What is the recommended evaluation and management approach for a patient with suspected hepatitis B virus infection?

Hepatitis B Evaluation and Management

Initial Screening and Diagnosis

All patients with suspected hepatitis B should be tested with three serologic markers: HBsAg, anti-HBc (total IgG or IgG), and anti-HBs to determine infection status. 1, 2

Serologic Interpretation

• HBsAg positivity for >6 months confirms chronic hepatitis B infection 1, 2
• Acute infection is distinguished by positive IgM anti-HBc alongside HBsAg 1
• Resolved infection shows negative HBsAg with positive anti-HBc and/or anti-HBs 1
• Isolated anti-HBc positivity may indicate occult hepatitis B and warrants HBV DNA testing 1

Comprehensive Initial Evaluation for HBsAg-Positive Patients

Essential History Elements

• Family history of HBV infection and hepatocellular carcinoma 1
• Risk factors for coinfection (HIV, HCV, HDV) and alcohol consumption 1
• Medication history and potential immunosuppressive therapy 1

Required Laboratory Testing

Liver disease assessment: 1, 2

• Complete blood count
• AST/ALT, alkaline phosphatase, gamma-glutamyl transpeptidase
• Bilirubin, albumin, creatinine, prothrombin time

Viral replication markers: 1, 2

• HBeAg/anti-HBe status
• Quantitative HBV DNA level

Coinfection screening: 1

• Anti-HCV, anti-HDV (in persons with injection drug use history), anti-HIV (in high-risk groups)

Vaccination status: 1

• IgG anti-HAV (hepatitis A immunity testing)

Fibrosis Assessment

• Non-invasive transient elastography is preferred over liver biopsy for initial fibrosis staging 1, 2
• Liver biopsy remains optional and reserved for indeterminate cases or suspected additional liver pathology 1, 2

Hepatocellular Carcinoma Screening

• Baseline abdominal ultrasound and serum α-fetoprotein should be obtained in all HBsAg-positive patients ≥20 years old 1, 2
• This applies even to younger patients, as HCC can develop before age 40 1

Disease Phase Classification

HBeAg-Positive Chronic Hepatitis B (Immune-Active Phase)

• HBeAg positive, HBV DNA ≥20,000 IU/mL, elevated ALT, moderate-to-severe liver inflammation 1, 2

HBeAg-Negative Chronic Hepatitis B

• HBeAg negative, anti-HBe positive, HBV DNA ≥2,000 IU/mL, elevated ALT 1, 2

Inactive Carrier State

• HBeAg negative, anti-HBe positive, HBV DNA <2,000 IU/mL, persistently normal ALT 1, 2

Immune-Tolerant Phase

• HBeAg positive, very high HBV DNA (≥10,000 IU/mL), normal ALT, minimal inflammation 2

Treatment Indications

Antiviral therapy should be initiated in the following scenarios: 2

• HBeAg-positive chronic hepatitis B: HBV DNA ≥20,000 IU/mL AND ALT >2× upper limit of normal for 3-6 months 2
• HBeAg-negative chronic hepatitis B: HBV DNA ≥2,000 IU/mL AND elevated ALT 2
• Any patient with cirrhosis and detectable HBV DNA, regardless of ALT level 2

First-Line Antiviral Agents

Entecavir or tenofovir (TDF/TAF) are the only recommended first-line agents due to their high barrier to resistance 1, 2

• Avoid lamivudine, emtricitabine, and telbivudine monotherapy due to high resistance rates 1, 2

Monitoring Protocol for Untreated Patients

Laboratory Monitoring Frequency

• ALT and AST every 3-6 months to detect disease activation 2
• Quantitative HBV DNA every 3-6 months, as 15-35% of inactive carriers develop viral reactivation 2
• HBeAg and anti-HBe status every 6-12 months in HBeAg-positive patients 2

HCC Surveillance

• Ultrasound examination every 6 months for all patients with cirrhosis, Asian men >40 years, Asian women >50 years, Africans >20 years, and those with family history of HCC 1, 2
• α-fetoprotein can supplement ultrasound but should not replace it 2

Special Considerations: Immunosuppression and Cancer Therapy

Prophylaxis Requirements

All HBsAg-positive patients must receive antiviral prophylaxis before any immunosuppressive therapy, including chemotherapy, anti-CD20 antibodies, TNF-α inhibitors, or stem-cell transplantation 1, 2

• Prophylaxis should start before immunosuppression and continue for at least 12 months after therapy completion (18 months for rituximab-based regimens) 1
• This applies even to inactive carriers with undetectable HBV DNA, as reactivation can cause fulminant hepatic failure and death 1

Patients with Past HBV Infection (HBsAg-negative, anti-HBc-positive)

• Require antiviral prophylaxis if receiving anti-CD20 therapy or stem-cell transplantation 1
• For other systemic anticancer therapies, monitor HBsAg and ALT every 3 months with immediate antiviral therapy if HBsAg becomes positive 1

Transmission Prevention and Contact Management

Patient Counseling

• HBV spreads via blood, sexual contact, and perinatal transmission 1, 2
• Patients must refrain from donating blood, plasma, tissue, or semen 1
• Avoid sharing toothbrushes, razors, or personal injection equipment 1
• Clean blood spills with bleach solution 1

Contact Screening and Vaccination

• Screen all household members, sexual partners, and needle-sharing contacts for HBsAg, anti-HBc, and anti-HBs 1, 2
• Vaccinate all susceptible contacts immediately without awaiting serologic results 1, 2
• HBsAg-positive pregnant women require their newborns to receive hepatitis B vaccine and hepatitis B immune globulin at birth 1

Hepatitis A Vaccination

• All HBsAg-positive patients without hepatitis A immunity should receive 2 doses of hepatitis A vaccine 6-18 months apart 1

Specialist Referral

All HBsAg-positive persons should be referred to a specialist or primary care provider experienced in treating hepatitis B, as specialist care is associated with more complete evaluation and appropriate antiviral therapy 1, 2

Critical Pitfalls to Avoid

• Do not delay cancer therapy while obtaining HBV testing or specialist referrals 1
• Never assume inactive carriers are at low risk during immunosuppression 1
• Do not rely solely on ALT levels to guide treatment in cirrhotic patients 2
• Avoid using lamivudine as first-line therapy due to resistance 1, 2