The hepatitis C virus infects over 170 million people worldwide and is a leading cause of cirrhosis and hepatocellular carcinoma. The severity of chronic hepatitis C is highly variable among patients and over time. Some individuals show a mild indolent clinical course for decades, others rapidly progress to end-stage liver disease, whereas about 20–30% of cases remain asymptomatic with normal serum alanine aminotransferase levels lifelong. According to the Italian guidelines,BAY-588 the definition of an anti-HCV carrier with persistently normal ALT serum values applies to a subject with at least 9 consecutive ALT normal values observed at two-monthly intervals over an 18- month observation period and identifies a subclinical form of CHC. The majority of carriers with PNALT show histological evidence of necroinflammation and fibrosis, but the liver lesions are clearly less severe than those observed in subjects with abnormal ALT. Most of them show a slow fibrosis progression, but liver cirrhosis may develop after an ALT flare-up has occurred. Several factors have been found to be linked to the progression and severity of CHC, including virus-related and host factors, co-morbidities, and lifestyle factors. Moreover,PDD00017273 the data from a recent study suggested the involvement in CHC of the rs35761398 variant of the CNR2 gene encoding for CB2, since the CB2-63 QQ variant was associated with more severe necroinflammation in anti-HCV-positive patients with abnormal ALT. Instead, only a few published data on factors possibly associated with the subclinical form of chronic HCV infection are available at present. The present paper analyzes the role of CB2 variants in 53 consecutive HCV carriers with PNALT in comparison with 200 consecutive patients with abnormal ALT. All 253 cases underwent complete physical examination, liver ultrasound scan, liver function tests, assessment of triglycerides, cholesterol, blood cell counts, alpha-fetoprotein and HBV, HCV, hepatitis delta virus and HIV serum markers. All patients enrolled were asymptomatic, negative for anti-HIV, HBsAg and anti-HDV.