Higher Concentrations of Alanine Aminotransferase Within the Reference Interval Predict Nonalcoholic Fatty Liver Disease (Lipids, Lipoproteins, And Cardiovascular Risk Factors) (Clinical Report‪)‬

Hepatic steatosis unrelated to excessive alcohol consumption is termed nonalcoholic fatty liver disease (NAFLD). [5] NAFLD encompasses the entire spectrum of liver conditions, ranging from simple steatosis through steatohepatitis to advanced fibrosis and cirrhosis (1). Concurrent with the worldwide epidemic of obesity, NAFLD is considered to be the most common cause of unexplained abnormal results of liver function tests (2). Although hepatic steatosis was long believed to be a benign disease, NAFLD has recently gained much interest (3). Percentage hepatic fat has been reported to be a feature highly associated with insulin resistance (4,5). Furthermore, several studies have suggested an association between NAFLD and features of the metabolic syndrome, including dyslipidemia and obesity, thereby stressing the association with insulin resistance as an important feature of NAFLD (6,7). Currently, NAFLD is recognized as a pathogenic factor of insulin resistance and type 2 diabetes (3). Several prospective epidemiological studies have demonstrated that increased concentrations of hepatic enzyme in serum, even within the reference interval, may be related to increased risk of type 2 diabetes and the metabolic syndrome, as well as death (8-10). Among the hepatic enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT), and y-glutamyltransferase (GGT), ALT is most closely related to liver fat accumulation (11). In cross-sectional studies (12), participants with NAFLD often have increased circulating concentrations of ALT. Paradoxically, the complete spectrum of NAFLD was reported in patients with normal ALT activity, even after the cutoff value was decreased to [less than or equal to]19 U/L (13). Moreover, increased ALT not associated with fatty liver was observed frequently in obese participants (14). ALT actually is a glucogenic enzyme, and increased ALT has been demonstrated to be an indicator of impaired insulin signaling, which might not necessarily be associated with liver injury due to hepatic steatosis (3,15). To date, although an increased ALT concentration is considered a consequence of hepatocyte damage in NAFLD (3), it is unclear what underlies the relationship between ALT and NAFLD. Of more recent interest, an inverse correlation between ALT concentrations and adiponectin concentrations has been demonstrated (16-18). As these previous observational findings are consistent with a biological link between ALT and development of NAFLD, we performed a prospective study to test whether higher concentrations of ALT within its reference interval predict future NAFLD in apparently healthy men in Korea.