Risk of Liver Fibrosis in Patients With Psoriasis on Long-term Methotrexate: Role of Cumulative Dose and...

Methotrexate (MTX) remains the cornerstone in the treatment of psoriasis. However, concerns about its potential to contribute to liver fibrosis or cirrhosis have remained. We aimed to define the relationship between MTX exposure or other risk factors with liver fibrosis in patients with psoriasis.

We examined the liver stiffness measurement (LSM) in patients with psoriasis from a single center between 2019 and 2024. At the time of LSM, baseline clinical, demographic, comorbidities, laboratory, and medication information were obtained. Psoriasis patients were stratified into two groups: one that had not been exposed to MTX (no MTX), and another that had been exposed to MTX for more than 6 months. Liver fibrosis was measured by transient elastography (TE) and FIB 4. We used a cut-off of ≤7.9 kPa to rule out advanced fibrosis and ≥11.5 kPa to rule in cirrhosis, respectively.

Of the 483 individuals with psoriasis, 101 (21%) patients showed TE values ≥ 7.9 kPa. Sixty-five (22.3%) of MTX-exposed group showed TE ≥ 7.9 kPa compared to thirty-six (19.3% with no-MTX (P = 0.33). On multivariate logistic regression analysis, the only significant factor linked to stiffness ≥ 7.9 was type 2 diabetes mellitus (T2DM) (adjusted odds ratio = 2.8; 95% CI 1.44-5.43; P = 0.002). Liver fibrosis did not correlate with age, MTX cumulative dose, hyperlipidemia, obesity, or hypertension in multivariate analysis, despite some of these factors showing significance on univarite analysis.

T2DM, not cumulative methotrexate dose, was associated with liver stiffness. These findings reinforce the need to revise methotrexate monitoring guidelines to incorporate transient elastography, particularly for patients with metabolic risk factors.