BACKGROUND & AIMS: Liver fibrosis is an important prognostic factor in patients with hepatitis C. The effect of pegylated (PEG) interferon alone or its combination with ribavirin on fibrosis has not been established.METHODS: We pooled individual data from 3010 naive patients with pretreatment and posttreatment biopsies from 4 randomized trials. Ten different regimens combining standard interferon, PEG interferon, and ribavirin were compared. The impact of each regimen was estimated by the percentage of patients with at least 1 grade improvement in the necrosis and inflammation (METAVIR score), the percentage of patients with at least 1 stage worsening in fibrosis METAVIR score, and by the fibrosis progression rate per year.RESULTS: Necrosis and inflammation improvement ranged from 39% (interferon 24 weeks) to 73% (optimized PEG 1.5 and ribavirin; P < 0.001). Fibrosis worsening ranges from 23% (interferon 24 weeks) to 8% (optimized PEG 1.5 and ribavirin; P < 0.001). All regimens significantly reduced the fibrosis progression rates in comparison to rates before treatment. The reversal of cirrhosis was observed in 75 patients (49%) of 153 patients with baseline cirrhosis. Six factors were independently associated with the absence of significant fibrosis after treatment: baseline fibrosis stage (odds ratio [OR] = 0.12; P < 0.0001), sustained viral response (OR = 0.36; P < 0.0001), age < 40 years (OR = 0.51; P < 0.001), body mass index < 27 kg/m(2) (OR = 0.65; P < 0.001), no or minimal baseline activity (OR = 0.70; P = 0.02), and viral load < 3.5 millions copies per milliliter (OR = 0.79; P = 0.03).CONCLUSIONS: PEG-interferon and ribavirin combination significantly reduces the rate of fibrosis progression in patients with hepatitis C.