Detection of hepatitis C virus (HCV) RNA in the liver of healthy, anti-HCV antibody-positive, serum HCV RNA-negative patients with normal alanine aminotransferase levels.
BACKGROUND
It is unknown whether hepatitis C virus (HCV) is present in the liver of anti-HCV antibody-positive patients with persistently normal alanine aminotransferase (ALT) levels and undetectable serum HCV RNA levels.


METHODS
We determined the presence of genomic and antigenomic HCV RNA strands in liver biopsy specimens and peripheral blood mononuclear cell (PBMC) samples obtained from 12 anti-HCV antibody-positive patients who had normal ALT levels and who had been serum HCV RNA negative for at least 12 months, according to the results of quantitative, strand-specific, real-time reverse-transcription-polymerase chain reaction and, also, in situ hybridization of liver cells. Intrahepatic HCV RNA was cloned and sequenced.


RESULTS
All patients remained anti-HCV antibody positive and serum HCV RNA negative, and all had normal ALT values during follow-up (mean duration +/- SD, 29.2 +/- 19.8 months). Genomic HCV RNA was detected in liver biopsy specimens obtained from 10 (83%) of 12 patients, and the antigenomic strand was detected in 10 (100%) of 10 liver biopsy specimens in which genomic HCV RNA was detected. Results were confirmed by in situ hybridization. Intrahepatic HCV was of genotype 1b, and HCV sequencing demonstrated no cross-contamination among samples. Genomic HCV RNA was found in 6 (50%) of 12 PBMC samples, and antigenomic HCV RNA was also detected in 5 (83%) of these 6 PBMC samples.


CONCLUSIONS
HCV may persist and replicate in the liver and PBMCs of healthy, anti-HCV antibody-positive, serum HCV RNA-negative patients who have persistently normal ALT levels. These patients should be followed up, because they have an ongoing viral infection.
Carreño
Vicente
V
Fundación para el Estudio de las Hepatitis Virales, Madrid, Spain. fehvhpa@fehv.org
Pardo
Margarita
M
López-Alcorocho
Juan Manuel
JM
Rodríguez-Iñigo
Elena
E
Bartolomé
Javier
J
Castillo
Inmaculada
I
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood*; D001706:Biopsy; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D018937:Hepatitis C Antibodies / Q000097:blood*; D006801:Humans; D017403:In Situ Hybridization; D007963:Leukocytes, Mononuclear / Q000502:physiology; D008099:Liver / Q000473:pathology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D010802:Phylogeny; D012367:RNA, Viral / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors
D017931:DNA Primers; D018937:Hepatitis C Antibodies; D012367:RNA, Viral; D000410:Alanine Transaminase