戊型肝炎是由戊型肝炎病毒(hepatitis E virus,HEV)引起、主要经粪-口途径传播的急性病毒性肝炎[1]。
引用本文
通信作者:
庄 辉 北京大学基础医学院病原生物学系暨感染病研究中心
徐小元 北京大学第一医院感染疾病科
中华医学会肝病学分会. 指南与共识戊型肝炎防治共识[J]. 中华肝脏病杂志, DOI: 10.3760/cma.j.cn501113-20220729-00401
|摘 要|
本共识是由中华医学会肝病学分会制定的,其内容包括前言、病原学、流行病学和预防、病理学、实验室检查、临床表现、治疗、尚待研究和解决的问题以及7条推荐意见。
戊型肝炎是由戊型肝炎病毒(hepatitis E virus,HEV)引起、主要经粪-口途径传播的急性病毒性肝炎[1]。免疫抑制患者感染HEV后,可进展为慢性戊型肝炎,甚至肝硬化[2-3]。
目前我国戊型肝炎的诊断、治疗和预防多依据中国医师协会感染科医师分会于2009年7月制订的《戊型病毒性肝炎诊疗规范》[4]、英国公共卫生局于2015年发布的《戊型肝炎公共卫生操作指导》[5]、英国移植学会于2017年发布的《戊型肝炎与实体器官移植指导》[6-7],以及欧洲肝病学会于2018年6月发布的《戊型肝炎病毒感染临床实践指南》[8]。鉴于近年来,戊型肝炎的病原学、临床诊断、治疗和预防等方面有较大进展[9],以及医疗单位对戊型肝炎诊断、治疗和预防方面的迫切需求,中华医学会肝病学分会特组织有关专家,查阅大量已发表的戊型肝炎文献,收集并汇总临床热点问题,经专家们认真讨论,形成此共识,供有关医务人员在制定戊型肝炎预防、诊断和治疗决策时参考。在戊型肝炎防治实践中,需结合疫情和患者的具体情况,综合评价后做出防治决策。今后本分会将根据国内外研究进展,对本共识进行更新和完善。
本共识采用推荐、评估、制订和评价(Grades of Recommendation, Assessment,Development,and Evaluation,GRADE)系统,对证据质量和推荐意见进行分级,证据质量分为A、B和C等3个级别,推荐意见分为强推荐(1)和弱推荐(2)等2个级别(表1)。
一
|病原学|
HEV属于戊型肝炎病毒科(Hepeviridae),直径为30~40 nm。HEV基因组为单股正链RNA,全长约7.2 kb,含有3个部分重叠的开放阅读框架(open reading frame,ORF)[10-12]。ORF1编码病毒复制功能的非结构聚合蛋白;ORF2编码衣壳结构蛋白及一种分泌型蛋白;ORF3编码一种小的蛋白,其在病毒颗粒组装和出胞等过程中发挥重要作用。
戊型肝炎病毒科可分2个属(genera),即正戊型肝炎病毒属( Orthohepevirus)和鱼类戊型肝炎病毒属(Piscihepevirus)。正戊型肝炎病毒属分A、B、C和D共4种(species)[13]。A种有8个基因型。人类主要感染1~4型[9];1型和2型只感染人;3型和4型可感染人和多种动物[14-17];5型和6型感染野猪,尚未见感染人的报道[18-19];7型和8型可感染骆驼,已有报道7型可感染人[20-22]。B种感染禽类,无感染人报道[23];C种感染大鼠等,也可感染人[24-28];D种感染蝙蝠,无感染人报道[29]。因此,HEV被认为是人兽共患病病毒(zoonotic virus)。
二
|流行病学和预防|
(一)流行病学
HEV是全球急性散发性病毒性肝炎的重要病因之一。全球每年约有2 000万例新发HEV感染,其中330万例有肝炎症状,2015年死亡44 000例,占病毒性肝炎死亡病例的3.3%[30-31]。血清流行病学研究表明,全球约1/3人感染过HEV[32]。戊型肝炎的流行病学与HEV基因型有关[33]。1型和2型主要分布于卫生条件较差、经济欠发达的发展中国家,多由被粪便污染的水源引起的暴发或流行[34-35];基因3型主要发生在发达国家,4型主要流行于中国和东南亚地区,多为散发[36-37]。
