Assessment of liver stiffness in patients with HCV and mixed cryoglobulinemia undergoing rituximab treatment
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RESEARCH
Open Access
Assessment of liver stiffness in patients with HCV and mixed cryoglobulinemia undergoing rituximab treatment Cristina Stasi1,2*, Elisa Triboli1,2, Umberto Arena1,2, Teresa Urraro1,2, Antonio Petrarca1,2, Laura Gragnani1,2, Giacomo Laffi1,2 and Anna Linda Zignego1,2
Abstract Introduction: Mixed cryoglobulinemia (MC) is a HCV-related lymphoproliferative disorder generally associated with advanced liver disease. Liver stiffness has been significantly correlated with histopathological stage of fibrosis. Moreover, it was influenced by necroinflammatory activity. Rituximab (RTX) is a chimeric anti-CD20 monoclonal antibody inducing transient B lymphocytes depletion that was shown to be useful and safe in the majority of HCV MC patients, leading also to improvement of cirrhotic syndrome. Aim of this study was to evaluate the modifications of liver stiffness following RTX treatment in HCV-related MC patients. Materials and methods: Fourteen consecutive patients (10 F, 4 M; mean age 60.43 ± 43) with HCV-related chronic hepatitis (n = 10) or cirrhosis (n = 4) and MC, eligible for RTX treatment, were prospectively enrolled. Intravenous injection of 1 g of RTX was performed at day 0 and at day 15. Assessment of stiffness was carried out by Fibroscan® (Echosens, Paris-France) at baseline, 15 days after the first infusion, and at month 1, 3 and 6 after therapy. Results: MC symptoms significantly improved during the study, especially during the first 3 months. Liver stiffness observed 3 months after treatment was significantly reduced when compared with pre-treatment values (p = 0.01). This difference disappeared after 6 months of follow-up. Cytofluorimetric analysis showed a decrease of CD19+ peripheral blood cells, with the nadir at month 3 after therapy and B cell compartment reconstitution after 6 months. Conclusion: This study, for the first time showed that RTX-treatment in HCV-related MC induces a reduction of liver stiffness that is strictly associated with the B-cell depletion. Keywords: Hepatitis C virus infection, Elastography, Rituximab, Mixed cryoglobulinemia
Introduction It is known that Hepatitis C virus (HCV) can infect mononuclear cells [1-3] and is associated with several autoimmune/lymphoproliferative disorders, whose prototype is mixed cryoglobulinemia (MC) [4]. MC is a both autoimmune and B-cell lymphoproliferative disorder characterized by immune complexes that reversibly precipitate at low temperature (cryoglobulins). A striking association between HCV and MC was shown [5,6]: HCV infection was detected in a percentage from 70% to >90% of MC * Correspondence: [email protected] 1 Interdepartmental Center for Systemic Manifestations of Hepatitis Viruses MASVE, University of Florence, Florence, Italy 2 Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla 3, 50134 Florence, Italy
patients and cryoglobulins in about half of HCV patients [7,8]. MC is a benign, but pre-lymphomatous condition whose clinical manifestations - the so-called mixed cryo
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