Moderate Alcohol Intake While on Methotrexate Appears Prudent Save
Research presented at the annual British Society for Rheumatology conference revealed that rheumatoid arthritis (RA) patients who drink moderately while taking methotrexate (MTX) appear to be at no greater risk for liver damage than nondrinkers. They found the risk of increased liver function tests were not different between drinkers and nondrinkers (Hazard Ratio 1.12; 95% CI 0.82-1.51). These findings were previewed in the current issue of Rheumatology News.
In the UK, it is advised that patients keep their alcoholic intake under 14 units per week. Similar to practitioners in the United States, UK rheumatologists tend to restrict alcohol consumption by their patients, as they believe alcohol to be hepatotoxic. But the evidence supporting a presumed adverse interaction is scant.
Dr. Jenny Humphreys of the Arthritis Research U.K. Centre for Epidemiology at the University of Manchesterl presented findings from a database of more than 8,000 RA patients from the Clinical Practice Research Datalink (CPRD) who started MTX between 1987 and 2011. They correlated alcohol intake with routinely collected serum alanine or aspartate aminotransferase (ALT/AST) levels.
With 38,000 person-years of follow-up, they found 241 patients with abnormal LFTs (ALT/AST levels more than three times the upper limit of normal). The crude incidence rates of abnormal LFTs per 1,000 person-years was 5.58 in nondrinkers, 5.57 in those who drank 1-7 units of alcohol per week, 5.99 in those who drank 8-14 units, 7.58 in those who drank 15-21 units, 8.61 in those who drank 22-28 units, and 9.05 in those who drank more than 28 units. The adjusted hazard ratios ranged from 1.02 (lightest drinkers) to 1.92 (heaviest drinkers), yet these were not significant compared to nondrinkers. For each alcohol unit they found a mean LFT increase of 1%, but were unable to define if or when that increase was significant.
They concluded that alcohol consumption does not significantly increase your risk of abnormal LFTs, especially if you drink less than 14 units a week. Hence, moderation appears to be prudent.
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What is a "unit" of alcohol in terms of number of drinks?
It was disclosed in the article, " In the United Kingdom, a unit of alcohol is defined as 10 mL (8 g) of pure alcohol, and the typical alcoholic beverage may contain 1-3 units of alcohol"
These investigators only counted elevations of transaminase enzymes of 3x as "significant". THey did not performe liver biopsies.
When we performed our studies of patients on long-term MTX which were used in the Guidlines (36. Kremer JM, Alarcon GS, Lightfoot RW, Wilkens RF, Furst DE, Williams HJ, Weinblatt ME. Methotrexate for rheumatoid arthritis: suggested guidelines for monitoring liver toxicity. Arthritis and Rheumatism, 37:3:316-328, 1994) we used prospective transaminase enzymes monitored every 4 weeks for 11 years. We found that when baseline and annual liver biopsies were performed (avg of 11 biopsies per participant) that there were highly significant correlations between the number of any elevation of transaminase enzymes into the abnormal range and worsening hepatic pathology measured by light and EM.
So the British study definition of an abnormal transaminase enzyme is misleading. The differences in methodology (definition of abnormality and correlation of transaminase elevations with annual liver histology grade) are enormous in the new study.
I'm afraid that the blog has not performed a service by featuring this article.
Joel Kremer
Thanks Joel. Your wisdom and insight here is certainly appreciated by all. There are clearly short comings to this data and its kind. I posted it because since your report there hasnt been any detailed look at alcohol intake with MTX use from a large cohort and thus I thought it would be good to revisit this issue and bring up what was previously done. I do believe there is some value in showing that low/moderate EtOH use was not associated with >3x elevations of LFTs - less may not have impressed or been meaningful. I admit we dont know the long term or tissue consequences of the EtOH intake or LFT elevations referenced but who will ever get us such data? Arent we still operating in a vacumn of limited information? I would really like more information to know what to tell my patient, since I long ago gave up on "no alcohol" and "dont dring more than your rheumatologist". JJC
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