What is the significance of an AST (Aspartate Aminotransferase) to ALT (Alanine Aminotransferase) ratio greater than 2:1 in patients with a history of excessive alcohol use?

AST to ALT Ratio in Alcohol Use

In patients with excessive alcohol consumption, an AST/ALT ratio greater than 2:1 is highly suggestive of alcoholic liver disease, particularly alcoholic hepatitis, though this ratio more reliably indicates advanced liver disease or cirrhosis rather than simply heavy drinking. 1

Diagnostic Significance of the Ratio

Classic Pattern in Alcoholic Liver Disease

• AST elevation is typically more prominent than ALT in alcoholic liver disease, with the AST/ALT ratio usually exceeding 1.0 and often greater than 2.0. 1
• When the AST/ALT ratio exceeds 2, alcoholic hepatitis may be suspected, and when it exceeds 3, the probability becomes very high. 1
• Both AST and ALT levels usually do not exceed 300 IU/L in alcoholic liver disease; levels above this threshold suggest alternative or additional causes of liver injury. 1, 2

What the Ratio Actually Indicates

• Only 2% of excessive drinkers without cirrhosis have an AST/ALT ratio >2, whereas 51% of patients with alcoholic cirrhosis demonstrate this ratio. 3
• The ratio of 1.22 suggests early alcoholic liver injury, though ratios >1.5-2.0 are more specific for alcohol-related disease. 4
• In about 70% of patients with alcoholic hepatitis, the AST/ALT ratio is higher than 2. 2

Critical Clinical Pitfalls

The Ratio Does Not Confirm Heavy Drinking Alone

• Most patients with high alcohol consumption but without severe liver disease do not have an AST/ALT ratio above 1.0; high AST/ALT ratio suggests advanced alcoholic liver disease rather than simply excessive drinking. 5
• Among patients with alcohol dependence admitted for withdrawal treatment, 64% had a ratio ≤1.0, and only exceptionally was the ratio ≥2. 5
• In contrast, 69% of patients with alcohol-related cirrhosis had a ratio ≥2, and only 8% had a ratio ≤1.0. 5

Loss of Specificity in Cirrhosis

• The AST/ALT ratio as a means of separating alcoholic from nonalcoholic liver disease becomes less helpful in the presence of cirrhosis, as the ratio often rises to >1.0 when cirrhosis develops regardless of etiology. 6
• In chronic hepatitis B without cirrhosis, the mean AST/ALT ratio was 0.59, but rose to 1.02 in those with cirrhosis. 6
• The AST/ALT ratio is neither specific nor sensitive in the cirrhotic stage of disease. 2

Normal Enzymes Do Not Exclude Disease

• More than 50% of patients with advanced fibrosis from alcohol have normal or minimally elevated transaminases, making AST and ALT levels potentially misleading. 4
• Normal transaminases do not exclude significant alcohol-related liver disease; ALT levels can be normal in more than 50% of patients with advanced fibrosis. 4, 2

Distinguishing Alcoholic from Non-Alcoholic Liver Disease

Comparative Ratios

• An AST/ALT ratio ≥2 is strongly suggestive of alcoholic liver disease, while values <1 suggest non-alcoholic steatohepatitis (NASH). 7
• Patients with NASH have a mean AST/ALT ratio of 0.9 (median 0.7), compared to 2.6 (median 2.0) in alcoholic liver disease. 7
• In NASH, subset analysis revealed mean ratios of 0.7 for no fibrosis, 0.9 for mild fibrosis, and 1.4 for cirrhosis. 7

Supporting Laboratory Markers

• Gamma-glutamyl transferase (GGT) is elevated in about 75% of habitual drinkers and is useful for determining whether a patient has abstained from drinking. 1
• Carbohydrate deficient transferrin (CDT) provides the highest diagnostic performance (AUC 0.77) for detecting excessive drinkers, followed by GGT (AUC 0.68). 3
• Mean corpuscular volume (MCV) may be elevated by heavy drinking when daily alcohol consumption exceeds 60 g, though MCV elevation alone has low sensitivity. 1

Practical Application

Calculating Alcohol Consumption

• Average daily alcohol intake is calculated using: [amount consumed (mL) × alcohol by volume (%) × 0.785 × number of drinking days per week] ÷ 7. 1, 4
• Risk thresholds are >40 g/day for men and >20 g/day for women. 1, 2

When to Suspect Advanced Disease

• An AST/ALT ratio >2 in the context of alcohol use should prompt urgent non-invasive fibrosis assessment (FibroScan or FibroTest) rather than relying on transaminases alone. 4, 8
• If FibroScan >12-15 kPa, this suggests advanced fibrosis in alcohol-related liver disease. 4
• If FibroScan >16 kPa, referral to hepatology for advanced liver disease management is warranted. 4