title: Occult hepatitis C virus infection in patients in whom the etiology of persistently abnormal results of liver-function tests is unknown.
abstract: BACKGROUND
  There are patients in whom the etiology of long-standing abnormal results of liver-function tests is unknown (ALF-EU) after exclusion of all known causes of liver diseases. We analyzed the presence of hepatitis C virus (HCV) RNA in liver-biopsy specimens from 100 patients who were negative for anti-HCV antibodies and for serum HCV RNA and who had ALF-EU.
  
  
  METHODS
  HCV RNA status was tested by reverse-transcription polymerase chain reaction (RT-PCR) and by in situ hybridization, in liver and peripheral-blood mononuclear cells (PBMCs).
  
  
  RESULTS
  HCV RNA was detected in liver-biopsy specimens from 57 of 100 patients negative for anti-HCV antibodies and for serum HCV RNA (i.e., who had occult HCV infection). HCV RNA of negative polarity was found in the liver of 48 (84.2%) of these 57 patients with occult HCV infection. Nucleotide-sequence analysis confirmed the specificity of detection of HCV RNA and that patients were infected with the HCV 1b genotype. Of these 57 patients with intrahepatic HCV RNA, 40 (70%) had viral RNA in their PBMCs. With regard to liver histology, patients with occult HCV infection were more likely to have necroinflammatory activity (P=.017) and fibrosis (P=.022) than were patients without intrahepatic HCV RNA.
  
  
  CONCLUSIONS
  Patients with ALF-EU may have intrahepatic HCV RNA in the absence of anti-HCV antibodies and of serum HCV RNA.
authors.affiliation: Fundación para el Estudio de las Hepatitis Virales, Clínica Puerta de Hierro, Madrid, Spain.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Castillo
authors.forename: Margarita
authors.initials: M
authors.lastname: Pardo
authors.forename: Javier
authors.initials: J
authors.lastname: Bartolomé
authors.forename: Nuria
authors.initials: N
authors.lastname: Ortiz-Movilla
authors.forename: Elena
authors.initials: E
authors.lastname: Rodríguez-Iñigo
authors.forename: Susana
authors.initials: S
authors.lastname: de Lucas
authors.forename: Clara
authors.initials: C
authors.lastname: Salas
authors.forename: Jose A
authors.initials: JA
authors.lastname: Jiménez-Heffernan
authors.forename: Arturo
authors.initials: A
authors.lastname: Pérez-Mota
authors.forename: Javier
authors.initials: J
authors.lastname: Graus
authors.forename: Juan Manuel
authors.initials: JM
authors.lastname: López-Alcorocho
authors.forename: Vicente
authors.initials: V
authors.lastname: Carreño
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D001706:Biopsy; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D043384:Glutamyl Aminopeptidase / Q000097:blood; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification* / Q000472:pathogenicity; D006526:Hepatitis C / Q000097:blood / Q000150:complications / Q000175:diagnosis*; D018937:Hepatitis C Antibodies / Q000097:blood; D006801:Humans; D017403:In Situ Hybridization; D007963:Leukocytes, Mononuclear / Q000821:virology; D008099:Liver / Q000201:enzymology* / Q000821:virology; D008107:Liver Diseases / Q000201:enzymology / Q000209:etiology*; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000032:analysis* / Q000097:blood; D020133:Reverse Transcriptase Polymerase Chain Reaction; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D018937:Hepatitis C Antibodies; D012367:RNA, Viral; D005723:gamma-Glutamyltransferase; D000410:Alanine Transaminase; D043384:Glutamyl Aminopeptidase