Smoking cannabis does not accelerate progression of liver disease in people with HIV/HCV co-infection

Smoking cannabis does not worsen liver disease in people with HIV and hepatitis C virus (HCV) co-infection, Canadian research published in the online edition of Clinical Infectious Diseases shows.

“We found no evidence that cannabis smoking increases the risk of progression to significant liver fibrosis or cirrhosis,” write the authors. Results also showed that cannabis was widely used for pain relief by co-infected people.

Up to 30% of people with HIV in resource-rich countries are co-infected with HCV. Liver disease caused by HCV is a leading cause of serious illness and death in these co-infected individuals.

Cannabis (marijuana) is believed to be widely used by people with HIV. In a study conducted in Ontario, Canada, 43% of participants reported use of cannabis in the previous year, 29% saying they had self-medicated with the drug.

Previous research examining the effects of cannabis consumption on liver disease outcomes has produced conflicting results. Three cross-sectional – or 'snapshot' – studies involving people with chronic HCV infection found an association between cannabis use and liver cirrhosis. In contrast, a small study involving 58 people with HIV showed no association between cannabis use and significant changes in liver enzyme levels over one year.

Given this uncertainty, investigators in Canada designed a prospective study involving 690 HIV-positive people with chronic HCV co-infection and no significant fibrosis at baseline enrolled in the Canadian Coinfection Cohort study. Every six months, participants were asked if they had used cannabis. Users of the drug were asked how often they smoked cannabis and the number of joints they consumed on the days they smoked.

The investigators then examined the association between cannabis use and progression to significant fibrosis, cirrhosis and end-stage liver disease. Significant fibrosis was defined as an AST platelet ratio index (APRI) score of 1.5 or above. An APRI score of 2.0 was used to diagnose cirrhosis and the authors also looked at the relationship between cannabis use and progression to a clinical cirrhosis diagnosis.

The investigators were concerned that participants might start to consume cannabis – or intensify their use of the drug – to alleviate symptoms related to advancing liver disease. By collecting concurrent data on exposure to cannabis and disease outcomes it could appear that cannabis caused liver disease when in fact this was present before the participant changed their drug-use behaviour. The investigators therefore repeated their analyses looking at cannabis use in the six to twelve month period before liver disease assessments. They called this method of analysis “lagging”.

The participants were followed for a median of 2.7 years and contributed a total of 1875 person-years of follow-up. The majority of participants were male and the median age at baseline was 44 years. Most of the participants had an undetectable HIV viral load and the median CD4 cell count at the start of the study was 400 cells/mm³. Injecting drug use was reported by 38% of participants and 15% had alcohol abuse issues.

Over half (53%) of participants reported use of cannabis at baseline with similar proportion of individuals using the drug through follow-up. On entry to the study, approximately 40% of participants who used cannabis said they did so for symptom relief, and this proportion increased to over 50% during follow-up. Turning to frequency of use, the investigators found that 40% of cannabis smokers consumed the drug on a daily basis.

During follow-up, 19% of participants developed significant fibrosis, 15% cirrhosis (diagnosed by APRI score), 1% received a clinical diagnosis of cirrhosis and 2% progressed to end-stage liver disease.

The incidence rate of progression to APRI 1.5 or above was 39.2 per 1000 person-visits; incidence of progression to APRI 2.0 or above was 29.2 per 1000 person-visits; incidence of progression to a clinical cirrhosis diagnosis was 2.1 per 1000 person-visits; and incidence of progression to end-stage liver disease was 2.9 per 1000 person-visits. There were no differences in these incidence rates between users and non-users of cannabis.

The investigators’ initial analysis appeared to show that smoking cannabis accelerated progression to a clinical diagnosis of cirrhosis (HR = 1.33; 95% CI, 1.09-1.62 per ten joints/week). However, after lagging this association ceased to be significant. Smoking cannabis was also initially associated with a combined outcome of clinically diagnosed cirrhosis and end-stage liver disease (HR = 1.13; 95% CI, 1.01-1.28). But once again this association ceased to be significant when the researchers looked at cannabis consumption in the six to twelve months before the clinical outcomes were diagnosed.

“Reported use for symptom relief was very prevalent suggesting that the association of daily cannabis use and more advanced fibrosis may, in fact, be related to an increased use for symptoms management of the disease,” the authors suggest. “Previous cross-sectional studies reporting an association between marijuana smoking and liver fibrosis may be biased by reverse causation due to self-medication with marijuana for relief of symptoms related to significant liver fibrosis.”

They conclude, “We could not demonstrate any important effect of marijuana on liver disease outcomes.”