Switching to Tenofovir versus Continuing Entecavir in Chronic Hepatitis B Patients with Partial Virologic Response during Entecavir Therapy: STEEP Study

Abstract

Background Entecavir has been widely used for treatment-naive chronic hepatitis B (CHB) patients. However, about 20% of patients show partial virologic response (PVR) after 2 year of entecavir therapy [Yoon, et al, 2011]. If the HBV DNA continues to be detected, underlying liver disease may progress, and the risk of hepatocellular carcinoma can be increased. Therefore, switching to a more effective and potent antiviral therapy may be needed. In this study, we compared the efficacy of switching to tenofovir with continuing entecavir in CHB patients who showed PVR to entecavir.

Patients and Methods This is an investigator initiated open label randomized controlled trial conducted in Korea between April 2013 and December 2015. Primary end point was a virologic response (HBV DNA < 20 IU/mL) rate at year 1 (12 months). Secondary end points were degree of HBV DNA reduction, mean levels of HBV DNA, bio-chemical and serologic response rates, virologic breakthrough, antiviral resistance, and adverse events. We included CHB patients receiving entecavir 0.5 mg more than 12 months, but having datable HBV DNA over 60 IU/mL despite no resistance to entecavir.

Results A total of 45 patients were enrolled. Twenty two patients were randomized to tenofovir arm and 23 patients to entecavir arm. Baseline characteristics were not significantly different between the groups. After 12 months of treatment, virologic response rate was significantly higher in the tenofovir group compared with in the entecavir group by per protocol analysis (55% vs 20%, P = 0.022) as well as intention-to-treat analysis (50% vs 17.4%, P = 0.020). At month 12, the mean HBV DNA level was lower (1.54 vs. 2.01 log IU/mL, P = 0.011) and the degree of HBV DNA reduction was greater (-1.13 vs. -0.67 log IU/mL, P = 0.024) in the tenofovir group than in the entecavir group, respectively. Proportions of patients with normal ALT and HBeAg loss/seroconversion rates were not different between the groups. There was no virologic breakthrough in both groups, and no significant adverse events were observed. We also analyzed factors related to virologic response by multivariate logistic regression model. Baseline serum HBV DNA level (Odds ratio 0.152 [0.030-0.786], P = 0.025) and type of antiviral agent (Odds ratio 6.661 [1.421-31.233], P = 0.016) were significant factors.

Conclusion In CHB patients with PVR to entecavir, switching to tenofovir resulted in higher virologic response rate and better suppression of viral replication than continuing entecavir. Therefore, switching to tenofovir would be a better strategy in entecavir partial responders to achieve optimal response.