In a patient with new‑onset jaundice, which hepatitis serologic tests should be ordered to screen for hepatitis A (HAV), hepatitis B (HBV), and hepatitis C (HCV)?

Hepatitis Serologic Testing for New-Onset Jaundice

In a patient with new-onset jaundice, order anti-HAV IgM, HBsAg, and anti-HCV antibody with reflex HCV RNA testing to screen for hepatitis A, B, and C.

Initial Serologic Panel

Hepatitis A Screening

• Anti-HAV IgM is the definitive test for acute hepatitis A infection and is present in almost all patients at symptom onset 1
• Anti-HAV IgM remains detectable for approximately 6 months after acute infection 1
• Important caveat: Rare cases may test negative for anti-HAV IgM at initial presentation despite active symptoms, requiring repeat testing 1-2 weeks later if clinical suspicion remains high 2

Hepatitis B Screening

• HBsAg (hepatitis B surface antigen) identifies both acute and chronic HBV infection and is the most efficient initial screening test 3
• Anti-HBs (antibodies to HBsAg) can be added to distinguish immunity from vaccination versus past infection, though this is less critical in the acute jaundice setting 3
• The combination of HBsAg and anti-HBs testing is considered the most efficient and cost-effective method for hepatitis B screening 3

Hepatitis C Screening

• Anti-HCV antibody should be the initial test, followed by HCV RNA testing if antibody is reactive 4
• Anti-HCV antibodies may be undetectable in early acute infection or in profoundly immunosuppressed patients 4
• Critical timing issue: If the initial anti-HCV test is negative but clinical suspicion persists, repeat testing at 4-6 months is essential, as antibodies may not yet be detectable in very early acute infection 4
• HCV RNA by nucleic acid testing (NAT) with a lower limit of detection <15 IU/ml is recommended for confirming active infection 4
• For earlier diagnosis when acute hepatitis C is suspected, HCV RNA testing can be performed at 4-6 weeks after exposure 4

Testing Sequence Algorithm

1. Draw initial panel: Anti-HAV IgM, HBsAg, anti-HCV antibody 4

2. If anti-HCV is reactive: Immediately order HCV RNA testing to distinguish current infection from past resolved infection 4

3. If all tests are negative but viral hepatitis remains suspected:

   • Repeat anti-HAV IgM in 1-2 weeks (for rare delayed seroconversion) 2
   • Repeat anti-HCV and consider HCV RNA at 4-6 weeks (for early acute infection) 4
   • Retest anti-HCV at 4-6 months if initial testing was very early in disease course 4

Common Pitfalls to Avoid

• Do not rely solely on anti-HCV antibody without confirmatory HCV RNA testing, as antibodies persist after viral clearance and cannot distinguish active from resolved infection 4
• Do not assume negative anti-HAV IgM rules out hepatitis A if tested within the first few days of symptoms—rare cases require repeat testing 2
• Do not order anti-HBc (hepatitis B core antibody) alone as the initial screening test for hepatitis B; HBsAg is the appropriate first-line test 3
• Do not forget that anti-HCV may be negative in the first 4-8 weeks of acute hepatitis C infection, necessitating HCV RNA testing or repeat antibody testing 4

Additional Context for Jaundice Evaluation

While viral hepatitis accounts for only 0.2% of severe jaundice cases in some studies, it remains a critical diagnosis not to miss 4. The most common causes of jaundice in the United States are sepsis (22%), decompensated chronic liver disease (20.5%), alcoholic hepatitis (16%), and gallstone disease (14%) 4. However, the testing sequence above ensures viral hepatitis is appropriately excluded or confirmed regardless of its relative frequency 4.

Patients diagnosed with chronic hepatitis C are candidates for hepatitis A and hepatitis B vaccination if they lack immunity 4. Therefore, comprehensive screening serves both diagnostic and preventive purposes 4, 3.