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FDA issues boxed warning for HBV recurrence from DAA use
The FDA now requires a boxed warning — its most prominent warning — on certain direct-acting antiviral agents, saying that patients with hepatitis C virus infection might be at risk for recurrence of hepatitis B virus infection, potentially causing serious liver problems and death. Two dozen such instances in patients treated from Nov. 22, 2013 through July 18 have been identified, according to a safety announcement from the agency.
“This number includes only cases submitted to FDA, so there are likely additional cases about which FDA is unaware,” the safety announcement said.
Of the reported cases, two patients with HCV died and one required a liver transplant. Most HBV reactivations occurred within 4 to 8 weeks of starting DAA therapy, according to the FDA.
Clinicians should test all patients for existing or previous HBV infections before giving patients DAAs; they should also conduct blood tests to check for flare-ups and recurrences. Patients are encouraged to meet with their health care professional before ceasing DAA treatment; they should tell their clinician if they have a history of HBV or other liver problems, or if they develop light-colored stools, yellowing of the eyes or skin, vomiting, nausea, loss of appetite, weakness or fatigue, as these may indicate serious liver problems, the safety announcement said.
Both patients and health care professionals are also encouraged to notify the FDA’s MedWatch Safety Information and Adverse Event Reporting Program if adverse events occur.
The reactivation — the cause of which is unknown — was not reported in clinical trials because patients with HBV coinfection were excluded from such trials, according to the FDA.
The HCV Guidance Panel — which recently recommended HBV testing as part of a HCV guidelines update — told Infectious Disease News in a statement that this warning by the FDA now shows the threat and absolute importance of testing for HBV.
“In an update posted online Sept. 16, we raised concerns regarding the accumulating evidence for reactivation of hepatitis B in HCV–coinfected persons undergoing therapy with direct-acting antiviral agents for HCV. Now, the FDA warning represents a clear acknowledgment of this threat. ... These reports highlight the importance of screening HCV–infected persons for the presence of current or prior infection with [HBV] prior to embarking on a course of DAA therapy, and of taking appropriate steps to treat or closely monitor HBV when coinfection is identified.” – by Janel Miller
- Reference:
- FDA. FDA Drug Safety Communication: FDA warns about the risk of hepatitis B reactivating in some patients treated with direct-acting antivirals for hepatitis C. http://www.fda.gov/Drugs/DrugSafety/ucm522932.htm. Accessed October 4, 2016.
Perspective
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There have been several case reports of activation of hepatitis B infection, occasionally fulminant, in the setting of clearance of hepatitis C virus using direct-acting antiviral agents. As such, the American Association for the Study of Liver Diseases/Infectious Diseases Society of America guidelines now recommend assessment of HBV status prior to initiation of HCV DAA therapy. All patients who are not infected with HBV should receive vaccination against hepatitis A and B prior to therapy initiation. For those who are HBsAg- and HBeAg-positive, an HBV DNA level should be obtained prior to HCV treatment with DAA therapy, and those who meet treatment criteria for HBV should have such therapy initiated prior to starting HCV DAA therapy. Those persons infected with HBV not meeting criteria for treatment should be monitored at least every 4 weeks while on DAA therapy and just after.