Obesity Abstracts

Background: Approximately 15-25% of the world population has non-alcoholic fatty liver disease (NAFLD) and nearly quarter go on to develop non-alcoholic steatohepatitis (NASH). Obesity and T2DM are strong risk factors with prevalence of NAFLD rising to 90% in obesity and 60% in T2DM. Liver biopsy remains the gold standard in diagnosis and prognosis; nevertheless, it is expensive and invasive. The underlying fibrosis stage is key in determining clinical outcomes hence, a reliable non-invasive biomarker, which identifies early stages of fibrosis, could improve clinical management.

Aim: To compare two biomarkers; perilipin-2 (PLIN2) and Ras-related protein-14 (RAB14), with cytokeration-18 (CY18) in NASH and liver fibrosis diagnosis and resolution.

Methods: BRAVES (NCT03524365) study included fifty patients with histologically proven NASH who underwent RYGB. All had an ultrasound-guided needle liver biopsy at 1-year follow-up to assess improvement/resolution of NASH and/or fibrosis. PLIN2 and RAB14 (using flow cytometry) and CY18 (using Simple Plex, Ella and M65 ELISA, PREVIA) were analysed on pre and post-surgery samples. A uni-variable logistic model followed by a multi-variable logistic model with a step-wise elimination procedure was assessed to investigate the role of covariates (such as presence/absence of T2DM, triglycerides, gender) in predicting NASH resolution without worsening of fibrosis and fibrosis improvement without worsening of NASH post-surgery. For both NASH and fibrosis, improvement was defined as NAFLD Activity Score (NAS)/Steatosis Activity Fibrosis (SAF-F) values at 1-year follow-up smaller than pre-surgery values.

Results: Patients were aged 49±9 (mean±SD) years, 56% were male and 54% had T2DM. 15 had NAS=3; 21, NAS=4; and 14, NAS≥5. F1, F2 and F3 were reported in 23, 23 and 4 respectively. After RYGB, resolution of NASH without worsening of fibrosis occurred in 37 patients. From step-wise selection procedure it emerged that only PLIN2 was a significant predictor of NASH resolution (P0.0016). PLIN2 was also able to predict NASH severity. RAB14 predicted severity of fibrosis changes for SAF-F>1 (P0.008) with 84% accuracy.

Conclusion: PLIN2 and RAB14 are reliable non-invasive biomarkers in diagnosing the presence and severity of NASH/liver fibrosis in obesity as well as resolution of NASH after metabolic surgery.