title: Hepatitis B Virus (HBV) Variants in Untreated and Tenofovir Treated Chronic Hepatitis B (CHB) Patients during Pregnancy and Post-Partum Follow-Up.
abstract: BACKGROUND
  Chronic hepatitis B (CHB) is a dynamic disease that may be affected by immune changes in pregnancy. Guidelines suggest consideration of nucleos/tide analogs (NA), i.e., tenofovir, (TDF) in highly viremic mothers to reduce vertical transmission risk. HBV variability affects CHB outcome, but little is known about HBV genetic changes in pregnancy due to immune or NA selection.
  
  
  OBJECTIVE
  To evaluate HBV diversity in NA treated or untreated pregnant vs. post-partum CHB carriers.
  
  
  METHODS
  In plasma collected from 21 mothers (7 matching pre/post-partum), HBV serological tests, genotype and viral load were assayed. The HBV pre-surface (S) /S overlapping polymerase (P) (N = 20), pre-core (C) /C (N = 11) and/or full genome PCR amplicons (N = 3) underwent clonal sequence analysis.
  
  
  RESULTS
  The median age was 31 y, 71% Asian, 68% genotype B or C, 33% HBV eAg+, 5 received TDF (median HBV DNA 8.5 log IU/ml). In untreated mothers, median antepartum vs. post-partum ALT was 21 vs. 24 U/L and HBV DNA was 2.7 vs. 2.4 log(10) IU/ml. ALT and/or HBV DNA flares occurred during pregnant and/or post-partum period in 47% (10/21). Clonal sequencing antepartum showed the presence of minor "a determinant" and/or vaccine escape mutants (VEM) but drug resistant variants were infrequent. Analysis of pregnant vs. post-partum samples showed different HBV variants and viral diversity.
  
  
  CONCLUSIONS
  Differences in immune and/or by NA selective pressures during pregnancy may affect HBV evolution during pregnancy. The presence of minor VEM warrant infant follow-up.
authors.affiliation: Liver Unit, Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Department of Microbiology, Immunology and Infectious Diseases, Cumming School of Medicine, 3280 Hospital Drive NW, University of Calgary, Calgary, AB, Canada.
authors.forename: Boris
authors.initials: B
authors.lastname: Virine
authors.affiliation: Bloodborne Pathogens and Hepatitis Laboratory of the National Microbiology Laboratory, Winnipeg, MB, Canada.
authors.forename: Carla
authors.initials: C
authors.lastname: Osiowy
authors.affiliation: Liver Unit, Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Department of Microbiology, Immunology and Infectious Diseases, Cumming School of Medicine, 3280 Hospital Drive NW, University of Calgary, Calgary, AB, Canada; Artifical Liver Centre, Beijing YouAn Hospital, Capital Medical University, Beijing, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Gao
authors.affiliation: Liver Unit, Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
authors.forename: Tong
authors.initials: T
authors.lastname: Wang
authors.affiliation: Maternal Disorders in Pregnancy, Section of Internal Medicine, Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
authors.forename: Eliana
authors.initials: E
authors.lastname: Castillo
authors.affiliation: Department of Pediatrics, Alberta Children's Hospital, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Martin
authors.affiliation: Liver Unit, Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
authors.forename: Samuel S
authors.initials: SS
authors.lastname: Lee
authors.affiliation: Alberta Health, Government of Alberta, Edmonton, AB, Canada.
authors.forename: Kimberley
authors.initials: K
authors.lastname: Simmonds
authors.affiliation: Department of Microbiology, Immunology and Infectious Diseases, Cumming School of Medicine, 3280 Hospital Drive NW, University of Calgary, Calgary, AB, Canada.
authors.forename: Guido
authors.initials: G
authors.lastname: van Marle
authors.affiliation: Liver Unit, Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Department of Microbiology, Immunology and Infectious Diseases, Cumming School of Medicine, 3280 Hospital Drive NW, University of Calgary, Calgary, AB, Canada.
authors.forename: Carla S
authors.initials: CS
authors.lastname: Coffin
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000032:analysis; D004279:DNA, Viral / Q000235:genetics*; D005260:Female; D016679:Genome, Viral; D006509:Hepatitis B / Q000175:diagnosis / Q000188:drug therapy* / Q000635:transmission; D006513:Hepatitis B e Antigens / Q000378:metabolism; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D049590:Postpartum Period / Q000235:genetics*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000175:diagnosis / Q000188:drug therapy* / Q000821:virology; D011256:Pregnancy Outcome; D000068698:Tenofovir / Q000627:therapeutic use*; D013997:Time Factors; D019562:Viral Load / Q000235:genetics; D014764:Viral Proteins / Q000378:metabolism; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D014764:Viral Proteins; D000068698:Tenofovir