Is ALT > AST Indicative of Fatty Liver Disease?
Yes, an ALT greater than AST (AST:ALT ratio <1) is characteristic of nonalcoholic fatty liver disease (NAFLD), though this pattern is not diagnostic on its own and does not exclude other causes of liver disease. 1
Understanding the AST:ALT Ratio in Fatty Liver Disease
The pattern of transaminase elevation provides important diagnostic clues:
- In NAFLD, the AST:ALT ratio is typically <1, meaning ALT is elevated more than AST 1, 2
- This contrasts sharply with alcoholic liver disease, where the AST:ALT ratio is generally >1.5-2.0, with ratios >3 being highly specific for alcohol-related injury 3, 4
- The NAFLD liver fat score (NLFS) specifically incorporates the AST/ALT ratio as a diagnostic parameter, with lower ratios supporting NAFLD diagnosis 1
Important Clinical Caveats
The Ratio Can Reverse in Advanced Disease
A critical pitfall to avoid: the AST:ALT ratio may reverse to >1 when NAFLD progresses to cirrhosis, so finding AST > ALT does not exclude NAFLD 1, 4. Among patients with chronic hepatitis B, the mean AST:ALT ratio was 0.59 in those without cirrhosis but rose to 1.02 in those with cirrhosis 4.
Normal ALT Does Not Exclude Significant Disease
- Up to 50% of NAFLD patients have normal liver chemistries, though 80% of those with nonalcoholic steatohepatitis (NASH) may be identified through elevated transaminases 1
- Even patients with ALT <0.5× upper limit of normal can have NASH (42%) and significant fibrosis (16%) 5
- Metabolic factors, not ALT level, are the primary drivers of histological severity in NAFLD 5
Diagnostic Approach When ALT > AST
When you encounter ALT > AST, follow this algorithmic approach:
Step 1: Assess Metabolic Risk Factors
- Evaluate for obesity, type 2 diabetes, hypertension, and dyslipidemia—the core components of metabolic syndrome that drive NAFLD 1, 6
- In patients with type 2 diabetes, 42-65% have hepatic steatosis 6
Step 2: Exclude Other Causes
- Obtain detailed alcohol consumption history (even moderate consumption can elevate enzymes) 2
- Review all medications and supplements for hepatotoxic agents 1, 2
- Check viral hepatitis serologies (HBsAg, anti-HCV) 2
- Consider autoimmune markers if clinical suspicion warrants 2
Step 3: Obtain Baseline Imaging
- Abdominal ultrasound is first-line, with 84.8% sensitivity and 93.6% specificity for moderate-to-severe steatosis 2, 6
- Ultrasound also identifies biliary obstruction, focal lesions, and other structural abnormalities 2
Step 4: Risk Stratification
- Calculate FIB-4 score to assess fibrosis risk (score >2.67 indicates high risk for advanced fibrosis) 2
- Use sex-specific ALT thresholds: >33 U/L in males and >25 U/L in females for better identification of clinically significant disease 6
Distinguishing NAFLD from Alcoholic Liver Disease
The AST:ALT ratio is your most useful discriminator:
- AST:ALT <1: Think NAFLD, viral hepatitis, or medication-induced injury 1, 2
- AST:ALT ≥2: Strongly suggests alcoholic liver disease (70% of cases have ratio >2) 3
- AST:ALT >3: Highly specific for alcoholic etiology 3
The mechanism: alcohol causes mitochondrial damage, leading to preferential AST release over ALT 3.
Clinical Pearls
- ALT is more liver-specific than AST, which can be elevated from cardiac muscle, skeletal muscle, kidney, or red blood cell disorders 2
- The combination of elevated triglycerides, total cholesterol, and low HDL is independently associated with elevated transaminases in NAFLD 6
- GGT elevation combined with AST predominance (AST:ALT >1.5) strongly suggests chronic alcohol use rather than NAFLD 3
- Wilson disease should be considered in younger patients with atypical presentations, though it may show AST > ALT in acute liver failure 1
When to Refer
Consider hepatology referral if: