Impact of Cryoglobulinemic Syndrome on the Outcome of Chronic Hepatitis C Virus Infection

Lauletta, Gianfranco; Russi, Sabino; Conteduca, Vincenza; Sansonno, Loredana; Dammacco, Franco; Sansonno, Domenico

doi:10.1097/md.0b013e31829d2abc

Cited by 42 publications

(32 citation statements)

References 50 publications

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“…Moreover, high frequency of splenic involvement in DLBCL patients suggests that these cases derive from splenic MZL. These clinical and pathological data are consistent with a stepwise model of lymphomagenesis induced by chronic antigenic stimulation contributing to the occurrence of RF, MC, MZL and transformed DLBCL [23]. In contrast, lymphomas in patients with no RF or MC may be induced by other mechanisms including direct infection of B cells by HCV [24].…”

Section: Discussionsupporting

confidence: 83%

Antiviral therapy is associated with a better survival in patients with hepatitis C virus and B‐cell non‐Hodgkin lymphomas, ANRS HC‐13 lympho‐C study

et al. 2014

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on behalf of the ANRS HC-13 Lympho-C Study Group Hepatitis C virus (HCV) infection increases the risk of B-cell non-Hodgkin lymphomas (B-NHL). Antiviral treatment (AT) can induce hematological responses in patients with marginal zone lymphomas (MZL). The ANRS HC-13 Lympho-C study aimed at a better understanding of the impact of AT on HCV associated B-NHL. This multicentric study enrolled 116 HCV-positive patients with B-NHL between 2006 and 2012. Cytological and histological samples were collected for centralized review. At lymphoma diagnosis, median age was 61 years and gender ratio M/F was 1. Cytohistological distribution was marginal zone lymphoma (MZL) n 5 45 (39%), diffuse large B-cell lymphoma (DLBCL) n 5 45 (39%), and other types n 5 26 (22%). MZL patients had more frequent detection of rheumatoid factor (68% vs. 35%; P 5 0.001) and more frequently mixed cryoglobulinemia (74% vs. 44%; P 5 0.021) than patients with DLBCL. Among patients receiving AT, a sustained virologic response was achieved in 23 of 38 (61%) patients with MZL and in 9 of 17 (53%) with DLBCL (P 5 0.42). Three-year overall survival (OS) and progression-free survival were 78% 95%CI and 64% , respectively, without difference between cytohistological groups. Outcome analysis showed a favorable association between OS and AT in all patients (P 5 0.05) and in the subgroup of MZL patients only (P 5 0.04). Our data support that AT improves the outcomes of HCV-associated NHLs. The impact of new AT regimen with protease inhibitor needs to be investigated in this setting. [clinicalTrials.gov Identification number NCT01545544]Am.

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Section: Discussionsupporting

confidence: 83%

Antiviral therapy is associated with a better survival in patients with hepatitis C virus and B‐cell non‐Hodgkin lymphomas, ANRS HC‐13 lympho‐C study

et al. 2014

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“…Several clinical studies on a large cohort of HCV-infected patients with long-term follow-up revealed that viral infection is characterized by a multistep process, which often advances from mild manifestations to systemic disorders such as cryoglobulinemic vasculitis and malignancies (FIGURE 1) [96-98]. On the contrary, some individuals may abruptly develop one of the most severe complications after a long-lasting mild clinical course of disease [96,102,103].…”

Section: Hcv Syndromementioning

confidence: 99%

Virus-driven autoimmunity and lymphoproliferation: the example of HCV infection

Zignego

Gragnani

Piluso

et al. 2014

Expert Review of Clinical Immunology

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HCV chronic infection is characterized by possible development of both hepatic and extrahepatic manifestations. The infection by this both hepatotropic and lymphotropic virus is responsible for polyoligoclonal B-lymphocyte expansion, leading to several immune-mediated disorders. Mixed cryoglobulinemia syndrome that in some cases may evolve to frank B-cell non-Hodgkin's lymphoma is the prototype of HCV-driven autoimmune and lymphoproliferative disorders. The HCV oncogenic potential has been suggested by several clinicoepidemiological and laboratory studies; it includes hepatocellular carcinoma, B-cell non-Hodgkin's lymphoma and papillary thyroid cancer. The definition HCV syndrome refers to the complex of HCV-driven diseases; these latter are characterized by heterogeneous geographical distribution, suggesting a role of other important genetic and/or environmental cofactors. The natural history of HCV syndrome is the result of a multifactorial and multistep pathogenetic process, which may evolve from mild manifestations to systemic autoimmune disorders, and less frequently to malignant neoplasias. The present updated review analyzes the clinical and pathogenetic aspects of the main HCV-associated diseases.

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“…The relationship between chronic HCV infection and B cell non-Hodgkin's lymphoma (B-NHL) may provide a model for the kinetics of progression. Approximately 15% of HCV patients show disease progression to B-NHL after a median of 15 years [36]. The degree of somatic hypermutation in the IgH chain gene and the levels of AID expression by B cells may represent powerful prognostic factors.…”

Section: Discussionmentioning

confidence: 99%

Activation-induced cytidine deaminase in B cells of hepatits C virus-related cryoglobulinaemic vasculitis

Russi

Dammacco

Sansonno

et al. 2015

Clinical and Experimental Immunology

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SummaryImmunoglobulin variable region heavy chain (IgV H ) somatic gene diversification is instrumental in the transformation process that characterizes hepatitis C virus (HCV)-related B cell lymphoproliferative disorders. However, the extent to which activation-induced cytidine deaminase (AID), an enzyme essential for IgV gene somatic hypermutation (SHM), is active in cryoglobulinaemic vasculitis (CV) remains unclear. AID mRNA expression in the peripheral blood of 102 chronically hepatitis C virus (HCV)-infected patients (58 with and 44 without CV) and 26 healthy subjects was investigated using real-time reverse transcription-polymerase chain reaction (RT-PCR). The features of activation-induced cytidine deaminase (AID) protein and mRNA transcripts were explored in liver tissue biopsies and portal tracts isolated using laser capture microdissection. In chronically HCV-infected patients, AID mRNA expression was almost threefold higher in those with than in those without CV and sevenfold higher than in healthy subjects (median-fold: 6Á68 versus 2Á54, P 5 0Á03 and versus 0Á95, P 5 0Á0003). AID transcript levels were significantly higher in polyclonal than in clonally restricted B cell preparations in either CV or non-CV patients (median-fold, 15Á0 versus 2Á70, P 5 0Á009 and 3Á46 versus 1Á58, P 5 0Á02, respectively). AID gene expression was found to be related negatively to age and virological parameters. AID protein was found in portal tracts containing inflammatory cells that, in several instances, expressed AID mRNA transcripts. Our data indicate that the aberrant expression of AID may reflect continuous B cell activation and sustained survival signals in HCV-related CV patients.

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Impact of Cryoglobulinemic Syndrome on the Outcome of Chronic Hepatitis C Virus Infection

Cited by 42 publications

References 50 publications

Antiviral therapy is associated with a better survival in patients with hepatitis C virus and B‐cell non‐Hodgkin lymphomas, ANRS HC‐13 lympho‐C study

Antiviral therapy is associated with a better survival in patients with hepatitis C virus and B‐cell non‐Hodgkin lymphomas, ANRS HC‐13 lympho‐C study

Virus-driven autoimmunity and lymphoproliferation: the example of HCV infection

Activation-induced cytidine deaminase in B cells of hepatits C virus-related cryoglobulinaemic vasculitis

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