Treatment of Hepatitis B Virus Infection
For chronic hepatitis B, initiate treatment with entecavir or tenofovir as first-line therapy, as these agents achieve superior virologic suppression (>90% at 3 years) with minimal resistance rates (<1% for entecavir at 4 years) compared to older agents like lamivudine. 1, 2
First-Line Treatment Selection
Preferred agents are entecavir, tenofovir disoproxil fumarate (TDF), or tenofovir alafenamide (TAF) due to their high genetic barrier to resistance and potent antiviral activity 3, 1. These medications should be prioritized over lamivudine, which carries up to 70% resistance rates within 5 years 3.
Specific Dosing
- Entecavir: 0.5 mg daily for treatment-naïve patients; 1 mg daily for lamivudine-refractory patients 3, 2
- Tenofovir (TDF or TAF): Standard adult dosing as per FDA labeling 3, 4
Treatment Initiation Criteria
Immediate Treatment Required (High Priority)
All patients with cirrhosis and any detectable HBV DNA must be treated immediately, regardless of ALT levels 3, 5. This is non-negotiable due to risk of decompensation.
Treat immediately without liver biopsy if:
- HBV DNA ≥20,000 IU/mL AND ALT >2× upper limit of normal (ULN) 1, 5
- HBV DNA ≥2,000 IU/mL AND ALT elevation with evidence of at least moderate fibrosis (liver stiffness ≥9 kPa with normal ALT or ≥12 kPa with ALT <5× ULN) 5, 6
- HBV DNA ≥2,000 IU/mL with family history of hepatocellular carcinoma or cirrhosis 5, 6
Age-Based Considerations
HBeAg-positive patients over age 30 with persistently elevated HBV DNA (>20,000 IU/mL) should be treated regardless of ALT levels or histological severity 5, 7, as this represents a critical transition point where immune-active disease commonly develops.
Special Populations Requiring Prophylactic Treatment
Immunosuppression and Chemotherapy
All HBsAg-positive patients receiving chemotherapy or immunosuppressive therapy must receive prophylactic antiviral therapy with entecavir, TDF, or TAF 3. This is particularly critical for:
- High-risk regimens (rituximab, anti-CD20 antibodies, stem cell transplantation): Continue prophylaxis through treatment and for minimum 18 months after completion 3
- Moderate-risk regimens: Continue for minimum 12 months after cessation 3
For HBsAg-negative, anti-HBc-positive patients:
- High-risk groups (rituximab-containing regimens, stem cell transplantation) require prophylactic treatment 3
- Moderate-risk groups can be monitored with HBsAg, ALT, and HBV DNA testing every 3 months, with immediate preemptive therapy upon detection of HBsAg or HBV DNA positivity 3
Pregnancy
Tenofovir DF is the preferred agent during pregnancy 5. For women with HBV DNA >200,000 IU/mL, initiate prophylactic tenofovir at 24-32 weeks gestation to prevent mother-to-child transmission 5. Treatment should continue through delivery, with close monitoring postpartum as hepatitis flares commonly occur 3.
Decompensated Cirrhosis
Patients with decompensated cirrhosis (Child-Turcotte-Pugh score ≥7) require urgent antiviral treatment with entecavir or tenofovir and simultaneous evaluation for liver transplantation 5, 2. At 48 weeks, entecavir achieves 57% undetectable HBV DNA in this population 2.
HIV-HBV Coinfection
All HIV-HBV coinfected patients should receive antiretroviral therapy including tenofovir (TDF or TAF) regardless of CD4 count 5. Entecavir should not be used as monotherapy in HIV-positive patients due to potential HIV resistance development 3.
Treatment Duration and Monitoring
Duration
Long-term, potentially indefinite treatment is typically required with nucleos(t)ide analogues 5. Treatment may be considered for discontinuation in:
- HBeAg-positive patients who achieve HBeAg seroconversion with undetectable HBV DNA and complete at least 12 months of consolidation therapy 5
- Optimal endpoint: HBsAg loss (functional cure), though rarely achieved with current therapies 5
Monitoring Protocol
During treatment:
- HBV DNA every 3 months until undetectable, then every 6 months 1, 5
- ALT/AST every 3-6 months 1, 5
- Annual quantitative HBsAg to assess for functional cure 5
- Renal function monitoring if on tenofovir 5
After treatment discontinuation:
- Monitor for at least 12 months with liver function tests and HBV DNA every 3-6 months, as reactivation commonly occurs post-discontinuation 3
Hepatocellular Carcinoma Surveillance
Ultrasound screening every 6 months is mandatory for high-risk patients, including 3, 5:
- Asian men >40 years
- Asian women >50 years
- Any patient with cirrhosis
- Family history of HCC
- Africans >20 years
- Age >40 years with persistent/intermittent ALT elevation and/or high HBV DNA
Alpha-fetoprotein (AFP) should be measured every 6 months in conjunction with ultrasound 5, 7.
Additional Preventive Measures
Hepatitis A vaccination is essential if anti-HAV negative, as HAV coinfection in chronic HBV patients substantially increases mortality risk 5, 7.
Screen for coinfections: anti-HCV, anti-HDV (if injection drug use history), anti-HIV 5, 7.
Counsel on strict alcohol abstinence, as even limited consumption worsens outcomes 5.
Vaccinate household and sexual contacts against HBV to prevent transmission 3, 7.
Critical Pitfalls to Avoid
Never use lamivudine as first-line therapy due to high resistance rates (up to 70% in 5 years), which leads to treatment failure and potential hepatitis flares 3.
Do not delay treatment in cirrhotic patients awaiting additional testing—any detectable HBV DNA warrants immediate initiation 3, 5.
Do not stop monitoring after treatment discontinuation—the majority of HBV reactivations develop after nucleos(t)ide analogue withdrawal, requiring vigilant follow-up for at least 12 months 3.