title: No evidence of in vitro and in vivo porcine endogenous retrovirus infection after plasmapheresis through the AMC-bioartificial liver.
abstract: BACKGROUND
  Currently a number of bioartificial livers (BAL) based on porcine liver cells have been developed as a treatment to bridge acute liver failure patients to orthotopic liver transplantation or liver regeneration. These xenotransplantation related treatments hold the risk of infection of treated patients by porcine endogenous retrovirus (PERV) released from the porcine cells, as in vitro infection experiments and transplantations in immunocompromised mice have shown that PERV is able to infect human cells. The Academic Medical Center (AMC)-BAL, unlike other BALs, is characterized by direct contact between porcine liver cells and human plasma, and might therefore be permissive for PERV transfer.
  
  
  METHODS
  Prior to a clinical phase I trial, human plasma perfused through the AMC-BAL was investigated for PERV DNA and RNA. Moreover productive infectivity was analyzed by exposing the plasma to HEK-293 cells that were subsequently tested for PERV DNA, PERV RNA and reverse transcriptase activity.
  
  
  RESULTS
  Although PERV DNA was detected in the perfused plasma, no productive infectivity was detected. Consequently fourteen patients were treated with the AMC-BAL and monitored for PERV transmission. Immediately after treatment the plasma of the patients was positive for PERV DNA, most probably due to porcine liver cell lysis. The PERV DNA was cleared within 2 weeks post-treatment and no PERV RNA was detected. No productive infectivity in human embryonic kidney (HEK)-293 cells exposed to plasma of treated patients was detectable.
  
  
  CONCLUSIONS
  To conclude, no release of infective PERV particles from the AMC-BAL was observed. Therefore we consider the AMC-BAL as safe, however careful surveillance of patients will be continued.
authors.affiliation: Laboratory of Virology, D. Cotugno Hospital, Naples, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Di Nicuolo
authors.forename: Maarten-Paul
authors.initials: MP
authors.lastname: van de Kerkhove
authors.forename: Ruurdtje
authors.initials: R
authors.lastname: Hoekstra
authors.forename: Marcel G H M
authors.initials: MG
authors.lastname: Beld
authors.forename: Pietro
authors.initials: P
authors.lastname: Amoroso
authors.forename: Sonia
authors.initials: S
authors.lastname: Battisti
authors.forename: Maria
authors.initials: M
authors.lastname: Starace
authors.forename: Ernesto
authors.initials: E
authors.lastname: di Florio
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Scuderi
authors.forename: Simona
authors.initials: S
authors.lastname: Scala
authors.forename: Adele
authors.initials: A
authors.lastname: Bracco
authors.forename: Antonio
authors.initials: A
authors.lastname: Mancini
authors.forename: Robert A F M
authors.initials: RA
authors.lastname: Chamuleau
authors.forename: Fulvio
authors.initials: F
authors.lastname: Calise
mesh_terms: D000328:Adult; D000818:Animals; D002460:Cell Line; D020077:Endogenous Retroviruses / Q000302:isolation & purification* / Q000502:physiology; D005500:Follow-Up Studies; D006801:Humans; D019164:Liver, Artificial / Q000821:virology*; D008875:Middle Aged; D010956:Plasmapheresis / Q000009:adverse effects*; D012192:Retroviridae Infections / Q000175:diagnosis* / Q000821:virology; D013552:Swine / Q000601:surgery* / Q000821:virology*