Peginterferon Alfa-2a and ribavirin in patients with chronic hepatitis C who have failed prior treatment, ,

doi:10.1053/j.gastro.2004.01.014

Gastroenterology

Volume 126, Issue 4, April 2004, Pages 1015-1023

https://doi.org/10.1053/j.gastro.2004.01.014 Get rights and content

Abstract

$Background & Aims:$ The most effective therapy currently available for treatment of chronic hepatitis C virus (HCV) is the combination of peginterferon and ribavirin. This study evaluated the effectiveness of this treatment in patients who were nonresponders to previous interferon-based therapy. $Methods:$ The first 604 patients enrolled in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) Trial were evaluated. All were HCV RNA positive, previous nonresponders to interferon, with or without ribavirin, and had bridging fibrosis or cirrhosis on liver biopsy (Ishak fibrosis stage 3–6). Patients were retreated with peginterferon alfa-2a 180 μg/wk plus ribavirin 1000–1200 mg/day. Those with no detectable HCV RNA in serum at week 20 continued treatment for a total of 48 weeks and were then followed for an additional 24 weeks. $Results:$ Thirty-five percent of patients had no detectable HCV RNA in serum at treatment week 20, and 18% achieved sustained virologic response (SVR). Factors associated with an SVR included previous treatment with interferon monotherapy, infection with genotypes 2 or 3, a lower AST:ALT ratio, and absence of cirrhosis. Reducing the dose of ribavirin from ≥80% to ≤60% of the starting dose during the first 20 weeks of treatment was associated with a decline in SVR from 21% to 11% (P ≤ 0.05). In contrast, reducing the dose of peginterferon or reducing ribavirin after week 20, when HCV RNA was already undetectable, did not significantly affect SVR. $Conclusions:$ Selected nonresponders to previous interferon-based therapy can achieve SVR following retreatment with peginterferon alfa-2a and ribavirin.

Section snippets

Patients and methods

The HALT-C trial is a prospective, randomized, controlled study of long-term peginterferon therapy vs. no treatment for patients with chronic hepatitis C and advanced fibrosis or cirrhosis who failed to achieve an SVR following treatment with peginterferon and ribavirin. The study is being conducted at 10 clinical centers in the United States. Randomization, data collection, and analyses are performed by a central data-coordinating center (New England Research Institutes, Watertown, MA), and

Patient population

The study population consisted of the first 604 patients enrolled in the lead-in phase of the HALT-C trial between August 2000 and December 2001. The demographic and clinical characteristics of these patients are summarized in Table 1. All patients were nonresponders to their most recent course of interferon-based therapy. Sixty-four percent had been previously treated with interferon and ribavirin. The mean age of the patients was 49.9 years; 73% were male and 77% white. The average estimated

Discussion

Impressive gains have been made in the treatment of chronic hepatitis C virus infection during the past decade. The currently accepted primary end point of therapy is an SVR. With the combination of peginterferon and ribavirin, this can be achieved in 40%–45% of patients with HCV genotype 1 and approximately 80% of patients with genotype 2 or 3 infection.1, 2 These are significantly improved outcomes when compared with those achieved with standard interferon monotherapy or interferon and

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^☆: Supported by the National Institute of Diabetes and Digestive and Kidney Diseases (contract numbers are listed below); the National Institute of Allergy and Infectious Diseases (NIAID), the National Cancer Institute, the National Center for Minority Health and Health Disparities, and by General Clinical Research Center grants from the National Center for Research Resources, National Institutes of Health (grant numbers are listed below); and Hoffmann-La Roche, Inc., through a Cooperative Research and Development Agreement (CRADA) with the National Institutes of Health.

¹: This is publication number 1 from the HALT-C Trial Group.

²: Financial relationships of the authors with Hoffman-La Roche, Inc., are as follows: M.L. Shiffman is a consultant, is on the speaker’s bureau, and receives research support; A.M. Di Bisceglie is on the scientific advisory board and receives research support; K.L. Lindsay receives research support; C. Morishima is the recipient of an educational program gift; E.C. Wright has no financial relationship; G.T. Everson is a consultant, is on the speaker’s bureau, and receives research support; A.S. Lok is a consultant and receives research support; T.R. Morgan is on the speaker’s bureau; H.L. Bonkovsky is on the Speaker’s Bureau and receives research support; W.M. Lee is on the speaker’s bureau and receives research support; J.L. Dienstag is on the speaker’s bureau; M.G. Ghany has no financial relationship; Z.D. Goodman has no financial relationship; and J.E. Everhart has no financial relationship. In addition, M.L. Shiffman receives support from Schering Plough and InterMune; A.M. Di Bisceglie receives support from Schering Plough, Gilead Sciences, Idenix, SciClone Pharmaceuticals, MDS Nordian, InterMune, Chiron, and Novartis; G.T. Everson receives support from Schering, Amgen, InterMune, OrthoBiotech, Novo Nordisk, and Metabolic Solutions; and T.R. Morgan receives support from Schering Plough.

