HBV: React Before the Virus Does

The Key to Preventing HBV Reactivation

William F. Balistreri, MD


April 01, 2015

In This Article

Hepatitis B Reactivation

Those who cannot remember the past are condemned to repeat it.

George Santayana, The Life of Reason, 1905

Let me begin by paraphrasing Santayana: "Those who cannot recognize the past are condemned to repeat it."

I refer specifically to the importance of recognizing past infection with the hepatitis B virus (HBV) to forestall reactivation of clinically significant viral hepatitis during immunosuppressive therapy.

In 2013, the US Food and Drug Administration (FDA) issued a Drug Safety Communication titled, "Boxed Warning and New Recommendations to Decrease Risk of Hepatitis B Reactivation With the Immune-Suppressing and Anti-cancer Drugs Ofatumumab and Rituximab."[1] With this black box alert, the FDA sent a strong message, reminding healthcare professionals to screen all patients for HBV infection before starting treatment with these or similar agents.

HBV reactivation, which has been cited as "an underappreciated clinical challenge," was explored in depth at a recent conference sponsored by the American Association for the Study of Liver Disease (AASLD), with support from the American Academy of Dermatology, the American College of Rheumatology, and the American Society of Clinical Oncology.[2] Furthermore, the American Gastroenterological Association (AGA) recently published their official guidelines on the prevention and treatment of HBV reactivation.[3,4]

These timely documents address a topic of increasing concern in view of the widespread application of potent biologic immunosuppressive agents across the subspecialty spectrum—gastroenterology, hepatology, transplantation medicine, dermatology, rheumatology, and oncology, among others.[2,3,4,5] These interventions have the potential to "awaken" HBV in carriers with inactive disease and even in those with resolved infection.

What is HBV reactivation, what is the clinical impact, and what can we do to prevent or manage the consequences?

HBV Infection: Clinical Sequence

Despite a significant reduction in the incidence of HBV infection and HBV-related end-stage liver diseases through national vaccination programs, chronic infection remains a worldwide problem, affecting approximately 350 million persons.[6,7,8,9]

HBV infection is typically recognized by detecting hepatitis B surface antigen (HBsAg) in serum along with variable amounts of HBV DNA and usually HBV-e antigen (HBeAg). Following the inflammatory phase of HBV infection, there may be clearance of HBeAg with seroconversion to the anti-HBe–positive state, with an undetectable or low HBV DNA level, reflecting an inactive HBsAg carrierstate.

With full recovery, antibody to HBsAg (anti-HBs), a marker of immunity to HBV, arises. Antibody to HBV core antigen (Anti-HBc), which appears in all patients infected with HBV, persists after clearance of HBsAg and thus is an accurate marker of current as well as past infection with HBV.


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