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Testing (HCV); Those with No HCV RNA May Have Cleared Virus

Hepatitis Weekly via Individual Inc. :
People with confirmed hepatitis C virus (HCV) infection who have persistently normal liver tests and undetectable HCV RNA have probably spontaneously cleared HCV infection, according to a report from southern California.

Confirmed anti-HCV reactive blood donors with normal alanine aminotransferase (ALT) may or may not have detectable HCV RNA in serum. Earlier research has suggested that the presence of HCV RNA in the serum is often associated with some degree of hepatic necro-inflammatory activity. "Anti-HCV reactive patients with persistently normal liver tests, but without detectable HCV RNA in the serum, may have occult chronic hepatitis C infection, or have recovered from previous hepatitis C infection," researcher Tse-Ling Fong and colleagues wrote ("Clinical Significance of HCV RNA Status and its Correlation to Antibodies to Structural HCV Antigens in Anti-HCV Reactive Patients with Normal Liver Tests," Journal of Medical Virology, July 1996;49:253-258).

"We undertook this study to determine the clinical significance of anti-HCV antibodies in patients with persistently normal liver tests; some of whom had detectable HCV RNA in serum and some who did not." Extensive serological testing and HCV RNA determination by RT-PCR was performed in serum, peripheral blood mononuclear cells (PBMC), and liver tissue in thirteen anti-HCV reactive patients with persistently normal liver tests. Absolute concordance in the status of HCV RNA between serum, PBMCs and liver was noted.

Five patients were HCV RNA positive but only three had mild histological changes. Eight patients were HCV RNA negative in all three sites and had virtually normal liver histology.

Patterns of reactivity in RIBA 2.0 strip immunoblot assay did not differentiate viremic from nonviremic patients. ELISA testing using multiple individual HCV recombinant antigens from the structural and non- structural regions of HCV demonstrated mean antibody titers to the structural antigens, in particular HCV E2 antibodies, to be significantly lower in HCV RNA negative patients.

"The status of HCV RNA in the serum appears to infer the status of HCV RNA in the liver and PBMCs in patients with persistently normal liver tests," Fong et al. wrote.

The researchers suggest that patients with persistently normal liver tests and undetectable HCV RNA probably have cleared HCV infection. "We found in our patients with persistently normal liver tests, that serum HCV RNA correlated absolutely with liver and PBMC HCV RNA," they wrote. "Patients with no detectable HCV RNA presumably have had spontaneous resolution of their HCV infection. Also, the patients we studied, even those who were RNA positive, had only mild histological changes in the liver. Additionally, anti-E2 titer appears to be a useful marker of ongoing viral replication."

The corresponding author for this study is Tse-Ling Fong, USC Liver Unit, Building 500, Room 114, Ranch Los Amigos Medical Center, 7601 East Imperial Highway, Downey, California 90242.

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