K. Ishii et al., HIGH TITERS OF ANTIBODIES INHIBITING THE BINDING OF ENVELOPE TO HUMAN-CELLS CORRELATE WITH NATURAL RESOLUTION OF CHRONIC HEPATITIS-C, Hepatology, 28(4), 1998, pp. 1117-1120
Most cases of hepatitis C virus (HCV) infection result in chronic dise
ase; however, a very small fraction of patients naturally clear the vi
rus and resolve chronic hepatitis. In an attempt to correlate immune r
esponse with chronic disease resolution, we compared the antibody resp
onse in patients with different outcomes of the infection. Antibody re
sponses to HCV structural proteins were assessed in 34 patients origin
ally diagnosed with acute hepatitis. Five cases resolved acute infecti
on, 22 developed chronic hepatitis, and 7 naturally resolved chronic h
epatitis C, To estimate HCV neutralizing antibodies we used the neutra
lization of binding (NOB) assay, which evaluates inhibition of the env
elope-2 protein binding to human cells, Enzyme-linked immunosorbent as
say was used for the quantitative assessment of serum antibodies, The
presence of HCV RNA was ascertained by reverse transcription-polymeras
e chain reaction. In 6 of 7 patients naturally recovered from chronic
hepatitis C, the emergence and the persistence (for more than 3 months
) of high serum titers (>1/600) of NOB antibodies coincided with virus
clearance and clinical resolution of hepatitis, NOB antibody activity
was observed in only 2 of 5 patients recovered from acute hepatitis C
, Chronic patients who did not show any resolution during the course o
f the study developed low or no NOB antibodies. Because of the correla
tion between prolonged high NOB titers and natural resolution of chron
ic hepatitis C, vaccination or passive immunization aimed at high tite
rs of NOB antibodies may be valuable new therapeutic approaches for ch
ronic hepatitis C.