Detection of hepatitis C virus in paraffin-embedded liver biopsies of patients negative for viral RNA in serum

Citation
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
Citations number
28
Categorie Soggetti
Gastroenerology and Hepatology","da verificare
Journal title
HEPATOLOGY
ISSN journal
02709139 → ACNP
Volume
29
Issue
1
Year of publication
1999
Pages
223 - 229
Database
ISI
SICI code
0270-9139(199901)29:1<223:DOHCVI>2.0.ZU;2-M
Abstract
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.