Management of Transaminitis in Severe Dengue
Supportive care is the cornerstone of treatment for transaminitis in severe dengue, as there is no specific antiviral therapy or hepatoprotective agent proven effective for dengue-associated liver injury. 1, 2
Severity Assessment and Monitoring
The transaminitis in severe dengue should be graded according to standard criteria to guide monitoring intensity 2:
- Grade 1 (AST/ALT >ULN to 3× ULN): Monitor liver function tests 1-2 times weekly
- Grade 2 (AST/ALT >3× to 5× ULN): Increase monitoring frequency to every 3 days
- Grade 3 (AST/ALT >5× to 20× ULN): Consider hepatology consultation and monitor for signs of acute liver failure
- Grade 4 (AST/ALT >20× ULN): Immediate hospitalization, preferably at a liver center
In dengue specifically, AST and ALT elevations are nearly universal (97% and 75.3% respectively), with peak levels typically occurring on days 6-7 of illness, often 24 hours after peak viremia 3, 4. Severe dengue patients demonstrate significantly higher AST and GGT levels on days 5-6 compared to non-severe dengue 4.
Core Management Principles
Discontinue Hepatotoxic Medications
Immediately discontinue all potentially hepatotoxic medications, particularly aspirin and NSAIDs 2:
- Aspirin is contraindicated due to hemorrhagic complications risk in dengue 2
- Limit acetaminophen to **<3000 mg/day** (1000 mg every 8 hours maximum), as doses >8 grams correlate with increased transaminitis (OR 4.62,95% CI 1.37-13.18) 3
- Male gender is an additional risk factor for severe transaminitis (OR 3.62,95% CI 1.38-9.42) 3
Supportive Care Measures
The mainstay of treatment focuses on 2, 5:
- Fluid management: Careful monitoring and correction of plasma leakage, which typically peaks 24 hours after maximum liver enzyme elevation 4
- Platelet monitoring: Severe thrombocytopenia (as low as 6×10⁹/L) commonly accompanies hepatic dysfunction 6
- Hematocrit surveillance: Rising hematocrit indicates plasma leakage severity
- Coagulation monitoring: Assess for bleeding diathesis with PT/INR
Monitor for Acute Liver Failure
Watch for signs requiring urgent escalation 2:
- Bilirubin ≥2× ULN or INR >1.5 suggests potential acute liver failure
- Hepatic encephalopathy, ascites, or spontaneous bleeding
- AST/ALT >1000 IU/L can occur even without significant plasma leakage in severe dengue 4
Monitoring Frequency Based on Severity
For moderate to severe transaminitis (Grade 2 or higher), monitor liver function tests every 2-3 days until improvement, then continue monitoring until complete normalization 2. The Clinical and Molecular Hepatology society recommends continuing surveillance until full enzyme normalization 2.
Pathophysiology Considerations
Dengue-associated liver injury results from multiple mechanisms 6, 4, 7:
- Direct viral infection of hepatocytes and Kupffer cells
- Immune-mediated injury (elevated IL-10 and IL-17 correlate with severity)
- Hypoxic injury from decreased perfusion during plasma leakage
- Inflammatory response (CRP levels correlate positively with AST/ALT elevation, r=0.99, p<0.05) 7
Mixed hepatocellular and cholestatic injury patterns are most common (29.4% of cases), and approximately 85% of severe dengue patients develop significant liver injury 7.
Critical Pitfalls to Avoid
- Do not delay evaluation if transaminitis presents with bilirubin elevation or coagulopathy, as this indicates potential acute liver failure 2
- Do not assume peak liver injury occurs at presentation; enzymes typically peak on days 6-7, so early testing may underestimate severity 4
- Do not use high-dose acetaminophen for fever control; restrict to <3000 mg/day 3
- Do not initiate immunosuppression (unlike autoimmune hepatitis); dengue liver injury is self-limited with supportive care 6, 5
Prognosis
With appropriate supportive management, most patients achieve complete recovery within 5-7 days, even with severe transaminitis (AST >12,000 IU/L documented) 6, 5. Prognosis depends on age, comorbidities, and development of acute liver failure complications 6.