What is the recommended management for Hepatitis B (HBV)?

Management of Hepatitis B Virus Infection

Tenofovir or entecavir monotherapy is the first-line treatment for chronic hepatitis B due to their high potency and high genetic barrier to resistance. 1

Initial Assessment and Monitoring

Diagnostic Evaluation

• Complete serologic testing: HBsAg, anti-HBs, HBeAg, anti-HBe, HBV DNA levels
• Liver function tests: ALT, AST, bilirubin, albumin, prothrombin time
• Assessment for coinfections: HCV, HDV, and HIV 1
• Baseline alpha-fetoprotein and ultrasound for patients at risk of HCC
• Consider liver biopsy or non-invasive fibrosis assessment

Monitoring Schedule

• For chronic hepatitis with normal ALT: Liver function tests and HBV DNA every 2-6 months, HBeAg status every 6-12 months 1
• For chronic hepatitis with elevated ALT: Liver function tests every 1-3 months, HBV DNA and HBeAg status every 2-6 months 1
• For compensated cirrhosis: Liver function tests and HBV DNA every 2-6 months 1
• For decompensated cirrhosis: Liver function tests every 1-3 months, HBV DNA every 2-6 months 1

Treatment Indications

Chronic Hepatitis B (Non-cirrhotic)

• HBV DNA ≥2,000 IU/mL with elevated ALT and/or moderate-to-severe inflammation or fibrosis on liver biopsy 1

Compensated Cirrhosis

• Treat if HBV DNA ≥2,000 IU/mL regardless of ALT levels 1
• Consider treatment even with HBV DNA <2,000 IU/mL to reduce risk of decompensation 1

Decompensated Cirrhosis

• Prompt antiviral therapy if HBV DNA is detectable by PCR test regardless of ALT levels 1
• Consider liver transplantation evaluation 1

Special Populations

• Immunosuppressed patients: Prophylactic antiviral therapy for HBsAg-positive patients 1
• Pregnant women: Consider treatment if high viral load to prevent mother-to-child transmission 1
• Patients undergoing chemotherapy: Antiviral prophylaxis for HBsAg-positive or anti-HBc-positive patients 1

Treatment Options

First-Line Therapies

1. Nucleos(t)ide Analogues

   • Entecavir (0.5 mg daily for treatment-naïve, 1 mg daily for lamivudine-resistant) 1
   • Tenofovir disoproxil fumarate (300 mg daily) 1
   • Both have high genetic barrier to resistance and potent viral suppression

2. Pegylated Interferon alfa-2a

   • 180 μg weekly for 48 weeks
   • Consider in younger patients with high ALT, low HBV DNA, and without cirrhosis 1, 2
   • Contraindicated in decompensated cirrhosis 1

Management of Treatment Failure

• For patients with primary treatment failure and good compliance: Test for genotypic resistance mutations 1
• For patients on drugs with low genetic barrier (lamivudine, telbivudine, clevudine, adefovir): Switch to high-genetic-barrier drug (entecavir or tenofovir) 1
• For patients on high-genetic-barrier drugs: Continue treatment with regular monitoring for viral breakthrough 1
• In case of viral breakthrough: Implement rescue therapy based on genotypic resistance analysis 1, 3

Special Considerations

Acute Hepatitis B

• Generally does not require antiviral therapy as >95% recover spontaneously 1
• Consider antiviral therapy only in cases of persistent severe hepatitis or acute liver failure 1

HBV/HIV Coinfection

• Include tenofovir in HAART regimen 1
• Avoid entecavir monotherapy in HIV-infected patients not receiving effective HAART 4

HBV/HCV Coinfection

• Treat according to dominant virus or individual treatment strategies 1
• Monitor HBV DNA levels during and after HCV treatment as HBV reactivation may occur 1

HBV/HDV Coinfection

• Treat with peginterferon alfa for at least 1 year 1
• Consider nucleos(t)ide analogues if CHB treatment indications are met or cirrhosis is present 1

Treatment Duration and Endpoints

• HBeAg-positive patients: Continue treatment for at least 12 months after HBeAg seroconversion 1
• HBeAg-negative patients: Long-term therapy usually required due to high relapse rates 1
• Ideal endpoint is HBsAg loss with sustained HBV DNA suppression 1
• Monitor for at least 6-12 months after discontinuation of therapy 1

Cautions

• Severe acute exacerbations may occur upon discontinuation of therapy; monitor hepatic function closely for several months 5, 4
• Monitor renal function during therapy, particularly with tenofovir; dose adjustment may be required for renal impairment 5
• Lactic acidosis and severe hepatomegaly with steatosis have been reported; suspend treatment if suspected 5, 4

The management of hepatitis B requires careful assessment of disease phase, monitoring of viral markers, and appropriate selection of antiviral therapy to achieve long-term viral suppression and prevent disease progression.