1). Advanced fibrosis stages (F3) increased from 0% at 20 years to 1.5% at 25 years and 1.5% at 35 years after infection. The proportion of patients with clinical signs of liver cirrhosis increased from 0.4% at 20 years to 0.5% at 25 years and 7.8% at 35 years after infection (P = 1.1 × 10−35; 20 years after infection versus 25 years after infection: P = 0.783; 25 years after infection versus 35 years after infection: P = 1.9 × CP-673451 research buy 10−29). Transient elastography (Supporting Fig. 2) and liver biopsies (Supporting Fig. 3) further confirmed that the long-term

outcome in this otherwise healthy young female cohort depended on the natural respectively treatment-induced course of HCV infection. Characteristics of women with advanced (F3) fibrosis, respectively, end-stage liver cirrhosis, compared to women without significant liver disease at 35 years after infection, are shown in Table 2. Factors associated with fibrosis and cirrhosis progression in the univariate analysis are depicted in Table

3. In the multivariate analysis, cirrhosis was associated with the BMI (OR, 1.125; 95% CI: 1.038-1.22; P = 0.004), spontaneous HCV elimination (OR, 0.05; 95% CI: 0.006-0.365; Galunisertib solubility dmso P = 0.003), and SVR (OR, 0.05; 95% CI: 0.019-0.09; P = 0.019). Further analysis confirmed significant differences in the disease progression in relation to the individual BMI of the patients at 35 years after infection (Fig. 3). Figure 4 summarizes the overall mortality of the German HCV (1b)-contaminated anti-D cohort at 35 years after infection in relation to the HCV infection status. In total, 30 patients (4.2%) of the actual study cohort died since 1979. In the group of HCV RNA-negative patients, 10 (3.0%) died, among them 2 who were classified as inoculated patients without hepatitis, 7 with spontaneous recovery from HCV infection, and

1 with SVR after treatment who died of a malignant disease other than HCC. In the group of HCV RNA-positive patients, 20 (5.3%) died, among them 9 (1.3%) who succumbed to definite HCV-related end-stage liver complications, such as esophageal variceal bleeding or hepatic coma. The remaining 11 HCV RNA-positive patients (1.5%) died from additional non-liver-related causes, such as cardiac failure, nonliver malignancy, apoplectic insult, or accident. Kaplan-Meyer’s Tryptophan synthase analysis was used to describe overall survival probability in relation to individual HCV infection status at 35 years after infection. Survival was significantly improved in patients showing SVR after antiviral treatment, compared to chronic viremic treatment-naïve patients (Fig. 5A). The highest mortality was observed in the group of non-SVR patients who failed to clear the virus after antiviral therapy (P = 0.027). Irrespective of HCV infection status, obese and overweight patients showed higher cirrhosis rates (P = 4.7 × 10−8; P = 0.