What are the typical liver enzyme changes in alcoholic liver disease?

Liver Enzyme Changes in Alcoholic Liver Disease

Characteristic Enzyme Pattern

The hallmark of alcoholic liver disease is an AST/ALT ratio greater than 1, typically exceeding 2:1, with absolute aminotransferase levels rarely exceeding 300 IU/L. 1

AST and ALT Levels

• AST is characteristically elevated more than ALT in alcoholic liver disease, with the AST/ALT ratio typically greater than 1 and often exceeding 2:1 1
• An AST/ALT ratio ≥2.0 is strongly suggestive of alcoholic liver disease, while a ratio of 5.84 indicates advanced alcoholic hepatitis or cirrhosis 2
• In alcoholic hepatitis specifically, AST/ALT ratios >1.5 are seen in more than 98% of histologically proven cases 2
• AST and ALT levels rarely exceed 300-400 IU/L in alcoholic liver disease, which helps distinguish it from acute drug-induced liver injury or ischemic hepatitis where levels typically exceed 400 IU/L 1, 2
• AST elevation occurs in all forms of alcoholic liver disease with approximately 50% sensitivity and 80% specificity 1

Critical Caveat About Normal Enzymes

Normal or minimally elevated aminotransferases do NOT exclude advanced alcoholic liver disease or cirrhosis. This is a common and dangerous pitfall:

• More than 50% of patients with advanced fibrosis from alcohol have normal or minimally elevated transaminases 3
• In one study of 78 patients with alcoholic cirrhosis, 90% had normal ALT (average 27 U/L) and 15% had normal AST (average 59 U/L) 4
• Aminotransferase levels bear no relationship to clinical events, complications, or mortality in established alcoholic cirrhosis 4
• The AST/ALT ratio may be less helpful in distinguishing alcoholic from non-alcoholic liver disease when cirrhosis is present, as the ratio increases toward 1.0 or greater in any cirrhotic patient 5

GGT (Gamma-Glutamyl Transpeptidase)

GGT is the most frequently used and cost-effective marker for detecting chronic alcohol consumption:

• GGT has 73% sensitivity for detecting daily ethanol consumption >50g, compared to AST (50%) and ALT (35%) 1
• GGT specificity is approximately 75%, lower than carbohydrate-deficient transferrin (CDT) at 92% 1
• GGT is usually higher in alcoholic liver disease compared to other liver diseases 1
• GGT loses specificity in advanced liver disease because it elevates with extensive fibrosis regardless of cause 1
• GGT is influenced by alcohol consumption, body mass index (BMI), and sex 1
• GGT levels recover slowly over months following abstinence, making it useful for monitoring compliance 3

Other Laboratory Markers

Mean Corpuscular Volume (MCV)

• MCV elevation occurs with heavy drinking, particularly when daily alcohol consumption exceeds 60g 1
• MCV has 52% sensitivity for detecting chronic alcohol consumption 1
• MCV returns to normal after several months of abstinence 1
• Combining MCV with GGT increases diagnostic sensitivity 1

Carbohydrate-Deficient Transferrin (CDT)

• CDT has 69% sensitivity but 92% specificity for detecting daily ethanol consumption >50g 1
• CDT is the most specific marker but is not widely used due to cost and lower sensitivity 1

Advanced Disease Markers

When alcoholic liver disease progresses to cirrhosis or severe alcoholic hepatitis, synthetic function deteriorates:

• Decreased serum albumin 1
• Prolonged prothrombin time/elevated INR 1
• Elevated bilirubin 1
• Thrombocytopenia (decreased platelet count) 1

Diagnostic Algorithm

When evaluating suspected alcoholic liver disease:

1. Document alcohol consumption >30g/day in men or >20g/day in women using the formula: [volume (mL) × alcohol % × 0.785 × drinking days per week] ÷ 7 1, 3

2. Check routine blood tests: AST, ALT, GGT, MCV, albumin, bilirubin, INR, platelet count 1

3. Calculate AST/ALT ratio: Ratio >2 strongly suggests alcoholic liver disease; ratio >1.5 seen in >98% of alcoholic hepatitis 2

4. Do NOT rely on normal transaminases to exclude disease - immediately obtain non-invasive fibrosis assessment (FibroScan or FibroTest) as normal enzymes do not exclude advanced fibrosis 2, 3

5. FibroScan interpretation: >12-15 kPa suggests advanced fibrosis; >16 kPa warrants hepatology referral 3

6. Calculate FIB-4 score: [age × AST] / [platelet count × √ALT], where <1.45 has 90% negative predictive value for advanced fibrosis and >3.25 has 65% positive predictive value 2

Key Clinical Pitfalls to Avoid

• Never assume normal or mildly elevated transaminases exclude significant alcoholic liver disease - this is the most dangerous error 3, 4
• The AST/ALT ratio becomes less reliable for distinguishing alcoholic from non-alcoholic causes once cirrhosis develops 5
• GGT elevation is not specific to alcohol and can be elevated by obesity, diabetes, smoking, and medications 1
• Absolute aminotransferase levels >400 IU/L should prompt consideration of alternative diagnoses like drug-induced liver injury or ischemic hepatitis 2