Background and Aims: Hepatotoxicity, especially liver fibrosis, is the major concern with long‐term, ‘low‐dose’ oral methotrexate (MTX) therapy for psoriasis. The histological features are non‐specific and resemble those of non‐alcoholic steatohepatitis (NASH). Moreover, most of the risk factors of MTX‐induced liver injury are also associated with NASH. In this study, we investigate whether NASH contributes to the prevalence and progression of MTX‐induced liver injury in patients receiving MTX for psoriasis.

Methods: Clinical details, including MTX dosage schedules and risk factors for liver injury, was documented for 24 patients on long‐term MTX therapy for psoriasis. Serial liver biopsies were graded according to the Roenigk classification scale and a recently proposed grading and staging system for NASH.

Results: Thirteen of the 17 patients who had a NASH‐like pattern of liver injury also had the risk factors for NASH obesity and/or diabetes, and all had progressive liver injury. The other four patients had no risk factors, but a mean cumulative dose of 6.5 g. Seven patients, who did not have a NASH‐like pattern of injury, had a mean cumulative dose of 3.8 g. There was a positive correlation between the cumulative dose, risk factors and progression when the biopsies were scored by the modified grading and staging classification for NASH, but not with the Roenigk system.

Conclusions: Non‐steatohepatitis, probably aggravated by MTX, is an important cause of liver injury in patients on long‐term, ‘low‐dose’ MTX treatment for psoriasis. In addition, MTX alone can cause a NASH‐like pattern of injury that is at least, in part, caused by a higher cumulative dose.