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

Adrian M. Di Bisceglie, Anne M. Stoddard, Jules L. Dienstag, Mitchell L. Shiffman, Leonard B. Seeff, Herbert L. Bonkovsky, Chihiro Morishima, Elizabeth C. Wright, Kristin K. Snow, William M. Lee, Robert J. Fontana, Timothy R. Morgan, Marc G. Ghany

Research output: Contribution to journalArticlepeer-review

56 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1100-1108
Number of pages9
Issue number4
StatePublished - Apr 2011

ASJC Scopus subject areas

  • Hepatology


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