Obesity, Insulin Resistance Are Linked With Advanced Liver Fibrosis in Patients With Psoriasis

Patients with psoriasis are more likely than the general population to develop advanced liver fibrosis, and historically, this fact has been attributed to treatment with methotrexate, a disease-modifying drug. However, those with psoriasis also have higher rates of other independent risk factors for advanced liver fibrosis, including obesity, insulin resistance, and diabetes. A paper recently published in JAMA Dermatology sought to discuss the prevalence of advanced liver fibrosis in patients with psoriasis, and to explore associated factors.

Data for the study, derived from the Co-morbidities in Severe Psoriasis (CORE) cohort of 400 patients with severe chronic plaque psoriasis, recruited from 2012 to 2015 at a large specialist center in the United Kingdom. In total, 333 patients had evaluable transient elastography (TE) data; TE is a noninvasive alternative to biopsy to detect advanced fibrosis.

In total, 37% of patients had overweight, 37.2% had obesity, 79% had raised waist circumference, 53% were insulin resistant, 22% had diabetes, and 50% had nonalcoholic fatty liver disease (NAFLD). At enrollment, 66.6% of patients were taking a biologic (including adalimumab, etanercept, infliximab, ustekinumab, and secukinumab). While only 21% were taking methotrexate, 85% had methotrexate exposure in their history.

The study’s authors found that 14.1% of patients (95% CI, 10.4%-17.9%) had advanced fibrosis, representing a 7-fold increase compared with the general population. Univariate analysis revealed a significant association between advanced fibrosis and age, severity of psoriasis, psoriatic arthritis, body mass index, waist circumference, metabolic syndrome, physical activity score, NAFLD, fasting glucose level, and insulin resistance, as well as and triglyceride, high-density lipoprotein, cholesterol, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and γ-glutamyl transferase levels.

A multivariate analysis revealed that a combination of increased central obesity (waist circumference), insulin resistance, psoriasis severity, aspartate aminotransferase level, platelet count, and reduced alcohol use were linked with advanced fibrosis.

“Our data suggest that people with central obesity, insulin resistance, and active psoriasis are the most at risk for liver fibrosis,” wrote the authors, and “if use of methotrexate is a risk factor, it is not the only risk factor and for most patients it is unlikely to be the most important risk factor.”

The authors wrote that additional research will help to better understand how obesity, insulin resistance, and inflammation—as well as the use of systemic therapies—can impact personalized therapeutic decision-making to improve patient outcomes.

Reference

Maybury CM, Porter HF, Kloczko E, et al. Prevalence of advanced liver fibrosis in patients with severe psoriasis [published online June 5, 2019]. JAMA Dermatol. doi: 10.1001/jamadermatol.2019.0721.