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

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

Cytokines and HCV-Related Disorders

Cytokines are intercellular mediators involved in viral control and liver damage being induced by infection with hepatitis C virus (HCV). The complex cytokine network operating during initial infection allows a coordinated, effective development of both innate and adaptive immune responses. However, HCV interferes with cytokines at various levels and escapes immune response by inducing a T-helper (Th)2/T cytotoxic 2 cytokine profile. Inability to control infection leads to the recruitment of inflammatory infiltrates into the liver parenchyma by interferon (IFN)-gamma-inducible CXC chemokine ligand (CXCL)-9, -10, and -11 chemokines, which results in sustained liver damage and eventually in liver cirrhosis. The most important systemic HCV-related extrahepatic diseases—mixed cryoglobulinemia, lymphoproliferative disorders, thyroid autoimmune disorders, and type 2 diabetes—are associated with a complex dysregulation of the cytokine/chemokine network, involving proinflammatory and Th1 chemokines. The therapeutical administration of cytokines such as IFN-alpha may result in viral clearance during persistent infection and reverts this process

Hepatitis C virus-associated B-cell non-Hodgkin's lymphoma: clinical and therapeutic challenges

Hepatitis C virus (HCV) is a major cause of liver-related morbidity and is strongly associated with B cell lymphoproliferative disorders. Data from epidemiological, biological and clinical investigations support the hypothesis of a pathogenetic role of HCV in at least a subgroup of patients with B-cell non-Hodgkin's lymphoma (B-NHL). Morphologically, HCV-associated B-NHL represents a variety of histological subtypes. The comprehension of the mechanisms of HCV persistence and of its role in the lymphomagenesis will be useful to set new strategies with the aim to prevent and treat HCV-associated B-NHLs. This hypothesis of a virus-induced mechanism of lymphomagenesis arises from the growing evidence that successful antiviral treatment is often linked to regression of some types of HCV-related indolent B-NHLs