Occult hepatitis C virus infection in patients in whom the etiology of persistently abnormal results of liver-function tests is unknown.
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.
Castillo
Inmaculada
I
Fundación para el Estudio de las Hepatitis Virales, Clínica Puerta de Hierro, Madrid, Spain.
Pardo
Margarita
M
Bartolomé
Javier
J
Ortiz-Movilla
Nuria
N
Rodríguez-Iñigo
Elena
E
de Lucas
Susana
S
Salas
Clara
C
Jiménez-Heffernan
Jose A
JA
Pérez-Mota
Arturo
A
Graus
Javier
J
López-Alcorocho
Juan Manuel
JM
Carreño
Vicente
V
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
D018937:Hepatitis C Antibodies; D012367:RNA, Viral; D005723:gamma-Glutamyltransferase; D000410:Alanine Transaminase; D043384:Glutamyl Aminopeptidase