What is the recommended treatment for chronic Hepatitis B?

Treatment of Chronic Hepatitis B

The recommended first-line treatment for chronic hepatitis B is oral antiviral therapy with either tenofovir or entecavir due to their potent viral suppression, high genetic barrier to resistance, and excellent long-term safety profiles. 1

Treatment Indications

Treatment should be initiated in the following scenarios:

• Decompensated cirrhosis: Prompt antiviral therapy is recommended if HBV DNA is detectable by PCR test regardless of AST/ALT levels 2
• Compensated cirrhosis: Antiviral therapy should be performed if HBV DNA level is ≥2,000 IU/mL regardless of AST/ALT levels 2
• Non-cirrhotic chronic hepatitis B: Treatment is indicated for patients with:
  • HBV DNA >2000 IU/mL, elevated ALT, and/or at least moderate histological lesions 3
  • HBV DNA >20,000 IU/mL and ALT >2× ULN 1

First-Line Treatment Options

1. Nucleos(t)ide Analogues (NUCs)

• Preferred agents:

  • Tenofovir disoproxil fumarate (TDF): 300 mg daily 1, 4
  • Entecavir: 0.5 mg daily 1
  • Tenofovir alafenamide (TAF): 25 mg daily 1

• Advantages of NUCs:

  • High rates of viral suppression (67-76% achieve HBV DNA <60-80 IU/mL at 48-52 weeks) 1
  • Excellent safety profile
  • Convenient once-daily oral dosing
  • High genetic barrier to resistance (especially with newer agents) 5

2. Peginterferon-α

• Dosage: 5 million units daily or 10 MU thrice weekly 2
• Duration: 48 weeks for HBeAg-positive and 12 months for HBeAg-negative chronic hepatitis B 2
• Advantages:
  • Finite treatment duration
  • No development of viral resistance
  • Higher rates of HBeAg seroconversion and HBsAg loss compared to NUCs 1
• Disadvantages:
  • Lower rates of viral suppression (14% achieve HBV DNA <60-80 IU/mL at 48-52 weeks) 1
  • More side effects
  • Contraindicated in decompensated cirrhosis 2

Special Population Considerations

Cirrhosis

• Compensated cirrhosis:

  • Oral antiviral therapy with tenofovir or entecavir is preferred 2
  • Peginterferon-α may be used with careful monitoring in patients with preserved liver function 2

• Decompensated cirrhosis:

  • Oral antiviral therapy with tenofovir or entecavir is recommended 2
  • Peginterferon-α is contraindicated due to risk of serious complications 2
  • Liver transplantation should be considered 2

Renal Impairment

• For patients with creatinine clearance <50 mL/min:
  • Adjust tenofovir dosing interval 4
  • Entecavir is preferred in patients with renal impairment 1

Monitoring During Treatment

1. HBV DNA levels: Every 3 months until undetectable, then every 3-6 months 1
2. ALT/AST levels: Monthly until normalized, then every 3 months 1
3. HBeAg/anti-HBe status: Every 6 months in HBeAg-positive patients 1
4. Renal function: Regular monitoring, especially with tenofovir therapy 1

Treatment Duration

• HBeAg-positive chronic hepatitis B: Minimum of 1 year. Treatment should be continued for 3-6 months after HBeAg seroconversion is confirmed 2
• HBeAg-negative chronic hepatitis B: Longer than 1 year, but optimal duration not established 2

Management of Treatment Failure

• Virological breakthrough (increase in HBV DNA >1 log10 IU/ml from nadir) may indicate resistance 1
• For patients with lamivudine-resistant mutants, treatment with adefovir is recommended if there is worsening of liver disease 2
• The addition or change to an antiviral agent that is not cross-resistant is critical to restore suppression of viral replication 6

Important Cautions

• Discontinuation risk: Severe acute exacerbations of hepatitis have been reported in patients who discontinue anti-hepatitis B therapy 4
• Monitoring after discontinuation: Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months 4
• Sequential therapy risk: Sequential therapy increases the risk of multidrug resistance 5

The goal of therapy is to achieve long-term suppression of HBV DNA to prevent disease progression to cirrhosis and hepatocellular carcinoma. While current treatments rarely achieve HBV eradication, they can effectively control viral replication and improve long-term outcomes.