Full or partial seroreversion in patients infected by hepatitis C virus may occur in three circumstances: spontaneously, induced by alpha interferon therapy, in conjunction with HIV infection

Little is known about the natural history of the infection and the mechanis ms associated with the immunological responses to hepatitis C virus (HCV). in particular, due to the limited number of long-term sequential evaluation s of viremia and of anti-HCV immune response, the long-term fate of HCV ant ibodies after a self-limited infection or after a resolved infection induce d by alpha interferon is not fully known. A controversy exists regarding th e existence of cases of seroreversion to HCV. Cases of partial seroreversio n have been reported in hemodialyzed patients or in immunodepressed patient s such as graft recipients, but spontaneous or under-therapy clearance of v iremia associated to a total or a partial disappearance of specific antibod ies has not been precisely documented in immunocompetent HCV-infected indiv iduals. For this reason, we report three well-documented cases of partial o r full seroreversion observed in thalassemia major patients infected by HCV . This long-term follow-up study was made possible through serum samples se quentially collected over an eight-year period in a population of patients multitransfused by packed red cells. Detection of serum HCV antibodies was performed through a third generation Elisa (Elisa-3, Ortho HCV-Elisa test system, Ortho Diagnostic Systems, Rari tan, N,J,, USA), with validation of a positive Elisa-3 result (expressed in optical density (OD)/cut-off ratio) by a third generation recombinant immu noblotting assay (Riba-3, Ortho Diagnostic Systems). Serum HCV-RNA detectio n was performed through a branched-DNA (bDNA) signal amplification (bDNA) a ssay (Quantiplex HCV RNA 2.0, Chiron Corporation, Nucleic Acids Systems, Em eryville, CA), according to the manufacturer's instructions [1]. The HCV RN A quantity in the sample was expressed in HCV RNA-equivalents leg) per mt. The lower limit of sensitivity of this assay has been estimated to be 0.2 x 10(6) eq/mL. Our protocol stated that the sera giving negative bDNA result s would be assayed by an in-house nested reverse-transcription-coupled poly merase chain reaction (RT-PCR), using a protocol standardized [2] and valid ated by a multicentre quality control [3]. The serum levels of alanine amin otransferase (ALT) were determined by an automated method and expressed in IU/l. The upper limit of normal ALT level was 40 IU/L. The three seroreverters described here had a thalassemia major and had been transfused by packed red cells on a monthly basis since their childhood. T he results of the biological parameters of HCV infection determined in thes e three patients over their follow-up period are detailed in Table I.