Prevalence and risk factors of methotrexate hepatoxicity in Asian patients with psoriasis

To establish the prevalence of liver fibrosis and to evaluate the possible risk factors for fibrosis and progression in Asian with psoriasis treated with methotrexate (MTX) based on liver histology.

Patients with psoriasis treated with MTX referred to the Department of Gastroenterology, Tan Tock Seng Hospital for liver biopsy were identified and retrospectively studied. Patient case notes and electronic records were retrieved from the hospital database and relevant data collated. Histological changes of liver biopsies were staged according to Roengik score. The factors assessed were age, gender, ethnicity, cumulative dose of MTX, presence of comorbid conditions such as diabetes, hypertension, hyperlipidemia, and ethanol use. We also assessed the histological change in those with multiple liver biopsies. Statistical analysis was performed using Stata V.9.2.

There were altogether 59 patients (median age 50 years old, range 22-81 years old, male, 88%) with 98 biopsies liver biopsies; 6 normal [median cumulative dose (MCD), 2285 mg]; 62 grade I (MCD 2885 mg), 23 grade II (MCD 1800 mg) and 7 grade III (MCD 1500 mg). There was no grade IV or cirrhosis. The prevalence of liver fibrosis (grade III) was 12%. Of the factors assessed, diabetes (P = 0.001) and hypertension (P = 0.003) were significant for fibrosis on univariate analysis but not on multivariate analysis. Of the 26 patients who had more than one biopsy (median 2, range 2-6), 57.7% (n = 15) were stable, 34.6% (n = 9) had progression and 7.7% (n = 2) had regression of histological grades. On univariate analysis, non-Chinese ethnicity (P = 0.031), diabetes (P = 0.018), and hyperlipidemia (P = 0.011) were predictive of progression of grades, but these were not significant on multivariate analysis.

Liver fibrosis in Asian psoriatic population on MTX is comparable to the West. Cumulative dose was not associated with liver fibrosis. Metabolic syndrome is important factors.