Patients who are to undergo immunosuppressive therapy but are at high risk for reactivation of hepatitis B infection should receive antiviral prophylaxis, rather than being monitored for reactivation and treated only if it develops, according to a new guideline published online in Gastroenterology.
The American Gastroenterological Association conducted a rigorous review of the available evidence and compiled seven recommendations to guide clinicians and researchers in preventing HBV reactivation before patients initiate immunosuppressive therapy and in treating reactivated HBV if it arises during immunosuppressive therapy. “Despite the large number of published studies, in most cases our recommendations are weak because either (1) the quality of the available data and/or the baseline risk of HBV reactivation is low or uncertain, and/or (2) the balance of risks and benefits for a particular strategy does not overwhelmingly support its use,” said Dr. K. Rajender Reddy, lead writer of the guideline and professor of gastroenterology and hepatology at the University of Pennsylvania, Philadelphia, and his associates.
In contrast, the data supporting the recommendation to provide prophylaxis for high-risk patients are moderately robust, so that recommendation is strong, they noted.
Patients’ level of risk is based on their HBV serologic status and the type of immunosuppression they require. For example, patients are considered at high risk for HBV reactivation if they are hepatitis B surface antigen (HBsAg) positive/anti–hepatitis B core (HBc) positive or are HBsAg negative/anti-HBc positive and are to be treated with B-cell–depleting agents such as rituximab or ofatumumab. Also at high risk are HBsAg-positive/anti-HBc–positive patients to be treated with anthracycline derivatives such as doxorubicin or epirubicin, and HBsAg-positive/anti-HBc–positive patients to be treated with moderate- or high-dose corticosteroids for 4 weeks or longer.
In these high-risk patients, antiviral prophylaxis is definitely warranted, and it should extend for at least 6 months after the immunosuppressive therapy is completed, according to the guideline. In contrast, antiviral prophylaxis is “suggested” for moderate-risk patients, but those who place a higher value on avoiding antivirals and a lower value on avoiding HBV reactivation “may reasonably select no prophylaxis over antiviral prophylaxis,” Dr. Reddy and his associates said.
In contrast, routine antiviral prophylaxis is not recommended for patients undergoing immunosuppressive therapy who are at low risk for HBV reactivation.
Other recommendations in the new guideline concern which antiviral agents are preferred in different situations. The AGA strongly recommends antivirals that have a high barrier to resistance, in preference to lamivudine, in most patients. But it acknowledges that the evidence comparing various antivirals is weak, and that the drugs vary considerably in price. “Patients who put a higher value on cost and a lower value on avoiding the potentially small risk of resistance development may reasonably select the least expensive antiviral hepatitis B medication over more expensive antiviral drugs with a higher barrier to resistance,” Dr. Reddy and his associates said (Gastroenterol. 2014 [doi:10.1053/j.gastro.2014.10.039]).
The evidence regarding patient monitoring for HBV reactivation instead of prophylaxis is so sparse that the AGA makes no recommendation for or against this strategy at present. Most studies of the issue are of poor quality, use different definitions of HBV reactivation, have inconsistent reporting of patient outcomes, and disagree about the best methods and frequency of HBV DNA monitoring. Moreover, frequent monitoring requires “considerable” personnel resources, and the methods used in clinical studies may not even be adaptable to real world practice, the investigators said.