NEW YORK – – and probably in those with psoriatic arthritis (PsA) as well, according to a systematic review and meta-analysis presented at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.
“Our findings imply that psoriatic patients should be screened with an ultrasonographic exam in cases where there are metabolic features that are associated with NAFLD,” reported Francesco Bellinato, MD, a researcher in the section of dermatology and venereology, University of Verona (Italy).
Dr. Francesco Belinato
The data are strong. Of 76 nonduplicate publications found in the literature, the 11 observational studies included in the meta-analysis met stringent criteria, including a diagnosis of psoriasis and PsA based on objective criteria, NAFLD confirmed with liver biopsy or imaging, and odds rates calculated with 95% confidence intervals.
From these 11 studies, aggregate data were available for 249,333 psoriatic patients, of which 49% had NAFLD, and 1,491,402 were healthy controls. Among the controls, 36% had NAFLD. Four of the studies were from North America, four from Europe, and three from Asia.
In the pooled data, the risk of NAFLD among those with psoriasis relative to healthy controls fell just short of a twofold increase (odds ratio, 1.96; 95% CI, 1.70-2.26; P < .001). When stratified by studies that confirmed NAFLD by biopsy relative to ultrasonography, there was no significant heterogeneity.
Eight of the studies included an analysis of relative risk in the context of skin lesion severity defined by Psoriasis Area and Severity Index (PASI) score. Relative to those without NAFLD, psoriatic patients with NAFLD had a significant greater mean PASI score on a pooled weighted mean difference analysis (OR, 3.93; 95% CI, 2.01-5.84; P < .0001).
courtesy Dr. Francesco Belinato
NAFLD is readily detectable in psoriasis patients on ultrasonography as exemplified by this sonogram of a patient recently evaluated by Dr. Belinato.
For PsA relative to no PsA in the five studies that compared risk between these two groups, the risk of NAFLD was again nearly twofold higher. This fell short of conventional definition of statistical significance, but it was associated with a strong trend (OR, 1.83; 95% CI, 0.98-3.43; P = .06).
The risk of NAFLD among patients with psoriasis was not found to vary significantly when assessed by univariable meta-regressions across numerous characteristics, such as sex and body mass index.
In one of the largest of the observational studies included in the meta-analysis by Alexis Ogdie, MD, associate professor of medicine and epidemiology at the University of Pennsylvania, Philadelphia, and colleagues, data were analyzed in more than 1.5 million patients, which included 54,251 patients with rheumatoid arthritis. While the hazard ratio of NAFLD was increased for both psoriasis (HR, 2.23) and PsA (HR, 2.11), it was not elevated in those with RA (HR, 0.96).
Risk by severity, possible mechanisms
This study also included an analysis of NAFLD risk according to psoriasis severity. While risk was still significant among those with mild disease (HR, 1.18; 95% CI, 1.07-1.30), it was almost twofold greater in those with moderate to severe psoriasis (HR, 2.23; 95% CI, 1.73-2.87).
Dr. Bellinato conceded that the mechanisms underlying the association between psoriasis and NAFLD are unknown, but he said “metaflammation” is suspected.
“The secretion of proinflammatory, prothrombotic, and oxidative stress mediators in both psoriatic skin and adipose tissue might act systemically and promote insulin resistance and other metabolic derangements that promote the development and progression of NAFLD,” Dr. Bellinato explained.
He thinks that noninvasive screening methods, such as currently used methods to calculate fibrosis score, might be useful for evaluating patients with psoriasis for NAFLD and referring them to a hepatologist when appropriate.
Given the strong association with NAFLD, Dr. Bellinato suggested that “the findings of this meta-analysis pave the way for novel, large, prospective, and histologically based studies.”
Courtesy Dr. Joel M. Gelfand
Dr. Joel M. Gelfand
The association between psoriasis and NAFLD is clinically relevant, agreed Joel M. Gelfand, MD, vice-chair of clinical research and medical director of the clinical studies unit, department of dermatology, University of Pennsylvania, Philadelphia.
“It is not clear if psoriasis causes fatty liver disease or vice versa, but clinicians should be aware of this association,” he said in an interview. Dr. Gelfand was a coauthor of the study by Dr. Ogdie and colleagues and led another more recent population-based study that implicated methotrexate as a factor in psoriasis-related hepatotoxicity.
If NAFLD is identified in a patient with psoriasis, treatments are limited, but Dr. Gelfand suggested that patients should be made aware of the risk. “Clinicians should encourage patients with psoriasis to take measures to protect their liver, such as avoiding drinking alcohol to excess and trying to maintain a healthy body weight,” he said.
Dr. Bellinato reported no conflicts of interest. Dr. Gelfand has financial relationships with more than 10 pharmaceutical companies, including those that make therapies for psoriasis.