Treatment for Hepatitis B
First-Line Treatment Recommendation
Initiate monotherapy with entecavir (0.5-1 mg daily) or tenofovir (disoproxil fumarate 300 mg daily or alafenamide 25 mg daily) as first-line treatment for chronic hepatitis B, as these agents achieve >90% virologic suppression with minimal resistance. 1, 2
Treatment Indications by Disease Stage
HBeAg-Positive Chronic Hepatitis B
- Treat when HBV DNA >20,000 IU/mL AND serum ALT >2× upper limit of normal (ULN), or when liver biopsy shows significant inflammation/fibrosis (≥moderate necroinflammation or ≥periportal fibrosis) 3, 2
- For patients with HBV DNA >20,000 IU/mL and ALT between 1-2× ULN, perform liver biopsy or non-invasive fibrosis assessment; treat if moderate inflammation or fibrosis is present 3, 4
- Treatment can be delayed 3-6 months in compensated disease to allow for potential spontaneous HBeAg seroconversion, except in patients with signs of liver failure (jaundice, prolonged PT, hepatic encephalopathy, ascites) who require immediate treatment 3, 4
HBeAg-Negative Chronic Hepatitis B
- Treat when HBV DNA >2,000 IU/mL AND serum ALT >2× ULN, or when biopsy shows significant inflammation/fibrosis 3, 2
- For patients with HBV DNA >2,000 IU/mL and ALT <2× ULN, consider observation or liver biopsy; treat if subsequent ALT elevation occurs or biopsy shows significant disease 3
Compensated Cirrhosis
- Treat all patients with compensated cirrhosis when HBV DNA ≥2,000 IU/mL, regardless of ALT level, as they already have significant hepatic fibrosis and frequently have near-normal ALT levels 3, 2, 4
- Lamivudine or adefovir are preferred over interferon-α due to risk of hepatic decompensation from interferon-related hepatitis flares 3
Decompensated Cirrhosis
- Treat with lamivudine or adefovir; coordinate treatment with transplant centers 3
- Interferon-α is contraindicated in decompensated cirrhosis due to risk of severe hepatic decompensation 3
Preferred Antiviral Agents
First-Line Monotherapy Options
- Entecavir 0.5 mg daily: Achieves 83% virologic suppression (HBV DNA <50 IU/mL) at 96 weeks with only 1.2% resistance after 5 years in treatment-naïve patients 2, 4, 5
- Tenofovir disoproxil fumarate (TDF) 300 mg daily: Achieves 93% virologic suppression at 48 weeks with no resistance after 1.5 years 2, 4
- Tenofovir alafenamide (TAF) 25 mg daily: Equally effective as TDF but with superior renal and bone safety profile 2, 4
Agents NOT Recommended as First-Line
- Lamivudine and telbivudine: Not preferred due to weak antiviral potency and high resistance rates (up to 70% after 5 years for lamivudine) 3, 1, 6
- Adefovir: Not ideal due to weak antiviral activity and high resistance frequency after 48 weeks 3
- Peginterferon-α: Can be used as alternative first-line option but requires careful monitoring in cirrhotic patients due to risk of acute hepatitis exacerbation 3
Treatment Duration
HBeAg-Positive Patients
- Continue treatment for at least 1 year after HBeAg seroconversion, then an additional 3-6 months of consolidation therapy 2, 4
- Among entecavir responders, 76% sustained HBeAg seroconversion at end of follow-up 5
HBeAg-Negative Patients
- Lifelong (indefinite) therapy is typically required, as relapse rates reach 80-90% if stopped within 1-2 years 2, 4
- Treatment should continue until HBsAg loss is achieved and maintained for 6-12 months (ideal but uncommon endpoint) 1
Cirrhotic Patients
Monitoring During Treatment
Virologic and Biochemical Monitoring
- Check HBV DNA and ALT levels at baseline and every 3-6 months during therapy 1, 2, 4
- Monitor for hepatitis flares (ALT >100 U/mL and 3 times baseline) 1
Safety Monitoring
- Renal function monitoring: Check creatinine, estimated GFR, and serum phosphorus periodically with tenofovir-based therapy, particularly in patients with pre-existing renal disease 4
- HCC surveillance: Perform ultrasound and AFP every 6 months in all cirrhotic patients and high-risk non-cirrhotic patients (Asian men >40, Asian women >50, Africans >20, family history of HCC) 4
Baseline Assessment
- Perform liver fibrosis assessment (biopsy or non-invasive methods like transient elastography) to guide treatment decisions and duration 1
Special Clinical Scenarios
Lamivudine-Experienced Patients
- Do NOT use entecavir in patients with any prior lamivudine exposure, even if brief, due to risk of archived resistance mutations 2
- Treat with tenofovir (DF or AF) instead 2
HIV/HBV Co-infection
- Treat with tenofovir combined with emtricitabine or lamivudine for simultaneous treatment of both viruses 2
- Patients must be offered HIV antibody testing before starting entecavir therapy, as untreated HIV infection during entecavir therapy may increase HIV resistance to HIV medications 1, 5
Pregnancy
- Treat pregnant women with high viremia (typically HBV DNA >200,000 IU/mL) using tenofovir as the preferred agent to prevent mother-to-child transmission 4
Immunosuppression/Chemotherapy
- Initiate prophylactic antiviral therapy before starting immunosuppression or chemotherapy in all HBsAg-positive patients, regardless of HBV DNA or ALT levels, to prevent potentially fatal HBV reactivation 4
Treatment Goals
Primary Goal
- Sustained suppression of HBV DNA to undetectable levels to prevent progression to cirrhosis, hepatic decompensation, hepatocellular carcinoma, and liver-related mortality 1, 2, 7
Secondary Goals
- Normalization of ALT levels 1
- Histological improvement 1
- HBeAg seroconversion in HBeAg-positive patients 7
- HBsAg loss (ideal but uncommon endpoint) 1
Critical Pitfalls to Avoid
- Never discontinue therapy prematurely in HBeAg-negative patients or those with cirrhosis, as this can lead to severe hepatitis flares and hepatic decompensation 2, 5
- Never assume HBsAb presence indicates immunity when HBsAg is also positive 1
- Never use entecavir in lamivudine-experienced patients due to archived resistance mutations 2
- Never use interferon-α in decompensated cirrhosis 3
- Patients should be counseled that treatment is typically long-term and premature discontinuation can lead to severe hepatitis flares 1
- Treatment with entecavir does not reduce risk of HBV transmission to others through sexual contact or blood contamination 5
Managing Inadequate Response
- For patients with partial virologic response or virologic breakthrough with confirmed resistance, switch to tenofovir (DF or AF) or combine entecavir with tenofovir 2
- For lamivudine resistance, add adefovir if worsening liver disease, decompensated cirrhosis, recurrent hepatitis B after liver transplant, or need for concomitant immunosuppressive therapy 3