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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.


  • 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+


  • 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


  • AGA Institute Hepatitis B Reactivation Clinical Decision Support Tool