Management of Chronic Hepatitis B Infection
Patients with chronic Hepatitis B should be treated with high genetic barrier antiviral agents such as entecavir or tenofovir as first-line therapy, with treatment decisions based on HBeAg status, HBV DNA levels, ALT levels, and stage of liver disease. 1
Initial Evaluation
The initial evaluation of patients with chronic HBV infection should include:
- HBeAg/anti-HBe status
- HBV DNA quantification
- ALT/AST levels
- Assessment of liver fibrosis (biopsy or non-invasive methods)
- Screening for HCC in high-risk patients
- Testing for coinfections (HIV, HCV, HDV)
Treatment Indications
Treatment should be initiated in the following scenarios:
HBeAg-positive patients:
- HBV DNA >20,000 IU/mL AND ALT >2× ULN or significant inflammation/fibrosis on biopsy 2
- Treatment can be delayed for 3-6 months if spontaneous HBeAg seroconversion is anticipated 2
- Patients with liver failure (jaundice, prolonged PT, hepatic encephalopathy, ascites) should be promptly treated 2
HBeAg-negative patients:
- HBV DNA >2,000 IU/mL AND ALT >2× ULN or significant inflammation/fibrosis on biopsy 2
- For those with HBV DNA >2,000 IU/mL and ALT <2× ULN, observation or liver biopsy can be considered 2
Cirrhotic patients:
- Any detectable HBV DNA in compensated cirrhosis, regardless of ALT levels 1
- Urgent antiviral treatment for decompensated cirrhosis with any detectable HBV DNA 1
First-Line Treatment Options
Preferred agents (high genetic barrier to resistance):
- Entecavir: 0.5 mg daily 1
- Tenofovir disoproxil fumarate: 300 mg daily 1
- Tenofovir alafenamide: 25 mg daily 1
Alternative option for selected patients:
- Pegylated interferon alfa-2a: 180 μg weekly for 48 weeks 1
Monitoring During Treatment
- HBV DNA levels: Every 3-6 months 1
- ALT/AST: Every 3-6 months 1
- HBeAg/anti-HBe (in HBeAg-positive patients): Every 6-12 months 1
- Renal function: Every 6-12 months (especially with tenofovir) 1
- Non-invasive fibrosis assessment: Annually 1
Treatment Duration and Endpoints
- For HBeAg-positive patients: Continue treatment for at least 6 months after HBeAg loss and appearance of anti-HBe 2
- For HBeAg-negative patients: Long-term treatment is typically required as relapse rates are 80-90% if treatment is stopped within 1-2 years 2
- Serologic endpoints include:
- Loss of HBeAg and HBeAg seroconversion in initially HBeAg-positive patients
- Suppression of HBV DNA to undetectable levels
- Loss of HBsAg (optimal but rare outcome)
Managing Antiviral Resistance
- Viral resistance to lamivudine occurs in up to 70% of patients during the first 5 years of treatment 2
- Lower resistance rates with adefovir (30% in 5 years), entecavir (<1% at 4 years), and telbivudine (2.3-5% in 1 year) 2
If resistance develops:
- For lamivudine/telbivudine resistance: Add or switch to tenofovir 1
- For adefovir resistance: Add lamivudine or switch to tenofovir + emtricitabine, or add entecavir (if no prior lamivudine resistance) 1
- For entecavir resistance: Add adefovir or tenofovir 1
Special Populations
HIV Coinfection
- Include tenofovir in the HAART regimen 1
- HIV testing should be offered to all patients prior to initiating HBV treatment 3
Pregnancy
- Consider tenofovir in the third trimester for women with high viral load to prevent vertical transmission 1
Immunosuppressed Patients
- Use high genetic barrier drugs (entecavir or tenofovir) due to risk of severe hepatitis flares 1
- Prophylactic treatment is required for patients receiving immunosuppression/chemotherapy 1
Liver Transplant Patients
- Maintain antiviral therapy to prevent recurrence 1
Common Pitfalls and Caveats
Severe acute exacerbations after discontinuation: Monitor hepatic function closely for several months in patients who discontinue treatment 4
Nephrotoxicity risk: Monitor renal function during therapy, particularly with tenofovir. Dose adjustment may be required in renal impairment 3
Lactic acidosis risk: Suspend treatment if lactic acidosis or severe hepatomegaly with steatosis is suspected 4
Medication adherence: Critical for achieving adequate HBV DNA suppression and preventing resistance 5
Coadministration issues: Do not administer adefovir concurrently with tenofovir-containing products 3
Resistance development: The selection of a drug with high potency and low resistance rate is essential to achieve rapid and long-term viral suppression 5
By following these evidence-based guidelines, clinicians can effectively manage chronic HBV infection to prevent disease progression, development of cirrhosis, and hepatocellular carcinoma.