Quantifying the hepatotoxic risk of alcohol consumption in patients with rheumatoid arthritis taking methotrexate.
BACKGROUND
Patients with rheumatoid arthritis (RA) who take methotrexate (MTX) are advised to limit their alcohol intake due to potential combined hepatotoxicity. However, data are limited to support this. The aim of this study was to quantify the risk of developing abnormal liver blood tests at different levels of alcohol consumption, using routinely collected data from primary care.


METHODS
Patients with RA in the Clinical Practice Research Datalink starting MTX between 1987 and 2016 were included. Hepatotoxicity was defined as transaminitis: alanine transaminase or aspartate aminotransferase more than three times the upper limit of normal. Crude rates of transaminitis were calculated per 1000 person-years, categorised by weekly alcohol consumption in units. Cox proportional hazard models tested the association between alcohol consumption and transaminitis univariately, then age and gender adjusted.


RESULTS
11 839 patients were included, with 530 episodes of transaminitis occurring in 47 090 person-years follow-up. Increased weekly alcohol consumption as a continuous variable was associated with increased risk of transaminitis, adjusted HR (95% CI) per unit consumed 1.01 (1.00 to 1.02); consuming between 15 and 21 units was associated with a possible increased risk of hepatotoxicity, while drinking >21 units per week significantly increased rates of transaminitis, adjusted HR (95% CI) 1.85 (1.17 to 2.93).


CONCLUSIONS
Weekly alcohol consumption of <14 units per week does not appear to be associated with an increased risk of transaminitis.
Arthritis Research UK Centre for Epidemiology, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.
Jenny H
http://orcid.org/0000-0003-2497-4080
JH
Humphreys
Arthritis Research UK Centre for Epidemiology, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.
Alexander
A
Warner
Arthritis Research UK Centre for Epidemiology, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.
Ruth
http://orcid.org/0000-0003-2709-6666
R
Costello
Arthritis Research UK Centre for Epidemiology, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.
Mark
M
Lunt
Arthritis Research UK Centre for Epidemiology, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.
Suzanne M M
SMM
Verstappen
Arthritis Research UK Centre for Epidemiology, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.|NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.|Health eResearch Centre, Farr Institute, Manchester Academic Health Science Centre, University of Manchester, Manchester, UK.
William G
http://orcid.org/0000-0001-5881-4857
WG
Dixon
D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000428:Alcohol Drinking / Q000009:adverse effects* / Q000453:epidemiology; D018501:Antirheumatic Agents / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D001219:Aspartate Aminotransferases / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000453:epidemiology / Q000209:etiology*; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000009:adverse effects*; D008875:Middle Aged; D016016:Proportional Hazards Models; D012306:Risk
D018501:Antirheumatic Agents; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D008727:Methotrexate
Epidemiology; Methotrexate; Rheumatoid Arthritis; Treatment