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.
| Medication Class | Agents* |
|---|---|
| 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 agents | Obinutuzumab Ocrelizumab Ofatumumab Rituximab |
| Anthracycine derivatives | Doxorubicin Epirubicin (USED in TACE for HCC) |
| TNF inhibitors | Adalimumab Certolizumab Etanercept Infliximab |
| Other cytokine inhibitors and integrin inhibitors | Abatacept Mogamulizumab Natalizumab Ustekinumab Vedolizumab |
| Tyrosine kinase inhibitors | Imatinib Nilotinib |
| Proteasome inhibitors | Bortezomib Carfilzomib Ixazomib |
| Traditional immunosuppressive agents | Azathioprine 6-Mercaptopurine Methotrexate |
| Corticosteroids | Prednisone 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.
| Treatment | 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 agents | High risk Use prophylaxis | High risk Use prophylaxis |
| Anthracycine derivatives | High 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 inhibitors | Moderate risk Use prophylaxis | Moderate risk Use prophylaxis |
| Other cytokine inhibitors and integrin | Moderate risk Use prophylaxis | Moderate risk Use prophylaxis |
| Tyrosine kinase inhibitors | Moderate risk Use prophylaxis | Moderate risk Use prophylaxis |
| Proteasome inhibitors | Moderate risk Use prophylaxis | Moderate risk Use prophylaxis |
| Traditional immunosuppressive agents | Low risk No prophylaxis Monitor HBV DNA, ALT every 3 months | Low risk No prophylaxis Monitor HBsAg, HBV DNA, ALT every 3 months |
| Intra-articular steroids | Low 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.
| Nucleos(t)ide Analogue | QD Dose | Potential Side Effects | Use in HIV* | Lowest CrCl Without Dose Adjustment | Renal 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 mg | Lactic acidosis (decompensated cirrhosis) | N/A | 50 mL/min |
|
| Tenofovir disproxil fumarate | 300 mg | Nephropathy, Fanconi syndrome, osteomalacia, lactic acidosis | Yes | 50 mL/min |
|
| Tenofovir alafenamide | 25 mg | Lactic acidosis | Yes | 15 mL/min | <15: not recommended in HBV monoinfection |
Resources
- Hepatitis B Virus Screening and Management for Patients With Cancer Prior to Therapy: ASCO Provisional Clinical Opinion Update | Journal of Clinical Oncology (ascopubs.org)
- AGA Institute Guidelines on Hepatitis B Reactivation (HBVr): Clinical Decision Support Tool - Gastroenterology (gastrojournal.org)
- Reactivation of Hepatitis B Virus: A Review of Clinical Guidelines - PMC (nih.gov)
- Risk of HBV reactivation during therapies for HCC: A systematic review - Papatheodoridi - 2022 - Hepatology - Wiley Online Library
