V. Dries et al., Detection of hepatitis C virus in paraffin-embedded liver biopsies of patients negative for viral RNA in serum, HEPATOLOGY, 29(1), 1999, pp. 223-229
The diagnosis of hepatitis C is based on serological testing for antibodies
against various epitopes of the hepatitis C virus (HCV) and detection of H
CV RNA in serum, because anti-HCV antibodies alone cannot discriminate pati
ents who are infectious from those who have resolved the infection. If HCV
RNA is not detected, which is the case in at least 20% of enzyme immunoassa
y (EIA)-positive patients, diagnosis remains unclear in a state of disease
possibly well suited for therapeutic intervention. Therefore, we investigat
ed if detection of HCV antigens or HCV RNA in routinely processed, formalin
-fixed and paraffin-embedded (ffpe) liver biopsy specimens of patients posi
tive for anti-HCV, but negative for HCV RNA in serum, could confirm diagnos
is in this serological constellation. We detected HCV RNA by reverse-transc
ription polymerase chain reaction (RT-PCR) in 27 (61%) of 44 ffpe liver bio
psies from EIA-positive, but HCV-RNA-seronegative, patients. Testing of 18
of these biopsies by a panel of polyclonal antibodies against structural an
d nonstructural HCV proteins revealed positive immunostaining in 6 cases (3
3%), which were also positive by RT-PCR, Most biopsies showed necroinflamma
tion compatible with chronic hepatitis C, and the detection of tissue HCV R
NA correlated significantly with a higher grade of inflammatory activity. D
etectability of HCV RNA did not correlate with HCV subtype, In conclusion,
the search for HCV RNA by RT-PCR within the liver biopsy specimen can estab
lish rapid and unequivocal diagnosis of hepatitis C in at least 60% of anti
-HCV antibody-positive patients who are seronegative for HCV RNA, and thus
may help to avoid repeated testing and delayed therapy, Tissue RT-PCR may a
lso be more efficient than serological testing for surveillance of interfer
on therapy response, because ongoing chronic active hepatitis C is clearly
demonstrated in the absence of detectable serum HCV RNA.