Perihepatic lymph nodes and antiviral response in chronic HCV-associated hepatitis

Soresi, Maurizio; Bonfissuto, Giulio; Sesti, Roberta; Riili, Anna; Giovanni, G. Di; Carroccio, Antonio; Tripi, S; Montalto, Giuseppe

doi:10.1016/j.ultrasmedbio.2004.04.004

Cited by 11 publications

(9 citation statements)

References 26 publications

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“…It might be that other factors required to create the appropriate milieu for a GC reaction are usually missing in the liver microenvironment. A potential compartment where HCV can activate B cells might be perihepatic lymph nodes, which are frequently enlarged in patients with chronic HCV infection, and this is directly related to viral replication and to the recruitment of inflammatory cells [28,[43][44][45].Although we did not find indication for affinity maturation and hence antigen selection in the B-cell follicles, the IgV H gene segment usage indicated that antigen-specific B cells are preferentially recruited into these structures. In all seven follicles analysed, there was a preferential usage of the VH1-69 segment among the cloned V H 1 family rearrangements.…”

contrasting

confidence: 55%

Intrahepatic B‐cell follicles of chronically hepatitis C virus‐infected individuals lack signs of an ectopic germinal center reaction

et al. 2014

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Chronic infection with hepatitis C virus (HCV) often affects the B-cell compartment, leading to the occurrence of autoimmunity and B-cell lymphoproliferation, in particular mixed cryoglobulinemia and B-cell lymphomas. HCV presumably causes these lymphoproliferations by chronic antigenic stimulation and/or direct mutagenic effects on B cells. It has been speculated that the interaction of HCV with B cells and the expansion of antigen-triggered B cells happens in germinal center-like structures in the livers of HCV carriers. We studied rearranged immunoglobulin V H genes from seven B-cell folli-cles microdissected from the livers of three unselected chronic HCV patients. The follicles consisted of polyclonal naive and memory B-cell populations with only rare indication of minor clonal expansions and no evidence for active somatic hypermutation. Frequent detection of V H rearrangements using the VH1-69 gene segment nevertheless indicated that at least a fraction of the B cells is HCV-specific and/or autoreactive. Thus, the typical intrahepatic B-cell follicles in chronic HCV carriers do not function as ectopic germinal centers for clonal expansion and affinity maturation of B cells. Hence, autoreactive and HCV-specific B-cell clones might either develop in secondary lymphoid organs or in intrahepatic follicles only under particular, yet undefined, circumstances.Keywords: B-cell clonal expansion r Germinal centers r HCV r IgV H genes r Somatic hypermutation Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionChronic infection by hepatitis C virus (HCV) not only causes liver cirrhosis and hepatocellular carcinoma [1] but, in a subgroup of patients is also associated with the development of B-cell lymphoproliferative diseases [2]. These diseases include the autoimmune disease mixed cryoglobulinemia (MC) type II, characterized by Correspondence: Prof. Ralf Küppers e-mail: ralf.kueppers@uk-essen.de a monoclonal population of rheumatoid factor-producing B cells, and a subgroup of B-cell non-Hodgkin lymphomas [3]. There are currently two main -not mutually exclusive -models of HCVassociated lymphomagenesis [4]. The observation that some lymphomas in HCV-infected patients show regression upon successful anti-viral therapies [5] suggests chronic antigenic stimulation as a driving force in lymphoma development. This is further supported by the specificity of the B-cell receptor of HCV-associated lymphomas for viral antigens, in particular the HCV protein E2 [6,7] 1843HCV-associated B-cell lymphomas use the immunoglobulin variable (IgV) gene segment VH1-69, which is known to be used both by rheumatoid factors and by some E2-specific antibodies, further supporting a role of antigenic drive in HCV-associated B-cell expansion [8][9][10][11][12]. A second pathogenetic mechanism of HCV on B cells may be a direct mutagenic effect of the virus, including induction of reactive oxygen species [13,14], and of activation-induced cytidine deaminase [15], which is t...

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confidence: 55%

Intrahepatic B‐cell follicles of chronically hepatitis C virus‐infected individuals lack signs of an ectopic germinal center reaction

et al. 2014

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“…Soresi et al . reported that PLNE was more frequent in non‐responders to IFN‐α with RBV, although this association did not reach statistical significance by logistic regression analysis, in which the patients also had various genotypes . We also reported that the sustained virological response (SVR) rate in patients who received IFN therapy was significantly lower in patients with PLNE than in those without, although our patients also had various genotypes and viral loads, and treatment regimens were various including IFN‐α or pegylated IFN‐α (PEG IFN) with or without RBV .…”

Section: Introductionmentioning

confidence: 65%

“…THE FACT THAT chronic hepatitis C patients with PLNE are prone to treatment failure to IFN therapy has been previously reported . However, there were limitations because these analyses were performed in patients with various HCV genotypes, viral loads and treatment regimens.…”

Section: Discussionmentioning

confidence: 99%

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Perihepatic lymph node enlargement is a negative predictor for sustained responses to pegylated interferon‐α and ribavirin therapy for Japanese patients infected with hepatitis C virus genotype 1

Hikita

Enooku

Satoh

et al. 2013

Hepatology Research

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“…Other studies have suggested an association with increased hepatic inflammation and fibrosis [14,15]. Interestingly, a relationship between response to treatment with interferon and PLNE was found by two groups [16,17]. A question of utmost clinical consequence is the prediction of the rate of progression to cirrhosis and the development of end-stage liver disease in those HCV-infected patients with PLNE compared to those without PLNE.…”

Section: Introductionmentioning

confidence: 97%

Clinical Significance of Perihepatic Lymphadenopathy in Patients with Chronic Hepatitis C Infection

Tavakoli–Tabasi

Ninan

2011

Dig Dis Sci

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Perihepatic lymph nodes and antiviral response in chronic HCV-associated hepatitis

Cited by 11 publications

References 26 publications

Intrahepatic B‐cell follicles of chronically hepatitis C virus‐infected individuals lack signs of an ectopic germinal center reaction

Intrahepatic B‐cell follicles of chronically hepatitis C virus‐infected individuals lack signs of an ectopic germinal center reaction

Perihepatic lymph node enlargement is a negative predictor for sustained responses to pegylated interferon‐α and ribavirin therapy for Japanese patients infected with hepatitis C virus genotype 1

Clinical Significance of Perihepatic Lymphadenopathy in Patients with Chronic Hepatitis C Infection

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