Comparison of genetic heterogeneity of hepatitis C viral RNA in liver tissue and serum.
OBJECTIVE
Hepatitis C virus (HCV) is known to be heterogeneous and to circulate as a group of closely related quasispecies in individual patients, although hepatic viral genetic characteristics have not been well documented.


METHODS
Matched serum and liver samples were tested by reverse transcription polymerase chain reaction amplification and single stranded conformation polymorphism analysis of the hypervariable portion of the E2/NS1 region of the HCV genome. The number of quasispecies was compared with the amount of HCV RNA, HCV genotyping, and infection with the hepatitis G virus.


RESULTS
Sixteen of 40 patients had HCV RNA detectable in serum and liver. The HCV genotype was identical in serum and liver of all but one case. HCV RNA levels were approximately 10-fold higher in liver than serum. The number of HCV quasispecies in serum ranged between two and six (median 3.0) and in the liver between 2 and 19 (median 3.5, mean liver/serum ratio 1 to 6.3, median 1.8). The number of quasispecies in liver was equal to or greater than that in serum in all cases. HGV infection was found in 14 cases and did not influence serum or hepatic levels of HCV RNA.


CONCLUSIONS
The number of hepatic HCV quasispecies usually exceeds that in serum, independent of the amount of HCV RNA and HCV genotype. This finding is compatible with clearance of some quasispecies from serum, but not liver, by putative neutralizing antibodies.
Fan
X
X
Department of Internal Medicine, Saint Louis School of Medicine, Missouri 63104, USA.
Solomon
H
H
Poulos
J E
JE
Neuschwander-Tetri
B A
BA
Di Bisceglie
A M
AM
D000328:Adult; D000368:Aged; D005260:Female; D018067:Flaviviridae / Q000235:genetics; D014644:Genetic Variation; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000235:genetics*; D006526:Hepatitis C / Q000821:virology*; D006525:Hepatitis, Viral, Human / Q000150:complications / Q000821:virology; D006801:Humans; D008099:Liver / Q000821:virology*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012367:RNA, Viral / Q000032:analysis / Q000235:genetics; D012194:RNA-Directed DNA Polymerase; D014766:Viremia / Q000821:virology*
D012367:RNA, Viral; D012194:RNA-Directed DNA Polymerase