What is the recommended treatment for chronic Hepatitis B?

Treatment for Chronic Hepatitis B

First-line treatment for chronic hepatitis B should be entecavir or tenofovir due to their high potency and high genetic barrier to resistance. 1

Patient Assessment and Treatment Indications

Treatment decisions for chronic hepatitis B should be based on:

• HBV DNA levels: Treatment is indicated when HBV DNA ≥2,000 IU/mL for HBeAg-negative patients or higher levels for HBeAg-positive patients 1
• ALT levels: Treatment is recommended when ALT >2 times upper limit of normal 1
• Evidence of liver disease: Consider treatment if moderate/severe inflammation or significant fibrosis on biopsy or non-invasive tests 1
• HBeAg status: Influences treatment duration and endpoints 1

First-Line Treatment Options

Nucleos(t)ide Analogues (NAs)

• Entecavir: Highly potent with very low resistance rate (1.2% after 5 years in treatment-naïve patients) 1
• Tenofovir: Highly potent with no documented resistance in treatment-naïve patients after initial studies 1, 2
• Both medications provide durable viral suppression and are well-tolerated for long-term therapy 3, 4

Pegylated Interferon-α

• Finite duration of treatment (48 weeks) 1
• Higher rates of HBeAg and HBsAg loss compared to NAs in selected patients 1
• Best results in patients who are:
  • Young with HBV genotype A or B 1
  • Have ALT >2 times upper limit of normal 1
  • Have HBV DNA levels <10^9 copies/mL 1
• Disadvantages include administration by injection and numerous side effects 1

Treatment Duration

HBeAg-positive patients:

• Nucleos(t)ide analogues: Minimum 1 year, continue for 3-6 months after HBeAg seroconversion 1
• Peginterferon: Standard 48 weeks 1

HBeAg-negative patients:

• Nucleos(t)ide analogues: Long-term/indefinite treatment often required 1
• Peginterferon: 1 year 1

Cirrhotic patients:

• Compensated cirrhosis: Long-term NA therapy recommended 1
• Decompensated cirrhosis: Indefinite NA therapy; interferon contraindicated 1

Monitoring During Treatment

• Regular assessment of HBV DNA levels to evaluate virological response 5
• Monitor ALT levels for biochemical response 1
• Watch for:
  • Primary treatment failure: Inability to reduce HBV DNA by 1 log10 IU/ml after 6 months 1
  • Secondary treatment failure (virologic breakthrough): Increase in HBV DNA by 1 log10 above nadir on two occasions 1 month apart 1

Managing Treatment Failure and Resistance

• For lamivudine resistance: Switch to tenofovir (preferred) or add adefovir 1
• For adefovir resistance: Switch to or add entecavir 1
• For telbivudine resistance: Switch to or add tenofovir 1
• For entecavir resistance: Switch to or add tenofovir 1

Special Populations

Patients with Cirrhosis

• Antiviral therapy is recommended if HBV DNA ≥2,000 IU/mL regardless of ALT levels 1
• Oral NAs are preferred; peginterferon may be used with careful monitoring in compensated cirrhosis with preserved liver function 1
• In decompensated cirrhosis, interferon is contraindicated; use entecavir or tenofovir 1

Pregnant Women

• Telbivudine or tenofovir (both pregnancy category B) may be preferred during pregnancy 1, 5

Treatment Endpoints

• HBeAg-positive patients: HBeAg seroconversion with undetectable HBV DNA 1
• HBeAg-negative patients: Sustained normalization of ALT and undetectable HBV DNA 1
• Ideal endpoint for all patients: HBsAg loss with or without anti-HBs seroconversion 1, 5

Common Pitfalls and Caveats

• Abrupt discontinuation of antiviral therapy can lead to severe hepatitis flares 2
• Poor medication adherence is a common cause of virological breakthrough 5
• Long-term NA therapy may be associated with rare side effects including renal impairment, decreased bone mineral density, and lactic acidosis 6
• Monitoring for these complications is recommended during long-term therapy 6
• Treatment indications may need to be expanded for immune tolerant patients over age 40 and patients with evidence of active/advanced liver disease 1