Abstract
BackgroundType 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.AimsTo 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.MethodsThe 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.ResultsOf 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 μ 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%.ConclusionsThe 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.
Highlights
Non‐alcoholic fatty liver disease (NAFLD) is recognized as the liver component of the metabolic syndrome, a cluster of conditions including abdominal obesity, impaired glucose regulation or diabetes, hypertension, hypercholesterolemia, and hypertriglyceridemia, which are associated with increased cardiovascular risk.[1]
Serum hyaluronic acid in conjunction with the FIB‐4 risk‐stratification score reduced the number of false positive results in this cohort, without substantially increasing the false negative results, either in isolation or within the EASL‐EASD‐EASO algorithm
Addition of hyaluronic acid improved the association of the FIB‐ 4 model with incident cirrhosis/hepatocellular carcinoma (HCC)
Summary
Non‐alcoholic fatty liver disease (NAFLD) is recognized as the liver component of the metabolic syndrome, a cluster of conditions including abdominal obesity, impaired glucose regulation or diabetes, hypertension, hypercholesterolemia, and hypertriglyceridemia, which are associated with increased cardiovascular risk.[1] With rising population levels of obesity, prevalence of NAFLD is rising and 25% of people globally may be affected.[2] Type 2 diabetes(T2D) is associated with a further increased prevalence of NAFLD, the prevalence of NAFLD steatosis being 40–70%.3–6. People with T2D have a higher incidence of, and risk of progression to, cirrhosis and hepatocellular carcinoma (HCC).[7,8,9,10,11]. In T2D, identifying those at increased risk of developing cirrhosis/ HCC is important to prompt intensified lifestyle interventions, enhanced monitoring of disease progression, and timely initiation of surveillance for varices and HCC. Screening for NAFLD in T2D is advocated in European guidelines (European Association for the Study of the Liver, European Association for the Study of Diabetes, European Association for the Study of Obesity [EASL‐EASD‐EASO]).[12]
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