Treatment of Hepatitis B
The first-line treatment for chronic hepatitis B is long-term administration of potent nucleos(t)ide analogues with high barrier to resistance, specifically entecavir, tenofovir disoproxil fumarate, or tenofovir alafenamide. 1
Classification and Assessment
Chronic HBV infection can be classified into five phases:
- HBeAg-positive chronic infection
- HBeAg-positive chronic hepatitis
- HBeAg-negative chronic infection
- HBeAg-negative chronic hepatitis
- HBsAg-negative phase
Before initiating treatment, assess:
- HBV DNA levels
- ALT/AST levels
- HBeAg status
- Presence of cirrhosis
- Liver function tests
- Renal function
Treatment Indications
Treatment should be initiated in:
- Patients with HBV DNA ≥2,000 IU/mL, elevated ALT, and/or at least moderate histological lesions 1
- All cirrhotic patients with detectable HBV DNA, regardless of ALT levels 1
- Patients with decompensated cirrhosis with any detectable HBV DNA 2
First-Line Treatment Options
Nucleos(t)ide Analogues
Entecavir:
- Dosage: 0.5 mg daily (treatment-naïve); 1 mg daily (lamivudine-resistant or decompensated cirrhosis) 2
- Advantages: High genetic barrier to resistance, potent viral suppression
Tenofovir Disoproxil Fumarate (TDF):
- Dosage: 300 mg daily 3
- Advantages: High genetic barrier to resistance, potent viral suppression
- Caution: Monitor renal function
Tenofovir Alafenamide (TAF):
- Dosage: 25 mg daily 2
- Advantages: Less renal and bone toxicity than TDF
Alternative Option
Pegylated Interferon-alfa:
- Can be considered in mild to moderate chronic hepatitis B 1
- Duration: 48 weeks
- Contraindicated in decompensated cirrhosis 2
Treatment Outcomes
Expected outcomes with treatment 2:
- HBV DNA suppression (<60-80 IU/mL): 67-76% with nucleos(t)ide analogues
- ALT normalization: ~68% with nucleos(t)ide analogues
- HBeAg seroconversion: ~21% with nucleos(t)ide analogues
- HBsAg loss: 2-3% with nucleos(t)ide analogues
Treatment Duration
- HBeAg-positive patients: Continue until HBeAg seroconversion plus 6-12 months consolidation
- HBeAg-negative patients: Long-term or indefinite treatment
- Cirrhotic patients: Lifelong treatment 2
Monitoring During Treatment
Virologic monitoring:
Biochemical monitoring:
- ALT/AST every 3-6 months 2
Serologic monitoring:
- HBeAg/anti-HBe status every 6-12 months 2
Renal function:
- Every 6-12 months, more frequently with TDF in high-risk patients 2
Management of Treatment Failure
If inadequate response after 48 weeks (HBV DNA >2000 IU/mL) 1:
- For entecavir: Switch to tenofovir or add tenofovir
- For tenofovir: Continue if HBV DNA is declining; consider adding entecavir if high HBV DNA persists
Special Populations
Decompensated Cirrhosis
- Immediate treatment with entecavir 1 mg daily or tenofovir 300 mg daily 2
- Consider liver transplantation concurrently 2
- Peginterferon-α is contraindicated 2
Renal Impairment
- Dose adjustment required for all nucleos(t)ide analogues if creatinine clearance <50 ml/min 2
- Prefer entecavir or TAF over TDF 2
HIV Co-infection
Prevention of Transmission
- Vaccinate household contacts and sexual partners 2
- Pregnant women with high viral load should consider tenofovir in third trimester 2
- Newborns of HBsAg-positive mothers should receive hepatitis B vaccine and hepatitis B immune globulin at birth 2
Common Pitfalls to Avoid
- Using first-generation antivirals (lamivudine, adefovir, telbivudine) due to high resistance rates 2
- Using peginterferon in decompensated cirrhosis 2
- Failing to monitor for renal toxicity with tenofovir disoproxil fumarate 2
- Stopping treatment prematurely in cirrhotic patients 2
- Inadequate monitoring of viral suppression 1
The goal of therapy is to improve survival and quality of life by preventing disease progression and HCC development through long-term suppression of HBV replication 1.