How do SGOT (AST) and SGPT (ALT) differ, what are their normal ranges, and how should their levels and AST/ALT ratio be interpreted in evaluating liver injury?

SGOT (AST) vs SGPT (ALT): Key Differences and Clinical Interpretation

Fundamental Differences Between AST and ALT

ALT (SGPT) is the most liver-specific aminotransferase and should be prioritized for detecting hepatocellular injury. 1, 2

Tissue Distribution and Specificity

• ALT is highly specific for liver injury because it is primarily concentrated in hepatocytes with minimal presence in cardiac muscle, skeletal muscle, kidneys, and red blood cells 1, 2
• AST is significantly less liver-specific because it exists in cardiac muscle, skeletal muscle, kidneys, brain, and red blood cells, making elevations potentially attributable to non-hepatic sources 1, 2
• AST can be elevated from cardiac ischemia, extensive exercise, muscle injury (rhabdomyolysis), hemolysis, and thyroid disorders 1, 2

Normal Reference Ranges (Sex-Specific)

• Males: ALT 29-33 IU/L; AST values typically similar but less standardized 1, 2
• Females: ALT 19-25 IU/L (significantly lower than commercial laboratory cutoffs) 1, 2
• These sex-specific ranges are substantially lower than traditional laboratory upper limits, meaning mild elevations may be clinically significant 2

Severity Classification of Aminotransferase Elevations

Elevations are classified as: Mild (<5× ULN), Moderate (5-10× ULN), and Severe (>10× ULN). 1, 3

• For women with ULN of 25 IU/L: Mild <125 IU/L, Moderate 125-250 IU/L, Severe >250 IU/L 2
• For men with ULN of 33 IU/L: Mild <165 IU/L, Moderate 165-330 IU/L, Severe >330 IU/L 2

Clinical Interpretation of AST/ALT Ratio

AST/ALT Ratio <1 (ALT > AST)

• Characteristic pattern of non-alcoholic fatty liver disease (NAFLD), viral hepatitis, and most medication-induced liver injuries 1, 2
• Indicates hepatocellular injury in early stages before AST becomes significantly involved 2
• Most common pattern in metabolic liver disease 2

AST/ALT Ratio >1

• An AST:ALT ratio >1 indicates advanced fibrosis or cirrhosis in adults with chronic liver disease 1
• This ratio maintains utility even when both values are within normal reference intervals 1
• The ratio can help assess fibrosis risk without requiring both enzymes to be elevated 1

AST/ALT Ratio ≥2

• Highly suggestive of alcoholic liver disease, with ratios >3 being particularly specific for this diagnosis 4, 2
• In alcoholic hepatitis, 70% of patients demonstrate an AST/ALT ratio >2, compared to only 26% with post-necrotic cirrhosis 4
• AST typically 2-6 times ULN with mean AST around 152 U/L and ALT around 70 U/L in alcoholic hepatitis 2
• However, extreme AST/ALT ratios (>2) with very high absolute SGOT levels (>5× normal) should prompt evaluation for non-alcoholic causes of hepatocellular necrosis, including acetaminophen toxicity 5

Special Patterns

• In Wilson disease with fulminant hepatic failure: AST may exceed ALT, but more characteristic findings include modest aminotransferase elevations with markedly low alkaline phosphatase (ALP:bilirubin ratio <2) 2
• In primary sclerosing cholangitis (PSC): AST/ALT ratio ≥1 indicates cirrhosis with high specificity and predicts poor outcome with double the risk of liver-related death or transplantation 2

Recommended Initial Liver Panel

Initial investigation should include bilirubin, albumin, ALT, alkaline phosphatase (ALP), and GGT, together with a full blood count. 1

• AST is not routinely recommended in the initial panel because it did not improve detection of specific disease in the BALLETS study 1
• However, subsequent AST testing to calculate the AST:ALT ratio is clearly desirable and should be performed by "reflex" on the same sera following detection of abnormal ALT or GGT 1
• This reflex strategy is more cost-effective than ordering both enzymes upfront 1

When to Measure Both AST and ALT

• Calculate AST:ALT ratio when assessing for advanced fibrosis or cirrhosis in adults with abnormal liver blood tests 1
• Measure creatine kinase (CK) when AST is disproportionately elevated to exclude muscle injury as the source 2
• In alcoholic patients with suspected hepatotoxicity, both enzymes help differentiate alcoholic hepatitis from other causes 5, 4
• In blunt abdominal trauma, both SGOT and SGPT levels >130 IU/L are markers for intra-abdominal injury, with higher levels indicating liver injury 6, 7

Critical Clinical Pitfalls

• 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 2
• Both AST and ALT can be normal even in the setting of cirrhosis, yet the AST:ALT ratio utility persists 1
• Do not assume isolated AST elevation is hepatic—always consider cardiac, skeletal muscle, renal, and hematologic sources 1, 2
• ALT elevation ≥5× ULN is rare in NAFLD/NASH and should not be attributed to these conditions alone without excluding viral hepatitis, autoimmune hepatitis, and drug-induced liver injury 2
• An AST/ALT ratio >2 in non-alcoholic patients should raise suspicion for cirrhosis, not just alcoholic liver disease 2, 4

Monitoring Strategy Based on Enzyme Levels

For ALT <2× ULN

• Repeat in 2-4 weeks to establish trend 2
• If stable or improving, continue monitoring every 4-8 weeks until normalized 2

For ALT 2-3× ULN

• Repeat within 2-5 days and intensify evaluation 2
• Consider comprehensive metabolic and viral hepatitis workup 2

For ALT ≥3× ULN or ≥5× ULN

• ALT ≥3× ULN warrants close observation and more frequent monitoring 2
• ALT >5× ULN (>235 IU/L for males, >125 IU/L for females) requires hepatology referral 1, 2
• If ALT ≥3× ULN plus bilirubin ≥2× ULN (Hy's Law pattern), immediate cessation of suspected medications and urgent evaluation 2

For Patients on Hepatotoxic Medications

• Monitor weekly for first 2 weeks, then biweekly if ALT 2-5× normal 1, 2
• Stop rifampin, isoniazid, and pyrazinamide immediately if ALT ≥5× normal or bilirubin rises 1, 2