title: Excess mortality in patients with advanced chronic hepatitis C treated with long-term peginterferon.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine, St. Louis, MO, USA. dibiscam@slu.edu
authors.forename: Adrian M
authors.initials: AM
authors.lastname: Di Bisceglie
authors.forename: Anne M
authors.initials: AM
authors.lastname: Stoddard
authors.forename: Jules L
authors.initials: JL
authors.lastname: Dienstag
authors.forename: Mitchell L
authors.initials: ML
authors.lastname: Shiffman
authors.forename: Leonard B
authors.initials: LB
authors.lastname: Seeff
authors.forename: Herbert L
authors.initials: HL
authors.lastname: Bonkovsky
authors.forename: Chihiro
authors.initials: C
authors.lastname: Morishima
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Wright
authors.forename: Kristin K
authors.initials: KK
authors.lastname: Snow
authors.forename: William M
authors.initials: WM
authors.lastname: Lee
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Fontana
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Morgan
authors.forename: Marc G
authors.initials: MG
authors.lastname: Ghany
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000009:adverse effects*; D002423:Cause of Death; D018450:Disease Progression; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000401:mortality*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects*; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000401:mortality*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000009:adverse effects*; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a