What are the diagnostic tests and treatment options for Hepatitis B (HBV) infection?

Hepatitis B Diagnostic Tests and Treatment Options

The diagnosis of Hepatitis B requires serological testing for HBsAg as the primary marker, with additional testing for anti-HBc, anti-HBs, HBeAg, anti-HBe, and HBV DNA quantification to determine disease stage and guide treatment decisions. 1

Diagnostic Tests for HBV Infection

Serological Markers

1. HBsAg (Hepatitis B Surface Antigen)

   • Primary marker for diagnosis of HBV infection
   • Persistence for >6 months indicates chronic infection 1
   • Appears 1-10 weeks after exposure and typically disappears 4-6 months after recovery 1

2. Anti-HBc (Antibody to Hepatitis B Core Antigen)

   • IgM anti-HBc: Indicates acute infection; detectable for approximately 6 months 1
   • Total anti-HBc (IgG): Persists for life after infection; indicates previous or ongoing infection 1
   • Only marker present during the "window period" between disappearance of HBsAg and appearance of anti-HBs 1

3. Anti-HBs (Antibody to HBsAg)

   • Indicates recovery from infection or successful vaccination
   • Protective antibody (immunity) 1

4. HBeAg (Hepatitis B e Antigen)

   • Marker of active viral replication and high infectivity 1
   • Generally indicates higher HBV DNA levels 1

5. Anti-HBe (Antibody to HBeAg)

   • Usually indicates decreased viral replication and lower infectivity 1
   • May be present in patients with HBeAg-negative chronic hepatitis B (with precore mutations) 1

Virological Tests

1. HBV DNA Quantification

   • Essential for:
     • Assessing viral replication
     • Differentiating active from inactive infection
     • Monitoring response to treatment
     • Detecting drug resistance 1
   • Key thresholds:
     • HBeAg-positive CHB: ≥20,000 IU/mL
     • HBeAg-negative CHB: ≥2,000 IU/mL 1

2. HBV Genotyping

   • May help predict disease progression and treatment response
   • Certain genotypes (e.g., C) associated with increased risk of HCC 1

Interpretation of Common Serological Patterns

Serological Pattern	Interpretation
HBsAg+, IgM anti-HBc+	Acute HBV infection
HBsAg+, IgM anti-HBc-, HBV DNA+ (>6 months)	Chronic HBV infection
HBsAg-, anti-HBs+, anti-HBc+	Resolved HBV infection
HBsAg-, anti-HBs+, anti-HBc-	Vaccination-induced immunity
HBsAg-, anti-HBc+, anti-HBs-	Possible occult HBV infection or resolved infection with waning anti-HBs

Initial Evaluation of Patients with Chronic HBV

1. Comprehensive history and physical examination

   • Focus on risk factors: alcohol consumption, drug use
   • Family history of HBV infection and HCC
   • Assess for signs of advanced liver disease 1

2. Laboratory assessment

   • Complete blood count
   • Liver function tests (AST, ALT, alkaline phosphatase, GGT, bilirubin, albumin)
   • Prothrombin time/INR
   • Renal function tests (creatinine)
   • Tests for coinfections (anti-HCV, anti-HDV, anti-HIV) 1
   • Anti-HAV to assess need for hepatitis A vaccination 1

3. Assessment of liver fibrosis

   • Non-invasive methods: transient elastography (FibroScan)
   • Liver biopsy (when indicated): for assessing inflammation and fibrosis 1

4. HCC surveillance

   • Baseline ultrasound recommended for all HBsAg-positive persons ≥20 years 1

Treatment Options for Chronic Hepatitis B

Indications for Treatment

Treatment is indicated for patients with:

1. Cirrhosis and detectable HBV DNA
2. Elevated ALT (>2× ULN) with HBV DNA >20,000 IU/mL (HBeAg-positive)
3. Elevated ALT with HBV DNA >2,000 IU/mL (HBeAg-negative) 1

Available Treatments

1. Nucleos(t)ide Analogues

   • Tenofovir disoproxil fumarate (TDF)

     • High barrier to resistance
     • Recommended dose: 300 mg once daily
     • Requires dose adjustment in renal impairment
     • Monitor for renal toxicity and bone mineral density loss 2

   • Entecavir

     • High barrier to resistance
     • Preferred in treatment-naïve patients

2. Pegylated Interferon alfa

   • Finite treatment duration (48 weeks)
   • Higher rate of HBeAg and HBsAg clearance
   • Multiple side effects
   • Contraindicated in decompensated cirrhosis

Preventive Measures

1. Vaccination

   • Recommended for all persons negative for HBsAg and anti-HBs 1
   • Newborns of HBV-infected mothers should receive HBIG and hepatitis B vaccine at delivery 1

2. Lifestyle Modifications

   • Abstinence from alcohol and smoking 1
   • Maintain healthy weight

3. Prevention of Coinfection

   • Hepatitis A vaccination for those without anti-HAV 1

Monitoring During Treatment

1. Laboratory monitoring

   • ALT, HBV DNA every 3-6 months
   • Renal function and phosphate levels for patients on tenofovir
   • HBeAg/anti-HBe in HBeAg-positive patients

2. HCC surveillance

   • Ultrasound every 6 months for patients with cirrhosis or high risk factors

Common Pitfalls in HBV Diagnosis and Management

1. Missing occult HBV infection

   • HBsAg-negative but HBV DNA-positive patients
   • Consider in unexplained liver disease or isolated anti-HBc positive patients

2. Misinterpreting HBeAg-negative chronic hepatitis

   • May have active disease despite negative HBeAg due to precore/core promoter mutations
   • Requires HBV DNA testing for accurate assessment

3. Inadequate monitoring for HCC

   • Risk persists even with successful viral suppression
   • Regular surveillance is essential, especially in high-risk groups

4. Failing to screen and vaccinate contacts

   • Sexual and household contacts should be screened and vaccinated if susceptible

Remember that early diagnosis and appropriate treatment of chronic HBV infection significantly reduce the risk of progression to cirrhosis, development of HCC, and overall mortality.