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慢性丙型肝炎病毒感染患者的血小板减少症

Thrombocytopenia in Patients with Chronic Hepatitis C Virus Infection.

作者信息

Dahal Sumit, Upadhyay Smrity, Banjade Rashmi, Dhakal Prajwal, Khanal Nabin, Bhatt Vijaya Raj

机构信息

Interfaith Hospital, Department of Medicine, New York, USA.

Creighton University Medical Center, Department of Internal Medicine, Omaha, Nebraska, USA.

出版信息

Mediterr J Hematol Infect Dis. 2017 Mar 1;9(1):e2017019. doi: 10.4084/MJHID.2017.019. eCollection 2017.

Abstract

Thrombocytopenia in patients with chronic hepatitis C virus (HCV) infection is a major problem. The pathophysiology is multifactorial, with auto-immunogenicity, direct bone marrow suppression, hypersplenism, decreased production of thrombopoietin and therapeutic adverse effect all contributing to thrombocytopenia in different measures. The greatest challenge in the care of chronic HCV patients with thrombocytopenia is the difficulty in initiating or maintaining IFN containing anti-viral therapy. Although at present, it is possible to avoid this challenge with the use of the sole Direct Antiviral Agents (DAAs) as the primary treatment modality, thrombocytopenia remains of particular interest, especially in cases of advanced liver disease. The increased risk of bleeding with thrombocytopenia may also impede the initiation and maintenance of different invasive diagnostic and therapeutic procedures. While eradication of HCV infection itself is the most practical strategy for the remission of thrombocytopenia, various pharmacological and non-pharmacological therapeutic options, which vary in their effectiveness and adverse effect profiles, are available. Sustained increase in platelet count is seen with splenectomy and splenic artery embolization, in contrast to only transient rise with platelet transfusion. However, their routine use is limited by complications. Different thrombopoietin analogues have been tried. The use of synthetic thrombopoietins, such as recombinant human TPO and pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMDGF), has been hampered by the development of neutralizing antibodies. Thrombopoietin-mimetic agents, in particular, eltrombopag and romiplostim, have been shown to be safe and effective for HCV-related thrombocytopenia in various studies, and they increase platelet count without eliciting any immunogenicity Other treatment modalities including newer TPO analogues-AMG-51, PEG-TPOmp and AKR-501, recombinant human IL-11 (rhIL-11, Oprelvekin), recombinant human erythropoietin (rhEPO), danazol and L-carnitine have shown promising early result with improving thrombocytopenia. Thrombocytopenia in chronic HCV infection remain a major problem, however the recent change in DAAs without IFN, as the frontline therapy for HCV, permit to avoid the dilemmas associated with initiating or maintaining IFN based anti-viral therapy.

摘要

慢性丙型肝炎病毒(HCV)感染患者的血小板减少是一个主要问题。其病理生理学是多因素的,自身免疫原性、直接骨髓抑制、脾功能亢进、血小板生成素产生减少以及治疗不良反应均以不同程度导致血小板减少。在护理慢性HCV血小板减少患者时,最大的挑战在于启动或维持含干扰素的抗病毒治疗存在困难。尽管目前使用单一直接抗病毒药物(DAAs)作为主要治疗方式可以避免这一挑战,但血小板减少仍然备受关注,尤其是在晚期肝病患者中。血小板减少导致的出血风险增加也可能阻碍不同侵入性诊断和治疗程序的启动与维持。虽然根除HCV感染本身是缓解血小板减少的最实用策略,但也有各种药理和非药理治疗选择,其有效性和不良反应各不相同。脾切除术和脾动脉栓塞术可使血小板计数持续增加,而血小板输注仅导致短暂升高。然而,它们的常规使用受到并发症的限制。人们尝试了不同的血小板生成素类似物。合成血小板生成素,如重组人血小板生成素(TPO)和聚乙二醇化重组人巨核细胞生长和发育因子(PEG-rHuMDGF),因产生中和抗体而受到阻碍。血小板生成素模拟物,特别是艾曲泊帕和罗米司亭,在各种研究中已被证明对HCV相关血小板减少安全有效,且它们可增加血小板计数而不引发任何免疫原性。其他治疗方式,包括新型TPO类似物AMG-51、PEG-TPOmp和AKR-501、重组人白细胞介素-11(rhIL-11,奥曲肽)、重组人促红细胞生成素(rhEPO)、达那唑和L-肉碱,在改善血小板减少方面已显示出有希望的早期结果。慢性HCV感染中的血小板减少仍然是一个主要问题,然而,最近DAAs取代干扰素作为HCV一线治疗的变化,使得避免了与启动或维持基于干扰素的抗病毒治疗相关的困境。

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