Reactivation of Hepatitis B Virus After Treatment with Direct Acting Antivirals for Hepatitis C: What You Need to Know

Persons with hepatitis C virus (HCV) who are co-infected with hepatitis B virus (HBV) may be at risk for reactivation of HBV infection during or following HCV treatment. This includes those who are hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (HBsAb or anti-HBs) negative, but hepatitis B core antibody (HBcAb or anti-HBc) positive. A considerable number of people may be co-infected with these viruses. The U.S. Centers for Disease Control and Prevention (CDC) estimates that 2.7-3.9 million people in the United States are living with hepatitis C (with other estimates as high as 5 million), and up to 2.2 million people are living with chronic hepatitis B. HBV and HCV share similar modes of transmission, and co-infection with the two viruses does occur. Transmission of HBV and HCV can take place through intravenous drug use, sexual contact, unclean needles used for tattooing or other nonmedical purposes, or inadequate infection control such as unsterilized medical equipment and unscreened blood products (rare in the United States).

Reactivation of hepatitis B can occur in someone who has a current HBV infection, or who has recovered from a past HBV infection – and can lead to rapid liver failure and death. In early October 2016, the U.S. Food and Drug Administration (FDA) released a black box warning about the risk of hepatitis B virus (HBV) reactivation upon treatment with certain direct-acting antiviral agents (DAAs) for hepatitis C virus (HCV). This reactivation may occur in any patient with a current or previous HBV infection. A black box warning is designed to call attention to a serious or life-threatening risk associated with a prescription. According to the FDA, 24 cases of hepatitis B reactivation were identified in HBV/HCV co-infected patients over 20 months from 2013-2016. Of these, two patients died and one required a liver transplant. The FDA notes that it is highly likely that additional cases of hepatitis B reactivation occurred with DAA treatment for hepatitis C, which went unreported.

Chronic hepatitis B is generally a silent incurable infection, and in the U.S., only one-third of the people infected with HBV are diagnosed. Thus, it is critical that providers screen their patients for HBV infection using the three-part hepatitis B blood panel, prior to starting DAA treatment. Providers must also monitor patients on DAAs for signs of HBV reactivation with liver enzyme and liver function testing.

HBV reactivation can be managed with appropriate use of antiviral treatment for HBV during HCV treatment with DAAs. The clinical experts at Project ECHO, a program developed at the University of New Mexico Health Sciences Center to build primary care capacity to treat complex diseases through videoconferencing and case-based learning, have developed a simple algorithm to help providers monitor their patients for HBV reactivation during HCV treatment. The experience at Project ECHO thus far indicates that patients who are co-infected with HBV and HCV can be safely and successfully treated for HCV, with appropriate screening for HBV and monitoring for possible HBV reactivation.

Patients also play an important role. Those starting DAA treatment for hepatitis C should make sure their provider has tested them for hepatitis B. Patients should also be aware of possible symptoms of HBV reactivation, and report them immediately. These symptoms can include changes in eye and skin color (yellow), pain in the liver (right side of the belly below the ribs), changes in stool color (lighter), and fatigue.

Reactivation of HBV infection is a concern during treatment for HCV, in people with a current or past HBV infection. However, with proper screening and monitoring, patients with HBV/HCV co-infection can be successfully treated.

The views expressed on this post are those of the authors and do not necessarily reflect the views of ICHS.