title: Hepatitis B virus quasispecies evolution after liver transplantation in patients under long-term lamivudine prophylaxis with or without hepatitis B immune globulin.
abstract: OBJECTIVE
  To investigate an optimal long-term prophylactic strategy for prevention of hepatitis B virus (HBV) recurrence after liver transplantation, we conducted a randomized study of 29 transplant recipients receiving a short course of hepatitis B immune globulin (HBIg) + lamivudine (LAM), followed by randomization to long-term prophylaxis with LAM with or without HBIg.
  
  
  METHODS
  The efficacy and safety, and impact on survival and HBV recurrence of these 2 prophylactic regimens were compared over a mean period of 10 years. In patients with viral recurrence, the HBV quasispecies in the surface/polymerase region were studied by ultra-deep pyrosequencing (UDPS).
  
  
  RESULTS
  The 10-year survival rate was 76% and was not affected by the type of prophylaxis. Four patients had hepatitis B surface antigen (HBsAg) recurrence within the first 48 months after orthotopic liver transplantation (OLT). HBsAg-positive and -negative patients showed similar mean survival times, with no differences between the 2 regimens. Low HBV DNA levels were transiently detected in 32% of HBsAg-negative patients. UDPS showed major changes after OLT in the HBV quasispecies of patients with viral recurrence, which may be explained by a "bottleneck" effect of OLT together with prophylactic therapy.
  
  
  CONCLUSIONS
  Long-term survival after OLT in end-stage chronic hepatitis B patients was good with both prophylactic strategies. However, low, transient HBV DNA levels were detected even in the absence of HBsAg, showing the importance of continuing HBV prophylaxis.
authors: Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain; Liver Unit, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain.
authors: M
authors: M
authors: Buti
authors: D
authors: D
authors: Tabernero
authors: A
authors: A
authors: Mas
authors: M
authors: M
authors: Homs
authors: M
authors: M
authors: Prieto
authors: F
authors: F
authors: Rodríguez-Frías
authors: F
authors: F
authors: Casafont
authors: R
authors: R
authors: Casillas
authors: A
authors: A
authors: González
authors: M
authors: M
authors: Miras
authors: J I
authors: JI
authors: Herrero
authors: L
authors: L
authors: Castells
authors: R
authors: R
authors: Esteban
mesh_terms: D004279:DNA, Viral / Q000097:blood*; D058625:End Stage Liver Disease / Q000601:surgery* / Q000821:virology; D019143:Evolution, Molecular; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics* / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000276:immunology / Q000517:prevention & control* / Q000601:surgery; D006801:Humans; D007136:Immunoglobulins / Q000627:therapeutic use*; D019259:Lamivudine / Q000627:therapeutic use*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D055502:Secondary Prevention; D017422:Sequence Analysis, DNA; D016896:Treatment Outcome
chemical_list: D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D007136:Immunoglobulins; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; C045213:hepatitis B hyperimmune globulin
keywords: HBV DNA; HBV quasispecies; chronic hepatitis B; hepatitis B surface antigen (HBsAg); orthotopic liver transplantation; ultra-deep pyrosequencing (UDPS)