Assessment of total hepatitis C virus (HCV) core protein in HCV-related mixed cryoglobulinemia

Sabino Russi, Domenico Sansonno, Maria Addolorata Mariggiò, Angela Vinella, Fabio Pavone, Gianfranco Lauletta, Silvia Sansonno, Franco Dammacco, Sabino Russi, Domenico Sansonno, Maria Addolorata Mariggiò, Angela Vinella, Fabio Pavone, Gianfranco Lauletta, Silvia Sansonno, Franco Dammacco

Abstract

Introduction: In hepatitis C virus (HCV)-related mixed cryoglobulinemia (MCG), the nonenveloped HCV core protein (HCV-Cp) is a constituent of the characteristic cold-precipitating immune complexes (ICs). A possible correlation between HCV-Cp, virologic, laboratory, and clinical parameters in both untreated MCG patients and those undergoing specific treatment was explored.

Methods: HCV-Cp was quantified by a fully automated immune assay. Correlations between HCV-Cp and HCV RNA, cryocrit, and virus genotype (gt) were investigated in 102 chronically HCV-infected MCG patients.

Results: HCV-Cp concentrations strongly correlated with HCV RNA levels in baseline samples. An average ratio of 1,425 IU and 12,850 IU HCV RNA per picogram HCV-Cp was estimated in HCV gt-1 and gt-2 patients, respectively. This equation allowed us to estimate that, on average, HCV-Cp was associated with the viral genome in only 3.4% of the former and in 35% of the latter group of patients. The direct relation between HCV-Cp and the cryocrit level suggests that the protein directly influences the amount of cryoprecipitate. Although the therapy with rituximab (RTX) as a single agent resulted in the enhancement of HCV-Cp levels, in patients treated with RTX in combination with a specific antiviral therapy (pegylated interferon-α plus ribavirin), the prompt and effective clearance of HCV-Cp was documented.

Conclusions: Our data provide evidence that HCV-Cp has a direct effect on the cold-precipitation process in a virus genotype-dependence in HCV-related MCG patients.

Figures

Figure 1
Figure 1
Time-related effect on the detection of nonenveloped HCV-Cp in the cryoprecipitate samples over a period of 10 years of storage.
Figure 2
Figure 2
Comparison of HCV-Cp levels in unfractionated sera, cryoprecipitates, and supernatants in 51 MCG patients infected with HCV gt-1 and 49 MCG patients infected with HCV gt- 2.
Figure 3
Figure 3
Correlation between HCV-Cp and HCV RNA concentrations in all unfractionated serum samples (A) and in those grouped according to viral genotype 1 (B) and genotype 2 (C). Data on the axes are log scaled.
Figure 4
Figure 4
Correlation between HCV-Cp levels and cryocrit values in all patients (A) and in those grouped according to viral genotype 1 (B) and genotype 2 (C).
Figure 5
Figure 5
Effect of four-dose rituximab treatment on HCV RNA, HCV-Cp, and cryocrit in 16 patients with HCV-related MCG who were unresponsive to a combination of pegylated interferon-α and ribavirin.
Figure 6
Figure 6
HCV-Cp concentrations under treatment schedules comprising rituximab followed by pegylated interferon-α and ribavirin (A) and the simultaneous administration of these drugs (B).

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