AST:ALT Ratio in Diagnosing Liver Disease
Primary Diagnostic Significance
The AST:ALT ratio is most valuable for distinguishing alcoholic liver disease (ratio ≥2) from nonalcoholic liver disease (ratio <1) and for detecting the presence of cirrhosis regardless of etiology. 1, 2
Alcoholic Liver Disease
An AST:ALT ratio ≥2 is strongly suggestive of alcoholic liver disease, with ratios >3 being highly specific for this diagnosis. 1, 2
- In approximately 70% of patients with alcoholic liver disease, the AST/ALT ratio exceeds 2, though this finding has greater diagnostic value in patients without cirrhosis 1
- The mean AST:ALT ratio in alcoholic liver disease is 2.6 (range 1.1-11.2), compared to 0.9 in nonalcoholic steatohepatitis 3
- AST levels typically range from 2-6 times the upper limit of normal in severe alcoholic hepatitis, while levels >500 IU/L or ALT >200 IU/L should prompt consideration of alternative diagnoses such as drug-induced liver injury or ischemic hepatitis 1, 2
- The elevated ratio occurs because alcohol causes mitochondrial damage, leading to preferential release of AST over ALT 4
Nonalcoholic Fatty Liver Disease (NAFLD)
An AST:ALT ratio <1 is characteristic of NAFLD and nonalcoholic steatohepatitis (NASH), directly contrasting with the pattern seen in alcoholic liver disease. 1, 3
- Patients with NASH typically have a mean AST:ALT ratio of 0.9 (range 0.3-2.8), with ratios <1 in all cases in some series 3, 5
- In later stages of NAFLD, the ratio may reverse to >1, so an elevated ratio does not exclude NAFLD 1
- The ratio increases progressively with fibrosis severity in NASH: 0.7 in patients without fibrosis, 0.9 with mild fibrosis, and 1.4 with cirrhosis 3
Detection of Cirrhosis
An AST:ALT ratio >1 in patients with nonalcoholic liver disease strongly suggests the presence of cirrhosis, making this ratio valuable for assessing fibrosis stage across all etiologies. 1, 6
- In chronic hepatitis B, the mean AST/ALT ratio increases from 0.59 in patients without cirrhosis to 1.02 in those with cirrhosis 6
- The ratio often rises to >1 when cirrhosis first becomes manifest, providing an early noninvasive marker of disease progression 6
- This relationship persists even when both AST and ALT values remain within normal reference ranges 1
Clinical Application Algorithm
When interpreting the AST:ALT ratio, follow this diagnostic approach:
Ratio ≥2 (especially >3): Strongly suggests alcoholic liver disease; obtain detailed alcohol history and consider GGT measurement for confirmation 1, 2, 4
Ratio <1: Suggests nonalcoholic liver disease (NAFLD, viral hepatitis, autoimmune hepatitis); evaluate metabolic risk factors and screen for viral hepatitis 1, 3
Ratio >1 in nonalcoholic disease: Indicates probable cirrhosis; proceed with fibrosis assessment using FIB-4 score, APRI score, or transient elastography 1, 2, 6
Calculate FIB-4 score: (age × AST) / (platelet count × √ALT), where scores <1.45 have 90% negative predictive value for advanced fibrosis and scores >3.25 have 65% positive predictive value 2
Calculate APRI score: (AST/AST ULN) × 100/platelet count, where values >2 suggest cirrhosis 2
Important Caveats
The diagnostic utility of the AST:ALT ratio has critical limitations that must be recognized:
- Both AST and ALT can be normal even in established cirrhosis, so normal transaminases do not exclude advanced liver disease 1, 2
- The ratio's ability to distinguish alcoholic from nonalcoholic liver disease diminishes in the presence of cirrhosis, as both conditions may show ratios >1 6
- Non-hepatic causes of elevated AST include hemolysis, myopathy, thyroid disease, strenuous exercise, and cardiac injury, which can falsely elevate the ratio 4
- Combining the AST:ALT ratio with mean corpuscular volume (MCV) >90 fL improves sensitivity to 97.3% and specificity to 88.9% for detecting alcoholism 7
- The ratio should never be used in isolation; it must be interpreted alongside clinical history, other liver biochemistry, imaging, and fibrosis assessment 1, 2