Risk of HBV Reactivation During High Risk Immunosuppressive Therapy - Viral Hepatitis and Liver Disease
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Risk of HBV Reactivation During High Risk Immunosuppressive Therapy

for Health Care Providers

Risk of HBV Reactivation During High Risk Immunosuppressive Therapy - Hepatitis B

Key concepts

Patients with hepatitis B (HBV) including chronic inactive HBV or previous HBV infection are at risk of HBV reactivation during use of immunosuppressive therapies for diseases such as cancer, rheumatoid arthritis, multiple sclerosis, etc.

Definitions

  • Chronic HBV = HBsAg (+), quantifiable HBV DNA and ALT ranging from normal-elevated
  • Chronic inactive HBV = HBsAg (+), undetectable or low level HBV DNA and normal ALT
  • Previous HBV = HBsAg (-) HBsAb (-) HBcAb (+), undetectable HBV DNA and normal ALT

Hepatitis B Reactivation

Occurrence of significantly rising HBV DNA and rising ALT. This can range from a subclinical state with no symptoms to fulminant or even fatal hepatitis.

HBV Reactivation is a potential complication of immunosuppressive therapy:

  • can occur during immunosuppressive treatment
  • can occur following immunosuppressive treatment
  • can be prevented with HBV antivirals

HBV testing for all patients who are initiating immunosuppressive therapy is required:

  • Many patients are not aware of their HBV status
  • Among VHA patients, 1 in 125 have chronic hepatitis B with positive hepatitis B surface antigen (HBsAg+); 1 in 9 have had prior hepatitis B infection with positive hepatitis B core antibody (HBcAb+).

If HBV reactivation occurs during immunosuppressive treatment, it can disrupt the immunosuppressive treatment:

  • Interruption of chemotherapy can occur
  • HBV reactivation can increase cancer mortality
  • HBV reactivation can cause cause hepatitis 33%, liver failure 13% and death 7%

Hepatitis B antiviral prophylaxis:

  • Use of HBV antivirals during immunosuppressive therapy and for 6-12 months post-therapy is required or recommended in many situations
  • Recommendations depend on the HBV status of the patient and the particular immunosuppressive agent to be used

High or moderate risk immunosuppressive treatments
*Incidence of HBV reactivation: High risk > 10%, moderate risk 1-10%

  • B-cell depleting agents (rituximab, ofatumumab, obinutuzumab, and ocrelizumab)
    • High risk if HBSAg+ or HBSAg ⁄ HBcAb+
  • Anthracycline derivatives (doxorubicin, epirubicin)
    • High risk if HBSAg+, moderate risk if HBSAg ⁄ HBcAb+
  • Prednisone: ≥ 10 mg daily for ≥ 4 weeks (or equivalent corticosteroid)
    • High risk if HBSAg+, moderate risk if HBSAg ⁄ HBcAb+
  • Prednisone: < 10 mg daily for > 4 weeks (or equivalent corticosteroid)
    • Moderate risk if HBSAg+
  • TNF-a blockers (infliximab, adalimumab, certolizumab, golimumab)
  • Tyrosine kinase inhibitors(imatinib, nilotinib)
    • Moderate risk if HBSAg+ or HBSAg ⁄ HBcAb+
  • Other cytokine or integrin inhibitors(abatacept, ustekinumab, natalizumab, vedolizumab)
    • Moderate risk if HBSAg+ or HBSAg ⁄ HBcAb+

Recommendations

  • In all cases, before initiating immunosuppressive treatment → test for hepatitis B with HBsAg, HBsAb, HBcAb (total Ab)
  • Consider also a consultation or referral to GI ⁄ hepatology or ID to follow patient during and following their HBV antiviral treatment
  • If HBsAg POSITIVE, additionally check HIV and HBV DNA and ALT and consider consulting GI ⁄ hepatology or ID

Resources

  • AGA Institute Hepatitis B Reactivation Clinical Decision Support Tool
  • AGA Guidelines on the Prevention and Treatment of HBV Reactivation During Immunosuppressive Drug TherapyLink will take you outside the VA website. VA is not responsible for the content of the linked site.
  • American Society of Clinical Oncology Provisional Clinical Opinion Update: HBV Screening for Patients With Cancer Before TherapyLink will take you outside the VA website. VA is not responsible for the content of the linked site.