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The Impact of Pegylated Interferon Alfa-2b and Ribavirin on Liver Fibrosis

Gastroenterology 2002 May;122(5):1303-1313

Impact of pegylated interferon alfa-2b and ribavirin on liver fibrosis in patients with chronic hepatitis C.

Poynard T, McHutchison J, Manns M, Trepo C, Lindsay K, Goodman Z, Ling MH, Albrecht J
Service d'Hepato-Gastroenterologie, Groupe Hospitalier Pitie-Salpetriere, Universite Paris VI, Paris, France; Scripps Clinic and Research Foundation, Division of Gastroenterology/Hepatology, La Jolla, California; Division of Gastroenterology and Hepatology, Medical School of Hannover, Hannover, Germany; Service d'Hepato-Gastroenterologie, Hotel Dieu, Lyon, France; Division of Gastrointestinal and Liver Disease, University of Southern California, Los Angeles, California; Department of Hepatic and Gastrointestinal Pathology, Armed Forces Institute of Pathology, Washington, DC; and Schering-Plough Research Institute, Kenilworth, New Jersey.

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.


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