What tests should be included in the initial work‑up for hepatitis B infection?

Initial Work-Up for Hepatitis B Infection

All patients with suspected or confirmed hepatitis B infection should undergo a comprehensive serologic panel including HBsAg, anti-HBs, anti-HBc (total and IgM), HBeAg/anti-HBe, quantitative HBV DNA, complete liver function tests (ALT, AST, bilirubin, albumin, alkaline phosphatase, PT/INR), complete blood count with platelets, and baseline abdominal ultrasound for hepatocellular carcinoma screening. 1, 2

Core Serologic Tests

Primary Diagnostic Panel

• HBsAg – confirms active infection (acute or chronic); persistence beyond 6 months defines chronic hepatitis B 1, 2
• Anti-HBc total (IgG + IgM) – distinguishes acute from chronic infection and detects past exposure 1, 2
• Anti-HBc IgM – high titers indicate acute infection; absent or low titers suggest chronic infection 1
• Anti-HBs – indicates immunity from vaccination or resolved infection 1, 2
• HBeAg and anti-HBe – determines replication status and guides treatment decisions 1

Virologic Assessment

• Quantitative HBV DNA – essential for assessing viral replication, determining treatment eligibility, and monitoring disease activity 1
• HBV DNA ≥20,000 IU/mL in HBeAg-positive patients or ≥2,000 IU/mL in HBeAg-negative patients with elevated ALT indicates chronic hepatitis requiring treatment consideration 1

Liver Disease Assessment

Biochemical Tests

• ALT and AST – primary markers of hepatocellular injury; ALT should be monitored every 3-6 months 1, 3
• Albumin – reflects hepatic synthetic function and chronicity of disease 1, 4
• Bilirubin – assesses hepatic excretory function 1, 4
• Alkaline phosphatase – evaluates for cholestatic disease 1, 4
• PT/INR – measures coagulation status and synthetic capacity 1, 4
• Complete blood count with platelets – thrombocytopenia suggests portal hypertension and advanced fibrosis 1, 4

Hepatocellular Carcinoma Screening

• Baseline abdominal ultrasound – mandatory in all HBsAg-positive patients ≥20 years old, even though HCC risk increases significantly after age 40 1, 2
• Alpha-fetoprotein (AFP) – baseline measurement, though specificity is limited 1

Coinfection Screening

Mandatory Testing for At-Risk Patients

• Anti-HCV – screen all patients for hepatitis C coinfection 1, 2
• Anti-HDV – test patients from endemic areas (Mediterranean, Middle East, parts of Africa) or with history of injection drug use 1, 2
• Anti-HIV – screen high-risk patients (men who have sex with men, injection drug users, multiple sexual partners) 1
• IgG anti-HAV – assess immunity status in patients <50 years; vaccinate if non-immune 1

Clinical History Elements

Critical Risk Factors to Document

• Family history – HBV infection in relatives, liver cancer in family members 1, 3
• Transmission risk factors – sexual history, injection drug use, blood transfusions (especially before 1992), tattoos, body piercings, occupational exposures (healthcare workers), country of birth (endemic areas with HBV prevalence >2%) 1, 3
• Alcohol consumption – quantify daily/weekly intake; abstinence should be strongly recommended 1
• Medication history – immunosuppressive drugs, chemotherapy, biologics (especially anti-CD20 agents like rituximab) that increase reactivation risk 1

Physical Examination Priorities

• Stigmata of chronic liver disease – jaundice, spider angiomata, palmar erythema, gynecomastia, testicular atrophy 1
• Hepatosplenomegaly – palpate liver and spleen size 1
• Ascites and edema – signs of hepatic decompensation 1

Optional but Valuable Tests

Fibrosis Assessment

• Liver biopsy – recommended but not mandatory in patients with intermittent or persistent ALT elevation to grade inflammation and stage fibrosis 1
• Transient elastography (FibroScan) – non-invasive alternative to biopsy; values >7.8 kPa suggest advanced fibrosis 1, 4
• FIB-4 score – calculated from age, AST, ALT, and platelets; <1.3 indicates low risk of advanced fibrosis 4

Genotype Testing

• HBV genotype – consider in selected patients as genotype C and certain mutations (basal core promoter, pre-S deletion) associate with increased HCC risk 1, 5

Common Pitfalls to Avoid

• Isolated anti-HBc positivity – can indicate occult hepatitis B (especially in immunocompromised patients), resolved infection with undetectable anti-HBs, or false positive; measure HBV DNA to clarify 1
• Window period – isolated IgM anti-HBc may occur between HBsAg clearance and anti-HBs development in acute infection; repeat testing in 3-6 months 1
• Occult HBV – HBsAg-negative but HBV DNA-positive patients exist, particularly among HIV-coinfected individuals; test HBV DNA if anti-HBc positive with unexplained transaminitis 1
• Ferritin elevation – can be falsely elevated in inflammatory states, necroinflammatory liver disease, and malignancy; interpret cautiously 4

Immediate Actions

• Referral to specialist – all HBsAg-positive patients should see a hepatologist or experienced provider for treatment evaluation 1, 2
• Contact vaccination – identify and vaccinate sexual partners, household contacts, and needle-sharing contacts 1, 3, 2
• Transmission counseling – educate on preventing spread through blood/serum and sexual contact 1, 3