Dr. Kremer, who coauthored 1994 guidelines for monitoring liver toxicity in RA patients receiving MTX, told Reuters Health by phone that in the mid-1990s, research found that any elevation of transaminase was associated with deterioration of liver biopsy.
“Transaminitis has been defined in different ways in the literature,” Dr. Dixon noted. The researchers chose three times ULN to avoid including mild transaminitis, but “lower values might still be clinically important,” he said.
Dr. Dixon pointed out that a sensitivity analysis defining transaminitis as any persistent elevation (three sequential levels greater than ULN) produced the same findings, that fewer than 14 units of alcohol per week was not associated with an increased risk of transaminitis.
“I suspect that a number of my patients (receiving MTX for RA) simply do not admit to having an alcoholic beverage on a fairly regular basis,” Dr. Christopher Morris, a member of the American College of Rheumatology’s Committee on Government Affairs, told Reuters Health in an email. “I am not too certain that it causes patients not to comply with the methotrexate, as much as it results in the patient hiding their alcohol use.”
“This article can lead us to feel a bit better when we have a patient who admits having a drink or two over the weekend, as long as we stress that limiting the number of drinks a week is important,” he added.
Dr. Morris admitted to being uncomfortable with the setting of the alanine transaminase or aspartate aminotransferase threshold at 3x ULN, but added that “studies have suggested that liver biopsies do not correlate all that well with mild elevations” of liver function tests.
Dr. John J. Cush, executive editor of RheumNow.com, cited that website’s February survey of nearly 500 U.S. and non-U.S. rheumatologists, which found that roughly half of those surveyed will permit one to three alcoholic drinks per week for patients on MTX. A quarter allow only one to three drinks per month, while 15-20% forbid any alcohol use and 6-7% have no restrictions on alcohol, provided there is no underlying liver disease.
The study used a clinical practice database to evaluate the records of 11,839 patients (71% female, mean age 61) with RA and who had received MTX. The researchers found 530 first episodes of transaminitis during 47,090 person-years of follow-up.
Alcohol consumption below 14 units per week was associated with a very low probability (0.93%) of having an at least 50% increased risk of transaminitis. For greater weekly alcohol consumption, the probability of having such an increased risk of transaminitis was higher: 33% and 81% for consumption of 15-21 units and more than 21 units, respectively.
