title: Reactivation from occult HBV carrier status is characterized by low genetic heterogeneity with the wild-type or G1896A variant prevalence.
abstract: OBJECTIVE
  Individuals negative for hepatitis B surface antigen (HBsAg) but positive for antibodies to hepatitis B core antigen (anti-HBc) are at risk of hepatitis B virus (HBV) reactivation under immunosuppressive conditions. We investigated clinical features and viral genetics in patients with reactivation from occult HBV infection triggered by chemotherapy or immunosuppressive therapy.
  
  
  METHODS
  Clinical courses of 14 individuals originally HBsAg-negative but anti-HBc-positive that experienced HBV reactivation were examined. Ultra-deep sequencing analysis of the entire HBV genome in serum was conducted. Prevalence of the G1896A variant in latently infected livers was determined among 44 healthy individuals that were HBsAg-negative but anti-HBc-positive.
  
  
  RESULTS
  In 14 cases, HBV reactivation occurred during (n=7) and after (n=7) termination of immunosuppressive therapy. Ultra-deep sequencing revealed that the genetic heterogeneity of reactivated HBV was significantly lower in patients with reactivation from occult HBV carrier status compared with that in patients from HBsAg carrier status. The reactivated viruses in each case were almost exclusively the wild-type G1896 or G1896A variant. The G1896A variant was detected in 42.9% (6/14) of cases, including two cases with fatal liver failure. The G1896A variant was observed in the liver tissue of 11.4% (5/44) of individuals with occult HBV infection.
  
  
  CONCLUSIONS
  Reactivation from occult HBV infection is characterized by low genetic heterogeneity, with the wild-type G1896 or G1896A variant prevalent.
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Inuzuka
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Ueda
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Morimura
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Fujii
authors.affiliation: Department of Gastroenterology and Hepatology, Hyogo Prefectural Amagasaki Hospital, Hyogo, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Umeda
authors.affiliation: Department of Gastroenterology and Hepatology, Kitano Hospital, Osaka, Japan.
authors.forename: Tadayuki
authors.initials: T
authors.lastname: Kou
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka Red Cross Hospital, Osaka, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Osaki
authors.affiliation: Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Uemoto
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Chiba
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. Electronic address: maru@kuhp.kyoto-u.ac.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Marusawa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002353:Carrier State / Q000821:virology*; D004358:Drug Therapy; D005260:Female; D018740:Genetic Heterogeneity; D014644:Genetic Variation / Q000235:genetics*; D006509:Hepatitis B / Q000453:epidemiology / Q000235:genetics; D006512:Hepatitis B Core Antigens / Q000097:blood; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics* / Q000502:physiology*; D006579:Heterozygote; D006801:Humans; D007166:Immunosuppressive Agents; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D012189:Retrospective Studies; D012307:Risk Factors; D014775:Virus Activation / Q000502:physiology*
chemical_list: D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D007166:Immunosuppressive Agents
keywords: G1896A pre-core variant; Genetic heterogeneity; Immunosuppressive therapy; Occult HBV infection; Ultra-deep sequencing