What are the normal ranges and clinical significance of AST (aspartate aminotransferase) versus ALT (alanine aminotransferase), and how does the AST/ALT ratio help differentiate liver diseases?

AST vs ALT: Normal Ranges, Clinical Significance, and Diagnostic Utility

Normal Reference Ranges

ALT is significantly more liver-specific than AST and has sex-specific normal ranges that are lower than most commercial laboratory cutoffs. Normal ALT levels are 29-33 IU/L for males and 19-25 IU/L for females 1. AST is present not only in liver tissue but also in cardiac muscle, skeletal muscle, kidneys, brain, and red blood cells, making it less specific for hepatocellular injury 1, 2.

Clinical Significance and Specificity

ALT is the single most specific marker for liver injury because it is primarily concentrated in hepatocytes with minimal presence in skeletal muscle and kidney 1, 3. This makes ALT elevation particularly meaningful for identifying hepatocellular damage, whereas AST elevation can originate from multiple sources including:

• Cardiac muscle (myocardial infarction) 2, 4
• Skeletal muscle injury (rhabdomyolysis, vigorous exercise) 1
• Hemolysis (red blood cell disorders) 1
• Renal disease 1

Because of AST's broader tissue distribution, creatine kinase should be measured when AST is elevated to exclude muscle injury as the source 1.

Severity Classification of Transaminase Elevations

The American College of Radiology classifies aminotransferase elevations as 1, 5:

• Mild: <5 times the upper limit of normal (ULN)
• Moderate: 5-10 times ULN
• Severe: >10 times ULN

AST/ALT Ratio: Differentiating Liver Diseases

Alcoholic Liver Disease

An AST/ALT ratio ≥2 is highly suggestive of alcoholic liver disease, with ratios >3 being particularly specific 1, 6, 7. In alcoholic hepatitis, 70% of patients demonstrate an AST/ALT ratio >2, and the ratio is >1.5 in >98% of histologically proven cases 1. The mean AST level is typically around 152 U/L and ALT around 70 U/L, with both rarely exceeding 400 IU/mL 1.

Nonalcoholic Fatty Liver Disease (NAFLD)

NAFLD characteristically presents with an AST/ALT ratio <1, meaning ALT is higher than AST 1, 7. Patients with NASH have a mean AST/ALT ratio of 0.9 (range 0.3-2.8, median 0.7) 7. This pattern helps distinguish NAFLD from alcoholic liver disease 1, 7.

Cirrhosis Detection

In patients with chronic nonalcoholic liver disease, an AST/ALT ratio >1 strongly suggests the presence of cirrhosis 6. Among patients with chronic hepatitis B, the mean AST/ALT ratio is 0.59 in those without cirrhosis but rises to 1.02 in those with cirrhosis 6. The AST/ALT ratio often rises to >1.0 when cirrhosis first becomes manifest, making it a useful marker for disease progression 6.

Subset analysis of NASH patients reveals mean AST/ALT ratios of 7:

• 0.7 in patients with no fibrosis
• 0.9 in patients with mild fibrosis
• 1.4 in patients with cirrhosis

Viral Hepatitis

In chronic viral hepatitis, the AST/ALT ratio is typically <1.0 in the absence of cirrhosis 6. However, this ratio may reverse (become >1) when cirrhosis develops, even in nonalcoholic disease 1, 6.

Pattern of Liver Injury Classification

The R-value determines whether liver injury is hepatocellular, cholestatic, or mixed 8:

R-value = (ALT/ULN) ÷ (ALP/ULN)

• Hepatocellular pattern: R ≥5 (predominant transaminase elevation)
• Cholestatic pattern: R ≤2 (predominant alkaline phosphatase elevation)
• Mixed pattern: R >2 and <5

AST can replace ALT in this calculation when ALT is unavailable 8.

Critical Diagnostic Pitfalls

• Do not assume that the AST/ALT ratio reliably separates alcoholic from nonalcoholic liver disease in the presence of cirrhosis, as the ratio may be >1 in cirrhotic patients regardless of etiology 6.

• Normal ALT does not exclude significant liver disease—up to 50% of patients with NAFLD and 10% with advanced fibrosis may have normal ALT using conventional thresholds 1.

• The magnitude of transaminase elevation does not reliably predict clinical significance or severity; the overall clinical context, longitudinal trend, and pattern of enzyme elevation are more important 1.

• In acute choledocholithiasis, ALT can transiently surpass ALP, mimicking acute hepatitis, so do not assume elevated transaminases exclude biliary obstruction 1.

Practical Clinical Algorithm

1. When both AST and ALT are elevated:

   • Calculate the AST/ALT ratio
   • If ratio ≥2: strongly suspect alcoholic liver disease 1, 7
   • If ratio <1: consider NAFLD, viral hepatitis, or medication-induced injury 1, 7
   • If ratio >1 in nonalcoholic disease: evaluate for cirrhosis 6

2. When AST is elevated but ALT is normal or minimally elevated:

   • Check creatine kinase to exclude muscle injury 1
   • Consider cardiac causes (recent MI, heart failure) 2
   • Evaluate for hemolysis 1

3. For risk stratification in chronic liver disease:

   • Use the FIB-4 score (incorporating age, ALT, AST, and platelet count) to assess fibrosis risk 1
   • Monitor the AST/ALT ratio over time—a rising ratio suggests progression toward cirrhosis 6, 7