FDA warns about the risk of hepatitis B reactivating in some patients treated with direct-acting antivirals for hepatitis C

FDA is warning about the risk of hepatitis B virus (HBV) becoming an active infection again in any patient who has a current or previous infection with HBV and is treated with certain direct-acting antiviral (DAA) medicines for hepatitis C virus. In a few cases, HBV reactivation in patients treated with DAA medicines resulted in serious liver problems or death.

As a result, we are requiring a Boxed Warning, our most prominent warning, about the risk of HBV reactivation to be added to the drug labels of these DAAs directing health care professionals to screen and monitor for HBV in all patients receiving DAA treatment. This warning will also be included in the patient information leaflet or Medication Guides for these medicines.

Direct-acting antiviral medicines are used to treat chronic hepatitis C virus (HCV) infection, an infection that can last a lifetime. These medicines reduce the amount of HCV in the body by preventing HCV from multiplying, and in most cases, they cure HCV. Without treatment, HCV can lead to serious liver problems including cirrhosis, liver cancer, and death (see List of Direct-Acting Antivirals).

Patients should tell your health care professional if you have a history of hepatitis B infection or other liver problems before being treated for hepatitis C. Do not stop taking your DAA medicine without first talking to your health care professional. Stopping treatment early could result in your virus becoming less responsive to certain hepatitis C medicines. Read the patient information leaflet or Medication Guide that comes with each new prescription because the information may have changed. Contact your health care professional immediately if you develop fatigue, weakness, loss of appetite, nausea and vomiting, yellow eyes or skin, or light-colored stools, as these may be signs of serious liver problems.

We identified 24 cases of HBV reactivation reported to FDA1 and from the published literature in HCV/HBV co-infected patients treated with DAAs during the 31 months from November 22, 2013 to July 18, 2016.2-7 This number includes only cases submitted to FDA, so there are likely additional cases about which we are unaware. Of the cases reported, two patients died and one required a liver transplant. HBV reactivation was not reported as an adverse event in the clinical trials submitted for the DAA approvals because patients with HBV co-infection were excluded from the trials. The trials excluded these patients in order to specifically evaluate the safety of DAAs, including their effects on the liver, in patients infected with only HCV and without the presence of another virus which affects the liver (see Data Summary).

We urge health care professionals and patients to report side effects involving DAAs and other medicines to the FDA MedWatch program, using the information in the “Contact FDA” box at the bottom of the page.

New Guidance: Test for HBV Before Starting DAAs for HCV
It is important that all patients beginning hepatitis C (HCV) treatment using direct acting antiviral (DAA) therapies should be assessed for hepatitis B (HBV), according to the AASLD/Infectious Diseases Society of America (IDSA) Guidance Panel. The AASLD/IDSA Recommendations for Testing, Managing and Treating Hepatitis C have been updated to include this new practice guidance.

In addition to testing, the Guidance Panel recommends:

• HBV vaccination for all susceptible individuals.
• Obtaining a test for HBV DNA prior to DAA therapy in patients who could be actively replicating.
• Starting patients who meet criteria for treatment of active HBV infection on therapy at the same time — or before — HCV DAA therapy is started.
• Monitoring patients with low or undetectable HBV DNA levels at regular intervals as recommended by the AASLD’s HBV treatment guidelines.

Visit HCVguidelines.org for more information about the newest recommendations and to view the full report and to read the entire FDA Safety Communication on hepatitis B reactivating in some patients treated with direct-acting antivirals for hepatitis C.

Steve Morin
Office of Health and Constituent Affairs
Food and Drug Administration

Kimberly Struble
Division of Antiviral Products
Food and Drug Administration

Richard Klein
Office of Health and Constituent Affairs
Food and Drug Administration

For more information about the Hepatitis Liaison Program visit the FDA Patient Network