Published online Sep 18, 2017. doi: 10.4254/wjh.v9.i26.1092
Peer-review started: February 20, 2017
First decision: April 1, 2017
Revised: April 20, 2017
Accepted: July 7, 2017
Article in press: July 10, 2017
Published online: September 18, 2017
Methotrexate is the first line drug treatment for a number of rheumatic and non-rheumatic diseases. It is effective in controlling disease activity and preventing disease-related damage, and significantly cheaper than many alternatives. Use in rheumatoid arthritis infers a significant morbidity and mortality benefit. Methotrexate is generally well tolerated but can cause symptomatic adverse events. Multiple serious adverse events have been attributed to methotrexate, based largely on older reports using high or daily doses, and subsequent case reports and circumstantial evidence. The risk with modern dosing regimens: Lower doses, weekly schedules, and concomitant folic acid is less clear. Clarification and dissemination of the actual risk is crucial so appropriate judgements can be made for patients who may benefit from this treatment. Methotrexate has been associated with a range of liver related adverse events ranging from asymptomatic transaminase elevations to fibrosis and fatal hepatic necrosis. Concern over potential liver toxicity has resulted in treatment avoidance, cessation, or recommendations for investigations which may be costly, invasive and unwarranted. Modern laboratory monitoring of liver blood tests may also influence the risk of more serious complications. The majority of present day studies report an approximate doubling of the relative risk of elevated transaminases in methotrexate treated patients but no increased risk of symptomatic or severe liver related adverse events. In this article we will review the evidence around methotrexate and liver related adverse events.
Core tip: Methotrexate is a highly effective treatment for many diseases. In rheumatoid arthritis it controls symptoms, prevents damage, and reduces mortality. The risks of methotrexate use are often over-estimated. Methotrexate may result in asymptomatic transaminase elevations. Historically methotrexate has been infrequently associated with more severe liver adverse events. With modern monitoring and management of liver blood tests serious liver related adverse events related to methotrexate use appear to be avoidable.