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FDA issues boxed warning for HBV recurrence linked to certain DAAs

The FDA now requires a boxed warning — its most prominent warning — on certain direct-acting antiviral agents, saying patients with hepatitis C taking them might be at risk for hepatitis B recurring, potentially causing serious liver problems and death, according to a safety announcement. Two dozen such instances in patients treated from Nov. 22, 2013 through July 18, 2016 have been identified.  

“This number includes only cases submitted to FDA, so there are likely additional cases about which FDA is unaware,” according to the safety announcement.

Of the reported cases, two patients with HCV died and one required a liver transplant. Most HBV reactivations transpired 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 — whose cause is unknown — was not reported in clinical trials because patients with HBV co-infection 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 Healio.com/Hepatology in a statement this warning by the FDA now shows the threat and absolute importance of testing for HBV.

“In an update posted online Sept. 16, [2016], we raised concerns regarding the accumulating evidence for reactivation of hepatitis B in HCV co-infected 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 co-infection is identified.”   – by Janel Miller

Reference: FDA’s List of Direct-Acting Antivirals (DAAs). Published Oct. 4, 2016. Accessed Oct. 4, 2016

Editor’s Note: This story has been updated to include a quote from the HCV Guidance Panel.

The FDA now requires a boxed warning — its most prominent warning — on certain direct-acting antiviral agents, saying patients with hepatitis C taking them might be at risk for hepatitis B recurring, potentially causing serious liver problems and death, according to a safety announcement. Two dozen such instances in patients treated from Nov. 22, 2013 through July 18, 2016 have been identified.  

“This number includes only cases submitted to FDA, so there are likely additional cases about which FDA is unaware,” according to the safety announcement.

Of the reported cases, two patients with HCV died and one required a liver transplant. Most HBV reactivations transpired 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 — whose cause is unknown — was not reported in clinical trials because patients with HBV co-infection 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 Healio.com/Hepatology in a statement this warning by the FDA now shows the threat and absolute importance of testing for HBV.

“In an update posted online Sept. 16, [2016], we raised concerns regarding the accumulating evidence for reactivation of hepatitis B in HCV co-infected 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 co-infection is identified.”   – by Janel Miller

Reference: FDA’s List of Direct-Acting Antivirals (DAAs). Published Oct. 4, 2016. Accessed Oct. 4, 2016

Editor’s Note: This story has been updated to include a quote from the HCV Guidance Panel.

    Perspective
    Michael Saag

    Michael Saag

    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 AASLD-IDSA 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.

     

    • Michael Saag, MD
    • HCV Next Co-Editor in Chief Director, Center for AIDS Research, University of Alabama at Birmingham

    Disclosures: Saag reports no relevant financial disclosures.