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慢性炎症性疾病的乙型肝炎与免疫抑制治疗:何时以及如何应用预防措施,特别关注皮质类固醇治疗。

Hepatitis B and immunosuppressive therapies for chronic inflammatory diseases: When and how to apply prophylaxis, with a special focus on corticosteroid therapy.

作者信息

López-Serrano Pilar, de la Fuente Briongos Elsa, Alonso Elisa Carrera, Pérez-Calle Jose Lázaro, Rodríguez Conrado Fernández

机构信息

Pilar López-Serrano, Elsa de la Fuente Briongos, Jose Lázaro Pérez-Calle, Conrado Fernández Rodríguez, Department of Gastroenterology, University Hospital Fundación Alcorcón, 28922 Madrid, Spain.

出版信息

World J Hepatol. 2015 Mar 27;7(3):539-47. doi: 10.4254/wjh.v7.i3.539.

Abstract

Currently immunosuppressive and biological agents are used in a more extensive and earlier way in patients with inflammatory bowel disease, rheumatic or dermatologic diseases. Although these drugs have shown a significant clinical benefit, the safety of these treatments is a challenge. Hepatitis B virus (HBV) reactivations have been reported widely, even including liver failure and death, and it represents a deep concern in these patients. Current guidelines recommend to pre-emptive therapy in patients with immunosuppressants in general, but preventive measures focused in patients with corticosteroids and inflammatory diseases are scarce. Screening for HBV infection should be done at diagnosis. The patients who test positive for hepatitis B surface antigen, but do not meet criteria for antiviral treatment must receive prophylaxis before undergoing immunosuppression, including corticosteroids at higher doses than prednisone 20 mg/d during more than two weeks. Tenofovir and entecavir are preferred than lamivudine because of their better resistance profile in long-term immunosuppressant treatments. There is not a strong evidence, to make a general recommendation on the necessity of prophylaxis therapy in patients with inflammatory diseases that are taking low doses of corticosteroids in short term basis or low systemic bioavailability corticosteroids such as budesonide or beclomethasone dipropionate. In these cases regularly HBV DNA monitoring is recommended, starting early antiviral therapy if DNA levels begin to rise. In patients with occult or resolved hepatitis the risk of reactivation is much lower, and excepting for Rituximab treatment, the prophylaxis is not necessary.

摘要

目前,免疫抑制药物和生物制剂在炎症性肠病、风湿性疾病或皮肤病患者中使用得更为广泛且更早。尽管这些药物已显示出显著的临床益处,但这些治疗方法的安全性仍是一项挑战。乙肝病毒(HBV)再激活已被广泛报道,甚至包括肝衰竭和死亡,这在这些患者中引起了深切关注。目前的指南一般建议对使用免疫抑制剂的患者进行预防性治疗,但针对使用皮质类固醇和炎症性疾病患者的预防措施却很少。应在诊断时进行HBV感染筛查。乙肝表面抗原检测呈阳性但不符合抗病毒治疗标准的患者,在接受免疫抑制治疗(包括使用高于泼尼松20mg/d剂量的皮质类固醇超过两周)之前必须接受预防治疗。由于替诺福韦和恩替卡韦在长期免疫抑制治疗中的耐药性更好,因此比拉米夫定更受青睐。对于短期使用低剂量皮质类固醇或全身生物利用度低的皮质类固醇(如布地奈德或丙酸倍氯米松)的炎症性疾病患者,没有充分证据就预防治疗的必要性提出一般性建议。在这些情况下,建议定期监测HBV DNA,如果DNA水平开始上升则尽早开始抗病毒治疗。对于隐匿性或已治愈的肝炎患者,再激活的风险要低得多,除了利妥昔单抗治疗外,无需进行预防。

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