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Previous Volume 343:1673-1680 December 7, 2000 Number 23 Next

	Full Text PDF Editorial by Schafer, D. F. Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background Chronic hepatitis C virus (HCV) infection in patients with cirrhosis is difficult to treat. In patients with chronic hepatitis C but without cirrhosis, once-weekly administration of interferon modified by the attachment of a 40-kd branched-chain polyethylene glycol moiety (peginterferon alfa-2a) is more efficacious than a regimen of unmodified interferon. We examined the efficacy and safety of peginterferon alfa-2a in patients with HCV-related cirrhosis or bridging fibrosis.

Methods We randomly assigned 271 patients with cirrhosis or bridging fibrosis to receive subcutaneous treatment with 3 million units of interferon alfa-2a three times weekly (88 patients), 90 µg of peginterferon alfa-2a once weekly (96), or 180 µg of peginterferon alfa-2a once weekly (87). Treatment lasted 48 weeks and was followed by a 24-week follow-up period. We assessed efficacy by measuring HCV RNA and alanine aminotransferase and by evaluating liver-biopsy specimens. A histologic response was defined as a decrease of at least 2 points on the 22-point Histological Activity Index.

Results In an intention-to-treat analysis, HCV RNA was undetectable at week 72 in 8 percent, 15 percent, and 30 percent of the patients treated with interferon alfa-2a and with 90 µg and 180 µg of peginterferon alfa-2a, respectively (P=0.001 for the comparison between 180 µg of peginterferon alfa-2a and interferon alfa-2a). At week 72, alanine aminotransferase concentrations had normalized in 15 percent, 20 percent, and 34 percent of patients, respectively (P=0.004 for the comparison between 180 µg of peginterferon alfa-2a and interferon alfa-2a). In the subgroup of 184 patients with paired liver-biopsy specimens, the rates of histologic response at week 72 were 31 percent, 44 percent, and 54 percent, respectively (P=0.02 for the comparison between 180 µg of peginterferon alfa-2a and interferon alfa-2a). All three treatments were similarly tolerated.

Conclusions In patients with chronic hepatitis C and cirrhosis or bridging fibrosis, 180 µg of peginterferon alfa-2a administered once weekly is significantly more effective than 3 million units of standard interferon alfa-2a administered three times weekly.

Source Information

From the Department of Medicine, University Health Network, Toronto Western Hospital, Toronto (E.J.H.); the Hepatology Section, Department of Medicine, Medical College of Virginia, Richmond (M.L.S.); the Department of Medicine, Royal Brisbane Hospital, Brisbane, Australia (W.G.E.C.); the Clinical Research Department, Department of Medicine, Royal Free Hospital, London (G.M.D.); the Department of Medicine, Heritage Medical Research Clinic, Calgary, Alta., Canada (S.S.L.); the Department of Medicine, Louisiana State University Health Sciences Center, New Orleans (L.B.); Carolinas Center for Liver Disease, Department of Medicine, Charlotte, N.C. (R.R.); the Center for Liver Diseases, Department of Medicine, University of Miami School of Medicine, Miami (R.K.R.); the Gastroenterology Unit, Department of Medicine, Veterans Affairs Medical Center, San Francisco (T.L.W.); and Hoffmann–LaRoche, Nutley, N.J. (A.L., J.H., J.D.).

Address reprint requests to Dr. Heathcote at the University Health Network, Toronto Western Hospital, 399 Bathurst St., Toronto, ON M5T 2S8, Canada.

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