Prevention of Hepatitis B Reactivation During Immunosuppressive Therapy Hepatitis B - 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 all patients for HBsAg, HBsAb, and HBcAb Total (IgG) (if not done in the last 6 months).

Immunize for HBV if the patient is not exposed (HbcAb is negative) nor immune (HBcAB and HBsAb are both negative). Note, immunizations may be effective if given less than 4 weeks prior to a B cell depleting agent such as Rituximab and may need to be offered 6 months after completion of therapy.

Step 2

Review Table 1 to identify which class of immunosuppressant the patient is planned to receive.

Table 1. Immunosuppressant Medications by Class
Medication ClassAgents*
TACE: Trans arterial chemoembolization, HCC: Hepatocellular carcinoma
Note: medications used for TACE may not show up in the Pharmacy orders.
*Examples are for reference only and may not include all available agents.
B-cell depleting agentsObinutuzumab Ocrelizumab Ofatumumab Rituximab
Anthracycine derivativesDoxorubicin Epirubicin (USED in TACE for HCC)
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

Step 3

If the HBsAg and/or HBcAb (Total) is detectable, order tests for hepatitis B viral load (HBV-DNA) and ALT and consider additional factors for risk determination:

  • Older age, male gender, presence of liver disease/cirrhosis/HCC, and the indication for immunosuppressant. (Bone marrow/Stem cell or solid organ transplant are considered HIGH risk as well as some HCC treatments)
  • HBV factors: Presence of HBV virus, positive HBsAg & HBcAb, co-infection with viral hepatitis (C or D), or HIV.
  • The type and number of immunosuppressive agents: AntiCD-20 depleting agents (B cell depleting agent such as rituximab), Anthracycline agent (such as doxorubicin) or steroid exposure for 4 weeks or more (10-20mg/day considered medium risk and >20mg/day considered High risk).

Step 4

If the HBV DNA is detectable, or if there is evidence of advanced liver disease, refer the patient to a hepatology or infectious disease specialist for evaluation. Chemotherapy for cancer should not be delayed and HBV antiviral prophylaxis can be initiated until a risk assessment is completed.

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

Table 2. HBV Reactivation Risk Determination
HBsAg+, HBcAb+HBsAg-, HBcAb+
*NOTE: combinations of immunosuppressive treatments can increase the risk of reactivation. For example, adding a moderate risk dose of corticosteroid to a moderate risk immunosuppressant may result in a HIGH risk of HBV reactivation.
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
Corticosteroids*
< 10 mg/day for ≥ 4 weeks
Moderate risk
Use prophylaxis
Low risk
No prophylaxis
Monitor HBsAg, HBV DNA, ALT every 3 months
HCC treatments:
TACE
Surgical resection or
Immunotherapy
High risk
Use prophylaxis
Lack of date
Use Prophylaxis
HCC
Local Ablation
Systemic therapies
Moderate risk
Use prophylaxis
Lack of data
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
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

Step 5

If the patient is at low risk, no prophylaxis is needed. Monitor HBsAg, HBV DNA, ALT every 3 months (Table 2).

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 3. Recommended Nucleos(t)ide analogues for HBV
Nucleos(t)ide AnalogueQD DosePotential Side EffectsUse in HIV*Lowest CrCl Without Dose AdjustmentRenal Dose Reductions (CrCl, mL/min)
*All HIV/HBV co-infected patients should be initiated on HIV therapy that includes HBV active drug.
Entecavir [package insert].2015 Tenofovir disoproxil fumarate [package insert]. 2017. Tenofovir alafenamide [package insert]. 2017
Entecavir 0.5 mgLactic acidosis
(decompensated cirrhosis)
N/A50 mL/min
  • 30-49: 0.25 mg QD or 0.5 mg Q48
  • 10-29: 0.15 mg QD or 0.5 mg Q72
  • <10 or dialysis: 0.05 mg QD or 0.5 mg Q 7 days
Tenofovir disproxil fumarate300 mgNephropathy, Fanconi syndrome, osteomalacia, lactic acidosisYes50 mL/min
  • 30-49: 300 mg Q48hrs
  • 10-29: 300 mg Q72-96hrs
  • <10 without dialysis: no dose recommendation
  • Dialysis: 300 mg Q 7 days or after ˜12 hrs of dialysis
Tenofovir alafenamide25 mgLactic acidosisYes15 mL/min<15: not recommended in HBV monoinfection

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