title: Imaging of hepatitis C virus infection in liver grafts after liver transplantation.
abstract: OBJECTIVE
  The detection of native hepatitis C virus (HCV) antigens in liver tissue may be relevant to diagnostic purposes and to better understand the pathogenesis of HCV infection. The aim of our study was to characterize HCV antigens in liver grafts.
  
  
  METHODS
  We selected 32 liver transplant (LT) recipients with recurrent hepatitis C. HCV core and NS5A antigens were detected in formalin-fixed, paraffin-embedded (FFPE) liver biopsies obtained immediately after graft reperfusion (negative controls), during the acute phase of HCV infection (1-6 months) and during follow-up (7-74 months) after LT. Viral antigens were assessed by immunohistochemistry and confocal microscopy.
  
  
  RESULTS
  All reperfusion biopsies were negative for both antigens. Core protein was detected in 75% and 33% of acute phase and follow-up biopsies, respectively. HCV antigens were not detected in any of the 10 samples from patients who cleared HCV after antiviral treatment. Immunostaining was hepatocellular, with a granular cytoplasmic pattern and a wide spectrum of intensity. We found a significant association between viral load and the presence of HCV core-positive hepatocytes (p=0.004). NS5A colocalized strongly with core (66%) and adipophilin (36%), supporting the localization of core and NS5A around lipid droplets. A detailed three-dimensional analysis showed that NS5A surrounded the core and adipophilin-positive areas.
  
  
  CONCLUSIONS
  HCV antigens can be detected in FFPE liver biopsies by immunohistochemistry. The in vivo colocalization of core and NS5A proteins around the lipid droplets supports that the latter may play a role in virus particle production, similar to what reported in vitro.
authors.affiliation: Liver Unit, Hospital Clínic, IDIBAPS, CIBERehd, Barcelona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Mensa
authors.forename: Sofía
authors.initials: S
authors.lastname: Pérez-del-Pulgar
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Crespo
authors.forename: George
authors.initials: G
authors.lastname: Koutsoudakis
authors.forename: Carlos
authors.initials: C
authors.lastname: Fernández-Carrillo
authors.forename: Mairene
authors.initials: M
authors.lastname: Coto-Llerena
authors.forename: Rosa
authors.initials: R
authors.lastname: Miquel
authors.forename: Helena
authors.initials: H
authors.lastname: Allende
authors.forename: Lluís
authors.initials: L
authors.lastname: Castells
authors.forename: Miquel
authors.initials: M
authors.lastname: Navasa
authors.forename: Xavier
authors.initials: X
authors.lastname: Forns
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D005260:Female; D005500:Follow-Up Studies; D016174:Hepacivirus / Q000276:immunology / Q000302:isolation & purification; D006526:Hepatitis C / Q000175:diagnosis* / Q000209:etiology* / Q000821:virology; D018936:Hepatitis C Antigens / Q000378:metabolism*; D006801:Humans; D021621:Imaging, Three-Dimensional; D007150:Immunohistochemistry; D008099:Liver / Q000821:virology*; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D012008:Recurrence; D014758:Viral Core Proteins / Q000276:immunology / Q000378:metabolism; D017361:Viral Nonstructural Proteins / Q000378:metabolism; D012324:RNA-Dependent RNA Polymerase
chemical_list: D018936:Hepatitis C Antigens; D014758:Viral Core Proteins; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase
keywords: 3D; ALT; AST; Confocal microscopy; FFPE; HCV; HCV antigen detection; Hepatitis C virus; LT; Liver transplantation; ROI; SVR; VOOD; alanine aminotransferase; aspartate aminotransferase; formalin-fixed paraffin-embedded; hepatitis C virus; liver transplantation; region of interest; sustained virological response; three-dimensional; venous outflow obstruction disease