我国自1982年起即有本病流行或散发报道。1986-1988年,新疆南部地区发生戊型肝炎流行,共计发病119 280例,为迄今世界上最大的一次戊型肝炎流行[38]。用2006年全国乙型肝炎血清流行病学调查的血清标本检测抗-HEV结果显示,我国普通人群抗-HEV流行率为23.46%[39]。近年来,戊型肝炎报告发病率呈上升趋势,2004年为1.27/10万,2019年升至2.02/10万[40]。近20年来,随着我国公共卫生状况的明显改善,主要流行株逐渐从基因1型转变为基因4型,以散发病例为主,一般为11月至次年3月高发,偶有食源性小暴发[41-43]。我国东部地区曾报告基因3型HEV导致的戊型肝炎散发病例[42-44]。
慢性肝病患者感染HEV后一般病情较重。中国台湾地区报道,非肝硬化慢性乙型肝炎患者中,合并感染HEV感染占2.2%;乙型肝炎肝硬化患者合并HEV感染占2.4%。合并感染患者的1年病死率显著高于非合并感染者(30%对比0,P<0.001)[45]。荟萃分析显示,慢性乙型肝炎住院患者的合并HEV感染率为13.6%,其中肝衰竭发生率为34.7%[46]。
HEV主要经粪-口、血液、母婴和密切接触等途径传播[47]。其中粪-口传播是HEV最常见的传播途径,包括由粪便和尿液污染水源造成水型流行[48];由被HEV污染的食物、或生食含HEV的动物内脏或肉制品,以及刀具、案板等厨具生熟不分导致HEV污染蔬菜和水果等引起的食源性传播[49-50]。与戊型肝炎患者密切接触也可感染HEV,主要发生在难民营[51-57]。HEV家庭内密切接触传播的发生率低[53-56]。HEV也可经血液或血制品传播[58-61]。一项系统和荟萃分析表明,我国志愿供血员抗-HEV IgG、抗-HEV IgM、HEV RNA和HEV抗原流行率分别为29.2%、1.1%、0.1%和0.1%[62]。HEV通过器官移植传播也有报道[63-65]。我国一项研究报告显示,约4.0%(7/177)接受造血干细胞移植的患者在术后发生HEV感染[66]。造血干细胞移植受者感染HEV后,病死率为4%~16%[67-73]。HEV母婴传播的发生率较高,目前主要见于基因1型HEV,多数报道来自印度,由于诊断母亲和婴儿HEV感染的标准、检测样本(脐血或婴儿血)和检测方法各异,因此,报告的HEV母婴传播率差异较大,由30%到100%不等[74-83]。
(二)预防
1. 管理传染源:急性戊型肝炎患者视病情轻重居家或住院隔离治疗至发病后3周。患者粪便和排泄物应严格消毒。对疑似患者和密切接触者应进行医学观察4~6周。
2. 切断传播途径:加强水源卫生和改善供水条件。有研究报道,HEV对乙醇类消毒剂有一定的抵抗作用[84],因此要重视环境卫生和个人卫生,尤其对可能传播HEV的重点场所,如饲养场和屠宰场,要加强排泄物和污水处理,防止污染水源和周围环境。对动物内脏和肉类食品,加工时生熟分开,防止污染;烹煮应彻底。不摄食未完全煮熟的肉类食品[1,5,85]。对参加供血的戊型肝炎高危人群,如畜牧养殖者、疫区旅行者和餐饮业人员等可检测血清HEV RNA或HEV抗原,阳性者不应供血[6,86]。
3. 保护易感人群:易感人群是指未感染过HEV者,他们对HEV易感。但由于我国戊型肝炎发病率低(约2/10万),从成本效益考虑,对一般易感人群不进行戊型肝炎疫苗免疫,主要是通过传染源管理、切断传播途径,以及加强个人卫生和饮食卫生等措施,保护易感人群。因此,我国将戊型肝炎疫苗定为二类疫苗。
对于HEV感染风险高人群,如畜牧养殖者、疫区旅行者、餐饮业人员、集体生活人群等,以及感染后易发生肝衰竭甚至死亡的高危人群,如慢性肝病患者、育龄期妇女、老年人等人群,可进行戊型肝炎疫苗预防。
