Guidelines for Hepatitis B Management
Diagnosis and Initial Assessment
All patients with suspected chronic hepatitis B require HBsAg testing, and if positive for >6 months, this confirms chronic infection. 1
Essential Diagnostic Tests
- HBsAg and anti-HBs to determine infection status and immunity 2
- HBV DNA quantification by PCR to assess viral replication (critical for treatment decisions) 1, 3
- HBeAg and anti-HBe to classify disease phase 2
- ALT/AST levels to evaluate hepatic inflammation 1, 3
- Liver fibrosis assessment using non-invasive tests (liver stiffness measurement) or biopsy 2
- Anti-HBc IgM if acute infection suspected 2
Screening High-Risk Populations
- All pregnant women at first prenatal visit 4
- Persons born in endemic regions (Asia, Africa, Pacific Islands) 2
- HIV-infected individuals, dialysis patients, healthcare workers 2
- Household and sexual contacts of HBV carriers 2
Treatment Indications
The 2024 WHO guidelines have expanded treatment criteria, lowering the HBV DNA threshold from >20,000 IU/mL to >2,000 IU/mL, though this remains controversial among liver societies. 2
Immediate Treatment Required
- All patients with cirrhosis and any detectable HBV DNA, regardless of ALT levels 1, 3, 5
- Decompensated cirrhosis with any HBV replication - requires urgent treatment and transplant evaluation 1
- HBV DNA ≥20,000 IU/mL AND ALT >2× ULN - can start without liver biopsy 1, 3, 5
Treatment Recommended
- HBV DNA ≥2,000 IU/mL with elevated ALT and/or moderate-to-severe histological lesions 2, 1, 5
- HBV DNA ≥2,000 IU/mL with liver stiffness ≥9 kPa (normal ALT) or ≥12 kPa (ALT ≤5× ULN) 1, 3, 5
- HBeAg-positive patients >30 years with HBV DNA >20,000 IU/mL, regardless of histology 1, 3
- Family history of cirrhosis/HCC with HBV DNA >2,000 IU/mL 5
Special Circumstances Requiring Prophylactic Treatment
- Pregnant women with HBV DNA >200,000 IU/mL - start tenofovir DF at 24-32 weeks gestation 1, 3
- Patients receiving immunosuppression or chemotherapy (HBsAg-positive or HBcAb-positive) 3
- Liver transplant recipients - lifelong treatment mandatory 1
- HIV-HBV coinfected patients - treat regardless of CD4 count 1, 3
First-Line Treatment Options
Nucleos(t)ide analogues with high genetic barrier to resistance—entecavir, tenofovir disoproxil fumarate (TDF), or tenofovir alafenamide (TAF)—are the preferred first-line agents. 1, 6, 4
Recommended Regimens
- Entecavir 0.5 mg once daily (standard dose) 1, 7
- Entecavir 1 mg once daily for lamivudine-resistant patients or decompensated cirrhosis 7
- Tenofovir DF 300 mg once daily 1, 8
- Tenofovir alafenamide (TAF) - preferred over TDF for patients with renal/bone concerns 1
Alternative Option
- Pegylated interferon alfa for 48 weeks in selected patients with mild-to-moderate disease desiring finite therapy 1, 6, 4
- Contraindicated in decompensated cirrhosis 1
Agents to Avoid
- Lamivudine is NOT recommended due to high resistance rates (up to 70% at 5 years) 3, 9
- First-generation nucleos(t)ide analogues should not be used 1
Monitoring During Treatment
Virological and Biochemical Monitoring
- HBV DNA every 3 months until undetectable, then every 6 months 1, 3
- ALT/AST every 3-6 months 1, 3
- Quantitative HBsAg annually to assess for potential functional cure 3
- Renal function monitoring if on tenofovir 3, 8
Treatment Response Definitions
- Virological response: Undetectable HBV DNA by sensitive PCR assay 1
- Biochemical response: Normalization of ALT levels 1
