How to diagnose and manage chronic hepatitis B infection?

Diagnosis and Management of Chronic Hepatitis B Infection

Chronic hepatitis B infection should be diagnosed through serological testing for HBsAg persistence beyond 6 months, followed by assessment of viral replication and liver damage, and managed with appropriate antiviral therapy based on disease activity and risk of progression. 1

Diagnostic Approach

Initial Serological Testing

• HBsAg: Primary screening test; persistence beyond 6 months confirms chronic infection 1
• Anti-HBc (total): Indicates previous or ongoing HBV infection 1
• HBeAg/anti-HBe: Assesses viral replication status 1
• HBV DNA: Quantifies viral load; essential for disease staging and treatment decisions 1

Diagnostic Criteria for Chronic Hepatitis B

1. HBsAg positivity for longer than 6 months
2. HBV DNA levels:
   • HBeAg-positive CHB: ≥20,000 IU/mL
   • HBeAg-negative CHB: ≥2,000 IU/mL
3. Persistent or intermittent elevation of AST/ALT
4. Liver biopsy showing chronic hepatitis (optional) 1

Serological Patterns and Interpretation

• Acute HBV infection: Positive HBsAg and IgM anti-HBc 1
• Chronic HBV infection: Positive HBsAg (>6 months), positive total anti-HBc, negative IgM anti-HBc 1
• Resolved HBV infection: Negative HBsAg, positive anti-HBs and total anti-HBc 1
• Vaccination immunity: Positive anti-HBs, negative anti-HBc 1
• Isolated anti-HBc: May indicate occult HBV infection, recovery phase, or false positive 1

Initial Evaluation of Patients with Chronic HBV

Comprehensive Assessment

1. History and physical examination:

   • Risk factors (alcohol consumption, drug use)
   • Family history of liver disease and HCC 1

2. Laboratory tests:

   • Complete blood count
   • Liver function tests (AST/ALT, alkaline phosphatase, GGT, bilirubin, albumin)
   • Prothrombin time
   • Creatinine 1

3. Viral replication markers:

   • HBeAg/anti-HBe
   • HBV DNA quantification 1

4. Coinfection screening:

   • Anti-HCV, anti-HDV (if history of drug abuse)
   • HIV testing (for high-risk groups) 1

5. Hepatitis A immunity:

   • IgG anti-HAV (for vaccination planning) 1

6. Liver fibrosis assessment:

   • Liver biopsy (optional)
   • Non-invasive fibrosis markers when available 1

7. HCC screening:

   • Ultrasound
   • Serum α-fetoprotein 1

Management Strategy

Treatment Indications

Treatment should be considered for:

1. Patients with cirrhosis (compensated or decompensated) and detectable HBV DNA (highest priority) 1

2. HBeAg-positive patients with:

   • HBV DNA ≥20,000 IU/mL
   • Persistently elevated ALT (>2× ULN)
   • Evidence of moderate-severe inflammation or fibrosis 1

3. HBeAg-negative patients with:

   • HBV DNA ≥2,000 IU/mL
   • Persistently elevated ALT
   • Evidence of moderate-severe inflammation or fibrosis 1

4. HIV/HBV co-infected patients regardless of liver disease status 1

Treatment Options

Seven FDA-approved medications are available 1:

1. Nucleos(t)ide analogues:

   • Entecavir: 0.5 mg daily (treatment-naïve), 1 mg daily (lamivudine-resistant) 2
   • Tenofovir disoproxil fumarate
   • Lamivudine (higher resistance barrier options preferred)
   • Adefovir dipivoxil
   • Telbivudine

2. Interferons:

   • Peginterferon alfa-2a
   • Interferon alfa-2b

Monitoring During Treatment

• Regular assessment of liver enzymes (ALT/AST)
• HBV DNA levels
• HBeAg/anti-HBe status
• Renal function and bone density (for patients on tenofovir)
• HCC surveillance with ultrasound every 6 months 1, 3

Treatment Endpoints

• Loss of HBeAg and seroconversion to anti-HBe in initially HBeAg-positive patients
• Suppression of HBV DNA to undetectable levels
• Normalization of ALT
• Improvement in liver histology
• Ideally, HBsAg loss (although rare) 1

Special Considerations

HCC Surveillance

• Regular screening with ultrasound ± AFP every 6 months for:
  • Asian men >40 years
  • Asian women >50 years
  • Patients with cirrhosis
  • Family history of HCC
  • Africans >20 years
  • All patients >40 years with persistent/intermittent ALT elevation and/or high HBV DNA 1

Prevention of Transmission

• Vaccinate susceptible household and sexual contacts
• Counsel on avoiding sharing personal items that may have blood contact
• Avoid donating blood, plasma, organs, tissue, or semen 3

Lifestyle Modifications

• Abstain from alcohol or limit consumption
• Maintain healthy weight
• Avoid hepatotoxic medications 3

Hepatitis A Vaccination

• All chronic HBV patients without HAV immunity should receive hepatitis A vaccine (2 doses, 6-18 months apart) 1, 3

Common Pitfalls to Avoid

1. Misinterpreting serological patterns: Isolated anti-HBc requires careful evaluation for occult HBV infection
2. Inadequate monitoring: Regular follow-up is essential even in patients with normal ALT
3. Delayed treatment: Patients with cirrhosis need immediate treatment regardless of ALT or HBV DNA levels
4. Premature treatment discontinuation: Treatment should continue for at least 6 months after HBeAg seroconversion
5. Missing HCC surveillance: Regular screening is crucial even in well-controlled patients
6. Overlooking coinfections: Always screen for HIV, HCV, and HDV in high-risk patients

By following this systematic approach to diagnosis and management, chronic hepatitis B infection can be effectively controlled, reducing the risk of progression to cirrhosis, liver failure, and hepatocellular carcinoma.