³: In addition to the authors of this manuscript, the following individuals were instrumental in the planning, conduct and/or care of patients enrolled in this study at each of the participating institutions as follows: University of Massachusetts Medical Center, Worcester, MA: (Contract N01-DK-9-2326) Savant Mehta, M.D., Maureen Cormier, R.N.; University of Connecticut Health Center, Farmington, CT: (Grant M01RR-06192) Michelle Kelley, R.N., ANP; Saint Louis University School of Medicine, St. Louis, MO: (Contract N01-DK-9-2324) Bruce Bacon, M.D., Brent Tetri, M.D., Judith Thompson, R.N.; Massachusetts General Hospital, Boston, MA: (Contract N01-DK-9-2319, Grant M01RR-01066) Raymond T. Chung, M.D., Andrea E. Reid, M.D.; University of Colorado School of Medicine, Denver, CO: (Contract N01-DK-9-2327, Grant M01RR-00051) Marcelo Kugelmas, M.D., Jennifer DeSanto, R.N., Brenda Martin, R.N., Carol McKinley, R.N.; University of California-Irvine, Irvine, CA: (Contract N01-DK-9-2320, Grant M01RR-00827); Muhammad Sheikh, M.D., M Mazen Jamal, M.D., John Hoefs, M.D. (June 1999 to December 2000), Choon Park, R.N.; University of Texas Southwestern Medical Center, Dallas, TX: (Contract N01-DK-9-2321, Grant M01RR-00633) Peter F. Malet, M.D., Rivka Elbein, R.N., Nicole Crowder, LVN; University of Southern California, Los Angeles, CA: (Contract N01-DK-9-2325, Grant M01RR-00043) Maurizio Bonacini, M.D., Susan L. Milstein, R.N., Carol B. Jones, R.N.; University of Michigan Medical Center, Ann Arbor, MI: (Contract N01-DK-9-2323, Grant M01RR-00042) Robert J. Fontana, M.D., Amy C. Randall-Ray, MS, RD, CCRC, Pamela A. Richtmyer, LPN, CCRC; Virginia Commonwealth University Health System, Richmond, VA: (Contract N01-DK-9-2322, Grant M01RR-00065) Richard K. Sterling, M.D., Charlotte Hofmann, R.N., Paula Patrick, R.N.; National Institute of Diabetes and Digestive and Kidney Diseases, Liver Disease Section, Bethesda, M.D.: T. Jake Liang, M.D., Yoon Park, R.N., Brenda Cunningham, R.N.; National Institute of Diabetes and Digestive and Kidney Diseases, Division of Digestive Diseases and Nutrition, Bethesda, MD: Leonard B. Seeff, M.D., Patricia R Robuck, Ph.D., Jay H. Hoofnagle, M.D.; University of Washington, Seattle, WA: (Contract N01-DK-9-2318) David R. Gretch, M.D., Ph.D., Minjun Chung, B.S., ASCP, Sarah Chang, B.S., ASCP; and New England Research Institutes, Watertown, MA: (Contract N01-DK-9-2328) Maggie McCarthy, MCI, MPH, Margaret C. Bell, R.N., M.S., MPH, CS, Latha Padmanabhan, M.Sc., M.S., Kristin K. Snow, M.Sc., Sc.D.; Roche Laboratories, Inc., Nutley, NJ: Raymond S. Koff, M.D., Michael J. Brunda, Ph.D.

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Clinical-liver, pancreas, and biliary tractPeginterferon Alfa-2a and ribavirin in patients with chronic hepatitis C who have failed prior treatment1, 2, 3 1 2 3☆,

Abstract

Section snippets

Patients and methods

Patient population

Discussion

Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis Ca randomised trial

Lancet

Peginterferon alfa-2a plus ribavirin for patients with chronic hepatitis C virus infection

N Engl J Med

Peginterferon alfa-2a in patients with chronic hepatitis C

N Engl J Med

A randomized, double-blind trial comparing peginterferon alfa-2b to interferon alfa-2b as initial treatment for chronic hepatitis C

Hepatology

Peginterferon alfa-2a in patients with chronic hepatitis C and cirrhosis

N Engl J Med

Interferon and ribavirin vs interferon alone in the re-treatment of chronic hepatitis C previously nonresponsive to interferona meta-analysis of randomized trials

JAMA

Interferon alfa-2b alone or in combination with ribavirin the treatment of relapse of chronic hepatitis C

N Engl J Med

Management of interferon therapy non-responders

Clin Liver Dis

Retreatment of patients with chronic hepatitis C

Hepatology

The long-term pathological evolution of chronic hepatitis C

Hepatology

Clinical-liver, pancreas, and biliary tract
Peginterferon Alfa-2a and ribavirin in patients with chronic hepatitis C who have failed prior treatment1, 2, 3 ¹ ² ³☆,