Why is Aspartate Aminotransferase (AST) (SGOT) often elevated more than Alanine Aminotransferase (ALT) (SGPT) in patients with dengue fever?

Why AST (SGOT) is Higher Than ALT (SGPT) in Dengue Fever

In dengue fever, AST (SGOT) is typically elevated more than ALT (SGPT) due to the virus causing both direct hepatocyte damage and extrahepatic release of AST from damaged muscle cells, resulting in a characteristic AST:ALT ratio >1 that correlates with disease severity.

Pathophysiological Mechanisms

The elevation of liver enzymes in dengue fever occurs through several mechanisms:

1. Direct viral cytopathic effects:

   • SARS-CoV-2 binds to cells through angiotensin-converting enzyme 2 (ACE2), which is highly expressed in hepatocytes and bile duct epithelial cells 1
   • Dengue virus can directly infect and damage hepatocytes

2. Immune-mediated injury:

   • Inflammatory cytokines (IL-10, IL-17) are significantly elevated in severe dengue and contribute to hepatic damage 2
   • Immune-cytopathic damage follows direct cytotoxicity and inflammatory response 1

3. Extrahepatic sources of AST:

   • AST is present in multiple tissues (heart, skeletal muscle, kidneys, brain, and red blood cells)
   • ALT is primarily found in the liver
   • Muscle damage during dengue infection releases additional AST into circulation

Pattern of Liver Enzyme Elevation

• Timing: Liver enzyme elevation typically peaks around days 6-7 of illness 2
• Magnitude: AST elevation is consistently higher than ALT in dengue patients 3, 4
• Correlation with severity:
  • Both AST and ALT levels increase with disease severity 3, 4
  • In one study, AST was elevated in 66.7% of patients with dengue without warning signs, 78.6% with warning signs, and 91.7% with severe dengue 4
  • ALT was elevated in 42.4%, 52.4%, and 91.7% of these groups, respectively 4

AST:ALT Ratio in Dengue vs. Other Conditions

• Dengue fever: AST > ALT (similar to alcoholic liver disease)
• Viral hepatitis: ALT > AST typically
• Alcoholic liver disease: AST:ALT ratio >2 in about 70% of patients 1

Clinical Significance

1. Early diagnostic indicator:

   • The increase in aminotransferases, mainly AST, serves as an early indicator of dengue infection 3
   • AST:ALT ratio >1 can help differentiate dengue from other viral hepatitides

2. Severity marker:

   • Higher AST and ALT levels correlate with increased disease severity 3, 4
   • Negative correlation exists between transaminase levels and platelet count 4

3. Timing considerations:

   • Liver function tests performed too early may not reflect the extent of liver involvement 2
   • Peak AST levels occur approximately 24 hours before maximum fluid leakage and 24 hours after peak viremia 2

Important Considerations

• Severe liver involvement can occur in the absence of fluid leakage or rise in hematocrit 2
• While transaminase levels increase with dengue severity, they have poor discriminatory value between non-severe and severe dengue (AST area under ROC curve=0.62) 5
• WHO 2009 dengue guidelines defined AST or ALT ≥1000 U/L as a criterion for severe dengue, but this is relatively uncommon 5
• Hypoalbuminemia and A:G ratio reversal are more common in severe dengue and should be monitored alongside transaminases 4

Clinical Approach

When evaluating a patient with suspected dengue:

1. Monitor liver enzymes serially, especially around days 5-7 of illness
2. Pay attention to AST:ALT ratio >1 as supportive evidence for dengue
3. Consider the degree of transaminase elevation as one factor in assessing disease severity
4. Look for other markers of severity including thrombocytopenia, hypoalbuminemia, and evidence of plasma leakage

Understanding this characteristic pattern of liver enzyme elevation can aid in early diagnosis and appropriate management of dengue fever.