What is the recommended diagnostic workup and treatment approach for a patient suspected of having hepatitis B, particularly for individuals from endemic areas, healthcare workers, or those with high-risk behaviors?

Diagnosis of Hepatitis B

Initial Screening Test

Screen all adults aged 18 years and older with a three-test serologic panel: hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and total hepatitis B core antibody (anti-HBc). 1 This baseline assessment simultaneously identifies active infection, immunity status, and distinguishes natural infection from vaccine-induced immunity. 1

Priority Populations Requiring Mandatory Screening

The following groups must be tested regardless of vaccination history:

• Persons born in geographic regions with HBV prevalence >2% (includes most of Asia, Africa, Pacific Islands, Eastern Europe, Middle East, and parts of South America) 2
• U.S.-born persons not vaccinated as infants whose parents were born in regions with HBV endemicity >8% 2
• Men who have sex with men (HBsAg prevalence 6%, overall HBV serologic marker prevalence 35-80%) 2
• Injection drug users (HBsAg prevalence 7%, overall marker prevalence 60-80%) 2
• HIV-infected patients (HBsAg prevalence 8-11%, overall marker prevalence 89-90%) 2
• Household and sexual contacts of HBsAg-positive persons (HBsAg prevalence 3-6%, overall marker prevalence 30-60%) 2
• Dialysis patients (HBsAg prevalence 3-10%, overall marker prevalence 20-80%) 2
• Healthcare workers and others with occupational blood exposure 2
• Pregnant women (HBsAg prevalence 0.4-1.5% in USA) 2
• Persons with persistently elevated ALT or AST of unknown etiology 2
• Persons receiving or about to receive cytotoxic or immunosuppressive therapy (including chemotherapy, organ transplantation, biologics like anti-CD20 monoclonal antibodies) 2

Interpretation Algorithm for Initial Screening

All Three Tests Negative (HBsAg-, anti-HBs-, anti-HBc-)

• Patient is susceptible to HBV infection and requires immediate vaccination 1
• Administer first dose of hepatitis B vaccine at the same visit after blood draw 2

HBsAg Positive

• Patient has active HBV infection (acute or chronic) 1, 3
• Proceed immediately to comprehensive evaluation (see below)

Isolated Anti-HBc Positive (HBsAg-, anti-HBs-, anti-HBc+)

• Requires careful interpretation: may represent window period of acute infection, waning anti-HBs after remote infection, false positive, or occult hepatitis B 1
• Order HBV DNA quantitative testing to exclude occult infection 3
• Consider IgM anti-HBc if acute infection suspected 1, 3

Anti-HBs Positive Only (with or without anti-HBc)

• Patient is immune from vaccination (anti-HBc negative) or past cleared infection (anti-HBc positive) 1
• No further testing or vaccination needed

Comprehensive Evaluation for HBsAg-Positive Patients

All HBsAg-positive patients require immediate comprehensive laboratory evaluation to assess disease phase, viral replication, liver injury, and coinfections. 3

Mandatory Initial Laboratory Panel

Order the following tests at initial diagnosis:

• HBeAg and anti-HBe to determine disease phase and viral replication status 3
• Quantitative HBV DNA (essential for treatment decisions; levels ≥20,000 IU/mL in HBeAg-positive or ≥2,000 IU/mL in HBeAg-negative indicate active disease) 3
• Complete liver panel (ALT, AST, bilirubin, albumin, alkaline phosphatase, prothrombin time/INR) to assess synthetic function and identify decompensation 2, 3
• Complete blood count to establish baseline and assess for cytopenias suggesting cirrhosis 3
• Serum creatinine (mandatory before antiviral therapy, particularly with tenofovir or adefovir due to nephrotoxicity risk) 3

Mandatory Coinfection Screening

Screen all HBsAg-positive patients for the following coinfections:

• HIV antibody/antigen testing (coinfection accelerates liver disease and fundamentally alters treatment) 3
• Anti-HCV antibody (hepatitis C coinfection significantly worsens prognosis) 3
• Anti-HDV antibody (hepatitis D only infects in presence of HBV and dramatically worsens outcomes) 2, 3
• Anti-HAV IgG to assess immunity; if negative, administer 2 doses of hepatitis A vaccine 6-18 months apart 2, 3
• Schistosomiasis testing (S. mansoni or S. japonicum) for persons from endemic areas, as it increases progression to cirrhosis and HCC 2

Hepatocellular Carcinoma Surveillance

• Baseline abdominal ultrasound to assess for cirrhosis and exclude focal liver lesions 3
• Baseline alpha-fetoprotein (AFP) for ongoing HCC surveillance 2, 3
• High-risk patients (Asian men >40 years, Asian women >50 years, persons with cirrhosis, family history of HCC, Africans >20 years, HBV-infected persons >40 years with persistent ALT elevation) require ultrasound every 6-12 months with AFP 2

Distinguishing Acute from Chronic Infection

Chronic hepatitis B is confirmed by:

• HBsAg positive for ≥6 months, OR 2
• HBsAg positive with absence of IgM anti-HBc in the original specimen 2

Acute hepatitis B is indicated by:

• IgM anti-HBc positive in the setting of HBsAg positivity 3
• Clinical symptoms of acute hepatitis with recent exposure 4, 5

Diagnostic Criteria for Disease States

Chronic Hepatitis B (Active Disease)

1. HBsAg positive ≥6 months 2
2. Serum HBV DNA ≥10^5 copies/mL 2
3. Persistent or intermittent elevation in ALT/AST 2
4. Liver biopsy showing chronic hepatitis (optional) 2

Inactive HBsAg Carrier State

1. HBsAg positive ≥6 months 2
2. HBeAg negative, anti-HBe positive 2
3. Serum HBV DNA <10^5 copies/mL 2
4. Persistently normal ALT/AST 2
5. Liver biopsy confirms absence of significant hepatitis (optional) 2

Resolved Hepatitis B

1. Previous history of acute or chronic hepatitis B OR presence of anti-HBc with anti-HBs 2
2. HBsAg negative 2
3. Undetectable serum HBV DNA 2
4. Normal ALT 2

Ongoing Monitoring Schedule

For Patients NOT on Treatment

HBeAg-positive patients with normal ALT:

• Check ALT every 3-6 months 3

HBeAg-negative patients with normal ALT and HBV DNA <2,000 IU/mL:

• Check ALT every 3 months during first year 3

For Patients ON Antiviral Treatment

• Monitor ALT, HBV DNA, and HBeAg/anti-HBe every 12-24 weeks during treatment 3
• Monitor creatinine regularly if on tenofovir or adefovir 3

Critical Pitfalls to Avoid

Do not rely on vaccination history alone for persons from endemic areas – test all individuals born in regions with HBV prevalence >2% regardless of reported vaccination status, as most were born before full implementation of infant vaccination programs 2

Do not miss occult HBV infection – patients who are HBsAg-negative but anti-HBc-positive require hepatology referral before immunosuppressive or cancer therapy, as occult HBV can reactivate 3

Do not delay vaccination while awaiting test results – administer the first dose of hepatitis B vaccine at the same visit after blood draw for susceptible populations 2

Do not forget to test for hepatitis D – anti-HDV testing is mandatory when HBsAg is positive, as HDV dramatically worsens outcomes and is often missed 2, 3

Do not use isolated anti-HBc testing – always order the complete three-test panel (HBsAg, anti-HBs, anti-HBc) as isolated anti-HBc cannot distinguish immunity from occult infection 1