International therapeutic guidelines for patients with HCV-related extrahepatic disorders. A multidisciplinary expert statement

Hepatitis C virus (HCV) is both hepatotrophic and lymphotropic virus that causes liver as well extrahepatic manifestations including cryoglobulinemic vasculitis, the most frequent and studied condition, lymphoma, and neurologic, cardiovascular, endocrine-metabolic or renal diseases. HCV-extrahepatic manifestations (HCV-EHMs) may severely affect the overall prognosis, while viral eradication significantly reduces non-liver related deaths. Different clinical manifestations may coexist in the same patient. Due to the variety of HCV clinical manifestations, a multidisciplinary approach along with appropriate therapeutic strategies are required. In the era of interferon-free anti-HCV treatments, international recommendations for the therapeutic management of HCV-EHMs are needed. This implies the need to define the best criteria to use antivirals and/or other therapeutic approaches. The present recommendations, based on qualified expert experience and specific literature, will focus on etiological (antiviral) therapies and/or traditional pathogenetic treatments that still maintain their therapeutic utility

Cryoglobulinemia Vasculitis

International audienceCryoglobulinemic vasculitis (CryoVas) is a small vessel vasculitis involving mainly the skin, the joints, the peripheral nerve system and the kidneys. Type I CryoVas are single monoclonal immunoglobulins related to an underlying B-cell lymphoproliferative disorder. Type II and III cryoglobulins, often referred to as mixed cryoglobulinemia, consist of polyclonal IgG with or without monoclonal IgM with rheumatoid factor activity. Hepatitis C virus (HCV) infection represents the main cause of mixed CryoVas. The 10-year survival rates are 63%, 65% and 87% in HCV-positive mixed CryoVas, HCV-negative mixed CryoVas and type I CryoVas patients, respectively. In HCV-positive patients, baseline poor prognostic factors include the presence of severe liver fibrosis, and central nervous system, kidney, and heart involvement. Treatment with antivirals is associated with a good prognosis whereas use of immunosuppressant (including corticosteroids) is associated with a poor outcome. In HCV-negative patients, pulmonary and gastrointestinal involvement, renal insufficiency and age>65 years are independently associated with death. Increased risk of lymphoma should also be underlined. Treatment of type I CryoVas is that of the hemopathy; specific treatment also include plasma exchange, corticosteroids, rituximab and ilomedine. In HCV-CryoVas with mild to moderate disease, an optimal antiviral treatment should be given. For HCV-CryoVas with severe vasculitis (i.e. worsening of renal function, mononeuritis multiplex, extensive skin disease, intestinal ischemia…) control of disease with rituximab, with or without plasmapheresis, is required before initiation of antiviral therapy. Other immunosuppressants should be given only in case of refractory forms of CryoVas, frequently associated with underlying B-cell lymphoma

Cryoglobulinemia vasculitis

International audienceCryoglobulinemia is defined by the presence of circulating immunoglobulins that precipitate at cold temperature and dissolve with rewarming. Cry-oglobulinemia is categorized by immunochemical analysis into three types [1]. Type I cryoglobulins are monoclonal immunoglobulins. Type II cryoglobu-lins consist of a monoclonal immunoglobulin with a rheumatoid factor activity associated with poly-clonal IgG, whereastype III cryoglobulins com-prised polyclonal IgG and IgM with rheumatoidfactor activity. Type II and III are often referred toas mixed cryoglobulinemia

Rituximab therapy for Takayasu arteritis: A seven patients experience and a review of the literature

OBJECTIVES: To assess the efficacy and safety of rituximab (RTX) in patients with Takayasu arteritis (TAK). METHODS: We conducted a retrospective study on seven TAK patients treated with RTX. Six of the seven patients had a disease refractory to high dose glucocorticoids and conventional immunosuppressive and/or biologic agents. One newly diagnosed, treatment-naïve TAK patient refused glucocorticoids and received RTX alone. Clinical evaluation, laboratory tests and imaging modalities (CT or MR-angiography, and 18 F-fluorodeoxyglucose PET/CT) were performed at first RTX administration and every 6 months thereafter. Disease activity was assessed using the Kerr index. We also performed a literature review using PubMed, Ovid MEDLINE and Cochrane library. RESULTS: Seven patients (6 females) were included in the study. Mean ( s . d .) age was 32.4 (17.3) years. At first RTX administration, all patients had active disease according to the Kerr index (⩾2), and had also evidence of active disease at PET/CT. Despite RTX treatment, four of the seven patients had evidence of persistent disease activity and/or radiographic disease progression during follow-up. Three out of seven patients in whom RTX was employed as rescue therapy achieved complete remission. In the literature review, we identified five papers describing nine patients treated with RTX with good results in eight cases, but short follow-up. CONCLUSION: Our data do not support a role for RTX as first line biologic therapy in TAK patients, but it may have a role in some patients as second or third line biologic therapy.Objectives. To assess the efficacy and safety of rituximab (RTX) in patients with Takayasu arteritis (TAK). Methods. We conducted a retrospective study on seven TAK patients treated with RTX. Six of the seven patients had a disease refractory to high dose glucocorticoids and conventional immunosuppressive and/ or biologic agents. One newly diagnosed, treatment-naïve TAK patient refused glucocorticoids and received RTX alone. Clinical evaluation, laboratory tests and imaging modalities (CT or MR-angiography, and 18F-fluorodeoxyglucose PET/CT) were performed at first RTX administration and every 6 months thereafter. Disease activity was assessed using the Kerr index. We also performed a literature review using PubMed, Ovid MEDLINE and Cochrane library. Results. Seven patients (6 females) were included in the study. Mean (S.D.) age was 32.4 (17.3) years. At first RTX administration, all patients had active disease according to the Kerr index (≥), and had also evidence of active disease at PET/CT. Despite RTX treatment, four of the seven patients had evidence of persistent disease activity and/or radiographic disease progression during follow-up. Three out of seven patients in whom RTX was employed as rescue therapy achieved complete remission. In the literature review, we identified five papers describing nine patients treated with RTX with good results in eight cases, but short follow-up. Conclusion. Our data do not support a role for RTX as first line biologic therapy in TAK patients, but it may have a role in some patients as second or third line biologic therapy

mTOR Pathway Activation in Takayasu Arteriti

International audienc

Long-term Efficacy of Interferon-Free Antiviral Treatment Regimens in Patients With Hepatitis C Virus-Associated Cryoglobulinemia Vasculitis

In small-size and short-term studies of hepatitis C virus-associated cryoglobulinemia vasculitis (HCV-CryoVas), patients had a higher rate of response and tolerance to direct-acting antiviral (DAA) agents than interferon-containing regimens. We collected follow-up data from a clinical trial to determine the long-term effectiveness and tolerance of all-oral, interferon-free DAA regimens in patients with CryoVas

Occurrence of focal myositis during Behçet's disease: The identification of a specific vasculitis‐associated focal myopathy

International audienc