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 circ ulate as a group of closely related quasispecies in individual patients, al though hepatic viral genetic characteristics have not been well documented. METHODS: Matched serum and liver samples were tested by reverse transcripti on 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 numbe r 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 t han 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 live r, by putative neutralizing antibodies. (C) 1999 by Am. Cell. of Gastroente rology.