Excerpt
Non-alcoholic fatty liver disease (NAFLD), which is closely associated with type 2 diabetes and obesity [
1,
2], is now a major cause of liver disease in many countries and has contributed to an increase in liver disease-related mortality [
3,
4]. According to the most recent practice guidance published by the American Association for the Study of Liver Diseases (AASLD) [
5], the diagnosis of NAFLD is established by fulfillment of two criteria: evidence of hepatic steatosis by either imaging or histology and the exclusion of secondary etiologies such as significant alcohol ingestion, use of a medication known to cause steatosis, or liver disorders resulting in secondary steatosis such as hepatitis C, Wilson’s disease, and inborn errors of metabolism. Furthermore, the differentiation of NAFLD into either non-alcoholic fatty liver (NAFL) or non-alcoholic steatohepatitis (NASH) can only be made on histologic analysis of liver tissue [
5,
6]. This distinction is particularly significant as NASH is associated with an increased risk of cirrhosis, hepatocellular carcinoma, and liver-related mortality [
1,
2,
4,
7]. The use of liver biopsy is restricted by cost, risk of complications, and patient discomfort [
8], while diagnostic yield is limited by sampling variability and physician expertise [
9]. Therefore, there is a need for non-invasive means for diagnosis of NASH and advanced fibrosis among patients with NAFLD. Imaging modalities such as ultrasonography, computed tomography, magnetic resonance imaging, and magnetic resonance spectroscopy have been reviewed by Lee et al. [
10]. In addition, a number of blood-based tests have been examined for diagnosis and staging of NAFLD. Two indices that have demonstrated accuracy for detection of steatosis are the NAFLD Liver Fat Score (NLFS) and Hepatic Steatosis Index (HSI), components of which include the diagnosis of metabolic syndrome, diabetes mellitus, fasting serum insulin, AST, and AST/ALT ratio [
11,
12]. The NLFS has a sensitivity of 86% and specificity of 71% at a threshold of − 0.640 [
11]. The HSI has a sensitivity of 66% and specificity of 69% at a cutoff of 36 [
12]. …