Virological response to entecavir reduces the risk of liver disease progression in nucleos(t)ide analogue-experienced HBV-infected patients with prior resistant mutants

Objectives: This study investigated the influence of virological response (VR) to entecavir on clinical liver disease progression in nucleos(t)ide analogue (NA)-naive and -experienced patients. Methods: We investigated 487 chronic hepatitis B patients (323 NA-naive, 164 NA-experienced) treated with entecavir monotherapy for at least 12 months. VR was defined as hepatitis B virus DNA level ≤ 300 copies/mL during entecavir therapy. Clinical events were defined as hepatic decompensation, hepatocellular carcinoma (HCC), death and liver transplantation. Results: Of the 487 patients, 49 developed clinical events during entecavir treatment. Of those, 36 developed HCC. For all patients, Cox regression analysis showed that age, baseline cirrhosis, alanine aminotransferase level ≤ 200 U/L, albumin level and no VR during entecavir treatment were independent predictors for clinical events and HCC development. However, the benefit of VR to entecavir was significant for clinical events and HCC only in NA-experienced patients, but not in NA-naive patients. For the further analysis of the different subgroups of NAexperienced patients, the benefit of VR to entecavir was significant for clinical events or HCC only in patients with prior lamivudine- or adefovir-resistant mutants, but not in NA-experienced patients who had never developed lamivudine- or adefovir-resistant mutants. VR at month 12 (but not early VR at month 6) remained a significant predictor associated with the development of clinical events and HCC in NA-experienced patients. Conclusions: VR to entecavir was associated with a reduced risk of clinical events and HCC in NA-experienced patients, particularly in those who had prior lamivudine- or adefovir-resistant mutant.