humulene and Hepatitis-C--Chronic

Our purpose in this article is to review the effects of recreational drugs, used either on their own but principally combined with alcohol consumption, in determining hepatic injury or influencing the evolution of some chronic diseases of the liver, specifically HCV infection and NAFLD. A deleterious role of daily use of recreational drugs, in particularly cannabis, has been shown to demonstrate clearly a rapid progression of fibrosis and steatosis, leading to a major severity in patients with chronic hepatitis C. On the other hand, the effects of the misuse of these substances on NAFLD, the main obesity-related comorbidity, leading to addiction, is still to be elucidated even though some clues to the recreational drugs hepatotoxicity are already present in the literature. This short review aims at raising awareness about this topic.

Topics: Alcohol Drinking; Cannabis; Chemical and Drug Induced Liver Injury; Chronic Disease; Hepatitis C, Chronic; Humans; Illicit Drugs; Liver Diseases; Non-alcoholic Fatty Liver Disease

The cannabinoid system comprises specific G protein-coupled receptors (CB1 and CB2), exogenous (marijuana-derived cannabinoids) and endogenous (endocannabinoids) ligands, and a machinery dedicated to endocannabinoid synthesis and degradation. Studies over two decades have extensively documented the crucial role of the cannabinoid system in the regulation of a variety of pathophysiological conditions. However, its role in liver pathology has only been recently unravelled, probably given the low expression of CB1 and CB2 in the normal liver. We have recently demonstrated that CB1 and CB2 receptors display opposite effects in the regulation of liver fibrogenesis during chronic liver injury. Indeed, both receptors are up-regulated in the liver of cirrhotic patients, and expressed in liver fibrogenic cells. Moreover, CB1 receptors are profibrogenic and accordingly, the CB1 antagonist rimonabant reduces fibrosis progression in three experimental models. In keeping with these results, daily cannabis smoking is a risk factor for fibrosis progression in patients with chronic hepatitis C. In contrast, CB2 display antifibrogenic effects, by a mechanism involving reduction of liver fibrogenic cell accumulation. These results may offer new perspectives for the treatment of liver fibrosis, combining CB2 agonist and CB1 antagonist therapy.

Topics: Animals; Cannabinoid Receptor Modulators; Cannabis; Endocannabinoids; Hepatitis C, Chronic; Humans; Liver Cirrhosis; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2; Risk Factors

Thanks to direct-acting antivirals, hepatitis C virus (HCV) infection can be cured, with similar rates in HCV-infected and HIV-HCV co-infected patients. HCV cure is likely to foster behavioral changes in psychoactive substance use, which is highly prevalent in people living with HIV (PLWH). Cannabis is one substance that is very commonly used by PLWH, sometimes for therapeutic purposes. We aimed to identify correlates of cannabis use reduction following HCV cure in HIV-HCV co-infected cannabis users and to characterize persons who reduced their use.. We used data collected on HCV-cured cannabis users in a cross-sectional survey nested in the ANRS CO13 HEPAVIH cohort of HIV-HCV co-infected patients, to perform logistic regression, with post-HCV cure cannabis reduction as the outcome, and socio-behavioral characteristics as potential correlates. We also characterized the study sample by comparing post-cure substance use behaviors between those who reduced their cannabis use and those who did not.. Among 140 HIV-infected cannabis users, 50 and 5 had reduced and increased their use, respectively, while 85 had not changed their use since HCV cure. Cannabis use reduction was significantly associated with tobacco use reduction, a decrease in fatigue level, paying more attention to one's dietary habits since HCV cure, and pre-HCV cure alcohol abstinence (p = 0.063 for alcohol use reduction).. Among PLWH using cannabis, post-HCV cure cannabis reduction was associated with tobacco use reduction, improved well-being, and adoption of healthy behaviors. The management of addictive behaviors should therefore be encouraged during HCV treatment.

Topics: Antiviral Agents; Cannabis; Coinfection; Cross-Sectional Studies; Hepacivirus; Hepatitis C; Hepatitis C, Chronic; HIV Infections; Humans; Substance-Related Disorders

Topics: Cannabis; Coinfection; Hepacivirus; Hepatitis C; Hepatitis C, Chronic; HIV; HIV Infections; Humans; Plasma; RNA

Chronic hepatitis C virus (HCV) infection is a risk factor of insulin resistance, and HCV-infected patients are at a high risk of developing diabetes. In the general population, research has shown the potential benefit of cannabis use for the prevention of diabetes and related metabolic disorders. We aimed to test whether cannabis use is associated with a lower risk of diabetes in chronic HCV-infected patients. Chronic HCV-infected patients (n = 10 445) were selected from the French national, multicenter, observational ANRS CO22 Hepather cohort. Cross-sectional data collected at cohort enrollment were used to assess the association between patients' clinical and behavioural characteristics and the risk of diabetes. Logistic regression model was performed with cannabis use as the main independent variable and a significance level set at 5%. A similar model stratified by the presence of advanced liver fibrosis (FIB-4 > 3.25) was also run. After multivariable adjustment, current (AOR [95%CI]: 0.49 [0.38-0.63]) and former (0.81 [0.67-0.98], P < .001) cannabis use were both associated with a reduced odds of diabetes. Conversely, male gender, tobacco use, elevated BMI, poverty, being a migrant and advanced fibrosis were associated with increased odds of diabetes. The association between cannabis use and diabetes was maintained in the stratified analysis. In this large cross-sectional study of chronic HCV-infected patients, cannabis use was associated with a lower risk of diabetes independently of clinical and socio-behavioural factors. Further studies are needed to elucidate a potential causal link and shed light on cannabis compounds and mechanisms involved in this relationship.

Topics: Cannabis; Cross-Sectional Studies; Diabetes Mellitus; Hepatitis C, Chronic; HIV Infections; Humans; Liver Cirrhosis; Risk Factors

Topics: Cannabis; Hepatitis C, Chronic; Humans; Marijuana Abuse; Receptor, Cannabinoid, CB2