What are the diagnostic steps and treatment options for a patient suspected of having hepatitis B?

Hepatitis B Diagnosis

Begin with HBsAg testing as the primary screening tool, followed by a complete serologic panel including anti-HBs and anti-HBc to distinguish between active infection, past resolved infection, vaccine-induced immunity, or susceptibility. 1, 2

Initial Serologic Testing

The diagnostic approach requires three core markers tested simultaneously 2:

• HBsAg (Hepatitis B surface antigen): Positive result indicates active HBV infection 1
• Anti-HBs (Antibody to surface antigen): Positive result indicates immunity from either vaccination or past resolved infection 1, 3
• Anti-HBc (Antibody to core antigen): Positive result indicates current or past infection; absent in vaccine-induced immunity 1, 3

Interpretation of Serologic Patterns

Active chronic infection is confirmed by 2:

• HBsAg positive
• Anti-HBc positive (total, not IgM)
• Anti-HBs negative

Acute infection is diagnosed by 1, 3:

• HBsAg positive
• IgM anti-HBc positive (this distinguishes acute from chronic)
• Anti-HBs negative

Past resolved infection with immunity shows 1, 3, 2:

• HBsAg negative
• Anti-HBs positive
• Anti-HBc positive

Vaccine-induced immunity demonstrates 1, 3, 2:

• HBsAg negative
• Anti-HBs positive (≥10 mIU/mL is protective)
• Anti-HBc negative

Isolated anti-HBc (all other markers negative) requires 1, 3:

• Repeat testing in 3-6 months to clarify status
• Consider HBV DNA testing to rule out occult hepatitis B, particularly in immunocompromised patients

Confirming Chronic Infection

If HBsAg is positive, confirm chronicity by retesting HBsAg after 6 months 1:

• Persistent HBsAg positivity beyond 6 months defines chronic HBV infection 1, 2
• If HBsAg becomes negative on follow-up, the patient likely had transient acute infection 1

Distinguish acute from chronic infection using IgM anti-HBc 1:

• IgM anti-HBc positive indicates acute infection
• IgM anti-HBc negative with persistent HBsAg indicates chronic infection

Additional Testing for Chronic HBV

Once chronic infection is confirmed, obtain 1:

Viral replication markers:

• HBeAg and anti-HBe: HBeAg-positive indicates high viral replication; anti-HBe-positive suggests lower replication 1, 2
• Quantitative HBV DNA: Essential for treatment decisions; thresholds are ≥20,000 IU/mL for HBeAg-positive and ≥2,000 IU/mL for HBeAg-negative chronic hepatitis B 1, 2

Liver disease assessment 1:

• ALT, AST, bilirubin, albumin, prothrombin time
• Complete blood count with platelets
• Creatinine (baseline renal function)

Coinfection screening 1, 4:

• Anti-HCV antibody (hepatitis C)
• Anti-HDV antibody if HBsAg-positive (hepatitis D only infects with HBV)
• HIV antibody/antigen (all HBsAg-positive patients should be tested)

Hepatocellular carcinoma surveillance 1:

• Baseline abdominal ultrasound
• Serum alpha-fetoprotein (AFP)

Common Pitfalls

The "window period" can occur during acute infection when HBsAg has cleared but anti-HBs has not yet developed 1, 3:

• Only IgM anti-HBc will be positive
• Repeat testing in 3-6 months to confirm recovery

Occult hepatitis B presents as isolated anti-HBc or even negative serology with detectable HBV DNA 1, 3:

• More common in immunocompromised patients
• Requires HBV DNA testing for diagnosis
• Critical to identify before immunosuppressive therapy

Anti-HBs levels decline over time after vaccination but immune memory typically persists 1:

• Levels <10 mIU/mL do not necessarily indicate loss of protection in immunocompetent individuals
• Booster doses are not routinely recommended except for specific high-risk groups (hemodialysis patients, immunocompromised)

Treatment Considerations

All HBsAg-positive patients should be referred to a specialist experienced in hepatitis B management 1:

• Patients with compensated or decompensated cirrhosis require immediate treatment 1
• HIV/HBV coinfected patients require treatment with antiretroviral therapy that includes HBV-active agents 1, 5

First-line antiviral agents include 5, 6:

• Tenofovir disoproxil fumarate 300 mg daily (monitor renal function)
• Entecavir (avoid in HIV coinfection unless patient is on appropriate antiretroviral therapy)

Counsel all chronic HBV carriers on 1:

• Transmission prevention (no blood/organ donation, cover wounds, avoid sharing razors/toothbrushes)
• Screening and vaccinating household contacts and sexual partners using total anti-HBc as the screening test
• Alcohol abstinence
• Hepatitis A vaccination if anti-HAV negative