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Available from: Laura Gragnani, Jan 27, 2014
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    • "The reasons for a lower propensity to eradicate HCV are at present unknown. One possible interpretation could be related to the previously shown stronger involvement of the lymphatic cells (especially B cells) in patients with MC [23] [24] [25], which may imply more consistent viral reservoirs and, in the case of the use of a direct-acting antiviral, a higher risk of selection of viral mutants, with a consequent recurrence of viral replication after an initial response. Interestingly, in this study, the only patient with MCS who responded to treatment early and persistently was the one excluded from the comparative analysis owing to recent treatment with rituximab, which induced B-cell depletion and cryocrit disappearance before antiviral therapy (data not shown). "
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    ABSTRACT: Background Mixed cryoglobulinaemia is strongly related to hepatitis C virus infection. Treatment with peg-interferon and ribavirin has been indicated as first-line therapy for mild/moderate hepatitis C virus-related mixed cryoglobulinaemia. Aim To evaluate the safety and efficacy of triple boceprevir-based antiviral therapy in patients with or without mixed cryoglobulinaemia previously treated with peg-interferon and ribavirin, and with advanced liver disease. Methods Thirty-five hepatitis C virus-positive patients (17 with asymptomatic mixed cryoglobulinaemia, 5 with symptomatic mixed cryoglobulinaemia, and 11 without mixed cryoglobulinaemia) were treated with triple boceprevir-based antiviral therapy. Results In 19/22 cryoglobulinaemic subjects (86%), the addition of boceprevir induced cryocrit disappearance. Cryocrit behaviour was related to virological response, with improvement of symptoms upon undetectable viraemia and reappearance after virological breakthrough. The rate of sustained virological response was lower in cryoglobulinaemic patients than in patients without mixed cryoglobulinaemia (23.8% vs 70% respectively, p = 0.01). Conclusion Boceprevir-based therapy was safe and effective in cryoglobulinaemic patients. The correlation between direct inhibition of hepatitis C virus replication and clinical improvement in mixed cryoglobulinaemic patients is definitive proof of the key pathogenetic role played by viral replication. Further studies are needed to confirm and clarify the reduced virological response in patients with mixed cryoglobulinaemia.
    Digestive and Liver Disease 05/2014; 46(9). DOI:10.1016/j.dld.2014.05.017 · 2.96 Impact Factor
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    • "The regression of the expanded B-cell clones following effective antiviral treatment and, in some relapsing patients, a new expansion of the same clones was also shown [97]. Finally, in a long-term follow-up study, an occult HCV persistence limited to the lymphatic compartment was observed in some patients resulting sustained virological responders after antiviral therapy [98,99]. More interestingly, such a persistent occult lymphatic infection was associated with the initial diagnosis of MC, the persistence of some MC symptoms after therapy and of expanded translocated B-cell clones. "
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    ABSTRACT: The relationship between Hepatitis C Virus (HCV) infection and immunosuppression is complex and multifaceted. Although HCV-related hepatocytolysis is classically interpreted as secondary to the attack by cytotoxic T lymphocytes against infected cells, the liver disease is usually exacerbated and more rapidly evolutive in immunosuppressed patients. This generally occurs during the immunosuppression state, and not at the reconstitution of the host response after immunosuppressive therapy discontinuation. The field of immunosuppression and HCV infection is complicated both by the different outcome observed in different situations and/or by contrasting data obtained in the same conditions, with several still unanswered questions, such as the opportunity to modify treatment schedules in the setting of post-transplant follow-up. The complexity of this field is further complicated by the intrinsic tendency of HCV infection in itself to lead to disorders of the immune system. This review will briefly outline the current knowledge about the pathogenesis of both hepatic and extrahepatic HCV-related disorders and the principal available data concerning HCV infection in a condition of impairment of the immune system. Attention will be especially focused on some conditions - liver or kidney transplantation, the use of biologic drugs and cancer chemotherapy - for which more abundant and interesting data exist.
    Journal of Translational Medicine 08/2012; 10(1):158. DOI:10.1186/1479-5876-10-158 · 3.93 Impact Factor
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    • "Furthermore, a long-term follow-up study allowed the identification of occult HCV persistence limited to the lymphatic compartment in some patients resulting sustained viral responders after antiviral therapy [54, 55]. More interestingly, such a persistent occult lymphatic infection was associated with the initial diagnosis of MC, the persistence of some MC symptoms after therapy, and the persistence of expanded t(14;18)+ B-cell clones [54, 55]. The observation of the possibility, even if rare, of a persisting MC disease in spite of complete viral eradication suggested the existence of points of no return in the evolution of the HCV-related lymphoproliferation. "
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    ABSTRACT: Hepatitis C virus (HCV) infection is a serious public health problem because of its worldwide diffusion and sequelae. It is not only a hepatotropic but also a lymphotropic agent and is responsible not only for liver injury--potentially evolving to cirrhosis and hepatocellular carcinoma--but also for a series of sometimes severely disabling extrahepatic diseases and, in particular, B-cell lymphoproliferative disorders. These latter range from benign, but prelymphomatous conditions, like mixed cryoglobulinemia, to frank lymphomas. Analogously with Helicobacter pylori related lymphomagenesis, the study of the effects of viral eradication confirmed the etiopathogenetic role of HCV and showed it is an ideal model for better understanding of the molecular mechanisms involved. Concerning these latter, several hypotheses have been proposed over the past two decades which are not mutually exclusive. These hypotheses have variously emphasized the important role played by sustained stimulation of the immune system by HCV, infection of the lymphatic cells, viral proteins, chromosomal aberrations, cytokines, or microRNA molecules. In this paper we describe the main hypotheses that have been proposed with the corresponding principal supporting data.
    Clinical and Developmental Immunology 07/2012; 2012(5):980942. DOI:10.1155/2012/980942 · 2.93 Impact Factor
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