What is the initial work-up and management for a patient suspected of having hepatitis B?

Work-up for Hepatitis B

Begin with HBsAg testing as the primary screening marker, and if positive, proceed immediately with a comprehensive serological panel including anti-HBc (total and IgM), HBeAg/anti-HBe, HBV DNA quantification, complete liver function tests, and screening for coinfections to determine disease phase and guide management. 1, 2

Initial Serological Testing

Primary Screening Markers

• HBsAg is the hallmark marker for active HBV infection and must be checked first 2, 3
• Anti-HBc (total) indicates current or previous HBV infection 2
• Anti-HBs indicates either recovery from infection or successful vaccination 2
• IgM anti-HBc distinguishes acute infection (positive) from chronic infection (negative or low-level positive) 1, 2

Replication Markers

• HBeAg indicates high viral replication and increased infectivity 1, 2
• Anti-HBe typically indicates lower viral replication when HBeAg becomes negative 1, 2
• HBV DNA quantification is essential for assessing viral load, disease activity, and treatment decisions 1, 2

Critical thresholds for HBV DNA: HBeAg-positive chronic hepatitis B typically shows HBV DNA ≥20,000 IU/mL, while HBeAg-negative chronic hepatitis B shows HBV DNA ≥2,000 IU/mL 1, 2

Comprehensive Laboratory Assessment

Liver Function Panel

• Complete blood count to assess for cytopenias suggesting advanced disease 1
• AST/ALT to evaluate hepatocellular injury and inflammation 1, 2
• Alkaline phosphatase and gamma-glutamyl transpeptidase as additional markers of liver injury 1, 2
• Bilirubin to assess hepatic synthetic function 1, 2
• Albumin to evaluate synthetic liver function 1, 2
• Prothrombin time/INR to assess coagulation and synthetic function 1, 2
• Creatinine for baseline renal function 1

Coinfection Screening

• Anti-HCV to rule out hepatitis C coinfection 1, 2
• Anti-HDV in patients with injection drug use history or from endemic areas 1, 2
• Anti-HIV in high-risk groups (mandatory before initiating entecavir therapy) 1, 4
• Anti-HAV IgG to determine immunity status; vaccinate if negative 1, 2

Critical pitfall: HIV testing must be performed before starting entecavir, as using entecavir in untreated HIV/HBV coinfection can lead to HIV resistance 4

Hepatocellular Carcinoma Screening

Baseline Assessment

• Alpha-fetoprotein (AFP) at initial diagnosis 1, 2
• Abdominal ultrasound for high-risk patients including: Asian men >40 years, Asian women >50 years, patients with cirrhosis, family history of HCC, Africans >20 years, and HBV-infected persons >40 years with elevated ALT or high HBV DNA 1, 2

Fibrosis Assessment

Non-invasive and Invasive Options

• Liver biopsy (optional) to evaluate inflammation and fibrosis when initial laboratory tests suggest liver damage or when disease phase is unclear 1, 2
• Non-invasive fibrosis markers can be used as alternatives to biopsy when available 1, 2

Clinical History Requirements

Essential Historical Elements

• Alcohol consumption quantity and frequency (recommend abstinence or severe limitation) 1
• Drug use history including injection drug use and current medications 1
• Family history of HBV infection, liver disease, and hepatocellular carcinoma 1
• Risk factors for coinfection with HIV, HCV, or HDV 1

Interpretation of Common Serologic Patterns

Acute HBV Infection

• HBsAg positive, IgM anti-HBc positive 1, 2

Chronic HBV Infection

• HBsAg positive for >6 months, total anti-HBc positive, IgM anti-HBc negative 1, 2

Past Infection with Immunity

• HBsAg negative, anti-HBs positive, total anti-HBc positive 2

Vaccine-Induced Immunity

• HBsAg negative, anti-HBs positive, total anti-HBc negative 2

Window Period

• Both HBsAg and anti-HBs may be negative, but IgM anti-HBc is positive 1, 2

Common pitfall: Isolated anti-HBc positivity requires follow-up testing and HBV DNA measurement, as it may indicate occult hepatitis B or waning immunity 1, 2

Defining Disease Phase

Chronic Hepatitis B (Active Disease)

• HBsAg positive >6 months 1
• HBV DNA ≥20,000 IU/mL (HBeAg-positive) or ≥2,000 IU/mL (HBeAg-negative) 1, 2
• Persistent or intermittent AST/ALT elevation 1

Inactive Carrier State

• HBsAg positive >6 months 1
• HBeAg negative, anti-HBe positive 1
• HBV DNA <2,000 IU/mL 1, 2
• Persistently normal AST/ALT 1

Important caveat: HBeAg-negative chronic hepatitis B can have lower HBV DNA levels but still cause progressive liver disease, requiring careful monitoring 2

Follow-up Testing Schedule

For Untreated Patients

• ALT monitoring every 3-6 months 2
• HBV DNA every 6-12 months 2
• HBeAg/anti-HBe status annually 2

For Cirrhotic Patients

• More frequent monitoring of all parameters 2
• HCC surveillance with ultrasound every 6 months 2

After Initial Diagnosis

• Repeat HBsAg, anti-HBs, and anti-HBc in 3-6 months if initial pattern is unclear to confirm chronic infection versus acute infection 1

Management Considerations

Immediate Referral Indications

• Refer to or consult with a physician experienced in chronic liver disease management soon after HBV infection is identified 1
• 15-25% of chronic HBV patients are at risk for premature death from cirrhosis and liver cancer 1

Counseling Points

• Advise against blood, plasma, tissue, or semen donation 1
• Avoid sharing household articles that could be contaminated with blood (toothbrushes, razors, injection equipment) 1
• Newborns of HBsAg-positive mothers require HBIG and hepatitis B vaccine at delivery 1