How should acute liver injury be managed in a patient with confirmed dengue who develops elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than two to three times the upper limit of normal and shows signs of hepatic dysfunction such as jaundice, coagulopathy, or encephalopathy?

Management of Acute Liver Injury in Dengue

In dengue patients with acute liver injury (ALT/AST >2-3× ULN) and signs of hepatic dysfunction, management is primarily supportive with intensive monitoring, fluid resuscitation, and consideration of N-acetylcysteine for severe cases with ALT/AST >500 U/L or coagulopathy, while avoiding hepatotoxic medications and monitoring for progression to acute liver failure. 1, 2

Severity Assessment and Risk Stratification

Classify liver injury severity immediately upon presentation:

• Mild-moderate injury: ALT/AST 2-10× ULN without coagulopathy or encephalopathy—most dengue patients fall into this category with AST typically higher than ALT 3, 4
• Severe injury: ALT/AST >10× ULN or any elevation with INR >1.5, encephalopathy, or jaundice—indicates potential acute liver failure requiring ICU admission 5, 1
• Critical markers: AST >1000 U/L combined with gastrointestinal hemorrhage, encephalopathy, or lactic acidosis signals extremely high mortality risk 3, 2

The pattern in dengue characteristically shows AST > ALT (unlike typical viral hepatitis), reflecting both hepatocellular injury and extrahepatic sources including muscle breakdown and hemolysis 3, 4. Mixed hepatocellular-cholestatic injury occurs in approximately 29% of cases 4.

Immediate Monitoring Protocol

For ALT/AST >500 U/L or any patient with warning signs:

• Check complete liver panel (ALT, AST, alkaline phosphatase, total and direct bilirubin, albumin, PT/INR) every 12-24 hours initially 5, 1
• Monitor platelet count, hematocrit, and hemodynamic parameters every 4-6 hours during the critical phase (days 3-7 of illness) 1, 6
• Assess for encephalopathy with serial neurological examinations—cerebral edema risk increases dramatically with grade III-IV encephalopathy (25-75% incidence) 5
• Measure serum lactate if ALT/AST >1000 U/L—elevated lactate is a poor prognostic marker in dengue-related liver failure 2

For mild elevations (ALT/AST 2-5× ULN) without coagulopathy:

• Repeat liver panel every 2-3 days until declining 5, 7
• Continue monitoring for 8-12 weeks post-recovery, as transaminases should normalize within this timeframe 5

Supportive Management: The Foundation

Fluid management is critical but requires careful titration:

• Maintain adequate intravascular volume with crystalloids during the plasma leak phase (typically days 3-7), targeting urine output >0.5 mL/kg/hour 1, 6
• Avoid aggressive fluid resuscitation once capillary leak resolves—this precipitates pulmonary edema and heart failure, particularly in patients with concurrent acute kidney injury 2
• Monitor hematocrit closely—rising hematocrit indicates plasma leak requiring fluid replacement, while falling hematocrit during recovery indicates reabsorption 1, 2

Nutritional support and metabolic monitoring:

• Check glucose every 4-6 hours in severe cases—hypoglycemia is common with hepatic dysfunction 5
• Maintain nutrition enterally when possible; parenteral nutrition if encephalopathy precludes oral intake 5
• Monitor and correct electrolyte abnormalities, particularly in patients requiring renal replacement therapy 2

N-Acetylcysteine: Evidence-Based Intervention

Consider NAC infusion for severe dengue hepatitis based on emerging evidence:

• Indication: ALT/AST >500 U/L and/or INR >1.5, particularly with encephalopathy or shock 1, 2
• Dosing: 100 mg/hour continuous infusion for 3-5 days (not the standard acetaminophen overdose protocol) 1
• Mechanism: Improves hepatic blood flow, provides antioxidant effects, and may enhance systemic circulation in septic shock states 5, 1

A retrospective series of 30 patients with severe dengue hepatitis (median AST 1125 U/L, median ALT 752 U/L) showed statistically significant reduction in both ALT (p=0.034) and AST (p=0.049) from day 1 to day 4 after NAC infusion, with only 3.3% mortality 1. Another case report documented full recovery using NAC in a patient with acute liver failure (ALT >1000 U/L) and lactic acidosis 2.

Important caveat: While NAC shows promise, evidence comes from case series and reports, not randomized trials. However, given the high mortality of dengue-associated acute liver failure (historically approaching 50-80% in severe cases) and NAC's favorable safety profile, this intervention is reasonable in severe cases 5, 1, 2.

