Bazerbachi Fateh, Leise Michael D, Watt Kymberly D, Murad M Hassan, Prokop Larry J, Haffar Samir
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.
Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA.
Gastroenterol Rep (Oxf). 2017 Aug;5(3):178-184. doi: 10.1093/gastro/gox021. Epub 2017 May 19.
Mixed cryoglobulinemia (MC) has been associated with several viral infections, and chronic hepatitis C is recognized as a major cause. MC associated with hepatitis E virus (HEV) has been described and little is known about this rare association. The aim of this study is to perform a systematic review of MC associated with HEV, and examine the presence of a causal relationship. An experienced librarian conducted a search of databases from each database's inception to 12 December 2016 based on a priori criteria. The risk of bias was assessed, and Hill's criteria were applied to determine causality. Five publications met inclusion criteria, with a total of 15 cases. Three studies had low, one low to moderate and one moderate risk of bias. Median age was 43 years, and all patients came from Western Europe. Two patients were immunocompetent, while 13 were immunosuppressed, post solid organ transplant and had chronic hepatitis E. Renal involvement was observed in seven patients, mild to moderately severe cryoglobulinemic disease in one patient and severe cryoglobulinemic disease in three patients. One patient improved spontaneously, and another was treated with immunosuppressant reduction leading to viral clearance. Ten patients treated with peg-interferon or ribavirin for 3 months achieved loss of cryoglobulinemia and end-of-treatment response, but sustained virologic response was reported and achieved in two. Immunosuppressant achieved loss of cryoglobulinemia in three patients. One case of chronic renal failure, three cases of end-stage renal disease and one death were observed. Five of the nine Hill's criteria were fulfilled. MC has been described with HEV infection. A causal relationship between HEV infection and cryoglobulinemia is highly probable.
混合性冷球蛋白血症（MC）与多种病毒感染相关，其中慢性丙型肝炎被认为是主要病因。与戊型肝炎病毒（HEV）相关的MC已有报道，但对于这种罕见关联了解甚少。本研究旨在对与HEV相关的MC进行系统综述，并探讨因果关系的存在。一位经验丰富的图书馆员根据预先设定的标准，对各数据库自创建至2016年12月12日的数据进行了检索。评估了偏倚风险，并应用希尔标准来确定因果关系。五项出版物符合纳入标准，共15例病例。三项研究的偏倚风险较低，一项为低至中度，一项为中度。中位年龄为43岁，所有患者均来自西欧。两名患者免疫功能正常，而13名患者免疫抑制，为实体器官移植后且患有慢性戊型肝炎。七名患者出现肾脏受累，一名患者患有轻度至中度严重冷球蛋白血症疾病，三名患者患有严重冷球蛋白血症疾病。一名患者自发改善，另一名患者通过减少免疫抑制剂治疗实现了病毒清除。十名接受聚乙二醇干扰素或利巴韦林治疗3个月的患者实现了冷球蛋白血症消失和治疗结束时的反应，但报告并实现持续病毒学应答的有两名患者。免疫抑制剂使三名患者的冷球蛋白血症消失。观察到一例慢性肾衰竭、三例终末期肾病和一例死亡。希尔九条标准中的五条得到满足。已描述了与HEV感染相关的MC。HEV感染与冷球蛋白血症之间极有可能存在因果关系。
