Deaths in nine patients were categorized as “other” and included trauma (3), intoxication or overdose (2), pneumonia Dasatinib and respiratory failure (2), ischemic colitis (1), and status epilepticus (1). Special attention was given to whether peginterferon therapy was a direct contributing factor or cause of death in the treatment group. Most deaths in the treated group occurred well after peginterferon was stopped,

with only eight patients dying within 2 months of receiving peginterferon (11% of deaths in the treatment group). Independent assessment identified only one death as probably peginterferon-related. A 52-year-old man with chronic hepatitis C and advanced fibrosis had an episode of severe Staphylococcusaureus septicemia followed by multiorgan failure and death within a week of a last injection of peginterferon and after almost 2 years of maintenance therapy. The overall death rate in this cohort of patients Staurosporine datasheet with advanced chronic hepatitis C was remarkably high. Of the 1,050 patients, 18% died or underwent liver

transplantation during a median follow-up time of 5.7 years, and approximately two-thirds of deaths (62%) could be attributed to endstage liver disease or HCC. Among patients with cirrhosis at baseline, the rate of death or liver transplantation was particularly high (7-year cumulative rate 36%, annualized rate 5.2%). Among acetylcholine those with fibrosis without cirrhosis at baseline, rates of all outcomes were less frequent, and the overall rate of death or liver transplantation was lower (7-year cumulative rate 16%, annualized rate 2.2%). Several prospective studies have shown that chronic HCV infection is associated with an increased mortality rate,10-17 but the degree of this increase has been difficult to ascertain.18 The mortality rates observed

in the HALT-C Trial cohort were similar to those reported in similar cohorts from other areas of the world. For example, in a recent systematic analysis of natural history studies, the annual rate of death or transplantation among patients with compensated cirrhosis associated with hepatitis C averaged 4.6%.19 In comparison, the annual mortality rate among HALT-C Trial patients in the compensated cirrhosis stratum was 3.9%, and the annual rate of death or transplantation in this stratum was 5.2%. Although the HALT-C Trial did not include uninfected control patients for comparison, the high mortality rates observed, particularly in the cirrhosis stratum, confirm the poor outcomes among patients with chronic hepatitis C and advanced hepatic fibrosis. The unique finding of higher mortality among patients in the peginterferon-treatment group noted in the initial report of the randomized phase of the HALT-C Trial6 persisted when analyzed with a longer period of follow-up, the focus of the current analysis.