GEMS, a Genetic and Metabolic Staging Predicting the Outcome of Non-Alcoholic Fatty Liver Disease

Abstract

Background and Aim: Non-alcoholic fatty liver disease(NAFLD) is an emergent cause of liver-related events(LRE). We have assessed the ability of a composite score based on clinical features, metabolic comorbidities and genetic background, to predict LRE. Methods: 546 consecutive patients with NAFLD were recruited and stratified according to FIB-4(low risk <1.3;intermedium-high risk ≥1.3). LRE were defined as occurrence of HCC or hepatic decompensation. Cox regression multivariate analysis was used to identify baseline variables associated with LRE. Results: Over a median follow-up of 73.8 months, 58 patients experienced LRE(only 1 in the cohort of patients with FIB-4 65 years(HR 17.96), platelets between 110,000 and 150,000/mmc(HR 6.89), platelets < 110,000/mmc(HR 13.54) and albumin < 4 g/L(HR 1.5), metabolic variables like low HDL cholesterol(HR 1.88), genetic variables such as TM6SF2 rs58542926 CT/TT(HR1.94) and HSD17B13 rs72613567 T/TA(HR1.83), and the interactions between PNPLA3 rs738409 and both male gender(HR 0.32) and diabetes(HR 5.16) were independently associated with the development of LRE. The AUC of the model was of 0.87 at 1, 3 and 5 years. GEMS, derived from Cox model weighted coefficients, ranked from 0 to 10, and was categorized in 5 classes(0-5,5-6,6-7,7-8,8-10), the risk of LRE increasing from 4% in patients in the best (GEMS 0-5), to 91% in patients in the worst class(GEMS 8-10). Conclusions: GEMS score, based on an easy-to-obtain profile at presentation, has an adequate ability to predict the outcome of patients with NAFLD. Funding Statement: None. Declaration of Interests: None. Ethics Approval Statement: The study was carried out in accordance with the principles of the Helsinki Declaration and with local and national laws. Approval was obtained from the “Comitato Etico Palermo 1” ID 2014.