Steatosis is highly prevalent in patients with chronic hepatitis C (CHC) and has been reported to increase fibrosis and reduce the rate of sustained virologic response. Two recent studies have shown that endocannabinoids promote experimental liver steatosis via activation of hepatic CB1 cannabinoid receptors. We therefore investigated the impact of cannabis smoking on severity of steatosis in patients with CHC.

A total of 315 consecutive patients with untreated CHC undergoing liver biopsy were studied in a single tertiary care center. Demographic, epidemiologic, metabolic, and virologic data were recorded, including detailed histories of recent cannabis, alcohol, and tobacco use. Steatosis, activity grade, and fibrosis stage were assessed blindly by 2 pathologists according to the METAVIR system. 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%).

Logistic regression 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, 5.4; 95% CI, 2.6–11.3), hyperglycemia or diabetes (OR, 5.1; 95% CI, 1.8–15.0), body mass index >27 kg/m² (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 significantly more frequent in daily cannabis users compared with occasional users and nonusers (P = .03 and P = .008, respectively).

Our results identify daily cannabis smoking as a novel independent predictor of steatosis severity in CHC and strongly argue for a steatogenic role of the cannabinoid system. Cannabis use should be discouraged in patients with CHC.