On a specific home-made questionnaire none stated ongoing intravenous drug addiction at admission. Alcohol abuse was defined as the consumption of alcohol exceeding 30 g per day for females and 40 g per day for males in the last 6 months; the patient’s statements regarding intravenous drug addiction and alcohol abuse were corroborated by the patient’s family and by serum/urine tests in uncertain cases. Liver biopsy was performed for 186 patients. The liver biopsy was proposed for all patients in the abnormal ALT group,CATPB but it was not performed for 29 because of refusal in 20 cases and contraindication in 9. In the PNALT group the liver biopsy was advised for the 18 patients aged 50 to 65 years with genotype 1 and was performed only for 15 of these because of refusal by the remaining 3 patients. Liver specimens were fixed in formalin, embedded in paraffin and stained with hematoxylineosin and Masson’s trichrome stain. In each case, the liver specimens were more than 2 cm in length and had more than 11 portal tracts. Liver biopsies were examined by a pathologist who, unaware of the clinical and laboratory data,BTI-A-404 used the Ishak’s scoring system to grade necroinflammation and fibrosis. To assess liver steatosis we used a home-made scoring system obtained with a partial modification of Kleiner’s scoring system for nonalcoholic fatty liver diseases, extensively reported in previously published papers. This study analyzed the role of a functional polymorphism of the cannabinoid receptor type 2 in a cohort of 253 patients with HCV chronic infection and found the CB2-63 QQ variant independently associated with the PNALT status. Besides the CB2-63 QQ variant, the multivariate analysis identified another three factors independently associated with the PNALT status: HCV genotype 2, an older age and a lower BMI. HCV genotype 2 and a lower BMI have been suggested as independent predictors of PNALT in previous studies, and confirmed in the present investigation. Instead, this is the first time the CB2-63 QQ variant and an older age have been cited as independent predictors of the PNALT status.