Current and emerging therapeutic approaches in HCV-related mixed cryoglobulinemia.
Recognition 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.
Sansonno
D
D
Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, University of Bari Medical School, Bari, Italy. d.sansonno@dimo.uniba.it
Tucci
F A
FA
Troiani
L
L
Sansonno
L
L
Dammacco
F
F
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D000998:Antiviral Agents / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D003449:Cryoglobulinemia / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics / Q000821:virology*; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D016174:Hepacivirus / Q000187:drug effects* / Q000378:metabolism; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D007075:Immunoglobulin M / Q000378:metabolism; D007372:Interferons / Q000627:therapeutic use; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use; D012217:Rheumatoid Factor / Q000378:metabolism; D012254:Ribavirin / Q000627:therapeutic use; D000069283:Rituximab; D015398:Signal Transduction
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D007075:Immunoglobulin M; D016376:Oligonucleotides, Antisense; D012254:Ribavirin; D000069283:Rituximab; D007372:Interferons; D012217:Rheumatoid Factor