Delayed viral suppression during antiviral therapy is associated with increased hepatocellular carcinoma rates in HBeAg-positive high viral load chronic hepatitis B.

The treatment option in chronic hepatitis B (CHB) patients with persistent low-level viremia despite entecavir or tenofovir monotherapy is unclear. This study investigated the development of hepatocellular carcinoma (HCC) or cirrhosis in hepatitis B e antigen (HBeAg)-positive high viral load CHB patients, according to the time needed to achieve complete viral suppression. A total of 325 HBeAg-positive CHB patients with high viral load who were recently started on antiviral therapy with entecavir or tenofovir were included. The enrolled patients were divided into 2 groups with 4 separate criteria based on the time needed to achieve complete viral suppression: within 1, 2, 3 or 4years of therapy initiation. The outcomes were development of HCC and cirrhosis. The cumulative incidence of HCC was significantly higher in patients failing complete viral suppression within 1year (hazard ratio (HR), 4.54; 95% confidence interval (CI), 1.03-19.93; P=.045) or 2years (HR, 3.38; 95% CI, 1.24-9.23; P=.018), than patients who achieved complete viral suppression within 1 or 2years, respectively. Cumulative incidence of cirrhosis was also significantly higher in patients failing suppression within 1year (HR, 1.95; 95% CI, 1.04-3.66; P=.037) or 2years (HR, 2.44; 95% CI, 1.41-4.22; P=.001). When the time for achieving viral suppression exceeded 2years, the cumulative incidence of HCC or cirrhosis was not different regardless of viral suppression. Complete hepatitis B virus suppression within 2years of antiviral therapy initiation is associated with risk reduction in HCC or cirrhosis development.