Addition of hyaluronic acid to the FIB-4 liver fibrosis score improves prediction of incident cirrhosis and hepatocellular carcinoma in type 2 diabetes: The Edinburgh Type 2 Diabetes Study

Abstract

Background: Type 2 diabetes (T2D) is associated with increased risk of progression to cirrhosis and hepatocellular carcinoma (HCC) in people with chronic liver diseases, particularly non-alcoholic fatty liver disease (NAFLD). However, the absolute risk of progression is low. So, it is crucial to accurately identify patients who would benefit most from hepatology referral and intensified management. Current risk-stratification tools are suboptimal and perform worse in people with diabetes.

Aims: To determine whether the addition of complementary biomarker(s) to current NAFLD risk-stratification tools in people with T2D could improve the identification of people who are at increased risk of developing incident cirrhosis or HCC.

Methods: The Edinburgh Type 2 diabetes Study (ET2DS) is a cohort study of men and women with T2D (n = 1066, age 60-75 at baseline). Cases of cirrhosis and HCC were identified over 11 years of follow-up. Biomarkers were measured at baseline and year 1 and association with incident disease was assessed using logistic regression.

Results: Of existing risk-stratification scores tested, the Fibrosis-4 (FIB-4) index and the AST:platelet ratio index (APRI) performed best in this cohort. Addition of hyaluronic acid (cut-point ≥ 50 $\mu$ g/L) to FIB-4 (cut-point ≥ 1.3) maintained a false negative rate of ≤25% and reduced the number of people incorrectly identified as "high risk" for incident disease by ∼50%.

Conclusions: The addition of hyaluronic acid to FIB-4 reduced the proportion of people inappropriately identified as "high risk" for development of cirrhosis/HCC in a community population of otherwise asymptomatic people with T2D. These findings require a validation in independent cohorts.

Keywords: NAFLD; hyaluronic acid; risk prediction; type 2 diabetes.