Effects of Combined Antiviral Therapy on Asymptomatic Mixed Cryoglobulinemia in Naive Patients with Chronic Hepatitis C Virus Infection: A Preliminary Study

D'Amico, E; Chincoli, Caterina; Cacciatore, P.; Pasqua, G. Di; Cosentino, Luana; Riario-Sforza, G.; Pennese, Ernesta; Capani, F; Palazzi, Carlo

doi:10.1007/s10620-005-3059-x

Cited by 13 publications

(11 citation statements)

References 19 publications

(16 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…30,31 In addition, successful treatment of HCV infection with IFN/ribavirin, or elimination of B cells with novel anti-CD20 chimeric antibodies such as rituximab, leads to resolution of mixed cryoglobulinemia, regression of IgM overproduction and clearance of B-cell clones. [32][33][34][35][36] Our data clearly support a role for up-regulation of B-cell activation and immunoglobulin production in response to HCV core protein. We found that HCV core could bind gC1qR, a known receptor for HCV core that is expressed on CD20 + B cells.…”

Section: Discussionsupporting

confidence: 54%

Differential regulation of SOCS‐1 signalling in B and T lymphocytes by hepatitis C virus core protein

et al. 2008

View full text Add to dashboard Cite

SummaryHepatitis C virus (HCV) infection is characterized by a strong propensity toward chronicity, autoimmune phenomena and lymphomagenesis, supporting a role for lymphocyte dysregulation during persistent viral infection. We have shown that HCV core protein inhibits T-cell functions through interaction with a complement receptor, gC1qR. Here, we further report that B cells also express gC1qR that can be bound by HCV core protein. Importantly, using flow cytometry, we demonstrated differential regulation of B and T lymphocytes by the HCV core-gC1qR interaction, with down-regulation of CD69 activation in T cells but up-regulation of CD69 activation and cell proliferation in B cells. HCV core treatment led to decreased interferon-c production in CD8 + T cells but to increased immunoglobulin M and immunoglobulin G production as well as cell surface expression of costimulatory and chemokine receptors, including CD86 (B7-2), CD154 (CD40L) and CD195 (CCR5), in CD20 + B cells.Finally, we showed down-regulation of suppressor of cytokine signalling-1 (SOCS-1) using real-time reverse transcription-polymerase chain reaction, accompanied by up-regulation of signal transducer and activator of transcription-1 (STAT1) phosphorylation in B cells in response to HCV core protein, with the opposite pattern observed in HCV core-treated T cells. This study demonstrates differential regulation of B and T lymphocytes by HCV core and supports a mechanism by which lymphocyte dysregulation occurs in the course of persistent HCV infection.

show abstract

Section: Discussionsupporting

confidence: 54%

Differential regulation of SOCS‐1 signalling in B and T lymphocytes by hepatitis C virus core protein

et al. 2008

View full text Add to dashboard Cite

show abstract

“…However, CGs can persist despite SVR [44,47], suggesting that viral clearance and sustained disappearance of CGs are not necessarily closely coupled. The failure to completely clear CGs despite SVR supports the hypothesis that antiviral treatment only partially interferes with the B-cell activities responsible for persistent RF and CGs [66]. Overall, complete immunologic response should not be assumed upon clearance of peripheral HCV, even in sustained responders.…”

Section: Immunologic Responsementioning

confidence: 62%

Treatment of hepatitis C cryoglobulinemia: Mission and challenges

Kayali¹,

LaBrecque

Schmidt³

2006

Curr Treat Options Gastro

View full text Add to dashboard Cite

Mixed cryoglobulinemia (MC) is a syndrome resulting from cold-insoluble immunoglobulin complexes or cryoglobulins (CGs) that precipitate in the serum of 40% to 50% of patients with chronic hepatitis C virus (HCV) infection. The pathogenesis of cryoglobulinemia likely occurs due to chronic viremia and generation of rheumatoid factor following continuous presentation of antigen-immunoglobulin complexes to B cells. CGs are thought to be responsible for a variety of extrahepatic manifestations associated with HCV, including vasculitis, glomerulonephritis, arthritis, and neuropathies, which occur in approximately 10% of HCV patients with CGs. CGs also are a powerful predictive factor for progressive liver disease and the aggressive reoccurrence of liver disease in HCV-positive patients after liver transplantation. First-line therapy for MC due to HCV infection is antiviral therapy with pegylated interferon-alpha and ribavirin. Viral eradication usually produces marked reduction of physical complications and arrests end organ damage concomitant with clearance of CG. Additional prospective, controlled studies are necessary to determine whether CG influences patient virologic response and/or its durability to antiviral therapy. Immunomodulators such as corticosteroids and cyclophosphamide are efficacious for palliative treatment of the symptomatology of HCV cryoglobulinemia but may enhance viral replication. Consequently, prolonged therapy with immunomodulatory agents should be limited to severe vasculitis or aggressive glomerulonephritis in patients with MC due to HCV who have failed to respond to antiviral therapy. In acute, fulminant presentations, plasmapheresis may provide temporary relief and arrest the rapid progression of the disease so that additional therapy can be initiated.

show abstract

“…In a small case series of 25 patients, some patients achieved virologic clearance initially, but all had detectable HCV RNA at the end of therapy [11]. In another case series that included patients with asymptomatic MC, combination treatment with IFN and ribavirin was effective and led to permanent resolution of cryoglobulinemia; however, in rare cases, the disease initially can be detected distantly after successful treatment of HCV [12]. This argues against HCV being the only risk factor for MC in such patients.…”

Section: Mixed Cryoglobulinemiamentioning

confidence: 99%