Background/Purpose:  Methotrexate (MTX) has been recommended for the first line therapy of rheumatoid arthritis (RA), either alone or in combination with other DMARDs such as leflunomide. Although MTX is thought to have long term safety, there is still controversy whether long term use of MTX and its cumulative dose causes liver fibrosis in RA patients. This study was performed to assess the degree of liver fibrosis among the RA patients treated with MTX by transient elastography (TE), and to identify associated factors with liver fibrosis in those patients.

Methods:  We restrospectively reviewed the medical records of 160 patients with RA taking MTX over 3 years, and who had liver fibrosis examination using TE. Liver fibrosis was defined as liver stiffness value over 5.3 kPa according to the reference of healthy Korean organ donor. The duration, cumulative doses of medications including MTX and leflunomide, and serologic markers related to liver fibrosis were analyzed by comparing 2 groups with and without liver fibrosis. E), and to identify associated factors with liver fibrosis in those patients.

Results:  The mean disease duration of patients was 10.7 ± 5.1 years, and the median liver stiffness value was 4.5 ± 2.7 kPa. Twenty one (13.1%) patients showed liver fibrosis while only 1 (0.01%) patient progressed to liver cirrhosis. The cumulative dose of MTX and leflunomide showed no significant difference between 2 groups. A history of taking LFNM and concomitant medications did not affect to the development of liver fibrosis. Patients with liver fibrosis had higher glucose, aspirate aminotransferase (AST), and alkaline phosphate (ALP) level with a tendency of lower level of hemoglobin, platelet and longer treatment duration with MTX. The history of glucose abnormality including pre-diabetes and diabetes mellitus (odds ratio [OR] 5.154, P = 0.011), serum hemoglobin (OR 0.608, P = 0.023), platelet (OR 0.989, P = 0.025), AST (OR 1.052, P = 0.014), and ALP level (OR 1.034, P = 0.022) were related with liver fibrosis in multivariate analysis.

Conclusion:  Long term use of low dose MTX and combination of leflunomide in patients with RA were relatively safe in terms of severe liver fibrosis measured by TE. RA patients with risk factors such as impaired glucose tolerance should be more carefully monitored for development of liver fibrosis in long term use of MTX.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/assessment-of-liver-fibrosis-using-transient-elastography-in-patients-with-rheumatoid-arthritis-exposed-to-long-term-methotrexate/