Management of Hepatitis B Infection
Treatment for hepatitis B should be initiated in patients with HBV DNA levels above 2000 IU/ml, elevated ALT levels, and moderate to severe liver inflammation or fibrosis, with entecavir, tenofovir disoproxil fumarate (TDF), or tenofovir alafenamide (TAF) as first-line therapies. 1
Diagnosis and Initial Evaluation
Screening tests:
Additional testing for confirmed HBV infection:
Treatment Indications
Treatment should be initiated in:
All patients with decompensated cirrhosis and detectable HBV DNA (regardless of ALT levels) 2, 1
Patients with compensated cirrhosis and detectable HBV DNA (regardless of ALT levels) 2
Non-cirrhotic patients with:
Patients with obvious active CHB:
- ALT >2× ULN and HBV DNA >20,000 IU/ml (may start treatment without liver biopsy) 2
First-Line Treatment Options
Recommended antiviral agents:
- Entecavir: 0.5 mg daily (1 mg for lamivudine-resistant patients)
- Tenofovir disoproxil fumarate (TDF): 300 mg daily
- Tenofovir alafenamide (TAF): 25 mg daily 1
Alternative treatment option:
- Pegylated interferon alfa-2a: 180 μg weekly for 48 weeks (for selected patients without cirrhosis) 1, 3
Monitoring During Treatment
- HBV DNA levels: Every 3 months until undetectable, then every 3-6 months
- ALT/AST: Monthly until normalized, then every 3 months
- HBeAg/anti-HBe status: Every 6 months in HBeAg-positive patients
- Renal function: Every 3-6 months (especially with tenofovir)
- Non-invasive fibrosis assessment: Annually 1
Treatment Duration
- HBeAg-positive patients: Continue until HBeAg seroconversion and at least 12 months of consolidation therapy
- HBeAg-negative patients: Long-term treatment (typically indefinite)
- Cirrhotic patients: Lifelong treatment 1
Special Populations
Patients undergoing immunosuppressive therapy or chemotherapy:
- All candidates should be screened for HBV markers before immunosuppression
- HBsAg-positive patients: Should receive entecavir, TDF, or TAF as prophylaxis
- HBsAg-negative, anti-HBc positive patients: Should receive anti-HBV prophylaxis if at high risk of reactivation (e.g., rituximab therapy)
- Prophylaxis should continue for at least 12 months (18 months for rituximab-based regimens) after cessation of immunosuppressive treatment 2, 1
Pregnant women:
- Women with high HBV DNA levels (>200,000 IU/ml) should receive TDF starting at 24-28 weeks of gestation
- TDF is preferred over entecavir during pregnancy due to better safety data 1
Cancer patients:
- All patients with cancer anticipating systemic anticancer therapy should be tested for HBV
- Patients with chronic HBV receiving any systemic anticancer therapy should receive antiviral prophylaxis for the duration of anticancer therapy and at least 12 months afterward 2
Treatment Outcomes and Expectations
Treatment outcomes at 48-52 weeks for HBeAg-positive patients:
| Agent | HBV DNA <60-80 IU/mL | ALT normalization | HBeAg seroconversion | HBsAg loss |
|---|---|---|---|---|
| PEG-IFN-2a | 14% | 41% | 32% | 3% |
| Entecavir | 67% | 68% | 21% | 2% |
| Tenofovir | 76% | 68% | 21% | 3% |
Long-term viral suppression with nucleos(t)ide analogues improves hepatic inflammation and fibrosis, preventing progression to decompensated cirrhosis and reducing (but not eliminating) the risk of hepatocellular carcinoma 1.
Common Pitfalls and Caveats
Discontinuation of therapy: Premature discontinuation can lead to hepatitis flares. Monitor ALT levels frequently (at least monthly for the first 3 months) after stopping antivirals 2
Resistance development: Monitor for virological breakthrough (increase in HBV DNA >1 log10 IU/ml from nadir) which may indicate resistance 2
Renal toxicity: Regular monitoring of renal function is essential with tenofovir therapy 1
HBV reactivation: Can occur in patients receiving immunosuppressive therapy, even in those who are HBsAg-negative but anti-HBc positive 2
Incomplete response: Not all patients achieve HBeAg seroconversion or HBsAg loss with current therapies 1