Peginterferon Alfa-2a in Patients with Chronic Hepatitis C and Cirrhosis

E. Jenny Heathcote, M.D., Mitchell L. Shiffman, M.D., W. Graham E. Cooksley, M.D., Geoffrey M. Dusheiko, M.D., Samuel S. Lee, M.D., Luis Balart, M.D., Robert Reindollar, M.D., Rajender K. Reddy, M.D., Teresa L. Wright, M.D., Amy Lin, M.S., Joseph Hoffman, M.D., and Jean De Pamphilis, Ph.D.

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.).