- Optimal endpoint: HBsAg loss (functional cure), though rarely achieved 1, 3
Hepatocellular Carcinoma Surveillance
All cirrhotic patients and high-risk non-cirrhotic patients require ultrasound every 6 months, even with effective viral suppression. 1, 3
High-Risk Populations Requiring Surveillance
- Asian men >40 years, Asian women >50 years 3
- Any patient with cirrhosis 3
- Family history of HCC 3
- Age >40 with persistent ALT elevation 3
Treatment Duration and Discontinuation
Long-term, potentially indefinite treatment is typically required with nucleos(t)ide analogues until HBsAg loss occurs. 1, 3
Considerations for Stopping Therapy
- HBeAg-positive patients: May consider stopping after HBeAg seroconversion with undetectable HBV DNA and ≥12 months consolidation therapy 3
- Cirrhotic patients: Lifelong treatment mandatory 1
- Close monitoring required after discontinuation - severe acute exacerbations can occur 7
Prevention and Vaccination
Universal Vaccination Recommendations
- All persons negative for HBsAg and anti-HBs should receive HBV vaccination 2
- Medically stable newborns (≥2,000 g) within 24 hours of birth 4
- Newborns of HBV-infected mothers: HBIG plus hepatitis B vaccine at delivery, complete 3-dose series 2
Post-Vaccination Testing Required
- Newborns of HBV-infected mothers at 9-18 months 2
- Healthcare workers, dialysis patients, immunocompromised patients 1-2 months after series completion 2
- Anti-HBs <10 mIU/mL indicates need for booster in dialysis/immunocompromised patients 2
Additional Preventive Measures
- Hepatitis A vaccination for all HBV carriers negative for anti-HAV (coinfection increases mortality 5.6- to 29-fold) 2, 3
- Absolute alcohol abstinence or very limited consumption 2
- Smoking cessation 2
Special Populations
Pregnancy
- Tenofovir DF is the preferred agent during pregnancy 1, 3
- Prophylaxis starting at 24-32 weeks for HBV DNA >200,000 IU/mL prevents mother-to-child transmission 1, 3
- Breastfeeding generally not contraindicated even on tenofovir DF 3
Decompensated Cirrhosis
- Immediate treatment with entecavir 1 mg or tenofovir required 1, 7
- Simultaneous evaluation for liver transplantation 1, 3
- Pegylated interferon absolutely contraindicated 1
HIV-HBV Coinfection
- All coinfected patients should start antiretroviral therapy regardless of CD4 count 1
- TDF- or TAF-based ART regimens mandatory 1
- HIV antibody testing should be offered before initiating entecavir 7
Renal Impairment
- Entecavir dose adjustment required for creatinine clearance <50 mL/min 7
- CrCl 30-49: 0.5 mg every 48 hours (standard dose) or 1 mg once daily (lamivudine-refractory) 7
- CrCl 10-29: 0.5 mg every 72 hours or 1 mg every 72 hours 7
- CrCl <10 or hemodialysis: 0.5 mg every 7 days or 1 mg every 7 days 7
Critical Warnings and Pitfalls
Severe Acute Exacerbations
- Severe acute exacerbations of hepatitis B can occur after discontinuing antiviral therapy 7
- Monitor hepatic function closely with clinical and laboratory follow-up for several months after stopping treatment 7
Lactic Acidosis Risk
- Lactic acidosis and severe hepatomegaly with steatosis have been reported with nucleoside analogues 7, 8
- Suspend treatment if clinical or laboratory findings suggest lactic acidosis or pronounced hepatotoxicity 7
- Patients with decompensated liver disease at higher risk 7
Renal and Bone Toxicity
- New or worse kidney problems can occur with tenofovir DF 8
- Bone problems (pain, softening, thinning) may occur - TAF preferred over TDF for renal/bone concerns 1, 8