Noninvasive biomarkers for the diagnosis of steatohepatitis and advanced fibrosis in NAFLD

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of abnormal liver function test results in both adults and children [1,2]. NAFLD in fact covers a histological spectrum ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), advanced fibrosis, and cirrhosis [1]. Simple steatosis without fibrosis or inflammation has a benign clinical course in most but not in all cases without excess mortality [3]. NASH, on the other hand, may have a more progressive course that can lead to cirrhosis in 10-15% of patients [4]. Survival is lower in patients with NASH based on the findings from long-term longitudinal studies [3,5]. It is therefore imperative to distinguish simple steatosis from NASH in order to provide risk stratification and intervention slowing down disease progression for patients with the latter condition.Liver biopsy remains the gold standard for making the diagnosis of NASH. However, this procedure is invasive, costly, and is associated with rare but potential complications and sampling errors. Hence it is not suitable as a screening tool for a condition that affects one-third of the American population [6]. Imaging studies such as ultrasonography, computed tomography (CT), and magnetic resonance imaging have been used to diagnose NAFLD. These modalities have the advantages of being noninvasive and can be repetitively performed over a period of time. Nevertheless, none of them have sufficient sensitivity and specificity for staging the disease and cannot distinguish between simple steatosis and NASH with or without fibrosis [6].Alanine aminotransferase (ALT) has been used as a surrogate marker for liver injury. Several studies suggested that ALT is not an ideal biomarker for either diagnosis of NAFLD or distinguishing simple steatosis from NASH. In a cross-sectional population study, examining hepatic steatosis based on the measurement of hepatic triglyceride content by magnetic resonance spectroscopy, nearly one-third (31%) of the