Fluctuating antibody response in a cohort of hepatitis C patients

This project was designed to longitudinally study persons who had antibodies to hepatitis C virus (HCV) to characterise the serologic course of infection.

The subjects were 149 multitransfused patients (141 with thalassaemia major, 3 with thalassaemia intermedia, and 5 with sickle cell anaemia) who had been regularly followed up for 3 to 7 years. Sequential serum samples obtained semi-annually between January 1994 and January 2001 were tested, prospectively, by second or third generation HCV enzyme-linked immunosorbent assay (ELISA), followed by confirmatory recombinant immunoblot assay (RIBA-2 or RIBA-3).

Of the 149 patients, 90 did not seroconvert to HCV, whereas 59 had detectable antibodies. On the basis of RIBA results in these 59 patients, 24 (41%) had persistent high antibody levels to structural and non structural HCV antigens, 11 (19%) had persistent low antibody levels, 17 (29%) showed fluctuating antibody levels, and in 5 patients (8%) there was a total or a partial disappearance of specific antibodies (seroreversion), mainly anti-core antibodies. Two patients (3%) had antibody responses that did not fit into any of these four categories. In patients with fluctuating antibody levels, there were periods ranging from 6 months to 2 years when anti-HCV antibodies could not be detected.

This study shows that the antibody response to HCV in patients who receive frequent blood transfusions is very variable. Individuals who exhibit intermittent seropositivity are a challenge to diagnosis.