Cumulative dose and length of methotrexate treatment were not shown to be predictors of hepatic fibrosis by elastography - a monocentric cohort study

Objective: Methotrexate is used in several inflammatory diseases, such as rheumatoid arthritis (RA), spondyloarthritis (SpA) or inflammatory bowel disease (IBD). There has been some controversy regarding methotrexate liver toxicity, especially since the use of newer techniques. We aim to evaluate the prevalence of liver injury in methotrexate-treated patients with inflammatory diseases. Methods: We performed a cross-sectional study where consecutive patients diagnosed with RA, SpA or IBD, treated with methotrexate, were submitted to liver elastography. The cutoff for fibrosis was ≥7.1 kPa. Comparisons between groups were evaluated using chi-square, t test and Mann-Whitney U test. Correlations were made between continuous variables using Spearman correlation. Logistic regression was performed to determine predictors of fibrosis. Results: A total of 101 patients were included, 60 (59.4%) females, aged 46.2±12.6 years. Eleven patients (10.9%) had fibrosis, with a median score of 4.8 (4.1-5.9) kPa. Patients with fibrosis had higher rates of daily alcohol consumption (63.6% vs 31.1%, p=0.045). Methotrexate exposure time (OR 1.001, 95% CI 0.999-1.003, p=0.549) and cumulative dose (OR 1.000, 95% CI 1000-1000, p=0.629) were shown not to be predictors of fibrosis, unlike alcohol (OR 3.875, 95% CI 1.049-14.319, p=0.042). In multivariate logistic regression analysis, methotrexate cumulative and exposure times were not predictors of significant fibrosis, even when adjusted for alcohol consumption. Conclusions: In this study, we found that fibrosis detected on hepatic elastography was not associated with methotrexate, unlike alcohol. Therefore, it is of paramount importance to redefine risk factors for liver toxicity in patients with inflammatory diseases under treatment with methotrexate.