The relationship between dose of methotrexate and incidence of liver fibrosis in patients with rheumatoid arthritis.

Introduction: Methotrexate (MTX) is a chemotherapy agent and immune system suppressant that can cause liver fibrosis in long-term usage. This study aimed to investigate the relationship between the dose of MTX and the incidence of liver fibrosis in patients with rheumatoid arthritis (RA).

Material and methods: This cohort study was conducted on RA patients with normal liver function who took MTX. Liver FibroScan and laboratory tests, including α₂-macroglobulin, total bilirubin, g-glutamyltransferase, apolipoprotein A1, haptoglobin, and alanine transaminase was performed. The patients were divided into 2 groups regarding their cumulative dose of MTX and the rate of liver fibrosis incidence was compared between the 2 groups.

Results: In total, 60 RA patients with the mean age of 55.2 ±11.8 years were enrolled. The mean duration of MTX use in patients was 6.9 ±3.8 years, and it was higher in the higher cumulative dose MTX group (> 2 g) than in the lower cumulative dose group (< 2 g; p < 0.0001). The overall prevalence of grade 3 fibrosis was 3.33%. The prevalence of second- and third-degree liver fibrosis in patients receiving a lower cumulative dose was respectively 9 (28.1%) and 1 (3.1%), and in patients receiving a higher cumulative dose it was 7 (25%) and 1 (3.6%), respectively. There was no statistically significant difference between the 2 groups regarding the prevalence of liver fibrosis (p = 0.88). Both aspartate aminotransferase to platelet ratio index and Fibrosis Index Based on 4 Factors indices showed no significant difference between the 2 groups (p = 0.594, p = 0.232).

Conclusions: These results suggest that long-term treatment with a higher cumulative dose of MTX is not associated with a higher incidence of liver fibrosis in RA patients.