What are the latest guidelines for managing hepatitis B?

Latest Guidelines on Hepatitis B Management

The current standard of treatment for chronic hepatitis B (CHB) is long-term administration of potent nucleos(t)ide analogues (NAs) with high barrier to resistance, specifically entecavir, tenofovir disoproxil fumarate (TDF), or tenofovir alafenamide fumarate (TAF). 1

Classification and Diagnosis

• Chronic HBV infection can be classified into five phases: (I) HBeAg-positive chronic infection, (II) HBeAg-positive chronic hepatitis, (III) HBeAg-negative chronic infection, (IV) HBeAg-negative chronic hepatitis, and (V) HBsAg-negative phase 1
• Diagnosis requires evaluation of serum HBV DNA, ALT, HBeAg, and anti-HBe levels with regular monitoring 1
• Monitoring frequency should be every 2-6 months for liver function tests and HBV DNA in compensated patients, and every 1-3 months in decompensated patients 1

Treatment Indications

Non-Cirrhotic Patients

• Treatment is indicated for patients with:
  • HBV DNA ≥2,000 IU/mL, elevated ALT and/or at least moderate histological lesions 1
  • HBV DNA >20,000 IU/mL and ALT >2× upper limit of normal (ULN) 2
  • HBV DNA >2,000 IU/mL and significant liver stiffness (>9 kPa with normal ALT or >12 kPa with ALT ≤5× ULN) 2
  • HBV DNA >2,000 IU/mL and family history of cirrhosis and/or hepatocellular carcinoma (HCC) 2
  • HBeAg-positive patients >30 years old with HBV DNA >20,000 IU/mL 2

Cirrhotic Patients

• All patients with cirrhosis and detectable HBV DNA should receive treatment, regardless of ALT levels 1
• For compensated cirrhosis:
  • Treat if HBV DNA ≥2,000 IU/mL, regardless of ALT level 1
  • Consider treatment if HBV DNA is detectable but <2,000 IU/mL 1
• For decompensated cirrhosis:
  • Immediate treatment with a high barrier to resistance NA is required for any detectable HBV DNA 1
  • Consider liver transplantation evaluation 1

First-Line Treatment Options

Preferred Antiviral Agents

• Nucleos(t)ide analogues (NAs) with high genetic barrier to resistance are the treatment of choice: 1

  • Entecavir
  • Tenofovir disoproxil fumarate (TDF)
  • Tenofovir alafenamide fumarate (TAF)
  • Besifovir (approved in some countries)

• First-generation NAs (lamivudine, adefovir, telbivudine, clevudine) are not recommended due to low potency and high resistance rates 1

Pegylated Interferon-α

• Can be considered in mild to moderate CHB patients 1
• Advantages: finite treatment duration, no drug resistance 3
• Disadvantages: lower response rates, numerous contraindications, frequent side effects 3, 4
• Contraindicated in decompensated cirrhosis 1
• May be used with caution in compensated cirrhosis with preserved liver function 1

Treatment Considerations for Special Populations

Pregnant Women

• Tenofovir DF is the preferred NA during pregnancy 1
• Prophylactic use is recommended to prevent mother-to-child transmission beginning at 24-32 weeks of pregnancy for women with HBV DNA >200,000 IU/mL 1
• Breastfeeding is generally not contraindicated during tenofovir DF treatment 1

Acute Hepatitis B

• NA therapy is recommended for patients with severe acute hepatitis B (coagulopathy, severe jaundice, or liver failure) 1
• Entecavir or tenofovir DF/AF are preferred agents 1

Renal Impairment

• All NAs should be dose-adjusted in patients with renal impairment 1
• Consider TAF or entecavir in patients with or at risk for renal dysfunction 1
• Monitor renal function during antiviral treatment 1

Transplant Recipients

• All HBsAg-positive organ transplant recipients should receive lifelong antiviral therapy 1
• Tenofovir (TAF, TDF) and entecavir are preferred due to low resistance rates 1

Monitoring During Treatment

Treatment Response Definitions

• Virological response: undetectable HBV DNA by PCR assay 1
• Biochemical response: normalization of ALT levels 1
• Serological responses: HBeAg loss/seroconversion (HBeAg-positive patients) and HBsAg loss/seroconversion (all patients) 1

Monitoring Schedule

• Liver function tests every 3-6 months
• HBV DNA levels every 3-6 months
• HBeAg and anti-HBe every 6-12 months in HBeAg-positive patients
• Monitor for drug side effects, especially renal function with tenofovir DF 5

Treatment Duration and Discontinuation

• Long-term, potentially indefinite treatment is typically required with NAs 1
• HBsAg loss is considered the optimal endpoint but is rarely achieved 1
• Stopping NA therapy may be considered in:
  • HBeAg-positive patients who achieve HBeAg seroconversion with undetectable HBV DNA and have completed at least 12 months of consolidation therapy
  • HBeAg-negative patients only in selected cases with long-term (>3 years) virological suppression

Important Safety Considerations

• Severe acute exacerbations of hepatitis B can occur after discontinuation of treatment; monitor hepatic function closely for at least several months 6
• Tenofovir DF may cause renal impairment and decreased bone mineral density; monitor renal function and consider bone density testing in high-risk patients 5
• Lactic acidosis and severe hepatomegaly with steatosis are rare but serious potential side effects of NAs 6, 5

Future Directions

• Development of new therapeutic approaches, particularly immunomodulatory therapies, to enhance HBeAg and HBsAg seroconversion 1
• Assessment of the long-term impact of therapy on prevention of cirrhosis, its complications, and HCC 1
• Strategies to achieve functional cure of HBV infection 1