What is the management of hepatitis B (HBV)?

Management of Hepatitis B

Treatment Indications

All patients with cirrhosis and any detectable HBV DNA must be treated immediately, regardless of ALT levels. 1

For non-cirrhotic patients, treatment should be initiated based on the following criteria:

• Treat immediately if HBV DNA ≥2,000 IU/mL AND elevated ALT (>2× ULN) AND/OR at least moderate histological lesions on biopsy or non-invasive markers 1, 2
• Treat without liver biopsy if HBV DNA ≥20,000 IU/mL AND ALT >2× ULN 1
• Consider treatment even with normal ALT if HBV DNA ≥2,000 IU/mL AND liver stiffness ≥9 kPa (with normal ALT) or ≥12 kPa (with ALT <5× ULN) 1
• HBeAg-positive patients over age 30 with persistently normal ALT and HBV DNA >20,000 IU/mL should be treated regardless of histology 1, 2

First-Line Treatment Options

The preferred first-line agents are nucleos(t)ide analogues with high genetic barrier to resistance: entecavir, tenofovir disoproxil fumarate (TDF), or tenofovir alafenamide (TAF). 1, 3

Specific Dosing

• Entecavir: 0.5 mg daily orally on an empty stomach (at least 2 hours after a meal and 2 hours before the next meal) 3, 4
• Tenofovir disoproxil fumarate or tenofovir alafenamide: standard dosing per FDA labeling 1, 5

Alternative Option

• Pegylated interferon alfa-2a can be considered for finite-duration therapy (48 weeks) in selected patients with mild to moderate disease who desire time-limited treatment 1, 6
• This option offers the possibility of immune-mediated control and sustained off-treatment response 6

Avoid lamivudine due to high resistance rates (up to 70% in 5 years) 3

Special Populations Requiring Specific Management

Pregnancy

• Tenofovir disoproxil fumarate is the preferred agent during pregnancy 1, 6
• Initiate prophylactic antiviral therapy at 24-32 weeks gestation for women with HBV DNA >200,000 IU/mL to prevent mother-to-child transmission 3
• Breastfeeding is generally not contraindicated while on tenofovir 3

Patients Requiring Immunosuppression/Chemotherapy

• All HBsAg-positive patients receiving high-risk agents (rituximab, anthracyclines, high-dose steroids) must receive prophylactic antiviral therapy starting 2-4 weeks before immunosuppression 3
• Continue prophylaxis through treatment and for at least 12 months after completion (24 months for rituximab) 3
• Risk of HBV reactivation is 12-50% without prophylaxis 3

Decompensated Cirrhosis

• Patients with decompensated cirrhosis require urgent antiviral treatment with entecavir or tenofovir AND simultaneous evaluation for liver transplantation 3, 7

Acute Severe Hepatitis B

• Initiate nucleos(t)ide analogue therapy (entecavir or tenofovir) for patients with severe acute hepatitis B presenting with coagulopathy, severe jaundice, or liver failure 3
• Continue therapy for at least 3 months after anti-HBs seroconversion or 12 months after anti-HBe seroconversion 1

Healthcare Workers

• HBsAg-positive healthcare workers performing exposure-prone procedures with HBV DNA ≥2,000 IU/mL should be treated with entecavir or tenofovir to reduce HBV DNA to undetectable or <2,000 IU/mL before resuming such procedures 1

HIV-HBV Coinfection

• All HIV-HBV coinfected patients should receive antiretroviral therapy including tenofovir (TDF or TAF) regardless of CD4 count 3

Treatment Monitoring Protocol

During Active Treatment

• Monitor HBV DNA every 3 months until undetectable, then every 6 months 1, 3, 7
• Monitor liver enzymes (ALT/AST) every 3-6 months 3, 7
• Annual quantitative HBsAg testing to assess for potential HBsAg loss (functional cure) 3
• Monitor renal function if on tenofovir 3, 6

After Treatment Discontinuation

• If treatment is stopped, monitor closely with regular blood tests to check liver function, as HBV infection may worsen within 6 months 1, 4

Treatment Endpoints and Duration

HBsAg loss (functional cure) is the optimal treatment endpoint but is rarely achieved with current therapies. 1, 3

Realistic Treatment Goals

• Long-term, potentially indefinite treatment is typically required with nucleos(t)ide analogues 1, 6
• For HBeAg-positive patients: stopping therapy may be considered after achieving HBeAg seroconversion with undetectable HBV DNA and completing at least 12 months of consolidation therapy 3
• For patients with cirrhosis: indefinite treatment is mandatory 7

Hepatocellular Carcinoma Surveillance

All high-risk patients require ultrasound examination every 6 months, including: 3

• Asian men >40 years
• Asian women >50 years
• Any patient with cirrhosis
• Family history of HCC
• Age >40 years with persistent ALT elevation

Additional Preventive Measures

• Hepatitis A vaccination if anti-HAV negative, as coinfection increases mortality 5.6- to 29-fold 3
• Counsel on complete alcohol abstinence, as even limited consumption worsens outcomes 3
• Screen for coinfections: anti-HCV, anti-HDV (if injection drug use history), anti-HIV 3

Critical Warnings

Serious Adverse Events to Monitor

• Lactic acidosis: presents with severe weakness, unusual muscle pain, trouble breathing, stomach pain with nausea/vomiting, dizziness, or fast/irregular heartbeat—requires immediate emergency care 4
• Severe hepatotoxicity with hepatomegaly and steatosis: presents with jaundice, dark urine, light stools, prolonged anorexia, or lower abdominal pain—requires immediate evaluation 4, 5
• Risk is higher in females, obese patients, or those on long-term nucleoside analogue therapy 4

HIV Testing Requirement

• Obtain HIV test before starting entecavir or tenofovir, as untreated HIV may develop resistance to certain HIV medicines if exposed to these agents 4