Induction pegylated interferon Alfa-2a and high dose ribavirin do not increase SVR in heavy patients with HCV genotype 1 and high viral loads

Background & Aims Patients infected with hepatitis C virus (HCV) genotype 1, body weight <85 kg, and high baseline viral load respond poorly to standard doses of pegylated interferon (peginterferon) and ribavirin. We evaluated intensified therapy with peginterferon alfa-2a plus ribavirin. Methods This double-blind randomized trial included HCV genotype 1-infected outpatients from hepatology clinics with body weight <85 kg and HCV RNA titer <400,000 IU/mL. Patients were randomized to 180 μg/wk peginterferon alfa-2a for 48 weeks plus 1200 mg/day ribavirin (standard of care) (group A, n = 191) or 1400/1600 mg/day ribavirin (group B, n = 189). Additional groups included 360 μg/wk peginterferon alfa-2a for 12 weeks then 180 μg/wk peginterferon alfa-2a for 36 weeks plus 1200 mg/day ribavirin (group C, n = 382) or 1400/1600 mg/day ribavirin (group D, n = 383). Follow-up lasted 24 weeks after treatment. Results Sustained virologic response rates (HCV RNA level <15 IU/mL at end of follow-up) in groups A, B, C, and D were 38%, 43%, 44%, and 41%, respectively. There were no significant differences among the 4 groups or between pooled peginterferon alfa-2a regimens (A + B vs C + D: odds ratio [OR], 1.08; 95% confidence interval [CI], 0.831.39; P = .584) or pooled ribavirin regimens (A + C vs B + D: OR, 1.00; 95% CI, 0.791.28; P = .974). Conclusions In patients infected with HCV genotype 1 who are difficult to treat (high viral load, body weight <85 kg), a 12-week induction regimen of peginterferon alfa-2a and/or higher-dose ribavirin is not more effective than the standard regimen. © 2010 AGA Institute.

Keywords

Chronic Hepatitis C, Steatosis and Response to HCV Therapy, Tolerability of High-Dose Pegylated Interferon, Tolerability of High-Dose Ribavirin, colony stimulating factor, peginterferon alpha2a, ribavirin, virus RNA, adult, alopecia, anemia, arthralgia, asthenia, body weight, chill, clinical trial, controlled clinical trial, controlled study, coughing, decreased appetite, depression, diarrhea, dizziness, double blind procedure, drug dose reduction, drug efficacy, drug eruption, drug fever, drug induced headache, drug megadose, drug withdrawal, fatigue, female, follow up, genotype, hemoglobin blood level, hepatitis C, human, insomnia, irritability, major clinical study, male, mediastinum disease, multicenter study, myalgia, nausea, neutrophil count, outpatient, pneumonia, priority journal, pruritus, randomized controlled trial, respiratory tract disease, side effect, thorax disease, thrombocyte count, treatment duration, virus load, Adult, Antiviral Agents, Body Weight, Dose-Response Relationship, Drug, Drug Therapy, Combination, Fatty Liver, Female, Genotype, Hepacivirus, Hepatitis C, Chronic, Humans, Interferon Alfa-2a, Male, Middle Aged, Obesity, Polyethylene Glycols, Ribavirin, Viral Load