New Guidelines for Managing Hepatitis B Reactivation

American Gastroenterological Association Institute Guideline on the Prevention and Treatment of Hepatitis B Virus Reactivation During Immunosuppressive Drug Therapy

Reddy KR, Beavers KL, Hammond SP, Lim JK, Falck-Ytter YT; American Gastroenterological Association Institute
Gastroenterology. 2015;148:215-219

Guideline Summary

An estimated 400 million people worldwide are living with chronic hepatitis B virus (HBV) infection. The incidence of new cases of acute HBV infection has fallen dramatically in the United States over the past two decades, primarily as a result of the availability of immunization. Furthermore, effective antiviral therapies have been developed to control the viremia or hopefully cure the disease.^[1,2]

Patients who experience spontaneous viral clearance or who have received antiviral therapy have a clear risk for HBV reactivation. It has recently become more apparent that the relative risks vary depending on the type of immunosuppression administered. The guideline and technical review^[3] provide specific direction for the treating provider to assess risk and to initiate concomitant anti-HBV therapy. They also specify durations for the use of these agents after immunosuppressant agents are discontinued.

Treatment Recommendations

All clinicians who treat these patients must read these guidelines to better understand the provision of antiviral prophylaxis. The relative risk for reactivation was classified across the immunosuppressant agents.

High-Risk Patients (Anticipated Incidence of HBV Reactivation, > 10% of Cases).

Hepatitis B surface antigen (HBsAg)-positive/anti-hepatitis B core antibody (HBc)–positive patients treated with B-cell–depleting agents (eg, rituximab, ofatumumab);
HBsAg-positive/anti-HBc–positive patients treated with anthracycline derivatives (eg, doxorubicin, epirubicin); and
HBsAg-positive/anti-HBc–positive patients treated with moderate-dose (10-20 mg prednisone daily or equivalent) or high-dose (> 20 mg prednisone daily or equivalent) corticosteroids daily for ≥ 4 weeks.

Recommendation: Continue antiviral therapy for at least 6 months after discontinuation of immunosuppressive therapy (or at least 12 months for B-cell–depleting agents).

Moderate-Risk Patients (Anticipated Incidence of HBV Reactivation, 1%-10% of Cases).

HBsAg-positive/anti-HBc–positive or HBsAg-negative/anti-HBc–positive patients treated with tumor necrosis factor alpha inhibitors (eg, etanercept, adalimumab, certolizumab, infliximab);
HBsAg-positive/anti-HBc–positive or HBsAg-negative/anti-HBc–positive patients treated with other cytokine or integrin inhibitors (eg, abatacept, ustekinumab, natalizumab, vedolizumab);
HBsAg-positive/anti-HBc–positive or HBsAg-negative/anti-HBc–positive patients treated with tyrosine kinase inhibitors (eg, imatinib, nilotinib);
HBsAg-positive/anti-HBc–positive patients treated with low-dose (< 10 mg prednisone daily or equivalent) corticosteroids for ≥ 4 weeks;
HBsAg-negative/anti-HBc–positive patients treated with moderate-dose (10-20 mg prednisone daily or equivalent) or high-dose (> 20 mg prednisone daily or equivalent) corticosteroids daily for ≥ 4 weeks; and
HBsAg-negative/anti-HBc–positive patients treated with anthracycline derivatives (eg, doxorubicin, epirubicin).

Recommendation: Provide antiviral therapy rather than monitor for relapse. Continue treatment for 6 months after discontinuation of immunosuppressive therapy.

Low-Risk Patients (Anticipated Incidence of HBV Reactivation, < 1% of Cases).

HBsAg-positive/anti-HBc–positive or HBsAg-negative/anti-HBc–positive patients treated with traditional immunosuppressive agents (eg, azathioprine, 6-mercaptopurine, methotrexate);
HBsAg-positive/anti-HBc–positive or HBsAg-negative/anti-HBc–positive patients treated with intra-articular corticosteroids;
HBsAg-positive/anti-HBc–positive or HBsAg-negative/anti-HBc–positive patients treated with any dose of oral corticosteroids daily for ≤ 1 week; and
HBsAg-negative/anti-HBc–positive patients treated with low-dose (< 10 mg prednisone or equivalent) corticosteroids for ≥ 4 weeks.

Recommendation: No routine antiviral prophylaxis.

Prophylactic Treatment or Monitoring Recommendations

The guidelines address the choice of prophylactic treatment in patients at risk for HBV reactivation. Lamivudine, albeit first in class when introduced, is associated with a high rate of resistance, in particular with extended use beyond 1 year. The recommendation is to use antiviral agents with a higher barrier to resistance than lamivudine in patients who are undergoing immunosuppressive therapy and meet the above criteria for appropriate use.

The guidelines also discuss the option of HBV DNA level monitoring as a signal for initiation of antiviral therapy in patients at risk for reactivation. The overall rate of reactivation is considerably lower when prophylactic therapy is selected, and the intervals for appropriate DNA monitoring for best clinical outcomes have not been established.

Viewpoint

This discussion is meant to be an overview and does not substitute for reading the guidelines. Providers who prescribe immunosuppressant or biologic agents must understand the relative risks for reactivation of HBV infection. Risk mitigation strategies should be tailored as recommended in the guidelines to minimize the risk for HBV reactivation and HBV-related morbidity and mortality.

Abstract

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