How do you diagnose hepatitis B in a patient?

Diagnosis of Hepatitis B

Hepatitis B is diagnosed through specific serologic testing, with HBsAg positivity for at least 6 months being the primary marker for chronic infection. 1

Screening Recommendations

Screening for hepatitis B should be performed in the following high-risk populations:

• Persons born in endemic areas (13% prevalence)
• Men who have sex with men (6% prevalence)
• Injecting drug users (7% prevalence)
• Dialysis patients (3-10% prevalence)
• HIV-infected individuals (8-11% prevalence)
• Pregnant women (0.4-1.5% prevalence in USA)
• Family members, household members, and sexual contacts of HBV-infected persons (3-6% prevalence) 1

Diagnostic Algorithm

Step 1: Initial Serologic Testing

• HBsAg (hepatitis B surface antigen): Primary marker for active infection
• Anti-HBc (antibody to hepatitis B core antigen): Indicates previous or ongoing infection
• Anti-HBs (antibody to hepatitis B surface antigen): Indicates recovery or immunity 1

Step 2: Interpretation of Initial Results

Pattern	HBsAg	Anti-HBc	Anti-HBs	Interpretation
Positive	Positive	Positive	Negative	Chronic or acute HBV infection
Negative	Negative	Negative	Negative	Susceptible to HBV infection
Immune due to vaccination	Negative	Negative	Positive	Immune due to vaccination
Immune due to natural infection	Negative	Positive	Positive	Recovered from past HBV infection
Isolated anti-HBc	Negative	Positive	Negative	Various possibilities*

*Isolated anti-HBc may indicate: (1) resolved infection with waned anti-HBs, (2) chronic infection with undetectable HBsAg, or (3) false-positive result 1

Step 3: Additional Testing for Positive HBsAg

For patients with positive HBsAg, additional testing should include:

• IgM anti-HBc: To distinguish acute (positive) from chronic (typically negative) infection
• HBeAg and anti-HBe: To assess viral replication status and infectivity
• HBV DNA quantification: To determine viral load and replication activity
• Liver function tests: ALT/AST to assess liver inflammation
• Complete blood count, albumin, bilirubin, prothrombin time: To evaluate liver function 1

Diagnostic Criteria for Chronic Hepatitis B

Chronic hepatitis B is diagnosed when:

1. HBsAg remains positive for ≥6 months
2. Serum HBV DNA ≥105 copies/mL for HBeAg-positive or ≥2,000 IU/mL for HBeAg-negative CHB
3. Persistent or intermittent elevation in ALT/AST levels
4. Liver biopsy showing chronic hepatitis (optional) 1

Inactive HBsAg Carrier State

Diagnosed when:

1. HBsAg positive for ≥6 months
2. HBeAg negative, anti-HBe positive
3. Serum HBV DNA <105 copies/mL
4. Persistently normal ALT/AST levels
5. Liver biopsy confirms absence of significant hepatitis (optional) 1

Resolved Hepatitis B

Diagnosed when:

1. Previous known history of acute or chronic hepatitis B or presence of anti-HBc and anti-HBs
2. HBsAg negative
3. Undetectable serum HBV DNA
4. Normal ALT levels 1

Common Pitfalls in Diagnosis

1. Window period misdiagnosis: During acute infection, there may be a period when both HBsAg and anti-HBs are undetectable, but IgM anti-HBc is positive 1

2. False-negative HBsAg: May occur in patients with chronic liver disease; viral load measurement should be considered in patients with a history of hepatitis 1

3. Isolated anti-HBc: Requires follow-up testing in 3-6 months to determine if it represents resolved infection with waned anti-HBs, occult hepatitis B, or a false-positive result 1

4. Reactivation risk: HBcAb-positive patients (with or without HBsAb) may experience HBV reactivation during immunosuppressive therapy, particularly with anti-CD20 monoclonal antibodies 1

5. Unusual serologic patterns: Rare cases may present with atypical patterns such as simultaneous positivity for multiple markers (HBsAg, HBsAb, HBeAg, HBeAb, and HBcAb) 2

By following this systematic approach to testing and interpretation, clinicians can accurately diagnose hepatitis B infection, determine its chronicity, and assess disease activity to guide appropriate management decisions.