CHRONIC VIRAL HEPATITIS: FACTORS INFLUENCING LIVER DISEASE PROGRESSION IN CHRONIC HEPATITIS B AND RESPONSE TO THERAPY IN CHRONIC HEPATITIS C

My activity was focused on two main research lines on chronic viral hepatitis: 1. Chronic Hepatitis B Virus infection: Study of the clinical course and prognostic factors of chronic hepatitis B; 2. Chronic Hepatitis C Virus infection: Study of the role of insulin resistance, among other factors, as a predictor of SVR in CHC patients. PROGRESSION TO CIRRHOSIS, HEPATOCELLULAR CARCINOMA AND LIVER RELATED MORTALITY IN CHRONIC HEPATITIS B PATIENTS IN ITALY Background: The natural history of chronic hepatitis B is variable. We evaluated some risk factors for cirrhosis, hepatocellular carcinoma and liver-related mortality in Italian patients with chronic hepatitis B. Methods: A cohort of 105 untreated patients with chronic hepatitis B without cirrhosis at diagnosis was followed prospectively for a mean period of 23 years. Clinical, histological and ultrasound examinations, biochemical and virologic tests, and causes of death were analyzed. Results: Forty two (40%) patients became inactive carriers and 63 (60%) showed persistent alanine aminotransferase elevation: 13 (13%) associated with HBeAg persistence, 35 (33%) with detectable serum HBV-DNA but HBeAg-negative, 11 (10%) with concurrent virus infection and 4 (4%) with non alcoholic fatty liver disease. Cirrhosis incidence was 1.56/100 person-years. Older age and sustained HBV replication predicted cirrhosis occurrence independently. Hepatocellular carcinoma incidence was 2.1/100 person-years in patients who developed cirrhosis and 0.06 in those who did not. Cirrhosis occurrence was associated with an increased risk of hepatocellular carcinoma (Hazard ratio 20.4, 95% confidence interval 2.54-167.5) and liver-related death (16.5, 2.0-138.8). Conclusions: In Italian patients with chronic hepatitis B cirrhosis strongly predicts hepatocellular carcinoma occurrence and disease-related mortality, thus indicating that early antiviral treatment should be instituted before cirrhosis occurrence. POST-LOAD INSULIN RESISTANCE DOES NOT PREDICT VIROLOGICAL RESPONSE TO TREATMENT OF CHRONIC HEPATITIS C PATIENTS WITHOUT THE METABOLIC SYNDROME Background and aim: The role of insulin resistance (IR) in predicting virological response to therapy of chronic hepatitis C is debated. We assessed the association between basal (defined as Homeostasis Model Assessment [HOMA-IR] >2) and post-load IR (as oral glucose insulin sensitivity [OGIS] index < 9.8 mg/kg/min) with the rapid and sustained virological responses in chronic hepatitis C. Methods: Observational prospective study of 124 treatment-naïve patients with chronic hepatitis C not fulfilling the metabolic syndrome criteria, adherent to a standard treatment with pegylated interferon alpha plus ribavirin. Results: IR was detected in 50% (by HOMA-IR) and 29% (by OGIS) of patients. Independent predictors of rapid virologic response were HCV genotype 2 (OR 5.66; 95% CI 1.88-17.01), HCV genotype 3 (OR 5.23; 95% CI 1.84-14.84) and lower basal ferritin levels (OR 0.99; 95% CI 0.993-0.998). Independent predictors of sustained virologic response were HCV genotype 2 (OR 19.54; 95% CI 2.29-166.41) and HCV genotype 3 (OR 3.24; 95% CI 1.10-9.58). Rapid virologic response was by itself predictive of sustained virologic response (OR 40.90; 95% CI 5.37-311.53). Conclusions: IR, by both static and dynamic methods, does not predict rapid or sustained virologic response in chronic hepatitis C patients without the metabolic syndrome.