我国自行研发的重组戊型肝炎疫苗(大肠埃希菌)(简称戊型肝炎疫苗)于2011年12月1日由中国国家食品药品监督管理局正式批准,是至今全球正式批准的唯一戊型肝炎疫苗。该疫苗是由基因工程大肠埃希菌表达的HEV结构蛋白,经纯化并加铝佐剂混合后制成。接种该疫苗后,可刺激机体产生抗-HEV的中和抗体,预防HEV感染。该疫苗的III期临床试验表明,疫苗组于接种3针后12个月的保护率为100%;对HEV基因1型和4型感染均有保护作用;安全性良好,未发现与疫苗相关的严重不良事件[87]。长期有效性研究显示,在接种后4.5年,疫苗预防HEV感染的保护率为86.8%(95%可信区间为70%~94%)[88]。在慢性乙型肝炎患者中的开放性临床试验结果显示,慢性乙型肝炎患者接种戊型肝炎疫苗安全性和免疫原性良好[89]。在65岁以上老年人中的开放性临床试验结果显示,戊型肝炎疫苗在该人群中具有良好的免疫原性和耐受性,未发生与疫苗相关的严重不良事件[90]。
戊型肝炎疫苗的接种对象为16岁及以上易感人群,免疫程序为0-1-6个月,即接种第1针疫苗后,间隔1和6个月注射第2和第3针疫苗,每针剂量为30 μg/0.5 ml。接种部位为上臂三角肌肌内注射。为了获得最佳保护效果,应按规定程序完成3针疫苗全程接种。
推荐意见1:对畜牧养殖者、疫区旅行者、餐饮业人员、集体生活者等高风险人群,以及慢性肝病患者、育龄期妇女、老年人等高危人群可按0-1-6个月程序接种3针30 μg/0.5 ml戊型肝炎疫苗。(C1)
三
|病理学|
戊型肝炎病理学类型和病变程度呈多样化表现,包括急性普通型肝炎、急性淤胆型肝炎、重型肝炎和慢性肝炎病理学改变。
急性普通型戊型肝炎以轻型病毒性肝炎病理学改变为主,组织学上类似于急性甲型肝炎,呈小叶内点状坏死、肝细胞肿胀,部分呈气球样变,可见凋亡小体,小叶内及汇管区可见淋巴细胞为主的单个核细胞浸润。
急性淤胆型戊型肝炎呈明显的毛细胆管内淤胆,周围肝细胞羽毛状变性及气球样变,双核、多核肝细胞多见,有时明显淤胆的毛细胆管周围肝细胞呈现假腺样排布,凋亡小体偏大且不规整,库普弗细胞增生活化明显,偶见肝细胞脂变;小叶内及汇管区单个核细胞浸润,可见浆细胞,汇管区内反应性增生的小胆管周围可伴中性粒细胞浸润[91]。
重型戊型肝炎(肝衰竭)病理学改变,可见广泛的肝细胞坏死及肝实质塌陷,表现为融合性坏死、桥接坏死,残存的肝细胞高度肿胀或泡沫样变,严重的毛细胆管及肝细胞淤胆[92]。偶见门静脉和肝静脉的血管炎、淋巴细胞破坏性胆管炎[93]。
慢性戊型肝炎肝组织学呈轻到中等度小叶炎症坏死,可见轻到中等度的界面炎,汇管区及小叶内淋巴细胞为主的炎症细胞浸润,淋巴细胞和/或中性粒细胞浸润性小胆管炎,偶见破坏性胆管炎[94-95];少数有不同程度的纤维化改变[96]。
四
|实验室检查|
(一)肝脏生化学检查
1. 丙氨酸转氨酶(alanine transaminase,ALT)和天冬氨酸转氨酶(aspartate transaminase,AST):急性戊型肝炎患者多升高;慢性戊型肝炎患者的ALT和AST可持续或间歇异常[2]。
急性戊型肝炎也可有碱性磷酸酶(alkaline phosphatase,ALP)、γ-谷氨酰转移酶(γ-glutamyltrans- ferase,GGT)和乳酸脱氢酶(lactate dehydrogenase,LDH)等升高[97-100]。
2. 胆红素:胆汁淤积为戊型肝炎的常见表现,急性期、慢性期及肝衰竭患者均可有不同程度胆红素异常。重型肝炎患者总胆红素可>171 μmol/L,或每天上升>17.1 μmol/L[97,99-101]。
3. 血清白蛋白:重度肝脏炎症患者的血清白蛋白水平降低,肝衰竭患者可出现低白蛋白血症[99-101]。
4. 凝血酶原时间(prothrombin time,PT)、凝血酶原活动度(prothrombin time activity,PTA)及国际标准化比值(international normalized ratio,INR):可有不同程度异常,PTA≤40%,或INR≥1.5,应考虑肝衰竭[101-103]。
(二) 病原学检查
