Gastroenterology

Gastroenterology

Volume 122, Issue 5, May 2002, Pages 1303-1313
Gastroenterology

Clinical Research
Impact of pegylated interferon alfa-2b and ribavirin on liver fibrosis in patients with chronic hepatitis C,☆☆

https://doi.org/10.1053/gast.2002.33023Get rights and content

Abstract

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/m2 (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.

GASTROENTEROLOGY 2002;122:1303-1313

Section snippets

Materials and methods

The individual data from 4 randomized trials of PEG-interferon alfa-2b alone (Pegintron, Schering Plough, Kenilworth, NJ),8 or in combination with ribavirin,11 or of the combination interferon alfa-2b and ribavirin (Rebetron, Schering Plough)12, 13 were obtained. Patients with serologic confirmation of chronic hepatitis C were included if they had both pretreatment and posttreatment liver biopsies. Patients were excluded if they had HBV or human immunodeficiency virus infection, a daily alcohol

Progression of fibrosis was analyzed by 3 methods

First, we compared the impact of the different treatment regimens on the percentage of patients who improve by at least 1 fibrosis stage, remained stable, or worsened by at least 1 stage.

Secondly, we compared the different treatment regimens according to the fibrosis progression rates per year before and after treatment. These estimates have been extensively detailed and validated previously.2, 6, 19

The fibrosis progression rate after treatment was defined as the ratio between the difference in

Results

Of the 4493 naive patients enrolled in the 4 trials, 3010 had paired biopsies available with a 20-month mean duration between the biopsies (Table 1). There were no statistically significant differences between the original population and the population of patients with paired biopsies included in this analysis. At baseline, 2243 patients had no significant fibrosis (75%) and 767 significant fibrosis (25%), 673 (22%) had no significant activity, and 2337 (78%) significant activity. The mean

Discussion

This overview of 4 pivotal randomized trials has permitted us to assess the incremental benefit of 10 different regimens on the histological features of patients infected with hepatitis C virus. These regimens given for 24 or 48 weeks allowed us to observe an improvement of necrosis and inflammation grades and a reduction of fibrosis progression at least during the 2 years' histological follow-up. This analysis has also demonstrated that the histological improvement was related both to the

Acknowledgements

The authors thank all the investigators of PEG-FIBROSIS project including the investigators of the randomized trials.

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  • Cited by (0)

    Address requests for reprints to: Professeur Thierry Poynard, Service d'Hépato-Gastroentérologie Groupe Hospitalier Pitié-Salpêtrière 47-83 Boulevard de l'Hôpital, 75651 Paris, Cedex 13, France. e-mail: [email protected].

    ☆☆

    Supported by research grants from Schering Plough Research Institute, Kenilworth, New Jersey, by Direction de la Recherche Clinique Assistance Publique Hôpitaux de Paris, by Association pour la Recherche contre le Cancer, and by Association pour la Recherche sur les Maladies Hepatiques Viroles, Paris, France.

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