What is the full treatment for chronic hepatitis B?

Full Treatment of Chronic Hepatitis B

The preferred first-line treatments for chronic hepatitis B are entecavir, tenofovir, or peginterferon alfa-2a, with entecavir and tenofovir being the most commonly recommended options due to their high potency and low resistance rates. 1, 2

Treatment Decision Algorithm

Treatment decisions should be based on:

• HBV DNA levels
• ALT levels
• Presence of liver disease/fibrosis
• HBeAg status

When to Treat

• HBV DNA ≥2000 IU/mL with elevated ALT: Initiate treatment 1
• HBV DNA ≥2000 IU/mL with normal ALT: Consider liver biopsy or transient elastography; treat if disease present 1
• HBV DNA <2000 IU/mL with normal ALT: Monitor every 6-12 months; consider treatment if significant histologic disease 1
• Any detectable HBV DNA with cirrhosis (compensated or decompensated): Treat regardless of ALT level 1, 3

First-Line Treatment Options

Nucleos(t)ide Analogues

• Entecavir (0.5 mg daily): High potency with >90% virologic remission after 3 years and very low resistance rates 1
• Tenofovir (300 mg daily): High potency with >90% virologic remission after 3 years and minimal resistance 1, 4
• Both medications are administered orally and have favorable safety profiles 1, 5

Peginterferon alfa-2a

• 180 mg weekly subcutaneous injection for 48 weeks 1
• Higher rates of HBeAg seroconversion and HBsAg loss compared to nucleos(t)ide analogues 1
• Better response in patients with:
  • Genotype A or B infection
  • High ALT (>2× ULN)
  • Low HBV DNA (<10^9 copies/mL)
  • Younger age 1
• Contraindicated in decompensated cirrhosis 3

Treatment Based on Patient Characteristics

HBeAg-Positive Patients

• First-line options: entecavir, tenofovir, or peginterferon alfa-2a 1
• For high HBV DNA or normal ALT: prefer entecavir or tenofovir over peginterferon 1
• Consider stopping peginterferon if no decline in HBsAg or HBsAg >20,000 IU/mL at week 12 1

HBeAg-Negative Patients

• First-line options: entecavir, tenofovir, or peginterferon alfa-2a 1
• Long-term treatment required with oral agents 1

Compensated Cirrhosis

• Preferred: entecavir or tenofovir 2
• Peginterferon may be considered in select patients 2
• Lifelong treatment generally recommended 1

Decompensated Cirrhosis

• Preferred: entecavir (1 mg daily) or tenofovir 3
• Peginterferon is contraindicated 3
• Monitor closely for lactic acidosis 3
• Consider liver transplantation 3

Duration of Therapy

Peginterferon alfa-2a

• Standard duration: 48 weeks 1
• Consider stopping if no HBsAg decline at week 12 1

Nucleos(t)ide Analogues

• Decompensated cirrhosis: Lifelong treatment 1, 3
• Compensated cirrhosis: Lifelong treatment in most cases 1
• Non-cirrhotic patients:
  • HBeAg-positive: May consider discontinuation after HBeAg seroconversion with undetectable HBV DNA for at least 12 months 1
  • HBeAg-negative: Long-term (typically lifelong) treatment 1, 6
  • May discontinue if HBsAg loss is achieved and maintained for 6-12 months 1, 6

Monitoring During Treatment

• HBV DNA and ALT: Every 3-6 months 2
• HBeAg status (if initially positive): Every 6 months 3
• Renal function: Regularly, especially for patients on tenofovir 2, 7
• Watch for hepatitis flares during treatment 3
• Monitor for virologic breakthrough (increase in HBV DNA by >1 log from nadir) 1

Treatment of Special Populations

• Lamivudine-experienced patients: Avoid entecavir due to risk of resistance; use tenofovir 1
• Pregnant women: Telbivudine or tenofovir (pregnancy category B) may be considered to prevent vertical transmission 1
• Patients with renal impairment: Dose adjustment required for nucleos(t)ide analogues 4

Common Pitfalls to Avoid

• Using lamivudine as first-line therapy (high resistance rates) 1, 8
• Using adefovir as first-line therapy (inferior efficacy and resistance profile) 1, 9
• Discontinuing therapy prematurely (risk of severe hepatitis flares) 4, 10
• Failing to monitor for drug resistance 1
• Not considering lifelong HCC surveillance in cirrhotic patients 2

Goals of Therapy

• Primary goal: Suppress HBV replication to prevent progression to cirrhosis, liver failure, and HCC 1, 2
• Secondary goals: ALT normalization and histologic improvement 1
• Ideal but uncommon endpoints: HBeAg seroconversion (in HBeAg-positive patients) and HBsAg loss 1, 5