What liver function test (LFT) is most often elevated in fatty liver disease?

Most Commonly Elevated LFT in Fatty Liver Disease

Alanine aminotransferase (ALT) is the most commonly elevated liver function test in fatty liver disease, typically showing mild elevation (<5 times upper reference limit) with an AST:ALT ratio <1. 1

Pattern of Enzyme Elevation

• ALT is the predominant elevated enzyme in nonalcoholic fatty liver disease (NAFLD), with or without concurrent AST elevation 1, 2
• The characteristic pattern shows **AST:ALT ratio <1**, which distinguishes NAFLD from alcohol-induced liver disease (where the ratio is typically >2) 1, 2, 3
• Both aminotransferases may be mildly elevated together, but ALT elevation is more specific for hepatocellular injury in fatty liver 1

Additional Enzyme Patterns

• Alkaline phosphatase (ALP) and gamma-glutamyltransferase (GGT) may be mildly elevated in fatty liver disease, but this is less common than ALT elevation 1
• Bilirubin typically remains normal unless advanced disease or cirrhosis is present 1

Critical Clinical Pitfalls

• Normal or near-normal ALT does not exclude NAFLD or even nonalcoholic steatohepatitis (NASH) - approximately 50% of NAFLD patients have normal liver chemistries 1
• The magnitude of ALT elevation does not correlate with disease severity or fibrosis stage - patients with significant liver fibrosis may have enzymes in the normal reference range 2
• Up to 80% of patients with NASH may be identified based on elevated transaminases, but the absence of elevation is not reassuring 1

Diagnostic Utility

• ALT is more specific for liver injury than AST because ALT has low concentrations in skeletal muscle and kidney, whereas AST can be elevated from cardiac, skeletal muscle, kidney, brain, or red blood cell disorders 1
• Normal ALT reference ranges are 29-33 IU/L in men and 19-25 IU/L in women, though lower cutoffs (30 IU/L in men, 19 IU/L in women) may be more appropriate for screening fatty liver 1, 4
• ALT serves as both an indicator and predictor of fatty liver disease, with elevated levels associated with insulin resistance and endothelial dysfunction 5, 6, 4

Clinical Context

• NAFLD is the most common cause of elevated liver enzymes in developed countries, accounting for approximately 26% of incidental LFT abnormalities in primary care 2, 7
• When evaluating elevated transaminases, the AST:ALT ratio is the key discriminator: ratio <1 suggests NAFLD, while ratio >2 suggests alcohol-induced liver disease 1, 2, 3