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Viral Hepatitis and Liver Disease

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Prevention of Hepatitis B Reactivation During Immunosuppressive Therapy Hepatitis B

for Health Care Providers

Prevention of Hepatitis B Reactivation During Immunosuppressive Therapy - Hepatitis B

Step 1

Test the patient for HBsAg, HBsAb, and HBcAb Total (IgG).

Step 2

Refer to Table 1: Immunosuppresant Medications by Class to determine which class of immunosuppressant the patient is planned to receive.

Step 3

If the HBSAg and/or HBc-Ab Total is detectable, order tests for hepatitis B viral load (HBV-DNA) and ALT.

Step 4

If the HBV DNA is detectable, refer the patient to a hepatology or infectious disease specialist for an evaluation prior to starting immunosuppressive therapy.

If HBV DNA is undetectable, refer to Table 2: HBV Reactivation Risk Determination.

Step 5

If the patient is low risk, plan for monitoring based on recommendations in Table 2: HBV Reactivation Risk Determination.

If the patient is high or moderate risk, refer to Table 3: HBV Antiviral Medication Options for reactivation prophylaxis.

If a patient is on an immunosuppressant that is not listed below, please contact hepatology, gastrointestinal, or infectious disease specialists for guidance.

Table 1. Immunosuppressant Medications by Class
Medication ClassAgents
B-cell depleting agentsObinutuzumab Ocrelizumab Ofatumumab Rituximab
Anthracycine derivativesDoxorubicin Epirubicin
TNF inhibitorsAdalimumab Certolizumab Etanercept Infliximab
Other cytokine inhibitors and integrin inhibitorsAbatacept Mogamulizumab Natalizumab Ustekinumab Vedolizumab
Tyrosine kinase inhibitorsImatinib Nilotinib
Proteasome inhibitorsBortezomib Carfilzomib Ixazomib
Traditional immunosuppressive agentsAzathioprine 6-Mercaptopurine Methotrexate
CorticosteroidsPrednisone Prednisolone Methylprednisone Dexamethasone
Table 2. HBV Reactivation Risk Determination
HBsAg+, HBcAb+HBsAg-, HBcAb+
B cell depleting agentsHigh risk
Use prophylaxis
High risk
Use prophylaxis
Anthracycine derivativesHigh risk
Use prophylaxis
Moderate risk
Use prophylaxis
Corticosteroids
≥ 10 mg/day for ≥ 4 weeks
High risk
Use prophylaxis
Moderate risk
Use prophylaxis
TNF inhibitorsModerate risk
Use prophylaxis
Moderate risk
Use prophylaxis
Other cytokine inhibitors and integrinModerate risk
Use prophylaxis
Moderate risk
Use prophylaxis
Tyrosine kinase inhibitorsModerate risk
Use prophylaxis
Moderate risk
Use prophylaxis
Proteasome inhibitorsModerate risk
Use prophylaxis
Moderate risk
Use prophylaxis
Corticosteroids
< 10 mg/day for ≥ 4 weeks
Moderate risk
Use prophylaxis
Low risk
No prophylaxis
Monitor HBsAg, HBV DNA, ALT every 3 months
Traditional immunosuppressive agentsLow risk
No prophylaxis
Monitor HBV DNA, ALT every 3 months
Low risk
No prophylaxis
Monitor HBsAg, HBV DNA, ALT every 3 months
Intra-articular steroidsLow risk
No prophylaxis
Monitor HBV DNA, ALT every 3 months
Low risk
No prophylaxis
Monitor HBsAg, HBV DNA, ALT every 3 months
Corticosteroids
any dose for ≤ 1 week
Low risk
No prophylaxis
Monitor HBV DNA, ALT every 3 months
Low risk
No prophylaxis,
Monitor HBsAg, HBV DNA, ALT every 3 months
  • high risk: risk of HBV reactivation > 10%
  • moderate risk: risk of HBV reactivation 1-10%
  • low risk: risk of HBV reactivation < 1%
Table 3. HBV Antiviral Options for Reactivation Prophylaxis
Drug and DoseComment
Entecavir 0.5 mg dailyIf no prior lamivudine treatment
Entecavir 1.0 mg dailyIf prior lamivudine treatment
Tenofovir alafenamide 25 mg dailyIf CrCl ≥ 15 ml/min
Tenofovir disoproxil fumarate 300 mg by mouth dailyIf CrCl ≥ 50 ml/min