title: Tissue quantification of hepatitis C virus RNA with morphologic correlation in the diagnosis of recurrent hepatitis C virus in human liver transplants.
abstract: BACKGROUND
  Histologic findings and liver enzymes in liver transplants are often non-diagnostic of recurrent hepatitis C virus (HCV) disease. In addition, the relationship between HCV replication and the presence of recurrent HCV hepatitis after liver transplantation remains unclear. We studied liver transplant recipients to determine if quantitation of HCV RNA in liver tissue by reverse transcriptase-polymerase chain reaction (RT-PCR) correlates with histopathologic disease and/or liver enzymes.
  
  
  METHODS
  Twenty-six patients who received liver transplants for HCV infection were evaluated. Four sequential biopsies were analyzed for each patient. HCV RNA was extracted and quantified using the Amplicor HCV Monitor Test. Histologic examination and RNA quantitation were blinded. All available liver enzymes on the day of liver biopsy were analyzed.
  
  
  RESULTS
  HCV RNA quantity in liver tissue was significantly increased at the time of clinically-suspected recurrence (P < .0001). HCV RNA levels were highest in biopsies with lobular hepatitis and nonspecific inflammation, followed by biopsies with cytomegalovirus infection, chronic hepatitis, and acute cellular rejection. HCV RNA quantity had a significant correlation with increasing portal inflammation (P = .0002), decreasing amount of interface hepatitis (P = .0333), and presence of acidophilic bodies (P = .0316). Increasing HCV RNA levels significantly correlated with decreasing number of episodes of treated rejection. HCV RNA quantity did not correlate with other histologic features or liver enzymes.
  
  
  CONCLUSIONS
  HCV RNA levels are highest at the time of active hepatocellular destruction. Elevated HCV RNA indicates recurrence. HCV RNA quantitation may be a useful diagnostic test for determining recurrent disease and distinguishing it from other causes of inflammation, such as rejection.
authors.affiliation: Department of Pathology, Henry Ford Hospital, Detroit, Michigan 48202, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Aardema
authors.forename: R E
authors.initials: RE
authors.lastname: Nakhleh
authors.forename: L K
authors.initials: LK
authors.lastname: Terry
authors.forename: E M
authors.initials: EM
authors.lastname: Burd
authors.forename: C K
authors.initials: CK
authors.lastname: Ma
authors.forename: D K
authors.initials: DK
authors.lastname: Moonka
authors.forename: K A
authors.initials: KA
authors.lastname: Brown
authors.forename: M S
authors.initials: MS
authors.lastname: Abouljoud
mesh_terms: D000328:Adult; D005260:Female; D006084:Graft Rejection; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification*; D006526:Hepatitis C / Q000175:diagnosis* / Q000821:virology; D006801:Humans; D008099:Liver / Q000201:enzymology / Q000473:pathology; D016031:Liver Transplantation / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000302:isolation & purification*; D012008:Recurrence
chemical_list: D012367:RNA, Viral