EMA Releases New Guidelines for Direct-acting Antivirals in Patients with Hepatitis C

In a review released by the European Medicines Agency (EMA), the organization reports on new guidelines to screen hepatitis C patients for concurrent infection with hepatitis B before administering direct-acting antiviral (DAA) treatment.

Hepatitis C, whose causative agent is the hepatitis C virus, is treated by DAA therapy which blocks proteins essential for viral replication. If left untreated, hepatitis C can lead to life-threatening consequences such as liver cirrhosis and liver cancer. According to the review, treatment with DAA drugs leads to a rapid decrease in hepatitis C viral load. However, in many patients, coinfection with hepatitis C and B is common and is thought to hinder the effects of the hepatitis B virus. As a consequence, treating patients coinfected with hepatitis C and B with antiviral drugs against hepatitis C has been reported to lead to re-activation of the hepatitis B virus, which can have severe consequences on the liver.

The EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) conducted a review of current DAA drugs to determine if cases of hepatitis B re-activation exist in those treated with anti-hepatitis C drugs. The review examined six currently approved DAA drugs to treat hepatitis C infection. In addition, two more drugs in this same category have been approved in the European Union since the review was conducted.

The PRAC found approximately 30 cases of hepatitis B re-activation have been reported among thousands of patients treated with DAA drugs. Although the risk of hepatitis B re-activation seems to be relatively low, the PRAC made recommendations to healthcare professionals that all patients should be tested for hepatitis B infection before receiving DAA medication to treat hepatitis C. According to the EMA, patients with active hepatitis B and C infections should be monitored and treated according to present treatment strategies.

Furthermore, the PRAC made additional recommendations to add warnings when prescribing DAA drugs to treat hepatitis C infections, a decision approved by the Committee for Medicinal Products for Human Use (CHMP). The decision made by the CHMP will be passed along to the European commission and could be made into a requirement that will be effective across the European Union.

In addition to the PRAC’s review of DAA drugs in regards to hepatitis B re-activation, the committee also looked at data which suggested that those treated with these drugs who were also treated previously for liver cancer could be at risk for cancer relapse. However, more research is required to validate if such a risk of relapse is indeed possible when treating patients with DAAs. The PRAC has asked pharmaceutical companies that market DAA drugs to conduct prospective studies to determine the magnitude of the risk of cancer relapse in patients previously treated for liver cancer. Companies were also asked to evaluate the possibility that patients with liver cirrhosis could develop liver cancer de novo.

The Federal Drug Administration, which is the EMA’s counterpart in the United States, made similar recommendations in a safety communication published earlier this year.

Samar Mahmoud graduated from Drew University in 2011 with a BA in Biochemistry and Molecular Biology. After two years of working in industry as a Quality Control Technician for a blood bank, she went back to school and graduated from Montclair State University in 2016 with an MS in Pharmaceutical Biochemistry. She is currently pursuing her PhD in Molecular and Cellular Biology at the University of Massachusetts at Amherst.