Screening for non-alcoholic fatty liver disease in type 2 diabetes using non-invasive scores and association with diabetic complications
Stefano Ciardullo, Emanuele Muraca, Silvia Perra, Eleonora Bianconi, Francesca Zerbini, Alice Oltolini, Rosa Cannistraci, Paola Parmeggiani, Giuseppina Manzoni, Amalia Gastaldelli, Guido Lattuada, Gianluca Perseghin
Abstract
OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is prevalent in patients with type 2 diabetes. Here, we estimate the proportion of patients with type 2 diabetes that should be referred to hepatologists according to the European Association for the Study of the Liver (EASL)-European Association for the Study of Diabetes (EASD)-European Association for the Study of Obesity (EASO) Guidelines and evaluate the association between non-invasive biomarkers of steatosis and fibrosis and diabetic complications. RESEARCH DESIGN AND METHODS: This is a retrospective analysis of type 2 diabetes patients who attended on a regular basis our diabetes clinic between 2013 and 2018 (n=2770). Steatosis was assessed using Fatty Liver Index (FLI), Hepatic Steatosis Index and NAFLD Ridge Score and fibrosis using NAFLD Fibrosis Score (NFS), Fibrosis-4 (FIB-4), aspartate aminotransferase (AST) to platelet ratio index (APRI) and AST/alanine aminotransferase (ALT) ratio. Outcome measures were altered albumin excretion rate (AER), chronic kidney disease (CKD) and cardiovascular disease (CVD). RESULTS: The prevalence of advanced fibrosis varied from 1% (APRI) to 33% (NFS). The application of the guidelines using a sequential combination of FLI and FIB-4 would lead to referral of 28.3% of patients when using standard FIB-4 cut-offs, while this number dropped to 13.4% when age-adjusted FIB-4 thresholds were applied. A higher prevalence of altered AER was associated with liver steatosis (FLI: OR: 3.49; 95% CI 2.05 to 5.94, p<0.01), whereas liver fibrosis was associated with CKD (FIB-4: OR: 6.39; 95% CI 4.05 to 10.08, p<0.01) and CVD (FIB-4: OR: 2.62; 95% CI 1.69 to 4.04, p<0.01). CONCLUSIONS: While specific fibrosis scores identify different proportion of patients with advanced fibrosis, the use of age-adjusted FIB-4 cut-offs leads to a drop in gray-zone results, making referrals to hepatologists more sustainable. Interestingly non-invasive biomarkers were consistently associated with a different pattern of diabetic complications.