What are the next steps for a patient with a reactive Hepatitis B surface antigen (HBsAg) result?

Management of Reactive HBsAg

A reactive HBsAg result requires immediate confirmation testing, reporting to public health authorities, and comprehensive evaluation to distinguish acute from chronic infection and determine treatment eligibility. 1

Immediate Next Steps

Confirmatory Testing and Disease Classification

• Retest HBsAg to verify chronic HBV infection – the absence of IgM anti-HBc or persistence of HBsAg for ≥6 months confirms chronic infection rather than acute hepatitis B 1
• Measure HBV DNA by quantitative PCR to assess viral replication status, which is essential for treatment decisions 2
• Check HBeAg and anti-HBe status to classify the phase of infection (HBeAg-positive vs HBeAg-negative chronic hepatitis) 2, 3
• Obtain baseline ALT/AST levels to determine if active hepatic inflammation is present 2, 3
• Test for IgM anti-HBc – if positive, this suggests acute infection rather than chronic carrier state 1

Mandatory Reporting and Coinfection Screening

• Report all HBsAg-positive results to state or local health department as this is a legal requirement 1
• Test for HIV, hepatitis C (anti-HCV), hepatitis D (anti-HDV if injection drug use history), and syphilis as coinfections significantly alter prognosis and management 1, 2
• Screen for hepatitis A immunity (anti-HAV) – if negative, vaccinate immediately as HAV coinfection increases mortality 5.6- to 29-fold 2

Assessment of Disease Severity

Liver Fibrosis Evaluation

• Perform transient elastography (FibroScan) or other non-invasive fibrosis assessment to determine if cirrhosis is present 3
• Consider liver biopsy if HBV DNA ≥2,000 IU/mL with persistently normal ALT to assess degree of inflammation and fibrosis, particularly when non-invasive markers are indeterminate 1, 2
• Obtain baseline abdominal ultrasound to evaluate for cirrhosis and exclude focal liver lesions 4

Treatment Indication Algorithm

Immediate treatment is indicated if ANY of the following criteria are met:

• Cirrhosis with any detectable HBV DNA – treat immediately regardless of ALT level 2, 3
• HBV DNA ≥2,000 IU/mL AND elevated ALT – initiate first-line antiviral therapy with entecavir or tenofovir 1, 2, 3
• Decompensated liver disease – urgent treatment with nucleos(t)ide analogues and simultaneous liver transplant evaluation 2
• Moderate to severe fibrosis (liver stiffness ≥9 kPa with normal ALT or ≥12 kPa with elevated ALT) AND HBV DNA ≥2,000 IU/mL – treat even if ALT is normal 2

First-Line Treatment Selection

Preferred Antiviral Agents

• Entecavir 0.5 mg daily OR tenofovir disoproxil fumarate (TDF) OR tenofovir alafenamide (TAF) are the only recommended first-line options due to high barrier to resistance 2, 3
• Never use lamivudine monotherapy – resistance rates reach 70% at 5 years 2
• For lamivudine-resistant patients, use adefovir dipivoxil in combination with lamivudine, not as monotherapy 5

Special Population Considerations

• Pregnant women with HBV DNA >200,000 IU/mL – initiate tenofovir DF at 24-32 weeks gestation to prevent mother-to-child transmission, and report to perinatal hepatitis B prevention programs 1, 2
• Patients requiring immunosuppressive therapy or chemotherapy – start antiviral prophylaxis 2-4 weeks before treatment to prevent reactivation (risk 12-50% without prophylaxis), continue through treatment and for 12-24 months after completion 2, 6, 7, 8
• HIV-HBV coinfected patients – treat with tenofovir-containing antiretroviral therapy regardless of CD4 count 2

Contact Management and Transmission Prevention

Household and Sexual Contact Evaluation

• Identify and test all household members, sexual partners, and needle-sharing contacts for HBsAg, anti-HBs, and anti-HBc 1
• Vaccinate susceptible contacts immediately – give first dose at time of blood draw for serologic testing, complete series with age-appropriate schedule 1
• Counsel sexual partners to use latex condoms until immunity is documented (anti-HBs ≥10 mIU/mL) or prior infection confirmed (anti-HBc positive) 1

Patient Counseling on Transmission Prevention

• Advise patients to refrain from donating blood, plasma, organs, tissue, or semen 1
• Instruct to avoid sharing household items that could be contaminated with blood (toothbrushes, razors, personal injection equipment) 1
• Cover cuts and skin lesions to prevent spread through infectious secretions 1
• Clean blood spills with bleach solution 1

Hepatocellular Carcinoma Surveillance

High-Risk Screening Protocol

Initiate ultrasound screening every 6 months immediately if the patient meets ANY of these criteria: 2

• Asian men >40 years or Asian women >50 years
• Any patient with cirrhosis
• Family history of HCC
• Age >40 years with persistent ALT elevation

Treatment Monitoring Protocol

On-Treatment Surveillance

• Monitor HBV DNA every 3 months until undetectable, then every 6 months 2, 3
• Check ALT/AST every 3-6 months throughout treatment 2, 3
• Perform annual quantitative HBsAg testing to assess for functional cure (HBsAg loss) 2
• Monitor renal function if using tenofovir due to potential nephrotoxicity 2

Post-Treatment Discontinuation Monitoring

• If treatment is stopped, monitor closely for at least several months with frequent ALT and HBV DNA measurements, as severe hepatitis flares can occur with treatment discontinuation 1, 5

Liver Protection Measures

Hepatotoxin Avoidance

• Counsel complete alcohol abstinence or strict limitation as alcohol accelerates liver disease progression 1, 3
• Review all medications including over-the-counter and herbal products before starting, as many can cause hepatotoxicity 1

Common Pitfalls to Avoid

• Do not assume normal ALT means inactive disease – patients with HBV DNA ≥2,000 IU/mL and significant fibrosis require treatment even with normal ALT 2
• Do not use HBsAb positivity alone to exclude chronic infection – patients can have anti-HBs and still be HBsAg-positive chronic carriers 1
• Do not delay treatment in cirrhotic patients – any detectable HBV DNA in cirrhosis warrants immediate therapy regardless of other parameters 2, 3
• Do not forget to screen contacts – up to 85% of identified contacts can be successfully evaluated and vaccinated when systematic programs are implemented 1
• Do not use lamivudine as first-line therapy due to unacceptably high resistance rates 2