Large databases of consecutive patients followed for sufficiently long periods are needed to establish the rates, chronology, and hierarchy of complications of cirrhosis as well as the importance of other potential causes of liver disease. In accordance with this goal, a cohort of patients with compensated cirrhosis due to hepatitis C virus (HCV) was followed for 17 years. Two hundred and fourteen HCV RNA-seropositive patients with Child-Pugh class A cirrhosis who had no previous clinical decompensation were prospectively recruited and followed up with periodic clinical and abdominal ultrasound examinations. During 114 months (range 1-199), hepatocellular carcinoma (HCC) developed in 68 (32%), ascites in 50 (23%), jaundice in 36 (17%), upper gastrointestinal bleeding in 13 (6%), and encephalopathy in 2 (1%), with annual incidence rates of 3.9%, 2.9%, 2.0%, 0.7%, and 0.1%, respectively. Clinical status remained unchanged in 154 (72%) and progressed to Child-Pugh class B in 45 (21%) and class C in 15 (7%). HCC was the main cause of death (44%) and the first complication to develop in 58 (27%) patients, followed by ascites in 29 (14%), jaundice in 20 (9%), and upper gastrointestinal bleeding in 3 (1%). The annual mortality rate was 4.0% per year and was higher in patients with other potential causes of liver disease than in those without them (5.7% vs. 3.6%; P ‫؍‬ .04). In conclusion, hepatitis C-related cirrhosis is a slowly progressive disease that may be accelerated by other potential causes of liver disease. HCC was the first complication to develop and the dominant cause for increased mortality.

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Hepatitis C virus (HCV) infection is associated with insulin resistance (IR), which is a condition known to influence the progression of liver fibrosis and the response to pegylated interferon (PEG-IFN)/ribavirin (RBV) therapy. We aimed to assess whether a sustained virological response (SVR) after antiviral therapy prevents the development of IR in the long term. Members of the Milan Safety Tolerability study cohort, who received PEGIFNa2a/RBV or PEG-IFNa2b/RBV, underwent a homeostasis model assessment (HOMA) at the baseline and 24 months after treatment completion. For all patients (n 5 431), a liver biopsy sample was scored for grading, staging (Ishak), and steatosis. At the baseline, IR (HOMA value > 2) was detected in 48 patients (12%), and it was associated with body weight (P 5 0.03), an HCV load < 0.6 3 10 6 IU/L (P 5 0.006), fibrosis staging ! 4 (P 5 0.01), and moderate to severe steatosis (P 5 0.03). IR did not influence the rates of endof-treatment response (75% versus 69%, P 5 0.4), SVR (63% versus 60%, P 5 0.8), or relapse (19% versus 24%, P 5 0.5). After treatment, IR developed in 49 of the 384 nondiabetic patients (14%). Although the mean baseline and posttreatment HOMA values were similar in SVR patients (1.11 6 0.8 versus 1.18 6 1.1, P 5 0.25), patients experiencing treatment failure showed a significant increase in the mean HOMA value at the followup visit (1.20 6 0.85 versus 1.49 6 1.3, P 5 0.007), and there was an increased rate of de novo IR in non-SVR patients versus SVR patients (17% versus 7%, P 5 0.007). According to a logistic regression analysis, treatment failure (odds ratio 5 2.81, 95% confidence interval 5 1.39-5.67, P 5 0.004) and a 10% body mass index increase (odds ratio 5 6.42, 95% confidence interval 5 1.69-24.3, P 5 0.006) were significantly associated with the development of de novo IR. Conclusion: In nondiabetic patients with chronic HCV, the achievement of SVR with PEG-IFN and RBV prevents the development of de novo IR.