One of the approaches used to study the pathogenesis of hepatitis C vi
rus-associated disease is to follow its replicative pattern in infecte
d tissues and to establish anatomo-clinical correlations. As in other
viral infections, the techniques used to study hepatitis C virus repli
cation in tissues are the Northern gel analysis, the reverse transcrip
tion-polymerase chain reaction, the in situ hybridization and the in s
itu-polymerase chain reaction. The replicative bevel of hepatitis C vi
rus is, however low, and the results reported using the above techniqu
es are often discordant and difficult to reproduce, suggesting that bo
th sensitivity and specificity are major issues. Thus, a critical step
in the approach to the study of hepatitis C virus replication is the
design of appropriate specificity experiments. New technologies, such
as tissue microdissection coupled to the single-cell reverse transcrip
tion-polymerase chain reaction, may help to provide a definitive answe
r to the key questions concerning, hepatitis C virus tropism and inter
action with the host.