HBV: React Before the Virus Does

The Key to Preventing HBV Reactivation

William F. Balistreri, MD


April 01, 2015

In This Article

Protection Against HBV Reactivation

The effect of titer or level of anti-HBs on HBV reactivation and the clinical severity of hepatitis have not been well reported. In fact, HBV reactivation is observed in patients with detectable levels of anti-HBs with a frequency that is only slightly lower than among the total group of anti-HBc–positive patients.[3] Owing to a lack of studies that have used anti-HBs titers to guide the initiation of antiviral prophylaxis or infer protection, the AGA document concluded that there is insufficient evidence to support the use of anti-HBs titers in making a recommendation about antiviral prophylaxis.[3,4]

Vaccination. The protective role of hepatitis B vaccination in preventing HBV reactivation is also viewed as a knowledge gap.[3,4] Although universal vaccination against hepatitis B was implemented in the United States in 1991, up to 10% of vaccine recipients fail to respond with adequate anti-HBs titers after a primary series of vaccinations. Moreover, anti-HBs levels decline with time. This raises questions about whether a history of HBV vaccination is reassuring in someone about to receive immune suppression or chemotherapy.

Special populations. This has special relevance for patients with IBD, as many may ultimately need immunosuppressive drug therapy but relatively few have been vaccinated.[4] There is a low rate of response to the HBV vaccination in patients with IBD, which emphasizes the need for careful assessment of patients with this disease.[54] Moses and colleagues[53] determined HBV immunity in children with IBD receiving infliximab (Remicade®) therapy and the response to a single booster dose of the HBV vaccine in patients who were found to be nonimmune. In all, 87% had been vaccinated against HBV, but only 56% had immunity to HBV, as defined by anti-HBs level of 10 mIU/mL or more. Older age, lower serum albumin levels, and the presence of pancolitis were associated with the absence of protective antibodies. However, infliximab dose, frequency, duration, and concurrent use of immunomodulators were not significantly different between immune and nonimmune patients. Thirty-four patients received booster immunization, and 76% had an anamnestic response (anti-HBs level ≥10 mIU/mL after booster). Overall, 86% of previously immunized patients were considered immune against HBV infection. Therefore, of those previously vaccinated, 14% were at risk for HBV because protective anti-HBs levels were absent and could not be elicited through booster immunization. Given the high risk for severe HBV infection in this group, efforts should be made to screen for HBV immunity at the time of IBD diagnosis. Booster immunization should be considered in patients without protective antibodies.

What Can Be Done to Ensure Compliance?

In one large series of more than 8000 patients undergoing chemotherapy, only 16% had been screened for HBV infection.[55]

Two recent approaches to enhance the rates of screening have been published.

Sun and colleagues[56] used a reminder system to achieve an overall screening rate of 86% in patients with cancer who are receiving chemotherapy. The rate of HBV reactivation was lower in patients who received antiviral prophylaxis than in those who did not (2% vs 15%). However, the overall rate of antiviral prophylaxis was only 46%. The rates of antiviral prophylaxis were lower when treating lung, breast, and colorectal cancers than for hematologic malignancies.

In another approach, a simple alert was introduced into the computerized order-entry system to notify healthcare providers of the potential risk for viral reactivation when prescribing biologic therapies, thereby facilitating the request for serologic testing in patients who have not had these tests.[57] The use of the alert system increased the screening rate from less than 50% to 94% for HBsAg and from less than 30% to 85% for anti-HBc in patients to whom immunosuppressive agents are prescribed. This study demonstrates the feasibility of implementing an alert system to increase the rate of HBV screening, which, in turn, will facilitate the identification of patients at high risk for HBV reactivation and permit physicians to prescribe prophylactic measures according to current guidelines.

Bottom Line

The once-fatal condition of HBV reactivation can now be easily prevented by screening patients for HBV infection prior to start of immunosuppressive therapy and initiating prophylactic antiviral therapy in those with moderate-to-high risk for HBV reactivation.[34] However, awareness of the risk in patients receiving immunosuppressive therapy remains low more than 3 decades after the initial case reports.

The recent reports from the AASLD, the AGA, and other subspecialty societies support routine assessment of the HBV status of all patients prior to the initiation of immunosuppressive treatment or cancer chemotherapy. They also provide guidance on the rationale for the use of antiviral treatment to diminish the risk for severe or fatal reactivation of hepatitis B.[2,3,4] However, the current low rates of screening could be related to uncertainty about who should be screened, the cost of testing, and the fact that some do not consider HBV infection to be a major issue. Absence of knowledge does not mean absence of risk.[58] Specialists who treat patients with immunosuppressive therapy should not underestimate the potential severity of HBV reactivation and should not rely on the ability of antiviral therapy to rescue patients with life-threatening HBV reactivation.

Ludwig[49] recently commented that different subspecialty physicians may look at the data differently and be convinced—or not—of the clear rationale for prevention of HBV reactivation. However, she adds that, "if indeed it can be shown that there is a worse disease-specific clinical outcome secondary to reactivation of HBV, this discrepancy is likely to disappear. Absent those data, there will continue to be debate as to the importance of preventing HBV reactivation rather than treating it after it has occurred."


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