Differences in Sensitivity to Alcohol Exposure Among Liver Function Indicators and Their Methodological Impact on Dose-Response Research in ALD

Abstract

Dose-response studies in alcohol-related liver disease (ALD) vary widely in their choice of effect indicators, making low-risk drinking thresholds difficult to compare across studies. This narrative review examines recent literature to compare the sensitivity of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), the AST/ALT ratio, the AST-to-platelet ratio index (APRI), and the fibrosis-4 index (FIB-4) in reflecting alcoholic liver injury. We searched PubMed, CNKI, Wanfang, and other databases from inception to September 13,2026, focusing on ALD liver function indicators and non-invasive tests. The available evidence suggests that GGT and the AST/ALT ratio appear to be more sensitive to alcohol intake than ALT. GGT can rise even in light-to-moderate drinkers and often becomes abnormal earlier than ALT or AST. The AST/ALT ratio rises more steeply with increasing alcohol consumption. When ALT is used as the sole effect indicator, the dose-response curve tends to be flattened, which may lead to a higher estimated threshold. When GGT or the AST/ALT ratio is used as the effect indicator, the curve is steeper, and significant liver injury may detect biochemical abnormalities at lower doses. However, because this is a narrative review, most existing evidence is indirect, and few studies have directly compared the slopes of these indicators within the same cohort. We recommend that future studies combine multiple indicators in a comprehensive assessment model and use objective alcohol markers to calibrate dose assessment.