Cryoglobulinemia is associated with steatosis and fibrosis in chronic hepatitis C†

Saadoun, David; Asselah, Tarik; Resche-Rigon, Matthieu; Charlotte, Frédéric; Bédossa, Pierre; Valla, Dominique; Piette, Jean‐Charles; Marcellin, Patrick; Cacoub, Patrice

doi:10.1002/hep.21190

Cited by 89 publications

(61 citation statements)

References 44 publications

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“…Therefore, the finding that an enhanced frequency and function of CD4ϩ CD25 high cells was associated with a lower degree of HCV-associated liver inflammation (39,49), as well as the finding that activated Treg cells in patients with chronic HCV infection suppressed effector cell activity in a non-antigen-specific manner (41), may both suggest a beneficial role of Treg cells in reducing immunemediated bystander injury in chronic HCV infection. In this context, it is interesting to note that patients with HCV-induced MC vasculitis have more-severe liver injury, with a higher frequency of cirrhosis, compared with patients with chronic HCV infection without MC (50,51). In the present study, we demonstrated that autoimmune manifestations induced by HCV are associated with lower Treg cell levels.…”

supporting

confidence: 54%

Correlation of clinical and virologic responses to antiviral treatment and regulatory T cell evolution in patients with hepatitis C virus–induced mixed cryoglobulinemia vasculitis

Landau¹,

Rosenzwajg²,

Saadoun³

et al. 2008

Arthritis & Rheumatism

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Objective. Mixed cryoglobulinemia (MC) vasculitis is an autoimmune disorder associated with chronic hepatitis C virus (HCV) infection. We previously reported that MC vasculitis is associated with a quantitative defect of peripheral blood regulatory T cells. The aim of this study was to prospectively evaluate the evolution of this defect during the course of antiviral treatment.Methods. Treg cell frequencies and numbers were analyzed in 131 patients with chronic HCV infection (including 66 with MC vasculitis) and 20 healthy volunteer donors. Measurements were taken before, during, and after treatment with PEGylated interferon alfa-2b plus ribavirin.Results. At baseline, patients with MC vasculitis had a significantly lower frequency and number of Treg cells than did patients without MC vasculitis. Complete remission of MC vasculitis following antiviral treatment was associated with a significant increase in Treg cell levels compared with baseline. In contrast, Treg cell levels in nonresponders or partial responders, which did not differ from those in complete responders at baseline, remained unchanged over the course of the study. Conclusion. The strong positive correlation between clinical responses and Treg cell levels provides further support for the central role of Treg cells in the pathogenesis of HCV-induced MC vasculitis and emphasizes the dual role of Treg cells in chronic HCV infection: while Treg cells may hinder viral elimination, they also limit autoimmune injury.Chronic infection with hepatitis C virus (HCV) is the main cause of mixed cryoglobulinemia (MC) vasculitis, a potentially life-threatening systemic vasculitis (1). MC is a B cell proliferative disorder characterized by polyclonal or monoclonal activation and autoantibody production. MC may lead to clinical manifestations ranging from an MC syndrome (purpura, arthralgia, asthenia) to a more serious vasculitis with nervous system and renal involvement (1). The observation of T cells in the vascular infiltrates and the presence of autoantibodies, together with the observation that some HLA groups confer susceptibility to MC vasculitis in HCV-infected patients, suggest that autoimmune processes are implied in this virus-induced disease (2,3). It has been demonstrated that antiviral treatment can lead to the disappearance of symptoms and can induce an immunologic response, i.e., a significant decrease in plasma cryoglobulin levels (4). Furthermore, the clinical response is closely related to effective viral elimination (4,5), supporting the causal link between chronic HCV infection and the autoimmune process.During the past several years, CD4ϩCD25 high immunoregulatory T cells have been identified in

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supporting

confidence: 54%

Correlation of clinical and virologic responses to antiviral treatment and regulatory T cell evolution in patients with hepatitis C virus–induced mixed cryoglobulinemia vasculitis

Landau¹,

Rosenzwajg²,

Saadoun³

et al. 2008

Arthritis & Rheumatism

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“…The prognosis seems more severe in HBV-PAN, with 35% of deaths compared to 10% in patients with HCV infection. HCV-related vasculitis does not bear specific virologic features in term of genotype, viral load, or phylogenetic analysis (31)(32)(33). In contrast, in HBV-PAN most cases are associated with high levels of viral replication identified by high-serum HBV-DNA levels and hepatitis B antigen positivity, promoting the persistence of viral immune complexes in antigen excess (34).…”

Section: Pan-type Vasculitis Associated With Hcvmentioning

confidence: 99%

Hepatitis C virus–associated polyarteritis nodosa

Saadoun¹,

Terrier²,

Semoun³

et al. 2011

Arthritis Care & Research

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“…The evolution was fatal and the patient died a few hours after admission to intensive care, this reinforces the data of the literature concerning the severity of the central neurological manifestation. In addition, several cohort studies have shown the existence of epidemiological, clinical and biological factors strongly associated with the production of mixed cryoglobulinemia during chronic hepatitis C virus infection, including female sex, advanced age , Genotype 2 or 3 and extensive liver fibrosis [8,9]. Two of these factors are present in our case and which have led to the diagnosis of an extra-hepatic disorders of hepatitis C.…”

Section: Discussionmentioning

confidence: 53%