Daily cannabis use: A novel risk factor of steatosis severity in patients with chronic hepatitis C

Background & Aims: Steatosis is highly prevalent in patients with chronic hepatitis C (CHC) and has been reported to increase fibrosis and reduce the rate of viral eradication. Two recent studies indicate that endocannabinoids promote experimental steatosis via activation of hepatic CB1 receptors. We therefore investigated the impact of cannabis smoking on steatosis severity during CHC. Methods: A total of 315 consecutive patients with untreated CHC undergoing liver biopsy were included. Detailed histories of recent cannabis, alcohol, and tobacco use were recorded. Steatosis, activity, and fibrosis stage were assessed by 2 pathologists according to METAVIR. Marked steatosis was defined as >= 30%. Patients were categorized as cannabis nonusers (63.5%), occasional cannabis smokers (12.4%), or daily cannabis smokers (24.1%). Results: Multivariate analysis identified 6 predictors of marked steatosis: daily cannabis use (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.01-4.5]), activity grade >= A2 (OR, 2.1; 95% CI, 1.0-4.3), genotype 3 (OR, SA; 95% CI, 2.6-11.3), hyperglycemia or diabetes (OR, 5.1; 95% CI, 1.8-15.0), body mass index >27 kg/m(2) (OR, 2.1; 95% CI, 1.0-4.3), and serum HCV RNA load (OR, 1.7; 95% CI, 1.0-2.9). Upon adjustment of HCV genotype (3 vs non-3) or alcohol intake (<30 g/day vs >= 30 g/day), marked steatosis was more frequent in daily cannabis users compared with occasional users and nonusers (P = .03 and P = .008, respectively). Conclusions: Our results identify daily cannabis smoking as a novel independent predictor of steatosis severity during CHC and strongly argue for a steatogenic role of the cannabinoid system. Cannabis use should be discouraged in patients with CHC.