8 years (3.5 years plus a 3-month window around the final study milestone) after randomization when patients were being treated actively with peginterferon or followed on no therapy. The remaining 69 deaths

(57%) occurred after the conclusion of the randomized phase when all patients were being followed but no study treatment was offered. More deaths occurred in patients in the cirrhosis stratum (n = 80) selleck chemicals llc than the fibrosis stratum (n = 42), and the survival distributions differed significantly (P < 0.0001, Fig. 2). Seven-year cumulative mortality rates were more than two times higher in patients in the cirrhosis stratum than the fibrosis stratum (27% versus 11%), which is equivalent to average annual death rates of 3.9% in the cirrhosis and 1.5% in the fibrosis stratum. Similarly, the distributions of the combined outcome of death or liver transplantation differed significantly in the learn more two strata (P < 0.0001), resulting in a 7-year cumulative rate of 36% (n = 120) in the cirrhosis stratum compared to 16% (n = 66) in the fibrosis stratum. Of the 122 deaths, 76 were categorized as liver-related (62%) and 46 as nonliver-related (38%)

(Table 1). The majority of liver-related deaths were attributable directly to complications of endstage chronic hepatitis C or HCC; however, eight deaths (11%) were attributed to liver disease even though other potentially fatal medical conditions were present (e.g., cancer other than HCC, septicemia, influenza and pneumonia, or accident). The proportion of liver-related deaths was slightly higher among patients in the cirrhosis stratum compared to those in the fibrosis stratum, but this difference was not statistically significant (65% versus 57%, P = 0.39). Overall, as well as within each stratum, the death rate was higher in patients in the treatment group compared to patients in the control group (P = 0.049, Fig. 3). The cumulative 7-year death rate was 20% in treated and 15% in control patients. The mortality rates began to separate after 3 years of therapy and continued to separate during

the 2 to 3 years of follow-up observation find more after treatment. The difference in mortality rates between patients in the treatment and control groups was statistically significant in the fibrosis stratum (P = 0.01) but was not significant in the cirrhosis stratum (P = 0.49) (Fig. 4A). In the fibrosis stratum, at the end of the randomized phase (3.8 years) the cumulative mortality rate was 5.0% in patients in the treatment group compared to 1.9% in patients in the control group (P = 0.04).6 By 7 years these rates increased to 14% and 7%, respectively. In the cirrhosis stratum the mortality rates in patients in the treatment and control groups were 9.1% and 8.4% at the end of the randomized phase6 and, during follow-up observation, increased to 28% and 26%. In the fibrosis stratum, as in the group overall, the major separation of mortality rates occurred after 3 years of treatment.