title: Clinical Features of Chronic Hepatitis B in Treatment-naive Asian Patients With Positive HBeAg and Coexisting Precore and/or Basal Core Promoter Mutations.
abstract: BACKGROUND
  Precore or/and basal core promoter (PC/BCP) mutations are frequently detected in hepatitis B e antigen (HBeAg)-negative patients, but little is known about their clinical significance in HBeAg-positive patients.
  
  
  OBJECTIVE
  To characterize and report the clinical features of treatment-naive chronic hepatitis B patients who are HBeAg positive and harbor PC and/or BCP mutations.
  
  
  METHODS
  Consecutive treatment-naive patients with chronic hepatitis B between 2004 and 2014 were enrolled. Clinical characteristics were compared based on the stratification of HBeAg status and the presence of PC/BCP mutations. In addition, subset analysis in HBeAg-positive cohort was performed to compare clinical features of patients with and without PC/BCP mutations RESULTS:: Of the 267 patients enrolled from 3 centers, 177 were HBeAg positive and 90 HBeAg negative. When compared with HBeAg-negative patients, HBeAg-positive patients were significantly younger in mean age (37.93 vs. 44.40; P<0.001), had higher levels of median ALT (51 vs. 30.5 U/mL; P<0.001), higher levels of mean HBV DNA (7.50±1.48 vs. 5.10±1.44 log10 copies/mL; P<0.001), and lower frequency of detectable PC/BCP mutations (60.45% vs. 93.33%; P<0.001), but had significantly higher frequency of BCP when mutations were detected (37.85% vs. 22.22%; P=0.013). Among HBeAg-positive patients, when compared with patients with wild type, those with PC/BCP mutations were significantly older (30.63 vs. 42.71; P<0.001), had higher median ALT levels (29.5 vs. 73 U/mL; P<0.001), but there was no significant association with mean HBV DNA levels (7.96 vs. 7.20 log10 copies/mL; P=0.865) or HBV genotype (P=1.000). In the multivariate analysis, only age and ALT were independently associated with PC/BCP mutations in HBeAg-positive patients, but there was no association with HBV genotype or DNA.
  
  
  CONCLUSIONS
  PC/BCP mutants were frequent (up to 60%) in treatment-naive HBeAg-positive patients and were associated with distinct clinical characteristics when compared with patients with wild type or HBeAg negative. Future large studies are needed to substantiate the long-term clinical outcomes when PC/BCP mutations are detected in HBeAg-positive patients as it may impact the natural history or treatment response in such patients.
authors.affiliation: *Department of Medicine, Division of Gastroenterology, New York University Langone Medical Center, New York University School of Medicine, New York, NY †Division of Liver Diseases, The Fifth Hospital of Shijiazhuang, Hebei Medical University, Shijiazhuang §Department of Infectious Diseases, Peking University First Hospital, Beijing, China ‡Miami Transplant Institute, University of Miami, Miami, FL ∥St George's University School of Medicine, Grenada, West Indies.
authors.forename: Calvin Q
authors.initials: CQ
authors.lastname: Pan
authors.forename: Erhei
authors.initials: E
authors.lastname: Dai
authors.forename: Kalyan R
authors.initials: KR
authors.lastname: Bhamidimarri
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zeng
authors.forename: Paley
authors.initials: P
authors.lastname: Yin
mesh_terms: D000328:Adult; D044466:Asian People; D015415:Biomarkers / Q000097:blood*; D002681:China; D015331:Cohort Studies; D005260:Female; D006512:Hepatitis B Core Antigens / Q000235:genetics*; D006513:Hepatitis B e Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000235:genetics* / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000097:blood / Q000821:virology*; D006801:Humans; D008297:Male; D009154:Mutation
chemical_list: D015415:Biomarkers; D006512:Hepatitis B Core Antigens; D006513:Hepatitis B e Antigens