Rethinking noninvasive steatosis indices: Structural limitations and misclassification across the body mass index spectrum

Abstract

The rebranding of nonalcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated steatotic liver disease (MASLD) has shifted the clinical focus toward underlying metabolic drivers. This necessitates a re-evaluation of noninvasive diagnostic tools to better align with metabolic dysfunction as the primary driver of hepatic steatosis. Commonly used indices, including the fatty liver index, hepatic steatosis index, and NAFLD liver fat score, were originally developed to estimate liver fat in general populations but are now applied to diagnose or screen for NAFLD in diverse clinical settings. However, their diagnostic performance is not consistent across different patient populations. In individuals with obesity, these diagnostic indices tend to over-identify hepatic steatosis due to excessively high sensitivity and low specificity. Conversely, in lean populations, these same indices often have low sensitivity, leading to under-diagnosis. These findings indicate that steatosis indices are strongly influenced by body composition and metabolic context. This review proposes a unified conceptual framework in which these indices are interpreted as body composition-dependent tools rather than direct measures of hepatic fat. Their structural reliance on anthropometric variables may result in systematic misclassification across the body mass index spectrum, limiting their utility as universal diagnostic classifiers. Accordingly, a shift toward context-dependent interpretation and integrated diagnostic strategies is required. Effective MASLD management in clinical practice requires combining noninvasive markers with imaging, fibrosis staging, and metabolic assessment to refine risk stratification, particularly in atypical cases such as severe obesity or lean MASLD.

Keywords: Metabolic dysfunction-associated steatotic liver disease; Fatty liver index; Hepatic steatosis index; Nonalcoholic fatty liver disease liver fat score; Body mass index; Misclassification; Noninvasive indices; Hepatic steatosis

Core Tip: While noninvasive steatosis markers are widely used, their diagnostic accuracy varies across the body mass index spectrum. Their reliance on anthropometric parameters leads to systematic errors, resulting in overestimation of steatosis and underestimation in lean individuals. Consequently, these tools should be utilized in a context-dependent manner, interpreted alongside imaging and metabolic assessments.