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

Abstract

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 4 years 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 1 year (hazard ratio (HR), 4.54; 95% confidence interval (CI), 1.03-19.93; P = .045) or 2 years (HR, 3.38; 95% CI, 1.24-9.23; P = .018), than patients who achieved complete viral suppression within 1 or 2 years, respectively. Cumulative incidence of cirrhosis was also significantly higher in patients failing suppression within 1 year (HR, 1.95; 95% CI, 1.04-3.66; P = .037) or 2 years (HR, 2.44; 95% CI, 1.41-4.22; P = .001). When the time for achieving viral suppression exceeded 2 years, the cumulative incidence of HCC or cirrhosis was not different regardless of viral suppression. Complete hepatitis B virus suppression within 2 years of antiviral therapy initiation is associated with risk reduction in HCC or cirrhosis development.

Early Normalization of Alanine Aminotransferase during Antiviral Therapy Reduces Risk of Hepatocellular Carcinoma in HBV Patients

“…Most patients who used both drugs underwent a switch in their drug because they did not get a biochemical or viral response to the drug previously used. It was thought that a delayed biochemical or viral response would affect the development of HCC [ 31 ].…”

Entecavir and Low Genetic Barrier Antiviral Agents for Hepatocellular Carcinoma in Hepatitis B Viral Cirrhosis: Propensity Score Matching

“…21,22 A greater decrease of serum HBV DNA levels (<104 copies/mL) during patients' follow-up process indicate a lower incident HCC risk. 23,24 The authors believe that the virological breakthrough of HBV and consequent elevated alanine aminotransferase can be at least partially attributed to a higher risk of HCC during followup process. 6 Kurokawa et al reported that an average of 5 years' treatment with lamivudine reduced the incidence of HCC in HBV-related cirrhotic patients.…”

Is Combination Antiviral Therapy Mandatory for Maintenance Therapy in Fully Suppressed Multidrug-Resistant Hepatitis B Patients?

“…Nam et al recently reported that the rate of viral suppression was related to HCC or LC development [28]. Patients who failed to achieve CVS until 1 or 2 years showed higher incidences of HCC and LC compared with those who achieved CVS within 1 or 2 years [28].…”

“…Nam et al recently reported that the rate of viral suppression was related to HCC or LC development [28]. Patients who failed to achieve CVS until 1 or 2 years showed higher incidences of HCC and LC compared with those who achieved CVS within 1 or 2 years [28]. As the viral load and time to CVS are related to LC and HCC development, for a rapid viral load reduction, combination therapy is more favorable than TDF monotherapy [14, 29].…”