What is the recommended evaluation and management for a patient with hepatitis B infection, including serologic testing, vaccination, and indications for antiviral therapy?

Hepatitis B: Evaluation and Management

Initial Diagnostic Testing

All patients with suspected or confirmed hepatitis B require a comprehensive serologic panel including HBsAg, anti-HBc (total and IgM), anti-HBs, HBeAg, anti-HBe, and quantitative HBV DNA to distinguish acute from chronic infection and determine disease phase. 1, 2

Serologic Interpretation

• Chronic HBV infection is confirmed by HBsAg positivity persisting ≥6 months, positive total anti-HBc, negative or low-titer IgM anti-HBc, and negative anti-HBs 1, 2
• Acute HBV infection is diagnosed by HBsAg positive with high-titer IgM anti-HBc 1, 3
• Retest HBsAg in a second sample at least 6 months after initial detection to confirm chronicity 1

Assessment of Liver Disease Severity

Perform comprehensive biochemical evaluation at initial assessment and every 3-6 months during follow-up 4, 1:

• Liver enzymes: AST, ALT, GGT, alkaline phosphatase (ALT typically higher than AST until cirrhosis develops, when ratio reverses) 4, 2
• Liver synthetic function: Albumin, bilirubin, prothrombin time, platelet count 4, 2
• Abdominal ultrasound in all patients at initial evaluation 4, 2
• Non-invasive fibrosis assessment using transient elastography offers high accuracy for detecting cirrhosis, though results may be confounded by severe inflammation with elevated ALT 4
• Liver biopsy is indicated when biochemical and viral markers are inconclusive, but not required in patients with clinical cirrhosis or when treatment is indicated regardless of fibrosis stage 4

Hepatocellular Carcinoma Surveillance

Initiate HCC surveillance with baseline abdominal ultrasound at initial encounter in all HBsAg-positive patients ≥20 years old, with continued surveillance every 6 months in high-risk patients. 1, 2

Risk factors for HCC include 4:

• Cirrhosis (annual HCC risk 2-5%)
• Chronic hepatic inflammation
• Male sex, older age, African origin
• High HBV DNA and/or HBsAg levels
• HBV genotype C
• Diabetes, metabolic syndrome, alcohol abuse
• Coinfection with HCV, HDV, or HIV
• Positive family history of HCC

Testing for Coinfections and Comorbidities

Screen all chronic HBV patients for 4:

• HIV, HCV, HDV (particularly in endemic areas or severe disease) 4, 2
• Anti-HAV IgG - vaccinate all seronegative patients as acute HAV superinfection increases risk of fulminant hepatic failure 4, 3
• Syphilis, gonorrhea, chlamydia 4
• Metabolic liver disease, alcoholic liver disease, autoimmune conditions 4

Contact Management and Vaccination

Immediately identify and test all first-degree relatives, sexual partners, and household contacts for HBsAg, anti-HBs, and anti-HBc. 4, 1, 2

• Administer first vaccine dose on the same day as blood draw for susceptible contacts 1, 2
• Complete the hepatitis B vaccine series using age-appropriate dosing 4
• Vaccinate all seronegative contacts against hepatitis A 3

Indications for Antiviral Therapy

All cirrhotic patients with detectable HBV DNA require treatment regardless of ALT or HBeAg status. 3

For non-cirrhotic patients, treat when 4, 3:

• HBV DNA ≥2,000 IU/mL AND
• Elevated ALT AND
• At least moderate histological lesions on biopsy

First-Line Treatment Options

Long-term administration of entecavir, tenofovir disoproxil fumarate, or tenofovir alafenamide represents first-line therapy due to high potency and high barrier to resistance. 3, 5, 6

• These agents are superior to older nucleos(t)ide analogues (lamivudine, adefovir) which have higher resistance rates 6
• Pegylated interferon alfa-2a is an alternative for selected patients, offering finite 48-week treatment duration but limited by poor tolerability and contraindications 5, 6
• Most patients require indefinite therapy as cure rates (HBsAg loss) remain low at 1-12% with nucleos(t)ide analogues 6

Acute Hepatitis B Treatment

The vast majority of acute HBV cases require no treatment, as >95% of adults recover spontaneously. 3

• Treatment is indicated ONLY for severe acute hepatitis B with coagulopathy, protracted course, or acute liver failure 3
• When treatment is needed, use entecavir or tenofovir 3

Specialist Referral

All HBsAg-positive patients should be referred to a hepatologist or physician experienced in hepatitis B management for comprehensive evaluation and treatment decisions. 1, 2

Patient Counseling and Transmission Prevention

Advise patients to 4:

• Use condoms with non-immune sexual partners until partner immunity is documented (anti-HBs ≥10 mIU/mL) 4
• Cover cuts and skin lesions 4
• Avoid sharing toothbrushes, razors, or injection equipment 4
• Refrain from donating blood, organs, tissue, or semen 4
• Avoid or limit alcohol consumption 4, 2
• Obtain hepatitis A vaccination if seronegative 4, 3
• Inform healthcare providers of HBsAg status before medical/dental procedures 4

Monitoring During Treatment

• Measure HBV DNA and ALT every 3-6 months during treatment 4
• Continue HCC surveillance every 6 months even in patients with sustained viral suppression, as HCC risk persists 4
• Use the same HBV DNA assay for serial monitoring, with results expressed in IU/mL 4