Management of Coagulopathy

Approach bleeding risk pragmatically:

• Do not correct INR prophylactically with fresh frozen plasma unless active bleeding or invasive procedures planned—this risks volume overload during plasma leak phase 5, 1
• Platelet transfusion threshold: <10,000/μL with bleeding or <20,000/μL with high bleeding risk (severe thrombocytopenia is expected in dengue) 1, 6
• Avoid intramuscular injections, nasogastric tubes, and unnecessary invasive procedures during thrombocytopenic phase 1, 6

In one case series, packed cell transfusions targeting higher hematocrit were used to maintain tissue oxygenation during shock, even without active bleeding—this unconventional approach may be beneficial in acute liver failure to ensure adequate hepatic oxygen delivery 2.

Renal Replacement Therapy Considerations

For acute kidney injury with anuria in dengue hepatitis:

• Prefer continuous veno-venous hemodialysis (CVVHD) over intermittent hemodialysis—allows gradual fluid removal during the recovery phase when massive fluid reabsorption occurs 2
• Standard intermittent hemodialysis risks precipitating pulmonary edema when the 3-5 liters of third-space fluid reabsorbs into the intravascular space during recovery (days 7-10) 2
• One case required 138 hours of continuous CVVHD to safely manage fluid dynamics during recovery phase 2

Medications to Avoid

Strict avoidance of hepatotoxic agents:

• No NSAIDs (ibuprofen, aspirin)—increase bleeding risk and may worsen liver injury 1, 6
• No acetaminophen/paracetamol—even therapeutic doses are relatively contraindicated with significant transaminase elevation 1
• Avoid unnecessary antibiotics unless secondary bacterial infection confirmed—dengue patients with prolonged fever (>5 days) and acute kidney injury are at high risk for concurrent bacteremia and may require empiric coverage 6

Secondary Infection Surveillance

Maintain high suspicion for bacterial superinfection:

• Persistent fever beyond day 5-7 or recurrent fever after defervescence suggests secondary bacterial infection 6
• Neutrophil leukocytosis in dengue (which typically causes leukopenia) is a red flag for bacterial infection 6
• Consider blood cultures and echocardiography if fever persists—infective endocarditis has been reported as a complication 6

Dengue causes endothelial dysfunction allowing bacterial tissue invasion, immune cell dysfunction, and cytokine dysregulation predisposing to secondary infections 6.

Thrombotic Complications: An Underrecognized Risk

Despite thrombocytopenia and coagulopathy, paradoxical thrombosis can occur:

• Dengue interferes with the thrombomodulin-thrombin-protein C anticoagulant pathway and activates procoagulant factors 6
• Deep vein thrombosis has been reported even during the acute thrombocytopenic phase 6
• Consider thromboprophylaxis with low-dose subcutaneous heparin once platelet count recovers above 50,000/μL and bleeding risk subsides 6

ICU Admission Criteria

Transfer to ICU immediately if any of the following:

• Grade II or higher encephalopathy (any altered mental status) 5
• INR >1.5 with ALT/AST elevation 5, 1
• Dengue shock syndrome (systolic BP <90 mmHg, narrow pulse pressure <20 mmHg) 1, 6
• Acute kidney injury with oliguria/anuria 6, 2
• Gastrointestinal hemorrhage with hemodynamic instability 3

Patients with only grade I encephalopathy may sometimes be managed on a monitored medicine ward, but any progression warrants immediate ICU transfer as deterioration can be rapid 5.

Prognosis and Recovery

Most patients with mild-moderate liver injury recover completely:

• Transaminases typically peak around days 5-7 of illness and normalize within 2-8 weeks 5, 1
• In the NAC case series, mean hospital stay was 6.2 days with 96.7% survival despite severe hepatitis 1
• Acute liver failure with encephalopathy carries significantly higher mortality, but full recovery without sequelae is possible with aggressive supportive care 3, 2

Poor prognostic indicators:

• Massive gastrointestinal hemorrhage with AST/ALT >1000 U/L 3
• Lactic acidosis in the setting of liver failure 2
• Progression to grade IV encephalopathy with cerebral edema 5, 3

Critical Pitfalls to Avoid

• Don't attribute severe transaminase elevation (>10× ULN) to dengue alone—investigate for concurrent hepatotoxic drug exposure, ischemic hepatitis from shock, or other viral hepatitis 5, 8
• Don't aggressively fluid resuscitate during the recovery phase—this is when reabsorption occurs and pulmonary edema develops 2
• Don't use standard acute liver failure protocols designed for acetaminophen overdose—dengue hepatitis requires dengue-specific fluid and hemodynamic management 1, 2
• Don't delay ICU transfer for altered mental status—cerebral edema can progress rapidly to uncal herniation 5