What are the treatment guidelines for chronic Hepatitis B?

Treatment Guidelines for Chronic Hepatitis B

Monotherapy using nucleos(t)ide analogues (NAs) with high genetic barriers to resistance, specifically entecavir or tenofovir, is the recommended first-line treatment for chronic hepatitis B. 1

Patient Assessment and Treatment Indications

Treatment decisions should be based on:

• HBV DNA levels
• ALT/AST levels
• HBeAg status
• Presence of cirrhosis
• Age and comorbidities

Treatment Indications:

1. HBeAg-positive patients:

   • HBV DNA >20,000 IU/mL AND
   • ALT >2× upper limit of normal (ULN) OR
   • Significant liver inflammation/fibrosis on biopsy 1

2. HBeAg-negative patients:

   • HBV DNA >2,000 IU/mL AND
   • ALT >ULN OR
   • Significant liver inflammation/fibrosis on biopsy 1, 2

3. Cirrhotic patients:

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

First-Line Treatment Options

1. Nucleos(t)ide Analogues (NAs) with High Genetic Barrier to Resistance

Preferred options:

• Entecavir (0.5 mg daily)
• Tenofovir disoproxil fumarate (TDF) (300 mg daily)
• Tenofovir alafenamide fumarate (TAF) (25 mg daily)
• Besifovir (available in some countries) 1

These agents demonstrate:

• Potent viral suppression (>90% efficacy)
• Low resistance rates (<1% after 5 years)
• Good safety profiles 1, 2

2. Pegylated Interferon-α

• Peginterferon alfa-2a (180 μg weekly for 48 weeks)
• Advantages: Finite treatment duration, no resistance
• Disadvantages: Subcutaneous administration, frequent side effects
• Best candidates: Young patients with high ALT, low HBV DNA, without cirrhosis 1, 2

Treatment Strategy Based on Liver Disease Status

Non-Cirrhotic Patients

• HBeAg-positive: Monotherapy with high-barrier NAs or peginterferon alfa 1
• HBeAg-negative: Monotherapy with high-barrier NAs (preferred) or peginterferon alfa 1

Cirrhotic Patients

• Compensated cirrhosis: Monotherapy using NAs with high genetic barriers to resistance 1
• Decompensated cirrhosis: Monotherapy using NAs with high genetic barriers to resistance; peginterferon alfa is contraindicated 1

Monitoring During Treatment

1. For patients on NAs:

   • ALT and HBV DNA every 3-6 months
   • HBeAg/anti-HBe status every 6-12 months (if initially HBeAg-positive)
   • Renal function monitoring (especially with tenofovir) 1, 2

2. For patients on peginterferon:

   • Complete blood count, liver function tests monthly
   • HBV DNA at weeks 12,24,48
   • Thyroid function tests every 3 months 1, 2

Management of Antiviral Resistance

If virological breakthrough occurs:

1. For L-nucleoside analogue resistance (lamivudine, telbivudine, clevudine):

   • Switch to tenofovir monotherapy 1

2. For entecavir resistance:

   • Switch to tenofovir monotherapy OR
   • Add tenofovir 1

3. For adefovir resistance:

   • Switch to tenofovir monotherapy OR
   • Use tenofovir and entecavir combination therapy 1

4. For multidrug resistance:

   • Switch to tenofovir and entecavir combination therapy OR
   • Consider tenofovir monotherapy 1

Treatment Duration

1. HBeAg-positive patients:

   • Continue treatment for at least 12 months after HBeAg seroconversion
   • Consider discontinuation if HBV DNA is undetectable and ALT is normal for at least 12 months after seroconversion 1, 2

2. HBeAg-negative patients:

   • Long-term (indefinite) treatment is generally required due to high relapse rates (80-90%) 2

3. Cirrhotic patients:

   • Long-term (indefinite) treatment regardless of HBeAg status 1

Cautions and Considerations

• Renal impairment: Dose adjustment required for NAs; monitor renal function 2, 3
• Pregnancy: Tenofovir is preferred if treatment is necessary 2
• Drug discontinuation: Monitor closely for severe hepatitis flares after stopping treatment 1, 3
• Lamivudine, adefovir, and telbivudine are not recommended as first-line therapy due to high resistance rates and/or suboptimal potency 1, 4, 5

Treatment Goals

The primary goal of treatment is to prevent progression to cirrhosis, hepatocellular carcinoma, and liver-related death by achieving sustained viral suppression. The ideal endpoint is HBsAg loss with sustained HBV DNA suppression 2.