Sequential algorithm to stratify liver fibrosis risk in overweight/obese metabolic dysfunction-associated fatty liver disease

Abstract

BackgroundNon-diabetic overweight/obese metabolic dysfunction-associated fatty liver disease (MAFLD) represents the largest subgroup with heterogeneous liver fibrosis risk. Metabolic dysfunction promotes liver fibrosis. Here, we investigated whether incorporating additional metabolic risk factors into clinical evaluation improved liver fibrosis risk stratification among individuals with non-diabetic overweight/obese MAFLD.Materials and methodsComprehensive metabolic evaluation including 75-gram oral glucose tolerance test was performed in over 1000 participants from the New Hong Kong Cardiovascular Risk Factor Prevalence Study (HK-NCRISPS), a contemporary population-based study of HK Chinese. Hepatic steatosis and fibrosis were evaluated based on controlled attenuation parameter and liver stiffness (LS) measured using vibration-controlled transient elastography, respectively. Clinically significant liver fibrosis was defined as LS ≥8.0 kPa. Our findings were validated in an independent pooled cohort comprising individuals with obesity and/or polycystic ovarian syndrome.ResultsOf the 1020 recruited community-dwelling individuals, 312 (30.6%) had non-diabetic overweight/obese MAFLD. Among them, 6.4% had LS ≥8.0 kPa. In multivariable stepwise logistic regression analysis, abnormal serum aspartate aminotransferase (AST) (OR 7.95, p<0.001) and homeostasis model assessment of insulin resistance (HOMA-IR) ≥2.5 (OR 5.01, p=0.008) were independently associated with LS ≥8.0 kPa, in a model also consisting of other metabolic risk factors including central adiposity, hypertension, dyslipidaemia and prediabetes. A sequential screening algorithm using abnormal AST, followed by elevated HOMA-IR, was developed to identify individuals with LS ≥8.0 kPa, and externally validated with satisfactory sensitivity (>80%) and negative predictive value (>90%).ConclusionA sequential algorithm incorporating AST and HOMA-IR levels improves fibrosis risk stratification among non-diabetic overweight/obese MAFLD individuals.

Simple proxies of insulin resistance identify obese metabolic dysfunction‐associated fatty liver disease subjects with advanced liver disease

“…Non-diabetic obesity is characterised by a relevant prevalence of ongoing active chronic liver disease; it has been reported about 6% (defined as LS ≥8.0 kPa) in a contemporary Hong Kong cohort, 11 and a high waist is significantly associated with LS (adjusted OR 2.61, 95% CI: 1.17-5.82) in the NHANES 2017-2018 US adults. 24 The presence of serious liver metabolic abnormalities negatively affects patient prognosis, 25,26 although the impact of obesity itself deserved further exploration.…”

“…Individuals with NAFLD are more prone to develop advanced fibrosis, cirrhosis, and hepatocellular carcinoma in the presence of T2D, 8,9 while the role of body weight per se is less defined. Given that the majority of MAFLD individuals are obese, 10 while not all individuals with obesity are metabolically unhealthy nor share the same degree of liver involvement, 11 risk stratification tools would be useful to prompt the screening for advanced liver disease in the obese population.…”