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

Management of Positive Hepatitis B Surface Antigen (HBsAg)

All patients who test positive for HBsAg require immediate comprehensive evaluation to determine disease activity, assess need for antiviral treatment, and initiate prevention counseling. 1

Immediate Diagnostic Workup

When HBsAg is positive, the following tests must be ordered immediately to define the clinical status and guide management:

• Hepatitis B e antigen (HBeAg) and anti-HBe antibody to classify the phase of infection and determine replication status 1, 2
• Quantitative HBV DNA by PCR to measure viral load (≥2,000 IU/mL indicates active replication requiring treatment consideration) 2, 3
• Total anti-HBc (hepatitis B core antibody) to confirm chronic infection 1
• Anti-HBs (hepatitis B surface antibody) - though typically negative when HBsAg is positive, rare coexistence can occur 4
• Liver function tests including ALT, AST, bilirubin, albumin, and prothrombin time to assess hepatic inflammation and synthetic function 2, 3
• Complete blood count and creatinine to establish baseline organ function 2

Additional Essential Screening

• Hepatitis D virus (HDV) antibody in all HBsAg-positive patients, as coinfection fundamentally changes management 2
• Hepatitis C virus (HCV) antibody and HCV RNA to identify coinfection requiring coordinated treatment 2
• HIV antibody testing before starting any HBV therapy, as HIV coinfection alters treatment approach 1, 5
• Hepatitis A antibody (anti-HAV) with vaccination if non-immune, as HAV coinfection increases mortality 5.6- to 29-fold 2
• Abdominal ultrasound to assess for cirrhosis and exclude focal liver lesions 3

Liver Fibrosis Assessment

Assess liver fibrosis stage using transient elastography (FibroScan) or liver biopsy in patients with elevated ALT/AST to determine disease severity and treatment urgency. 2, 3 This is critical because patients with cirrhosis require indefinite antiviral therapy and lifelong hepatocellular carcinoma (HCC) surveillance. 1

Prevention Counseling

Provide immediate counseling on:

• Transmission prevention: HBsAg-positive patients can transmit HBV through blood, sexual contact, and perinatal exposure 1, 6
• Household and sexual contacts should be tested for HBsAg, anti-HBs, and anti-HBc, with immediate vaccination if all markers are negative 1
• Complete alcohol abstinence, as even moderate consumption accelerates fibrosis progression 2
• Avoiding hepatotoxic medications and supplements 2

Treatment Decision Algorithm

Patients Requiring Immediate Antiviral Therapy:

Start entecavir 0.5 mg daily or tenofovir (disoproxil fumarate 300 mg or alafenamide 25 mg) daily in the following scenarios: 1, 2

1. HBV DNA ≥2,000 IU/mL with elevated ALT (above upper limit of normal) 1, 2
2. Any detectable HBV DNA with evidence of cirrhosis (compensated or decompensated) 1
3. Decompensated liver disease regardless of HBV DNA level - use lamivudine or entecavir (avoid tenofovir due to nephrotoxicity risk) 3
4. Before starting immunosuppressive therapy or chemotherapy (see below) 1
5. Family history of HCC or cirrhosis with HBV DNA ≥2,000 IU/mL 2

Special Populations Requiring Prophylactic Antiviral Therapy:

Prophylactic antiviral therapy must be initiated in HBsAg-positive patients receiving: 1

• Anti-CD20 monoclonal antibodies (rituximab, obinutuzumab) - start antiviral therapy before first dose and continue for 18 months after completion 1
• Chemotherapy regimens containing corticosteroids - start at onset and continue for 6-12 months after completion 1
• Hematopoietic stem cell transplantation - continue indefinitely 1, 7
• CAR-T cell therapy - prophylaxis strongly recommended 7
• Solid organ transplantation - continue indefinitely 1
• Anti-TNF biologics (infliximab, adalimumab) for inflammatory bowel disease or rheumatoid arthritis 1
• Bruton's tyrosine kinase inhibitors or BCL-2 inhibitors for hematological malignancies 7

Avoid lamivudine for prophylaxis due to high resistance rates; use entecavir, tenofovir disoproxil fumarate, or tenofovir alafenamide instead. 1

Monitoring During Prophylaxis/Treatment

• HBV DNA every 3 months until undetectable, then every 6 months 1, 2
• ALT/AST every 3-6 months to detect hepatitis flares 2
• HBeAg and anti-HBe every 6-12 months in HBeAg-positive patients 1
• HBsAg quantification annually in patients with undetectable HBV DNA to assess for potential treatment discontinuation 1, 8
• Renal function monitoring in patients on tenofovir or adefovir 1, 5

Hepatocellular Carcinoma Surveillance

Initiate lifelong HCC surveillance with abdominal ultrasound every 6 months in: 2

• All patients with cirrhosis regardless of treatment status
• Asian men >40 years old
• Asian women >50 years old
• Any patient with family history of HCC
• Patients >40 years with persistent ALT elevation

Continue HCC surveillance even after HBsAg loss if significant fibrosis or cirrhosis was present at baseline. 2

Critical Warnings and Pitfalls

Never discontinue antiviral therapy abruptly without close monitoring, as severe hepatitis flares occur in 20-50% of patients and can be fatal. 1, 5, 9 If treatment must be stopped, monitor HBV DNA and ALT monthly for at least 6-12 months. 1

HBV reactivation can occur even in patients with undetectable baseline HBV DNA during immunosuppression, making prophylaxis essential rather than optional. 1, 2

In patients requiring urgent surgery, HBsAg positivity is NOT an absolute contraindication, but universal precautions including double gloving and hands-free sharp handling must be strictly implemented. 6

Patients with isolated anti-HBc positivity (HBsAg-negative, anti-HBc-positive) receiving high-risk immunosuppression also require prophylaxis or close monitoring, as occult HBV can reactivate. 1, 10