Hepatitis B: Diagnosis, Prevention, and Treatment
Diagnosis
Screen all high-risk individuals with HBsAg testing as the primary diagnostic tool, followed by comprehensive serological and virological workup to determine infection status and disease phase. 1
Initial Screening
- HBsAg (hepatitis B surface antigen) is the hallmark marker and first test for HBV infection 2, 3
- Screen these high-risk populations: individuals from high-endemic areas, persons with HIV, injection drug users, men who have sex with men, household and sexual contacts of HBV-infected persons, healthcare workers, and all pregnant women at first prenatal visit 1, 4
Diagnostic Workup for HBsAg-Positive Patients
- Serological markers: HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc IgM and IgG 5, 3
- HBV DNA quantification to determine viral load and replication status 1, 2
- Liver function tests: ALT, AST, bilirubin, albumin, prothrombin time 1, 5
- HBsAg persistence >6 months confirms chronic infection 4, 2
Disease Phase Classification
The AASLD classifies chronic HBV into five phases 1:
- HBeAg-positive chronic infection (immune-tolerant): HBV DNA typically >1 million IU/mL, normal/minimally elevated ALT, minimal liver inflammation 6
- HBeAg-positive chronic hepatitis (immune-active): HBV DNA >20,000 IU/mL, elevated ALT >2× ULN, moderate/severe inflammation 6
- HBeAg-negative chronic infection (inactive carrier): HBV DNA <2,000 IU/mL, persistently normal ALT 6
- HBeAg-negative chronic hepatitis: HBV DNA >2,000 IU/mL, elevated ALT >2× ULN 6
- HBsAg-negative phase (resolved infection) 1
Prevention
Vaccinate all household and sexual contacts of HBsAg-positive persons immediately after confirming they lack immunity. 6
Vaccination Strategy
- Universal infant vaccination within 24 hours of birth for medically stable infants ≥2,000g 4
- All adolescents not previously vaccinated 7
- Adults in high-risk groups and those requesting protection 4
- Hepatitis A vaccine (2 doses, 6-18 months apart) for all chronic HBV patients with chronic liver disease 6, 7
Transmission Prevention for HBsAg-Positive Persons
HBsAg-positive individuals must notify all household, sexual, and needle-sharing contacts for testing and vaccination. 6
- Use condoms with non-immune sexual partners until vaccination series completed and immunity documented 6
- Never share: toothbrushes, razors, injection equipment, glucose testing equipment 6
- Cover all cuts and skin lesions to prevent blood exposure 6
- Clean blood spills with bleach solution 6
- Do not donate blood, plasma, tissue, organs, or semen 6
Perinatal Prevention
- Screen all pregnant women for HBsAg at first prenatal visit 4
- Newborns of HBsAg-positive mothers must receive hepatitis B vaccine AND hepatitis B immune globulin beginning at birth 6, 7
Important Clarifications
- HBV is NOT spread by breastfeeding, kissing, hugging, coughing, sharing food/utensils, or casual contact 6
- Children and adults with HBV can participate in all activities including contact sports and should not be excluded from school, daycare, or work unless prone to biting 6
Treatment
Treat immediately with entecavir, tenofovir disoproxil fumarate, or tenofovir alafenamide for patients meeting specific criteria based on disease phase, viral load, ALT levels, and liver damage. 1, 4
Immediate Treatment Indications (No Delay)
- Acute liver failure 1
- Decompensated cirrhosis 1
- Severe acute exacerbation with icteric ALT flares 6, 1
- All patients with compensated or decompensated cirrhosis and detectable HBV DNA 1, 7
Treatment Criteria for Chronic HBV
HBeAg-Positive Chronic Hepatitis:
- Treat if: HBV DNA >20,000 IU/mL AND (ALT >2× ULN OR moderate/severe inflammation/fibrosis on biopsy) 6, 1
- Delay treatment 3-6 months in compensated disease to assess for spontaneous HBeAg seroconversion, EXCEPT in icteric flares 6
- Do NOT treat if ALT persistently normal or <2× ULN unless biopsy shows significant disease 6
HBeAg-Negative Chronic Hepatitis:
- Treat if: HBV DNA >2,000 IU/mL AND (ALT >2× ULN OR moderate/severe inflammation/fibrosis on biopsy) 6, 1
First-Line Treatment Options
Nucleos(t)ide analogues with high genetic barrier to resistance are preferred over pegylated interferon for most patients. 1, 4
Preferred first-line agents 1, 4:
- Entecavir
- Tenofovir disoproxil fumarate
- Tenofovir alafenamide
Alternative for selected patients 1:
- Pegylated interferon alfa-2a: Consider for finite duration in mild-moderate disease without cirrhosis 1
Critical Treatment Warnings
- Entecavir is NOT recommended for HBV/HIV co-infected patients unless receiving HAART 8
- Severe acute exacerbations can occur after discontinuation—monitor hepatic function closely for several months 8
- Lactic acidosis and hepatomegaly with steatosis: Suspend treatment if suspected 8
Monitoring During Treatment
- Liver function tests (ALT, AST, bilirubin, albumin, PT) every 3-6 months 1
- HBV DNA levels every 3-6 months 6, 1
- Check medication compliance in patients with virologic breakthrough 6
- Genotypic testing to confirm antiviral resistance 6
Treatment Duration and Endpoints
- Ideal endpoint: HBsAg loss with or without anti-HBs seroconversion 1, 4
- HBeAg-positive patients: Can discontinue after HBeAg seroconversion, undetectable HBV DNA, and ≥12 months consolidation therapy 1
- Cirrhotic patients: Indefinite treatment recommended 1
Liver Protection Measures
All HBsAg-positive persons must avoid/limit alcohol consumption due to accelerated liver damage. 6
- Seek care from providers experienced in hepatitis B management 6
- Refer for alcohol abuse evaluation if needed 6
- Vaccinate against hepatitis A if chronic liver disease present 6