Does Bilirubin Increase in Hepatitis A?
Yes, bilirubin levels increase significantly in hepatitis A infection, with serum bilirubin typically exceeding 3 mg/dL (>50 μmol/L) in symptomatic cases, and this elevation is a defining characteristic of the disease. 1
Typical Bilirubin Elevation Pattern
The bilirubin increase in hepatitis A follows a predictable pattern:
- Serum bilirubin concentrations reach peak levels after aminotransferases (ALT/AST) peak and decline more slowly than the transaminases. 2
- In most cases (approximately 85%), the period of jaundice persists for less than 2 weeks, though bilirubin normalization takes longer than clinical jaundice resolution. 2
- Nearly all adult patients experience complete normalization of serum bilirubin values by 6 months. 2
Clinical Significance of Bilirubin Levels
The degree of bilirubin elevation correlates with disease severity:
- Peak bilirubin level is an independent predictor of severe acute hepatitis in multivariate analysis (HR = 1.153, P = 0.003). 3
- In cholestatic variants of hepatitis A, serum bilirubin levels exceed 10 mg/dL and the clinical course extends at least 12 weeks. 4
- Extremely high bilirubin levels (427 to 1368 μmol/L or approximately 25-80 mg/dL) can occur when hepatitis A triggers intravascular hemolysis in patients with G6PD deficiency. 5
Pathophysiology of Bilirubin Elevation
The mechanism involves hepatocellular injury:
- Hepatitis A causes necroinflammatory liver damage that disrupts the transport of conjugated bilirubin, leading to predominantly conjugated hyperbilirubinemia. 6
- The diagnostic criteria for superimposed hepatitis A in chronic liver disease specifically require AST or ALT >400 IU/mL and serum bilirubin >3 mg/dL (>50 μmol/L). 1
Atypical Presentations
Important variants to recognize:
- Prolonged cholestasis occurs in some cases, characterized by pruritus, fever, diarrhea, weight loss, and bilirubin >10 mg/dL lasting at least 12 weeks, though this resolves spontaneously. 4
- Relapsing hepatitis A occurs in 6-10% of cases with a biphasic pattern, where bilirubin normalizes during remission then re-elevates during relapse over a total course of 16-40 weeks. 4
- Serum total bilirubin can influence liver stiffness measurements on FibroScan during acute hepatitis, with changes in bilirubin being the only biochemical factor significantly associated with changes in liver stiffness (P<0.001). 7
Critical Clinical Pitfalls
Do not confuse hepatitis A with unconjugated hyperbilirubinemia conditions like Gilbert syndrome, which presents with indirect bilirubin >70% of total, rarely exceeds 4-5 mg/dL, and lacks the marked transaminase elevation (>400 IU/mL) seen in hepatitis A. 1, 6
When bilirubin is detected in urine (bilirubinuria), this confirms conjugated hyperbilirubinemia and mandates evaluation for hepatitis A and other hepatobiliary causes through viral serologies and abdominal ultrasound. 8