New Study Evaluates Risk of HBV Reactivation in Veterans Receiving DAA Therapy

Hepatitis C (HCV) and hepatitis B (HBV) viral infections cause a considerable disease burden worldwide. Globally, it is estimated that 400 million individuals have HBV, and approximately 170 million have HCV.

Because HCV and HBV have shared modes of transmission, such as through sharing needles during intravenous drug use, it is common to find patients coinfected with both viruses. Patients coinfected with HCV and HBV have worsened disease prognosis, often leading to liver cirrhosis; they also have an increased chance of developing liver cancer.

Interestingly, HCV has been shown to suppress HBV, raising concerns that HBV reactivation may occur in patients treated with HCV antiviral therapy. Indeed, there have been isolated cases reported, leading the US Food and Drug Administration (FDA) to issue a warning about HBV reactivation in patients treated with direct-acting antiviral (DAA) therapy.

In a study published in the Journal of Hepatology, principal investigator Lisa Backus, MD, PhD, and her colleagues seek to evaluate the risk of HBV reactivation in patients treated with DAA therapy.

The study evaluated veterans who were receiving DAA therapy from the Department of Veteran’s Affairs (VA). The authors used the VA Corporate Data Warehouse, a national dataset that includes records of veterans who have received VA care. The authors evaluated baseline HBV infection status by identifying HBV laboratory data that was available before or on the first day that DAA therapy was initiated; this includes measuring HBV surface antigens, HBV core antibody, or HBV surface antibody. Using these testing results, the authors classified two groups of patients as being high-risk for reactivation of HBV, those who were positive for HBV surface antigens before starting DAA therapy, and those who were positive for HBV core antibody. In addition, the authors examined patient outcomes and classified them according to those who achieved sustained virologic response (SVR) and those who did not achieve SVR, meaning that their HCV RNA was above the limit of detection at the end of treatment.

In total, the authors included 62,920 veterans in the study. Before beginning DAA treatment, approximately 86% of patients were tested for HBV surface antigens and 0.70% of those tested were positive. In addition, around 85% of patients were tested for HBV core antibody and 42.2% of those tested were positive. Furthermore, around 64% of patients were tested for HBV surface antibody and, of those patients, 45.7% were positive.

Overall, out of the 62, 290 veterans treated with DAAs, 9 patients were found to have HBV reactivation, as evidenced by an increase in HBV DNA during the course of DAA treatment. Eight of the 9 patients were documented to be positive for HBV surface antigens, and the remaining patient was positive for HBV core antibodies. Seventeen other patients showed slight increases in HBV DNA levels. However, the authors did not classify these cases as instances of HBV reactivation.

The authors demonstrated that HBV reactivation can occur, although the risk of it resulting in severe hepatitis was determined to be a rare event. This work highlights the need for effective HBV screening prior to beginning DAA therapy to identify patients at risk of HBV reactivation.

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.