Thursday, 18 Jan 2018

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Debate over Alcohol and Methotrexate Precautions

Drs. Kremer and Weinblatt have responded to a recent Annals of Rheumatic Disease article regarding the hepatic risks of alcohol use with methotrexate (MTX) therapy authored by Humphries et al. (Citation source:

Kremer and Weinblatt noted that 2 decades ago it was not uncommon to do baseline and annual liver biopsies, but now we may erroneously be promoting the unhealthy or unmonitored use of alcohol in patients on MTX.

They reminded us of the MTX monitoring guidelines, based on their studies of MTX patients, wherein elevation of the transaminases (ALT, AST) was associated with a risk of fibrosis. Specifically, they found that if 5 of 9 measures over a year (or 6 of 12 if the measures if monthly) were abnormal there was resultant risk for histological hepatic fibrosis and damage. 

Their correspondence with the Humphries et al pointed to a significant correlation between a history of alcohol consumption prior to starting MTX and subsequent increases in overall hepatic histological grade. Hence, the guidelines were purposefully conservative with regard to the use of alcohol in those treated with MTX.

They point out that the study by Humphries et al, that examined alcohol use while on MTX, noted safety if hepatic enzymes did not rise 3 fold above the upper limites of normal and the number of alcoholic drinks was kept to 14 units or less per week.  Moreover, their studies looked only at hepatic enzymes and made no correlations with liver histology or other imaging or clinical outcomes.

Hence, Weinblatt and Kremer belive that it is erroneous to state that MTX and alcohol is safe (or has a low probabilty of hepatic disease) based solely on elevations of transaminase enzymes being less than 3 times the upper limit of normal and consuming only up to 14 units of alcohol per week.

They question Humphries definition of liver toxicity, noting it is rather arbitrary and not consistent with published research on this subject. 

Humphries and coworkers responded by agreeing with many of the points raised by Kremer and Weinblatt.  But, since liver biopsies and other data were not available, their objective was to produce practical evidence for what level of abnormal LFTs (3× ULN) might trigger a change in therapy.  They stated, "Our data do not mean that it is completely safe to drink up to 14 units of alcohol per week, merely that in terms of the outcome of transaminitis per our two definitions, we saw no evidence of an increased risk."

Clearly this issue needs to be carefully discussed with patients and closely monitored by prescribing physicians. 

The author has no conflicts of interest to disclose related to this subject

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