When to Start Antiviral Therapy for Hepatitis B
Antiviral therapy for chronic hepatitis B should be initiated based on HBV DNA levels, ALT levels, and the presence of significant liver inflammation or fibrosis, with specific thresholds differing between HBeAg-positive and HBeAg-negative patients. 1
HBeAg-Positive Chronic Hepatitis B
- Start treatment if HBV DNA ≥20,000 IU/mL AND ALT ≥2× ULN 2, 1
- Start treatment if HBV DNA ≥20,000 IU/mL AND ALT 1-2× ULN with moderate-to-severe inflammation or significant fibrosis on biopsy 2, 1
- Treatment can be delayed for 3-6 months if spontaneous HBeAg seroconversion is anticipated, except in patients with liver failure 2
- For patients with HBV DNA >20,000 IU/mL and normal or minimally elevated ALT (<2× ULN), observation or liver biopsy can be considered 2
HBeAg-Negative Chronic Hepatitis B
- Start treatment if HBV DNA >2,000 IU/mL AND ALT >2× ULN 2, 1
- Start treatment if HBV DNA >2,000 IU/mL AND ALT <2× ULN with moderate-to-severe inflammation or significant fibrosis on biopsy 2
- For those with HBV DNA >2,000 IU/mL and normal or minimally elevated ALT (<2× ULN), observation or liver biopsy can be considered 2
Patients with Cirrhosis
- All patients with compensated cirrhosis and detectable HBV DNA should receive antiviral therapy regardless of ALT levels 2, 1
- Patients with decompensated cirrhosis and detectable HBV DNA require immediate treatment and should be referred for liver transplant evaluation 2
- Interferon-α is contraindicated in patients with decompensated cirrhosis due to risk of hepatic decompensation 2, 3
Special Considerations
Age Factor
- European guidelines recommend treatment for patients >30 years old with high viral load, regardless of histological lesions 2, 1
Fibrosis Assessment
- Liver fibrosis assessment is crucial when ALT is borderline (1-2× ULN) 2, 1
- Non-invasive methods can be used as first screening tools:
- Liver biopsy should be considered when non-invasive tests suggest significant fibrosis 2
Immune Tolerance Phase
- Patients in the immune-tolerant phase (HBeAg positive with persistently normal ALT) are generally not indicated for antiviral therapy 2
- These patients should be monitored every 3-6 months for transition to immune-active phase 2
First-Line Antiviral Options
- Preferred first-line agents with high barrier to resistance:
Common Pitfalls to Avoid
- Delaying treatment in patients with cirrhosis can lead to decompensation 2, 3
- Using ALT cutoffs that are too high can lead to delayed treatment; lower thresholds (30 IU/L for men, 19 IU/L for women) may be more appropriate 2, 1
- Ignoring significant fibrosis in patients with normal ALT can lead to missed treatment opportunities 2, 1
- Stopping antiviral therapy prematurely can lead to severe hepatitis exacerbations, especially in patients with advanced liver disease 5
- Not monitoring renal function during treatment with certain antivirals like adefovir can lead to nephrotoxicity 5
- Not testing for HIV before starting HBV treatment can lead to HIV resistance 5
Monitoring During Treatment
- Monitor ALT, HBV DNA, HBeAg status, and renal function regularly during treatment 2, 5
- Consider treatment modification if serum HBV DNA remains above 1000 copies/mL with continued treatment to reduce the risk of resistance 5
- Patients should be closely monitored after stopping treatment due to risk of hepatitis exacerbations 5
The decision to initiate antiviral therapy requires careful assessment of viral replication status, liver disease severity, and patient factors. While current treatments effectively suppress viral replication and improve liver inflammation and fibrosis, they rarely achieve complete cure, and most patients will require long-term or indefinite therapy 4, 6.