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This systematic review addressed 3 issues regarding current treatments for chronic hepatitis C: (1) efficacy and safety in treatment-naive patients; (2) efficacy and safety in selected subgroups of patients; and (3) effects on long-term clinical outcomes. Electronic databases were searched for articles from January 1996 to March 2002. Additional articles were identified by searching references in pertinent articles and recent journals and by questioning experts. Articles were eligible for review if they reported original human data from a study that used virological, histological, or clinical outcome measures. For data collection, paired reviewers assessed the quality of each study and abstracted data. This systematic review found that the combination of high-dose peginterferon and ribavirin was more efficacious than standard interferon and ribavirin in persons infected with hepatitis C virus (HCV) genotype 1 (sustained virologic response [SVR] rate: 42% vs. 33%) and that ranges of SVR rates were higher with peginterferon than standard interferon monotherapy in naïve patients (10% to 39% vs. 3% to 19%). Reports were consistent in showing treatment with interferon and ribavirin was more efficacious than interferon monotherapy in treatment-naive persons and previous nonresponders and relapsers. Studies were moderately consistent in showing that treatment decreases the risk for hepatocellular carcinoma (HCC). The evidence on treatment in important subgroups was limited by a lack of randomized controlled trials. Thus, the combination of peginterferon and ribavirin was the most efficacious treatment in patients with HCV genotype 1. Long-term outcomes were improved in patients with hepatitis C who achieved an SVR with treatment.