Serum caspase activity and liver fibrosis in patients with hepatitis C

AASLD: Smoking Marijuana Raises Fibrosis Risk in Patients With Chronic Hepatitis C Infection

By Mark L. Fuerst

BOSTON, MA -- November 2, 2004 -- Daily marijuana smokers who have chronic hepatitis C infection risk having rapid progression of liver fibrosis, according to research presented here October 31^st at the 55^th Annual Meeting of the American Association of Liver Diseases.

Cannabis, the active ingredient in marijuana, exerts its biological effects through the binding of two receptors, CB1 and CB2. Ariane Mallat, Professor in the Hepatology and Gastroenterology Service at the Henri Mondor Hospital, Creteil, France, and colleagues previously demonstrated that CB1 receptors enhance fibrogenesis in mice, and set out to evaluate the clinical relevance of this finding in patients with chronic liver disease.

In 211 subjects with ongoing chronic hepatitis C infections, the researchers collected data on demographics, route of transmission, age at exposure, duration of hepatitis C virus infection, intakes of alcohol, tobacco, and cannabis over the course of the disease, maintenance treatment with methadone or buprenorphine, body mass index, fasting glucose level, genotype, steatosis, histological activity, and fibrosis level and progression.

Responses show that 32.2% of patients had used marijuana daily since the beginning of their disease (mean duration of 16 years), 16.6% were occasional smokers (once every other week), and 51.2% never smoked marijuana.

Univariate analysis showed that two-thirds of the daily smokers had a rapid rate of fibrosis progression compared to 40% of occasional smokers and 41% of non-smokers. In a multivariate analysis, a rapid fibrosis progression rate was related to daily cannabis use (odds ratio [OR] = 4.0), as was excessive daily alcohol intake (30 g; OR = 2.1), age at exposure of more than 24 years (OR = 4.8), and genotype 3 (OR = 3.1). There was no increased risk of progression among occasional smokers compared to non-smokers.

"In chronic hepatitis C infection, there is a strong relationship between daily cannabis use and fibrosis progression rate," Dr. Mallat said. "Patients with ongoing chronic hepatitis C should be advised against daily cannabis use, since regular use over the span of the disease is an aggravating factor regarding fibrosis progression."

This study supports the experimental data that demonstrated the profibrogenic role of CB1 receptors, she said, and noted that patients with chronic liver disease have a large amount of CB1 receptors in the liver, and that the impact of marijuana smoking is as a cofactor, and is not responsible for liver fibrosis per se.


[Presentation title: "Daily Cannabis Smoking as a Risk Factor for Fibrosis Progression in Chronic Hepatitis C." Abstract 67]
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By Jillian L. Lokere, MS

November 1, 2004 — Daily cannabis smoking is associated with an increased likelihood of rapid fibrosis progression in patients with chronic hepatitis C, according to a study presented by Christophe Hezode of the Hôpital Henri Mondor, Creteil, France, and colleagues at the 55th Annual Meeting of the American Association for the Study of Liver Diseases.

Cannabis sativa (marijuana) is sometimes used to treat the appetite loss and fatigue associated with chronic hepatitis C. It exerts its effects via 2 types of receptors, CB1 and CB2. Recent work from Hezode and colleagues has shown that CB1 receptors enhance liver fibrogenesis, prompting the prediction that cannabis smoking might hasten fibrosis progression during chronic hepatitis C.

To investigate this hypothesis, the authors collected questionnaire data from 211 treatment-naive patients with histologically proven chronic hepatitis C of known duration. The data collected included demographics, route of transmission, age at exposure, duration of HCV infection, alcohol, tobacco, and cannabis intake over the course of the disease, maintenance treatment with methadone or buprenorphine, body mass index, glucose fasting level, genotype, histologic activity grade, fibrosis and steatosis scores, and fibrosis progression rate. Patients were not coinfected with hepatitis B virus or HIV, were not taking immunosuppressive agents, or had not recently used other illicit drugs.

Patients were then classified into 3 groups according to cannabis consumption. Fifty-one percent of patients were nonsmokers; 17% were occasional smokers, defined as< 1 daily cannabis cigarette (median, 7 joints/month); and 32 % smoked at least 1 cannabis cigarette per day (median, 75 joints/month).

Daily cannabis smoking was significantly associated with a rapid fibrosis progression rate of > 0.08 U per year in both univariate and multivariate analyses. Specifically, 65% of daily smokers compared with 40% of occasional smokers and 41% of nonsmokers were classified as "rapid fibrosers." Other associated factors in multivariate analysis included acquiring HCV infection at age ≤ 24 years, an alcohol intake ≥ 30 grams per day, HCV genotype 3 infection, and a fibrosis activity ≥ 2. Tobacco usage was not associated with rapid fibrosis in either analysis.

The investigators concluded that the strong link between daily cannabis consumption and fibrosis progression rate clinically supports the experimentally determined profibrogenic role of CB1 receptors. "Patients with HCV infection who smoke cannabis to help with fatigue or appetite should really be aware that daily consumption could exacerbate their disease," they wrote.

Reference

Hezode C, Roudot-Thoraval F, Nguyen S, et al. Daily cannabis smoking as a risk factor for fibrosis progression in chronic hepatitis C. Program and abstracts of the 55th Annual Meeting of the American Association for the Study of Liver Diseases; October 29 - November 2; Boston, Massachusetts. Abstract 67.

http://clinicaloptions.com/hep/news/news_AASLD2004_67.asp