Bidirectional Association Between Psoriasis and Nonalcoholic Fatty Liver Disease: Real-World Evidence From Two Longitudinal Cohort Studies

The exclusion of other chronic liver diseases including "excess" alcohol intake has until now been necessary to establish a diagnosis of metabolic dysfunction-associated fatty liver disease (MAFLD). However, given our current understanding of the pathogenesis of MAFLD and its rising prevalence, "positive criteria" to diagnose the disease are required. In this work, a panel of international experts from 22 countries propose a new definition for the diagnosis of MAFLD that is both comprehensive and simple, and is independent of other liver diseases. The criteria are based on evidence of hepatic steatosis, in addition to one of the following three criteria, namely overweight/obesity, presence of type 2 diabetes mellitus, or evidence of metabolic dysregulation. We propose that disease assessment and stratification of severity should extend beyond a simple dichotomous classification to steatohepatitis vs. non-steatohepatitis. The group also suggests a set of criteria to define MAFLD-associated cirrhosis and proposes a conceptual framework to consider other causes of fatty liver disease. Finally, we bring clarity to the distinction between diagnostic criteria and inclusion criteria for research studies and clinical trials. Reaching consensus on the criteria for MAFLD will help unify the terminology (e.g. for ICD-coding), enhance the legitimacy of clinical practice and clinical trials, improve clinical care and move the clinical and scientific field of liver research forward.

As the epidemics of obesity and type 2 diabetes mellitus increase worldwide, the prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing proportionately. The subtype of NAFLD which can be characterised as non-alcoholic steatohepatitis (NASH) is a potentially progressive liver disease that can lead to cirrhosis, hepatocellular carcinoma, liver transplantation, and death. NAFLD is also associated with extrahepatic manifestations such as chronic kidney disease, cardiovascular disease and sleep apnoea. NAFLD and NASH carry a large economic burden and create poor health-related quality of life. Despite this important burden, we are only beginning to understand its mechanisms of pathogenesis and the contribution of environmental and genetic factors to the risk of developing a progressive course of disease. Research is underway to identify appropriate non-invasive diagnostic methods and effective treatments. Although the risk of liver-related mortality is increased in patients with NAFLD and liver fibrosis stages F3 or F4, the leading cause of death is cardiovascular disease. Given the rapidly growing global burden of NAFLD and NASH, efforts must continue to find accurate non-invasive diagnostic and prognostic biomarkers, to develop effective treatments for individuals with advanced NASH and prevention methods for individuals at high risk of NAFLD and progressive liver disease.

Psoriasis, a papulosquamous skin disease, was originally thought of as a disorder primarily of epidermal keratinocytes, but is now recognised as one of the commonest immune-mediated disorders. Tumour necrosis factor alpha, dendritic cells, and T-cells all contribute substantially to its pathogenesis. In early-onset psoriasis (beginning before age 40 years), carriage of HLA-Cw6 and environmental triggers, such as beta-haemolytic streptococcal infections, are major determinants of disease expression. Moreover, at least nine chromosomal psoriasis susceptibility loci have been identified. Several clinical phenotypes of psoriasis are recognised, with chronic plaque (psoriasis vulgaris) accounting for 90% of cases. Comorbidities of psoriasis are attracting interest, and include impairment of quality of life and associated depressive illness, cardiovascular disease, and a seronegative arthritis known as psoriatic arthritis. A more complete understanding of underlying pathomechanisms is leading to new treatments, which will be discussed in the second part of this Series.