title: Partial virological response to entecavir treatment in nucleos(t)ide-naïve patients with HBeAg-positive chronic hepatitis B is not caused by reduced sensitivity.
abstract: Some patients with chronic hepatitis B (CHB) receiving entecavir (ETV) exhibit partial virological response (PVR) to ETV and the mechanism is not clear. In this study, we aim to investigate the in vitro susceptibility of residual clinical strains isolated from the sera of nucleos(t)ide-naïve hepatitis B virus e antigen (HBeAg)-positive patients with CHB and PVR to ETV, and to evaluate the clinical and virological responses to prolonged ETV monotherapy in these patients. We followed 69 nucleos(t)ide-naïve HBeAg-positive CHB patients receiving ETV treatment, with 13 partial responders to ETV. And we found that no genotypic resistance mutants were detected among the 13 PVR patients. Phenotypic analysis revealed that the residual HBV strains had normal replication capacity, and were as susceptible to ETV as wild-type HBV. All PVR patients continued to receive ETV monotherapy, and serum HBV DNA of the majority became undetectable after prolonged treatment. However, none of these patients achieved HBeAg loss. In contrast, 25.6% and 23.2% of the patients with virological response achieved HBeAg loss (P < 0.001) and HBeAg seroconversion (P < 0.001) at week 144, respectively. Thus, we conclude suboptimal response to ETV might not be due to reduced HBV susceptibility to ETV, and prolonging ETV monotherapy in patients with PVR is recommended.
authors.affiliation: Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China; Department of Hepatitis Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
authors.forename: Xinyan
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Fahong
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Yaoyue
authors.initials: Y
authors.lastname: Kang
authors.affiliation: Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Yuxian
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China. Electronic address: richengmao@gmail.com.
authors.forename: Richeng
authors.initials: R
authors.lastname: Mao
authors.affiliation: Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China; Key Laboratory of Medical Molecular Virology of The Ministry of Education and Ministry of Health (MOH&MOE), Fudan University, Shanghai, China. Electronic address: jmzhang@fudan.edu.cn.
authors.forename: Jiming
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D024882:Drug Resistance, Viral / Q000187:drug effects*; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006513:Hepatitis B e Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000302:isolation & purification*; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D006513:Hepatitis B e Antigens; C413685:entecavir; D006147:Guanine
keywords: Chronic hepatitis B; Entecavir; Genotypic resistance; Partial virological response; Phenotypic analysis