Daily cannabis use associated with worse fibrosis in patients with chronic hepatitis C

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Regular cannabis use is associated with moderate to severe liver fibrosis in patients infected with chronic hepatitis C virus, according to a study published in Clinical Gastroenterology and Hepatology. A fifth of patients in the study were coinfected with HIV and hepatitis C and the association between daily or near-daily cannabis use and moderate to severe fibrosis was also present in these patients.

On the basis of their findings, the investigators recommend that patients with hepatitis C should be counselled that regular cannabis consumption is associated with severe fibrosis. This information is especially important for HIV/hepatitis C coinfected patients as HIV is already associated with accelerated hepatitis C disease progression. Furthermore HIV-positive patients in the study were significantly more likely to be regular users of cannabis and to use the drug for medicinal purposes.

Hepatitis C virus infection is a major public health concern, and it is thought that the amount of illness caused by hepatitis C-associated fibrosis and cirrhosis will increase significantly in the near future.

Glossary

fibrosis

Thickening and scarring of connective tissue. Often refers to fibrosis of the liver, which can be caused by an inflammatory reaction to long-term hepatitis infection. See also ‘cirrhosis’, which is more severe scarring.

cirrhosis

Severe fibrosis, or scarring of organs. The structure of the organs is altered, and their function diminished. The term cirrhosis is often used in relation to the liver. 

odds ratio (OR)

Comparing one group with another, expresses differences in the odds of something happening. An odds ratio above 1 means something is more likely to happen in the group of interest; an odds ratio below 1 means it is less likely to happen. Similar to ‘relative risk’. 

disease progression

The worsening of a disease.

biopsy

A procedure to remove a small sample of tissue so that it can be examined for signs of disease.

Factors associated with the progression of hepatitis C disease and the development of cirrhosis include male gender, older age at the time of hepatitis C infection, heavy alcohol consumption and coinfection with HIV.

Cannabis is widely used for recreational and medicinal purposes. The drug contains 60 active cannabinoids and cirrhotic livers are more receptive to cannabinoids. Earlier research suggests that cannabinoids have an important, but yet to be identified, role in the progression of liver fibrosis.

Given the prevalence of cannabis use and the suggestion that it could worsen liver disease, investigators from the University of California San Francisco designed a study to determine the effect of cannabis on the severity of fibrosis in patients with chronic hepatitis C virus.

The study recruited patients between 2001 – 2004. A total of 204 patients were eligible for inclusion in the investigators’ analysis, 21% of who were HIV-positive.

Patients were interviewed to obtain information about their demographics, risk factors for hepatitis C, and drug and alcohol use. Blood tests were performed to measure hepatitis C viral load (and, if coinfected, HIV viral load), and liver function. All the patients also had liver biopsies to determine their degree of fibrosis or cirrhosis.

The patients had a median age of 47 years, 69% were male, 49% were white and 33% African American. The majority of patients had the hard-to-treat hepatitis C genotype 1 and the estimated duration of hepatitis C infection was 26 years.

Daily or near daily cannabis use was reported by 14% of patients. Daily cannabis users had significantly lower median body mass index than non-daily users of the drug (25.2 kg/m2 vs. 26.4 kg/m2, p = 0.007), were more likely to be prescribed the drug for medicinal purposes (57% vs. 9%, p < 0.001), and were more likely to be coinfected with HIV (39% vs. 18%, p = 0.011).

CD4 cell counts were comparable in HIV-positive patients who used cannabis daily and non-daily users of the drug (368 cells/mm3 vs. 411 cells/mm3).

The proportion of patients with no fibrosis was 28%, mild fibrosis was present in 55% of individuals, and 17% had moderate-to-severe fibrosis.

Median AST was above the normal range at 48 iu/l, but median AST levels were just within the normal range at 56 iu/l.

There was no evidence that daily or near-daily cannabis use was associated with mild fibrosis. But the investigators did find that daily or near-daily use of cannabis was associated with moderate or severe fibrosis (odds ratio [OR], 6.78; p = 0.005 compared to non-daily users).

Less frequent users of cannabis, those who used the drug weekly or monthly, did not have an increased risk of moderate or severe fibrosis.

The effects of cannabis use on the risk of moderate and severe fibrosis were similar for patients who only had hepatitis C virus and for those who were coinfected with HIV.

Other risk factors for moderate to severe fibrosis included lifetime heavy alcohol consumption (OR, 1.72 per ten years, p = 0.044), and the number of portal tracts (eleven or above compare with five or below, OR, 6.92, p = 0.021).

“We have shown that daily cannabis use is an independent risk factor for moderate to severe fibrosis and one of substantial magnitude, with daily cannabis users having nearly 7-fold higher odds of moderate to severe fibrosis compared to non-daily users,” write the investigators.

Patients coinfected with HIV were significantly more likely to report daily use of cannabis and to have the drug prescribed for medicinal purposes, note the investigators. They therefore suggest “the recommendation to avoid cannabis use might be especially important for hepatitis C virus- HIV coinfected persons, given that fibrosis progression is already enhanced in this group.”

The investigators conclude, “we would advise that individuals with chronic hepatitis C virus infection be counselled to reduce or abstain from cannabis use.”

References

Ishida JH et al. Influence of cannabis use on severity of hepatitis C disease. Clinical Gastroenterology and Hepatology 6: 69 – 75, 2008.