When to start antiviral therapy in patients with chronic hepatitis B?

When to Start Antiviral Therapy in Chronic Hepatitis B

Antiviral therapy should be initiated in chronic hepatitis B patients 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

General Treatment Indications

HBeAg-Positive CHB

• Start treatment if:
  • HBV DNA ≥20,000 IU/mL AND ALT ≥2× ULN 1
  • HBV DNA ≥20,000 IU/mL AND ALT 1-2× ULN with moderate-to-severe inflammation (≥A2) or significant fibrosis (≥F2) on liver biopsy 1
  • Age >30-40 years with high viral load (≥1,000 IU/mL), even with normal ALT (varies by guideline) 1

HBeAg-Negative CHB

• Start treatment if:
  • HBV DNA ≥2,000 IU/mL AND ALT ≥2× ULN 1
  • HBV DNA ≥2,000 IU/mL AND ALT <2× ULN with moderate-to-severe inflammation (≥A2) or significant fibrosis (≥F2) on liver biopsy 1

Cirrhosis

• Compensated cirrhosis: Treat if HBV DNA ≥2,000 IU/mL regardless of ALT level 1
• Decompensated cirrhosis: Treat if any detectable HBV DNA, regardless of ALT level 1

Special Considerations

Immune Tolerant Phase

• Traditionally not treated (HBeAg-positive, very high HBV DNA, persistently normal ALT) 1
• Consider treatment in patients >30-40 years old, even in immune tolerant phase 1
• EASL specifically recommends treatment for patients >30 years regardless of histological lesions 1

Fibrosis Assessment

• When ALT is borderline (1-2× ULN), fibrosis assessment is crucial for treatment decisions 1
• Options include:
  • Liver biopsy (gold standard) 1
  • Non-invasive methods (transient elastography/Fibroscan with liver stiffness >8 kPa or APRI >1.5) 1, 2

Additional Treatment Indications

• Family history of HCC or cirrhosis 1, 2
• Extrahepatic manifestations of HBV 1, 2
• Patients receiving immunosuppressive therapy or chemotherapy (prophylaxis) 1, 2

First-Line Antiviral Agents

• Preferred options with high barrier to resistance:
  • Entecavir 1
  • Tenofovir disoproxil fumarate (TDF) 1, 3
  • Tenofovir alafenamide (TAF) 1, 4
  • Besifovir 1
  • Pegylated interferon-α 1

Common Pitfalls to Avoid

1. Delaying treatment in patients with cirrhosis: All patients with cirrhosis and detectable HBV DNA should receive prompt antiviral therapy to prevent decompensation 1

2. Using ALT cutoffs that are too high: The traditional ALT cutoff (>2× ULN) has been challenged; lower thresholds (30 IU/L for men, 19 IU/L for women) may be more appropriate 1

3. Ignoring significant fibrosis in patients with normal ALT: About two-thirds of CHB patients with mildly elevated ALT (1-2× ULN) may have significant fibrosis requiring treatment 1

4. Using antivirals with low barrier to resistance: Lamivudine and telbivudine are not preferred due to high rates of resistance 1, 5

5. Failing to monitor for treatment response: Regular monitoring of HBV DNA, ALT, and treatment adherence is essential for managing chronic hepatitis B 1, 5

Treatment Algorithm

1. Determine HBeAg status and measure HBV DNA and ALT levels 1

2. For HBeAg-positive patients:

   • If HBV DNA ≥20,000 IU/mL and ALT ≥2× ULN → Start treatment 1
   • If HBV DNA ≥20,000 IU/mL and ALT 1-2× ULN → Assess fibrosis (biopsy or non-invasive) 1
   • If age >30-40 years with high viral load → Consider treatment regardless of ALT 1

3. For HBeAg-negative patients:

   • If HBV DNA ≥2,000 IU/mL and ALT ≥2× ULN → Start treatment 1
   • If HBV DNA ≥2,000 IU/mL and ALT <2× ULN → Assess fibrosis 1

4. For patients with cirrhosis:

   • Compensated: Treat if HBV DNA ≥2,000 IU/mL 1
   • Decompensated: Treat if any detectable HBV DNA 1

5. Choose a high-barrier-to-resistance antiviral agent (entecavir, tenofovir DF, tenofovir AF) 1, 6