Sustained virological response is associated with clearance of hepatitis C virus RNA and a decrease in hepatitis C virus antibody

Abstract

Background/aim: Viral eradication in chronic hepatitis C patients with sustained virological response (SVR) after interferon (IFN) therapy remains controversial.

Methods: During a long-term follow-up study, 157 patients with SVR to IFN-alpha-2b-based therapy were investigated with a transcription-mediated amplification (TMA) assay in serum. The hepatitis C virus (HCV) antibody was assessed by measuring the optical density (OD) (Axsym HCV v3.0) and the semiquantitative titres (RIBA HCV v3.0) of the HCV antibodies directed against the core, NS3, NS4 and NS5 proteins. A control group included 23 untreated patients with persistently normal serum alanine aminotransferase and detectable serum HCV-RNA.

Results: The median duration of follow-up was 4.0 (0-10) years. Serum HCV-RNA remained undetectable in all patients. The mean HCV antibody OD were 93 +/- 19 and 45 +/- 21 before therapy and in the last available serum sample respectively (P=0.001). There was a marked decrease in the HCV antibodies directed against the NS3, NS4 and NS5 proteins (P=0.001), while the core protein titre remained strongly positive. The 23 control patients were followed for a median of 5 (2-14) years. The mean HCV antibody OD were 65 +/- 14 and 64 +/- 19 in the first and the last measurements, respectively (NS), and HCV antibody titres for structural and non-structural proteins remained unchanged.

Conclusion: This long-term study evaluating 157 patients demonstrated that SVR assessed by TMA is durable, and HCV antibodies were markedly decreased (mainly those directed against the non-structural proteins), emphasizing an absence of ongoing infection. These results strongly suggest that HCV infection cured in patients who achieve an SVR.

Fig. 1

Dynamics changes in hepatitis C virus (HCV) antibody in 157 patients during a long-term follow-up after sustained virological response (SVR) to interferon-based therapy. ^aExpressed as ratio (%) optical density (OD) generated by the last available serum sample/OD generated at baseline. ^bBaseline. ^cEnd of treatment.

Fig. 2

Changes in semiquantitative hepatitis C virus (HCV) antibody titres [recombinant immunoblot assay (RIBA)] measured before therapy and at the end of a long-term follow-up in 157 patients successfully treated with interferon-based therapy. ^aBaseline. ^bYears. (A) HCV antibody directed against NS4 protein (c100). (B) HCV antibody directed against core protein (c22). (C) HCV antibody directed against NS3 protein (c33). (D) HCV antibody directed against NS5 protein (NS5). During the follow-up, 3, 10 and 26% of NS3, NS4 and NS5 bands became undetectable respectively.

Fig. 3

Changes in semi-quantitative hepatitis C virus (HCV) antibody titres [recombinant immunoblot assay (RIBA)] measured in 23 untreated patients with persistently normal alanine aminotransferase (ALT) and detectable HCV-RNA followed for a long-term period. ^aBaseline. ^bYears. (A) HCV antibody directed against NS4 protein (c100). (B) HCV antibody directed against core protein (c22). (C) HCV antibody directed against NS3 protein (c33). (D) HCV antibody directed against NS5 protein (NS5).

Fig. 4

Long-term follow-up of the dynamics of alanine aminotransferase (HCV) antibody optical density (OD) and recombinant immunoblot assay (RIBA) profiles in one patient with sustained virological response (SVR) and one patient with persistently normal alanine aminotransferase (ALT) and detectable HCV-RNA. ^aBaseline. ^bEnd of treatment. (A) Patients with SVR (resolved infection). (B) Patient with persistently normal ALT and detectable serum HCV-RNA (ongoing infection).