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and gamma glutamyl transpeptidase (GGT) (≤ 85 IU/mL vs > 85 IU/mL), serum ferritin, serum HCV-RNA concentration (< 400 000 vs ≥ 400 000), genotype (1/4 vs 3/4), cirrhotic status and ribavirin dose (800/1000/1200 mg/d). A total of 1014 patients were included in the study. Mean age of the patients was 44.3 ± 9.8 years, 70% were male, and 97% were Caucasian. The main sources of HCV infection were intravenous drug abuse (25%) and blood transfusion (23%). Seventy-eight percent were infected with HCV genotype 1/4 (68% had genotype 1) and 22% with genotypes 2/3. The HCV-RNA level was > 400 000 IU/mL in 74% of patients. The mean ALT and AST levels were 88.4 ± 69.7 IU/mL and 73.9 ± 64.4 IU/mL, respectively, and mean GGT level was 82 ± 91.6 IU/mL. The mean ferritin level was 266 ± 284.8 μg/L. Only 6.2% of patients presented with cirrhosis. All patients received 180 mg of peginterferon α-2a. The most frequently used ribavirin doses were 1000 mg/d (41%) and 1200 mg/d (41%). The planned treatment duration was 48 wk for 92% of patients with genotype 2/3 and 24 wk for 97% of those with genotype 1/4 (P < 0.001). Seven percent of patients experienced at least one reduction in ribavirin or peginterferon α-2a dose, respectively. Only 2% of patients required a dose reduction of both drugs. Treatment was continued until week 12 in 99% of patients. Treatment compliance was ≥ 80% in 98% of patients. EVR was achieved in 87% of cases (96% vs 83% of patients with genotype 2/3 and 1/4, respectively; P < 0.001). The bivariate analysis showed that patients who failed to achieve EVR were older (P < 0.005), had higher ALT (P < 0.05), AST (P < 0.05), GGT (P < 0.001) and ferritin levels (P < 0.001), a diagnosis of cirrhosis (P < 0.001), and a higher baseline viral load (P < 0.05) than patients reaching an EVR. Age < 40 years [odds ratios (OR): 0.543, 95%CI: 0.373-0.790, P < 0.01], GGT < 85 IU/mL (OR: 3.301, 95%CI: 0.192-0.471, P < 0.001), low ferritin levels (OR: 0.999, 95%CI: 0.998-0.999, P < 0.01) and genotype other than 1/4 (OR: 4.716, 95%CI: 2.010-11.063, P < 0.001) were identified as independent predictors for EVR in the multivariate analysis. CHC patients treated with peginterferon-α-2a/ribavirin in clinical practice show high EVR. Older age, genotype 1/4, and high GGT were associated with lack of EVR.World Journal of Gastroenterology 03/2013; 19(12):1943-52. · 2.55 Impact Factor
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ABSTRACT: Pegylated interferon (peginterferon) and ribavirin is the current standard therapy for chronic hepatitis C. The aims of this study were to evaluate the efficacy of peginterferon and ribavirin and to identify predictors of a sustained virological response (SVR) to the retreatment of chronic hepatitis C in Korea. The clinical records of 91 patients with chronic hepatitis C who were retreated with peginterferon and ribavirin were retrospectively analyzed. None of the patients had previously attained a SVR, and the patients were categorized according to their previous responses (nonresponder, relapser, or inadequate treatment) to conventional interferon/ribavirin. The overall SVR rate was 54.9%. Independent predictors of a SVR were genotypes 2 and 3, relapse, an adherence to peginterferon of over 80%, and an early virological response (EVR). For genotype 1 patients, an adherence to peginterferon of over 80% was an independent predictor of a SVR. Peginterferon and ribavirin therapy is effective for the retreatment of Korean chronic hepatitis C patients who have failed interferon/ribavirin, especially in patients with genotypes 2 and 3, relapse, an adherence to peginterferon over 80%, and an EVR. For genotype 1 patients, retreatment was effective in patients with an adherence to peginterferon over 80%.Gut and liver 09/2013; 7(5):585-93. · 1.31 Impact Factor