Methotrexate and liver fibrosis in people with psoriasis: a systematic review of observational studies

Abstract

Methotrexate (MTX) is an effective treatment for psoriasis but concerns regarding the development of liver fibrosis prevent optimal use. The primary objective of this systematic review was to assess whether MTX use increases the risk of developing fibrosis in people with psoriasis. Searches were performed on Medline, Embase, the Cochrane Database and Clinical Trials Register from inception until September 2013 for studies including at least two liver biopsies in people with psoriasis. Double extraction using predefined data fields was performed. Randomized controlled trials and observational studies were considered. Statistical analysis was performed using Review Manager 5. Quality of observational studies was assessed using a study quality bias checklist. Eight observational studies met the inclusion criteria (n = 429 patients). The pooled risk difference (RD) of developing significant liver fibrosis was 0·09 [95% confidence interval (CI) -0·03 to 0·20]. The RD for developing 'any fibrosis' was 0·22 (95% CI 0·04-0·41). The RD for cirrhosis was 0·04 (95% CI 0·02-0·07). There was no clear association between cumulative dose of MTX and fibrosis. Obesity, diabetes and alcohol use were under-reported. The quality of the included studies was weak and the degree of selection bias means the results are not generalizable to all patients with psoriasis taking MTX. High-quality, population-based studies that consider potential confounders common in psoriasis population are justified for better prediction of the subset of patients at risk of liver fibrosis. In this highly selected review population, MTX use appears to contribute to the development of 'any' fibrosis without clear evidence of risk stratifiers.

Acute Severe Methotrexate Toxicity in Patients with Psoriasis: A Case Series and Discussion

“…Cumulative dose adverse events (category C) classically include chronic hepatic and pulmonary toxicity. However, a recent systematic review did not show an association between cumulative dose and hepatic fibrosis [11]. Furthermore, some patients may develop pulmonary toxicity with low MTX doses, suggesting an idiosyncratic mechanism.…”

Editor’s Highlight: Modeling Compound-Induced FibrogenesisIn VitroUsing Three-Dimensional Bioprinted Human Liver Tissues

“…MTX is a folate antagonist effectively used to manage inflammatory disorders (ie, rheumatoid arthritis, psoriasis) at low doses for extended periods of time. However, it is known to cause elevations in alanine aminotransferase (ALT) and fibrosis in a subset of patients over prolonged treatment periods (Lindsay et al, 2009;Maybury et al, 2014). TAA is a prototypical fibrogenic agent extensively used in rodent models to study the development of liver injury and fibrosis (Starkel and Leclercq, 2011).…”

Use of Methotrexate in the Treatment of Inflammatory Bowel Diseases

“…However, MTX associated advanced liver fibrosis is rarely seen in patients with IBD or RA, but is more often found in patients treated with MTX for psoriasis. 79 In the past, guidelines recommended a liver biopsy after a cumulative dose of 1,500 mg MTX. These recommendations were based on expert opinion and have been revised for IBD and RA patients.…”