Association between cumulative methotrexate dose, non-invasive scoring system and hepatic fibrosis detected by Fibroscan in rheumatoid arthritis patients receiving methotrexate

BACKGROUND: Methotrexate (MTX) is recommended by recent American College of Rheumatology and European League against Rheumatism guidelines as a first-line drug for rheumatoid arthritis (RA). Liver fibrosis, which occurs as a long-term side effect is of major concern. Monitoring aminotransferase and albumin is suggested in the guidelines, unfortunately this method is unreliable for detecting liver fibrosis. We try to find the association between clinical parameters, cumulative MTX dosage, liver fibrosis scoring systems and the presence of liver fibrosis assessed by transient elastography (TE; Fibroscan®). METHOD: Rheumatoid arthritis patients prescribed MTX were evaluated for liver fibrosis with TE. Two subgroups of patients were compared: non-fibrosis and fibrosis (TE > 7 kPa). Univariate and multivariate logistic regression analysis was performed to identify factors associated with liver fibrosis. RESULTS: One hundred and eight patients were recruited. Twenty-nine patients (26.8%) were classified by transient elastography as liver fibrosis cases. The multivariate analysis demonstrated statistical significance only in the association of body mass index (odds ratio [OR] = 1.22; 95% CI 1.05-1.41; P = 0.01); fatty liver (OR = 2.32; 95% CI 1.58-9.19; P = 0.02); alanine transaminase (OR = 1.04; 95% CI 1.02-1.09; P = 0.04) and cumulative MTX dosage (OR = 1.03; 95% CI 1.01-1.04; P = 0.001). CONCLUSIONS: Liver fibrosis measured with Fibroscan was associated with cumulative MTX. RA patients with metabolic syndrome including high body mass index and fatty liver, had a higher risk of MTX-induced hepatic fibrosis. RA patients with high cumulative MTX dose, especially patients with concurrent metabolic syndrome, should be cautiously monitored for liver fibrosis.