title: Long-term absence of porcine endogenous retrovirus infection in chronically immunosuppressed patients after treatment with the porcine cell-based Academic Medical Center bioartificial liver.
abstract: BACKGROUND
  Clinical use of porcine cell-based bioartificial liver (BAL) support in acute liver failure as bridging therapy for liver transplantation exposes the patient to the risk of transmission of porcine endogenous retroviruses (PERVs) to human. This risk may be enhanced when patients receive liver transplant and are subsequently immunosuppressed. As further follow-up of previously reported patients (Di Nicuolo et al. 2005), an assessment of PERV infection was made in the same patient population pharmacologically immunosuppressed for several years after BAL treatment and in healthcare workers (HCWs) involved in the clinical trial at that time.
  
  
  METHODS
  Plasma and peripheral blood mononuclear cells (PBMCs) from eight patients treated with the Academic Medical Center-BAL (AMC-BAL), who survived to transplant, and 13 HCWs, who were involved in the trial, were assessed to detect PERV infection. A novel quantitative real-time polymerase chain reaction assay has been used.
  
  
  RESULTS
  Eight patients who received a liver transplant after AMC-BAL treatment are still alive under long-term pharmacological immunosuppression. The current clinical follow-up ranges from 5.6 to 8.7 yr after BAL treatment. A new q-real-time PCR assay has been developed and validated to detect PERV infection. The limit of quantification of PERV DNA was ≥ 5 copies per 1 × 10(5) PBMCs. The linear dynamic range was from 5 × 10(0) to 5 × 10(6) copies. In both patients and HCWs, neither PERV DNA in PBMCs nor PERV RNA in plasma and PBMC samples have been found.
  
  
  CONCLUSIONS
  Up to 8.7 yr after exposure to treatment with porcine liver cell-based BAL, no PERV infection has been found in long-term immunosuppressed patients and in HCWs by a new highly sensitive and specific q-real-time PCR assay.
authors.affiliation: Laboratory of Virology, Cotugno Hospital, Naples, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Di Nicuolo
authors.forename: Alba
authors.initials: A
authors.lastname: D'Alessandro
authors.forename: Barbara
authors.initials: B
authors.lastname: Andria
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Scuderi
authors.forename: Michele
authors.initials: M
authors.lastname: Scognamiglio
authors.forename: Angela
authors.initials: A
authors.lastname: Tammaro
authors.forename: Antonio
authors.initials: A
authors.lastname: Mancini
authors.forename: Santolo
authors.initials: S
authors.lastname: Cozzolino
authors.forename: Ernesto
authors.initials: E
authors.lastname: Di Florio
authors.forename: Adele
authors.initials: A
authors.lastname: Bracco
authors.forename: Fulvio
authors.initials: F
authors.lastname: Calise
authors.forename: Robert A F M
authors.initials: RA
authors.lastname: Chamuleau
mesh_terms: D000818:Animals; D004279:DNA, Viral / Q000097:blood; D020077:Endogenous Retroviruses / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016031:Liver Transplantation / Q000009:adverse effects / Q000276:immunology; D019164:Liver, Artificial / Q000821:virology*; D012192:Retroviridae Infections / Q000209:etiology*; D013552:Swine; D014183:Transplantation, Heterologous / Q000009:adverse effects* / Q000276:immunology
chemical_list: D004279:DNA, Viral; D007166:Immunosuppressive Agents