Effect of Methotrexate Discontinuation on Psoriatic Patients with Significant Liver Fibrosis

Abstract

Background: Patients with psoriasis, particularly those receiving systemic therapies such as methotrexate (MTX), are at increased risk of developing significant liver fibrosis. Although MTX remains widely used, its hepatotoxic potential remains controversial. Transient elastography (TE) allows non-invasive monitoring of liver fibrosis; however, data on fibrosis regression after MTX discontinuation are limited. Objective: To assess the incidence of liver fibrosis regression in psoriasis patients following MTX withdrawal and to identify clinical and laboratory factors associated with this outcome. Methods: We conducted a pilot cross-sectional study involving 15 prospectively recruited psoriasis patients with significant liver fibrosis (liver stiffness measurement [LSM] ≥7.1 kPa) who had discontinued MTX for at least 6 months. Fibrosis regression was defined as a >30% reduction in LSM from baseline. Univariate logistic regression was used to evaluate associations between clinical variables and fibrosis regression. Results: Fibrosis regression was observed in 5 patients (33.3%) who had remained MTX-free for a mean duration of 3.6 ± 3.1 years. MTX treatment duration >4 years was significantly associated with fibrosis regression (OR = 16.00, 95% CI: 1.09–234.25; p = 0.043). A cumulative MTX dose >2 grams showed a non-significant trend toward increased odds of fibrosis regression (OR = 6.00, 95% CI: 0.56–63.98; p = 0.138). Male gender (OR = 0.17, 95% CI: 0.02–1.78; p = 0.138) showed a non-significant trend toward reduced odds of fibrosis regression. Conclusion: One-third of psoriasis patients with significant liver fibrosis showed regression after a mean MTX-free duration of 3.6 years, with MTX use duration of more than 4 years significantly associated with this outcome. Given the small sample size, these results should be interpreted with caution. Nonetheless, these findings suggest a potential benefit of MTX withdrawal in selected patients and warrant confirmation in larger, prospective studies.