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      Occult hepatitis C virus infection in patients in whom the etiology of persistently abnormal results of liver-function tests is unknown.

      The Journal of Infectious Diseases
      Adult, Aged, Alanine Transaminase, blood, Biopsy, Cohort Studies, Female, Genotype, Glutamyl Aminopeptidase, Hepacivirus, genetics, isolation & purification, pathogenicity, Hepatitis C, complications, diagnosis, Hepatitis C Antibodies, Humans, In Situ Hybridization, Leukocytes, Mononuclear, virology, Liver, enzymology, Liver Diseases, etiology, Liver Function Tests, Male, Middle Aged, RNA, Viral, analysis, Reverse Transcriptase Polymerase Chain Reaction, gamma-Glutamyltransferase

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          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. 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). 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. Patients with ALF-EU may have intrahepatic HCV RNA in the absence of anti-HCV antibodies and of serum HCV RNA.

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