Excess mortality in patients with advanced chronic hepatitis C treated with long-term peginterferon

Authors

  • Adrian M. Di Bisceglie,

    Corresponding author
    1. From the Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine, St. Louis, MO
    • Department of Internal Medicine, Saint Louis University School of Medicine; 1402 South Grand Blvd., St. Louis, MO 63104
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  • Anne M. Stoddard,

    1. New England Research Institutes, Watertown, MA
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  • Jules L. Dienstag,

    1. Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA
    2. Department of Medicine, Harvard Medical School, Boston, MA
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  • Mitchell L. Shiffman,

    1. Liver Institute of Virginia, Bon Secours Health System, Newport News, VA
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  • Leonard B. Seeff,

    1. Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD
    2. Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD
    Current affiliation:
    1. Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD
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  • Herbert L. Bonkovsky,

    1. Department of Medicine, University of Connecticut Health Center, Farmington, CT
    2. Carolinas Medical Center,Charlotte, NC
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  • Chihiro Morishima,

    1. Division of Virology, Department of Laboratory Medicine, University of Washington, Seattle, WA
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  • Elizabeth C. Wright,

    1. Office of the Director, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD
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  • Kristin K. Snow,

    1. New England Research Institutes, Watertown, MA
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  • William M. Lee,

    1. Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX
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  • Robert J. Fontana,

    1. Division of Gastroenterology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI
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  • Timothy R. Morgan,

    1. Division of Gastroenterology, University of California, Irvine, Irvine, CA
    2. Gastroenterology Service, VA Long Beach Healthcare System, Long Beach, CA
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  • Marc G. Ghany,

    1. Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD
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  • for the HALT-C Trial Group


  • This is publication #65 of the HALT-C Trial.

  • Conflicts of Interest: Financial relationships of the authors with Hoffmann-La Roche, Inc. (now Genentech), are as follows: A.M. Di Bisceglie is a consultant and receives research support; M.L. Shiffman is a consultant on the speaker's bureau and receives research support; W.M. Lee receives research support; R.J. Fontana is on the speaker's bureau; and T.R. Morgan receives research support.

    Dr. Stoddard owns stock in Johnson & Johnson, Bristol-Myers Squibb, and Proctor and Gamble.

    Dr. Bonkovsky consults for and advises Boehringer-Ingelheim and Novartis and received grants from Novartis and Vertex.

    Dr. Morishima consults for Vertex and Merck.

    Dr. Morgan received grants from Merck, Genentech, and Vertex. He consults for and advises Vertex.

Abstract

Chronic hepatitis C virus infection can cause chronic liver disease, cirrhosis and liver cancer. The Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial was a prospective, randomized controlled study of long-term, low-dose peginterferon therapy in patients with advanced chronic hepatitis C who failed to respond to a previous course of optimal antiviral therapy. The aim of this follow-up analysis is to describe the frequency and causes of death among this cohort of patients. Deaths occurring during and after the HALT-C Trial were reviewed by a committee of investigators to determine the cause of death and to categorize each death as liver- or nonliver-related and as related or not to complications of peginterferon. Rates of liver transplantation were also assessed. Over a median of 5.7 years, 122 deaths occurred among 1,050 randomized patients (12%), of which 76 were considered liver-related (62%) and 46 nonliver-related (38%); 74 patients (7%) underwent liver transplantation. At 7 years the cumulative mortality rate was higher in the treatment compared to the control group (20% versus 15%, P = 0.049); the primary difference in mortality was in patients in the fibrosis compared to the cirrhosis stratum (14% versus 7%, P = 0.01); comparable differences were observed when liver transplantation was included. Excess mortality, emerging after 3 years of treatment, was related largely to nonliver-related death; liver-related mortality was similar in the treatment and control groups. No specific cause of death accounted for the excess mortality and only one death was suspected to be a direct complication of peginterferon. Conclusion: Long-term maintenance peginterferon in patients with advanced chronic hepatitis C is associated with an excess overall mortality, which was primarily due to nonliver-related causes among patients with bridging fibrosis. (HEPATOLOGY 2011;)

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