1,720,984 research outputs found
Current and emerging therapeutic approaches in HCV-related mixed cryoglobulinemia
No full textRecognition of hepatitis C virus (HCV) as an etiological factor in mixed cryoglobulinemia (MC) has dramatically changed our point of view in its treatment. Emphasis is placed on abatement and clearance of viral load and deletion of clonal expansions of IgM molecules with rheumatoid factor activity-synthesising B cells. The purpose of this review is to discuss the underlying scientific rationale and results of clinical studies of new treatment approaches to MC, with a focus on cell-depleting therapies and chemokine blockade. Additional antiviral agents directed to several phases of HCV life cycle acting with different or alternate mechanisms are proposed with the goal to enhance response rates more broadly suitable for MC patients with vasculitis and peripheral neuropathies. The majority of the available data on these new treatment approaches stems from open-label studies, but controlled trials are under way. Therapy directed against chemokines and/or cytokines represents an interesting and promising future target
B CELLS AND HCV: AN INFECTION MODEL OF AUTOIMMUNITY
No full textIn addition to cause acute and chronic liver disease, hepatitis C virus (HCV) infection is frequently associated to autoimmune disorders, such as mixed cryoglobulinemia, primary glomerulonephritis, monoclonal gammopathy of undetermined significance and post-transplant proliferative disorders. Progression to malignant phenotype of B cells may be the consequence of additional genetic events or abnormal conditions resulting from modification of host cell genes involved in the control of oncogenes and oncoproteins. In this review, we will address the potential immune disregulatory mechanism(s) underlying HCV persistence. In addition, HCV/B-cell interaction that might explain defects in humoral immunity in individuals who develop chronic virus carriage and lymphoproliferative disorders will be emphasized
Molecular analysis of αβ and γδ T cell receptor repertoire in liver and blood of patients with HCV-related mixed cryoglobulinemia
No full textAssociation Between Mixed Cryoglobulinemia, Translocation (14;18), and Persistence of Occult HCV Lymphoid Infection After Treatment
No full textB-cell depletion in the treatment of mixed cryoglobulinemia.
No full textA controlled study has been carried out to assess the efficacy of rituximab (RTX), a chimeric antibody that binds to the B-cell surface
antigen CD20, in twenty patients with mixed cryoglobulinemia (MC) and HCV-positive chronic active liver disease, resistant to interferon-~,
(IFN-~,) therapy. They received an intravenous infusion of 375 mg/m 2 RTX once a week for 4 consecutive weeks. Infusion of RTX had
a good safety profile, and no severe side-effects were reported. Sixteen patients (80%) had a complete response (CR), characterized by
rapid improvement of clinical signs (disappearance of purpura, weakness, arthralgias and improvement of peripheral neuropathy), and
decreased cryocrit. CR was associated with a significant reduction in rheumatoid factor (RF) activity and anti-HCV antibody titers. Decline
of IgG anti-HCV titers in the cryoprecipitates was usually associated with a favorable response (r 0.81; p <0.005). No differences in
the dynamics of B-cell depletion and recovery were found between responders and non-responders. Molecular monitoring of the B-cell
response revealed disappearance/deletion of peripheral clones in the responders and great stability in the non-responders. RTX had a deep
impact on hepatitis C viremia: HCV RNA increased to approximately twice the baseline level in the responders, whereas it remained much
the same in the non-responders. Twelve out of 16 responders (75%) remained in remission throughout the follow-up. The results indicate
that RTX has clinical and biological activity in HCV-positive MC patients. However, in view of the increased viremia in the responders,
additional modes of application and combination of RTX with other agents need to be investigated
MONOCLONAL ANTIBODY TREATMENT OF MIXED CRYOGLOBULINEMIA RESISTANT TO INTERFERON ALPHA WITH AN ANTI-CD20
No full textA controlled study has been carried out to assess the efficacy of rituximab, a chimeric antibody that binds to the B-cell surface antigen CD20, in 20 patients with mixed cryoglobulinemia (MC) and hepatitis C virus (HCV)-positive chronic active liver disease, resistant to interferon alpha (IFN-alpha) therapy. They received an intravenous infusion of 375 mg/m(2) rituximab once a week for 4 consecutive weeks. Infusion of rituximab had a good safety profile and no severe side effects were reported. Sixteen patients (80%) showed a complete response (CR), characterized by rapid improvement of clinical signs (disappearance of purpura and weakness arthralgia and improvement of peripheral neuropathy), and decline of cryocrit. CR was associated with a significant reduction of rheumatoid factor (RF) activity and anti-HCV antibody titers. Decline of IgG anti-HCV titers in the cryoprecipitates was usually associated with a favorable response (r = 0.81; P <.005). No differences in the dynamics of B-cell depletion and recovery were found between responders and nonresponders. Molecular monitoring of the B-cell response revealed disappearance/deletion of peripheral clones in the responders and great stability in the nonresponders. Rituximab had a deep impact on hepatitis C viremia; HCV RNA increased approximately twice the baseline levels in the responders, whereas it remained much the same in the nonresponders. Twelve (75%) of 16 responders remained in remission throughout the follow-up. The results indicate that rituximab has clinical and biologic activity in patients with HCV(+) MC. However, in view of the increased viremia in the responders, additional modes of application and combination of rituximab with other agents need to be investigated
HCV-ASSOCIATED B CELL CLONALITIES IN THE LIVER DO NOT CARRY THE T(14; 18) CHROMOSOMAL TRANSLOCATION
No full textInfection with HCV can be associated with B-cell non-Hodgkin lymphoma. Polymerase chain
reaction (PCR) amplification assays for Bcl-2/IgH rearrangement were performed on nucleic
acids extracted from portal tract inflammatory infiltrates, isolated with laser capture microdissection
(LCM), from liver biopsy sections of 16 hepatitis C virus (HCV)-infected patients with
and without extrahepatic B cell–related disorders. Results were compared with total DNA extracted
from core liver biopsy specimens and from peripheral blood mononuclear cells (PBMCs).
We failed to demonstrate specific Bcl-2/IgH amplicons either in liver tissue or in PBMCs in all
patients of the current series. Multiple PCR assays for variable diversity joining (VDJ) IgH gene
rearrangements were also performed in the liver compartment. Selective amplification compatible
with mono or oligoclonal B cell clonotypes was demonstrated in 80% (6/8) and 25% (2/8)
of patients with and without clinical evidence of B-cell disorders. VH1 and VH3 were the most
represented VH families. In situ expression of Bcl-2 protein was carried out by immunohistochemistry
on liver biopsy sections. Bcl-2 protein was detected in 2 (12.5%) patients who did not
associate extrahepatic disorders. In conclusion, current data support the concept that production
of IgH gene rearrangements is not associated with Bcl-2/IgH chromosomal translocation in
hepatic compartment. Liver overexpression of Bcl-2 protein may occur in at least a minor
proportion of HCV-infected patients. (HEPATOLOGY 2005;42:1019-1027.
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