Diagnostic performance of FIB-4 in detecting advanced liver fibrosis in patients with rheumatoid arthritis, psoriatic arthritis and psoriasis using methotrexate

Abstract Background Methotrexate is a first-line therapy for rheumatoid arthritis, psoriatic arthritis, and psoriasis, but its long-term use has been associated with hepatic fibrosis, highlighting the need for effective screening strategies. In this context, and considering the limitations of liver biopsy as well as the high cost and limited availability of elastography, the FIB-4 score has emerged as the most widely used noninvasive screening tool. This multicenter cross-sectional study evaluated patients followed at specialized Rheumatology and Dermatology centers to assess the accuracy of FIB-4 in predicting advanced hepatic fibrosis in patients with rheumatoid arthritis, psoriatic arthritis, and psoriasis undergoing chronic methotrexate therapy. The specific objectives were to identify optimal cutoff values for FIB-4 in this population and factors associated with advanced fibrosis. Methods Medical records, interviews, and physical examinations were used to collect demographic, clinical, laboratory, lifestyle, and treatment data, calculate age-adjusted FIB-4 scores, and assess disease activity using validated indices. Liver fibrosis and steatosis were evaluated by vibration-controlled transient elastography, and FIB-4 performance for detecting advanced fibrosis was analysed using age-stratified Receiver Operating Characteristic curves and multivariable logistic regression. Results A total of 172 patients were included, predominantly women, with a mean age of 58 years; rheumatoid arthritis was the most common underlying disease. Advanced fibrosis was identified by elastography in 11%. FIB-4 values increased progressively with fibrosis stage, and Receiver Operating Characteristic curve analysis identified a cutoff of 1.62 — a threshold not previously reported for methotrexate-treated patients. This cutoff demonstrated better performance in individuals younger than 65 years (Area Under the Curve = 0.68 versus 0.64 in those aged 65 years or older) and showed particular utility for ruling out advanced fibrosis. In multivariable analysis, a high-risk FIB-4 category, obesity, diabetes mellitus , and advanced hepatic steatosis were independently associated with advanced fibrosis, whereas inflammatory disease activity and cumulative methotrexate dose were not. Conclusions FIB-4 is an accessible and potentially useful tool for ruling out advanced hepatic fibrosis in methotrexate-treated patients younger than 65 years, demonstrating reasonable performance in this population. Advanced fibrosis is primarily driven by metabolic factors rather than methotrexate exposure or inflammatory disease activity.