Interferon Alfa-2b Alone or in Combination with Ribavirin as Initial Treatment for Chronic Hepatitis C

The New England Journal of Medicine — November 19, 1998 — Volume 339, Number 21

John G. McHutchison, Stuart C. Gordon, Eugene R. Schiff, Mitchell L. Shiffman, William M. Lee, Vinod K. Rustgi, Zachary D. Goodman, Mei-Hsiu Ling, Susannah Cort, Janice K. Albrecht, for the Hepatitis Interventional Therapy Group

Abstract

Background. Only 15 to 20 percent of patients with chronic Hepatitis C have a sustained virologic response to interferon therapy. We compared the efficacy and safety of recombinant interferon alfa-2b alone with those of a combination of interferon alfa-2b and ribavirin for the initial treatment of patients with chronic Hepatitis C.

Methods. We randomly assigned 912 patients with chronic Hepatitis C to receive standard-dose interferon alfa-2b alone or in combination with ribavirin (1000 or 1200 mg orally per day, depending on body weight) for 24 or 48 weeks. Efficacy was assessed by measurements of serum Hepatitis C virus (HCV) RNA and serum aminotransferases and by liver biopsy.

Results. The rate of sustained virologic response (defined as an undetectable serum HCV RNA level 24 weeks after treatment was completed) was higher among patients who received combination therapy for either 24 weeks (70 of 228 patients, 31 percent) or 48 weeks (87 of 228 patients, 38 percent) than among patients who received interferon alone for either 24 weeks (13 of 231 patients, 6 percent) or 48 weeks (29 of 225 patients, 13 percent) (P<0.001 for the comparison of interferon alone with both 24 weeks and 48 weeks of combination treatment). Among patients with HCV genotype 1 infection, the best response occurred in those who were treated for 48 weeks with interferon and ribavirin. Histologic improvement was more common in patients who were treated with combination therapy for either 24 weeks (57 percent) or 48 weeks (61 percent) than in those who were treated with interferon alone for either 24 weeks (44 percent) or 48 weeks (41 percent). The drug doses had to be reduced and treatment discontinued more often in patients who were treated with combination therapy.

Conclusions. In patients with chronic Hepatitis C, initial therapy with interferon and ribavirin was more effective than treatment with interferon alone. (N Engl J Med 1998;339:1485-92.)

Source Information

From the Division of Gastroenterology-Hepatology, Scripps Clinic and Research Foundation, La Jolla, Calif. (J.G.M.); William Beaumont Hospital, Royal Oak, Mich. (S.C.G.); University of Miami, Miami (E.R.S.); Medical College of Virginia, Richmond (M.L.S.); University of Texas Southwestern Medical Center, Dallas (W.M.L.); Georgetown University, Washington, D.C. (V.K.R.); Armed Forces Institute of Pathology, Washington, D.C. (Z.D.G.); and Schering-Plough Research Institute, Kenilworth, N.J. (M.-H.L., S.C., J.K.A.). Address reprint requests to Dr. McHutchison at Scripps Clinic and Research Foundation, Division of Gastroenterology-Hepatology (203N), 10666 N. Torrey Pines Rd., La Jolla, CA 92037.

The other members of the Hepatitis Interventional Therapy Group are listed in the Appendix.

In addition to the authors, the members of the Hepatitis Interventional Therapy Group include the following: L. Balart, Center for Digestive Diseases, New Orleans; K. Benner, Oregon Health Sciences University, Portland; M. Black, Temple University, Philadelphia; S. Caldwell, University of Virginia, Charlottesville; R. Carithers, Jr., University of Washington, Seattle; W. Carey, Cleveland Clinic Foundation, Cleveland; H. Conjeevaram, University of Chicago, Chicago; G. Davis, University of Florida, Gainesville; A. DiBisceglie and B. Bacon, Saint Louis University, St. Louis; J. Dienstag, Massachusetts General Hospital, Boston; D. Dietrich, New York; J. Donovan, University of Nebraska, Omaha; G. Everson, University of Colorado, Denver; R. Gish, California Pacific Medical Center, San Francisco; N. Gitlin, Emory University, Atlanta; J. Gross, Jr., Mayo Clinic, Rochester, Minn.; J. Hoefs, University of California at Irvine, Orange; I. Jacobson, New York; D. Jensen, Rush-Presbyterian-St. Luke’s Medical Center, Chicago; P. King, University of Missouri, Columbia; R. Koff, Metro West Medical Center, Framingham, Mass.; E. Krawitt, University of Vermont, Burlington; D. LaBrecque, University of Iowa Hospital and Clinic, Iowa City; K. Lindsay, University of Southern California, Los Angeles; A. Lok, University of Michigan, Ann Arbor; P. Martin, University of California at Los Angeles, Los Angeles; T. Morgan, Veterans Affairs Medical Center, Long Beach, Calif.; R. Perrillo, Ochsner Clinic, New Orleans; J. Rakela, University of Pittsburgh, Pittsburgh; R. Reindollar, Charlotte Clinic for Gastrointestinal and Liver Diseases, Charlotte, N.C.; L. Rossaro, University of New Mexico, Albuquerque; L. Seeff, Veterans Affairs Medical Center, Washington, D.C.; L. Smith, St. Michael’s Hospital, Newark, N.J.; C. Smith, Minnesota Clinical Research Center, St. Paul; C. Tamburro, University of Louisville, Louisville, Ky.; J. Vierling, Cedars-Sinai Medical Center, Los Angeles; T. Wright, University of California at San Francisco, San Francisco.