For patients or death in a phase 3b, multicenter, open-label study.
“Although we observed increases in HBV DNA in most patients, these increases were [usually] not associated with ALT [alanine amino transferase] flares or clinical complications,” reported Chun-Jen Liu, MD, of National Taiwan University College of Medicine and Hospital, Taipei, and his associates. Although nearly two-thirds of patients developed HBV reactivation, less than 5% developed alanine aminotransferase rises at least twice the upper limit of normal, and only one patient had symptomatic HBV reactivation, which entecavir therapy resolved. This study was the first to prospectively evaluate the risk of HBV reactivation during HCV treatment, the researchers wrote in the March issue of Gastroenterology.
Because chronic hepatitis C virus infection tends to suppress HBV replication, peginterferon/ribavirin or direct-acting anti-HCV treatment can reactivate HBV infection, especially in patients who test positive for hepatitis B surface antigen (HBsAg). Left untreated, reactivated HBV can lead to fulminant hepatitis, liver failure, and death, as noted on recently mandated boxed warnings.
Accordingly, guidelines recommend testing patients for HBV infection before starting HCV treatment. The study enrolled 111 coinfected patients; about two-thirds were female, and 16% had compensated cirrhosis. All tested positive for HBsAg at screening, and all but one also tested positive at baseline. Mean baseline HBV DNA levels were 2.1 log10 IU/mL. Patients received 90 mg ledipasvir plus 400 mg sofosbuvir for 12 weeks, and levels of HCV RNA, HBV DNA, and HBsAg were tested at weeks 1, 2, 4, 8, 12, posttreatment week 4, and then every 12 weeks until posttreatment week 108.