Treatment Guidelines for Hepatitis B (HBV)
Nucleos(t)ide analogues (NAs) with high genetic barrier to resistance, specifically entecavir, tenofovir disoproxil fumarate (TDF), or tenofovir alafenamide fumarate (TAF), are the first-line treatments for chronic hepatitis B. 1, 2
Who to Treat
Non-Cirrhotic Patients
HBeAg-positive chronic hepatitis B:
- Treat patients with HBV DNA >20,000 IU/mL AND serum ALT >2× ULN or significant inflammation/fibrosis on biopsy 2
- For those with HBV DNA >20,000 IU/mL and ALT 1-2× ULN, consider liver biopsy; treat if significant inflammation or fibrosis is present 2
- Patients >30 years with normal ALT and elevated HBV DNA (>1,000 IU/mL) should be considered for treatment 2
HBeAg-negative chronic hepatitis B:
Cirrhotic Patients
- Compensated cirrhosis: Treat all patients with detectable HBV DNA regardless of ALT levels 2
- Decompensated cirrhosis: Immediate antiviral therapy is required if HBV DNA is detectable, regardless of ALT levels 2
Special Populations
Pregnant Women
- Antiviral therapy in the third trimester is recommended for mothers with high viral load to prevent mother-to-child transmission 2
- TDF is the preferred agent during pregnancy 2
Patients with Renal or Bone Disease
- Entecavir, TAF, or besifovir are preferred for patients with renal dysfunction or bone disease 2
- Consider switching to entecavir or TAF for patients on TDF who develop renal dysfunction or bone disease 2
Patients with HCC
- Antiviral therapy should be initiated in patients with HBV-related HCC if serum HBV DNA is detectable 2
Immunosuppression/Chemotherapy
- Prophylactic antiviral therapy should be initiated in HBsAg-positive patients before immunosuppression or chemotherapy 2
- HBsAg-negative, anti-HBc-positive patients should be monitored and treated if HBV reactivation occurs 2
Liver Transplantation
- HBsAg-positive patients on the transplant waiting list should receive NA therapy 2
- Post-transplantation, high-potency NAs (entecavir or tenofovir) should be used 2
Treatment Options
First-Line Therapies
Nucleos(t)ide analogues (NAs):
Pegylated interferon-α (PEG-IFN):
- Can be considered for a finite duration (48 weeks) in selected patients with mild to moderate chronic hepatitis B 1, 4
- Advantages include finite treatment duration and no resistance development 2
- Limitations include poor tolerability and adverse effects such as bone marrow suppression and exacerbation of neuropsychiatric symptoms 3
Treatment Monitoring
- Monitor HBV DNA levels, liver function tests, and serological markers regularly to assess treatment response 1
- For patients on NA therapy, check ALT every 3-6 months and HBV DNA every 6-12 months 5
- For patients with cirrhosis, more frequent monitoring is required 5
Treatment Goals and Endpoints
- Short-term goals: HBV DNA suppression, ALT normalization, and HBeAg seroconversion (in HBeAg-positive patients) 2
- Long-term goals: Prevention of cirrhosis, hepatic decompensation, and HCC 2
- Ideal endpoint: HBsAg loss with undetectable HBV DNA (functional cure) 1, 3
Common Pitfalls and Considerations
- Discontinuation of therapy can lead to severe acute exacerbations of hepatitis; close monitoring is essential if treatment is stopped 6, 7
- Drug resistance can develop with certain NAs; newer agents (entecavir, TDF, TAF) have significantly lower resistance rates compared to older agents (lamivudine, adefovir) 3, 4
- Renal function should be monitored in patients on TDF or adefovir 7, 2
- Patients with extrahepatic manifestations and active viral replication may benefit from antiviral therapy 2
Treatment Algorithm
- Assess disease phase using HBV DNA, ALT, HBeAg status, and liver fibrosis assessment 1, 5
- Determine treatment indication based on criteria above 2
- Select appropriate therapy:
- Monitor treatment response with regular HBV DNA, ALT, and serological testing 5
- Maintain therapy until treatment goals are achieved; for most patients on NAs, this means long-term or indefinite therapy 3, 2