title: Prolonged entecavir therapy is not effective for HBeAg seroconversion in treatment-naive chronic hepatitis B patients with a partial virological response.
abstract: The aims of this study were to investigate the efficacy of prolonged entecavir (ETV) therapy in treatment-naive chronic hepatitis B (CHB) patients and to determine whether continuous ETV therapy is feasible to achieve HBeAg seroconversion, particularly in patients with partial virological response (PVR). A total of 142 treatment-naive patients with CHB were enrolled. The mean duration of treatment was 65 (range, 26 to 90) months, and 86 patients (60.6%) were HBeAg positive. PVR was defined as detectable hepatitis B virus (HBV) DNA (>116 copies/ml) at year 1. The cumulative incidence of virological response (VR) increased from 54.9% at year 1 to 98.2% at year 7. HBeAg positivity (odds ratio [OR], 4.146; P = 0.001) and initial alanine aminotransferase (ALT) (OR, 0.997; P = 0.004) were independent risk factors for PVR. Among the 64 patients with PVR, 47 patients (73.4%) achieved VR within 4 years after prolonged ETV therapy without treatment adaptation. Three patients (2.1%) experienced virological breakthrough and HBV variants with genotypic resistance. The cumulative rate of HBeAg seroconversion was significantly higher in the patients with VR than in the patients with PVR (P = 0.018). None of the PVR patients with HBV DNA at ≥5,000 copies/ml at year 1 ever experienced HBeAg seroconversion. Multivariate analysis identified VR at year 1 as the only determinant of HBeAg seroconversion (hazard ratio [HR], 3.009; P = 0.010). In conclusion, although there were patients with PVR, prolonged ETV therapy showed excellent VR, with only 2.1% emergence of viral resistance during a 7-year follow-up. However, to achieve HBeAg seroconversion, drug modification is needed for HBeAg-positive patients with PVR (especially those with HBV DNA at ≥5,000 copies/ml at year 1).
authors.affiliation: Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hyun Woong
authors.identifier: http://orcid.org/0000-0002-6958-3035
authors.initials: HW
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Republic of Korea.
authors.forename: Jae-Cheol
authors.initials: JC
authors.lastname: Kwon
authors.affiliation: Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Republic of Korea.
authors.forename: In Soo
authors.initials: IS
authors.lastname: Oh
authors.affiliation: Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hye Young
authors.initials: HY
authors.lastname: Chang
authors.affiliation: Department of Laboratory Medicine, Chung-Ang University College of Medicine, Seoul, Republic of Korea.
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Cha
authors.affiliation: LSK Global Pharma Services Co., Ltd., Seoul, Republic of Korea.
authors.forename: Ik-Seong
authors.initials: IS
authors.lastname: Choi
authors.affiliation: Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Republic of Korea lhwdoc@cau.ac.kr.
authors.forename: Hyung Joon
authors.initials: HJ
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006513:Hepatitis B e Antigens / Q000378:metabolism*; D006515:Hepatitis B virus / Q000187:drug effects / Q000472:pathogenicity; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000069078:Seroconversion / Q000187:drug effects; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D006513:Hepatitis B e Antigens; C413685:entecavir; D006147:Guanine