1. 抗-HEV IgM和抗-HEV IgG:HEV感染后,首先出现抗-HEV IgM。抗-HEV IgM阳性是急性HEV感染重要标志,抗-HEV IgM阳性时间相对较短,约3~4个月转阴,但少数可持续6个月甚至1年[104]。在抗-HEV IgM出现1周后,可检测到抗-HEV IgG,并在短时间内迅速上升,通常在感染后6~10周到达高峰,1~2个月内快速下降至较低水平,然后持续阳性可达数年至数10年,但其确切阳性期限不详[105]。戊型肝炎患者一般在出现临床症状时才就诊,因此,绝大部分急性期患者可同时检测到抗-HEV IgM和抗-HEV IgG。
对于相关职业体检人员,如发现单纯抗-HEV IgM阳性时,还需进一步确认是否有临床症状、肝脏生化学异常,并同时检测抗-HEV IgG和HEV RNA。仅根据抗-HEV IgM阳性不能确认是感染HEV。
2. HEV RNA:感染HEV后,约3周即可在血中检测到HEV RNA,粪便排出HEV可长达约4~6周,粪便中检出HEV RNA持续时间比病毒血症长2~4周[8]。在出现戊型肝炎临床症状后1~2周内,70%~80%患者的粪便和血清中可检出HEV RNA,随后阳性率显著下降[33]。HEV RNA阳性是HEV现症感染的直接证据。约20%~30%患者在发病时体内HEV已基本被清除[106-109],因此,HEV RNA阴性并不能排除HEV急性感染。
目前HEV RNA的检测主要采用RT-PCR核酸扩增技术。因此,应注意因扩增引物特异度和灵敏度、操作不当或相关标本保存条件不佳而造成假阳性或假阴性结果。
3. HEV抗原:HEV抗原检测可用于急性和慢性HEV感染的辅助诊断,血清、粪便和尿液中HEV抗原阳性也是HEV现症感染的证据之一[48,110-113]。基于双抗体夹心法建立的HEV抗原检测系统具有较高的灵敏度和特异度,血清HEV抗原与HEV RNA的检测结果有较好的互补性[113-115]。有研究发现,在HEV感染患者中,HEV抗原在尿液中含量高于血清[48,110]。
急性和慢性戊型肝炎诊断流程见图1。
推荐意见2:对出现原因不明ALT异常和/或有肝炎临床症状的患者,应检测抗-HEV IgM和抗-HEV IgG;对免疫抑制患者,还应检测HEV RNA或抗原。(A1)
推荐意见3: 原有慢性肝病患者出现原因不明ALT异常或肝炎症状加重时,需检测抗-HEV IgM和抗-HEV IgG,以明确是否合并HEV感染。(A1)
推荐意见4:近期ALT异常,且血清抗-HEV IgM和抗-HEV IgG同时阳性,可诊断为急性戊型肝炎。(A1)
推荐意见5:免疫抑制患者如出现ALT异常,且血清和/或粪便HEV RNA持续阳性3个月以上,可诊断为慢性戊型肝炎。(B2)
五
|临床表现|
(一)急性肝炎
1. 急性无黄疸型肝炎:潜伏期为2~10周,平均为5~6周[1]。急性HEV感染多为无症状或轻微临床表现,无黄疸,肝酶轻度异常,为自限性,一般可自发康复。
2. 急性黄疸型肝炎:约占5%~30%[116],前驱期约1~10 d,主要症状为全身不适、轻度发热、恶心、偶有呕吐,可见肝酶异常。尔后进入黄疸期,出现巩膜和全身皮肤黄染、暗褐色尿[116-117],血清胆红素升高,可持续14~28 d,然后黄疸逐渐消退,进入恢复期。一般HEV基因1型和2型急性肝炎患者的病情较基因3型和4型严重[116,118]。老年男性感染基因3型和4型后病情较重;慢性肝病患者感染3型和4型后可导致急性肝炎竭或慢加急性肝衰竭[116]。
在急性戊型肝炎中,胆汁淤积型肝炎约占8%[119],临床可表现为瘙痒、乏力、尿色加深和黄疸等。黄疸持续时间较长,可达1个月以上。早期常无症状,仅表现为血清ALP和GGT水平升高,病情进展时,可出现高胆红素血症,在纠正维生素K缺乏后,PT无明显延长,胆汁淤积长期不愈和严重肝炎患者可导致肝衰竭甚至死亡[120]。
(二)重型肝炎(肝衰竭)
重型肝炎(肝衰竭)表现为胆红素升高,PT延长,不可被维生素K纠正。部分特殊人群如孕妇、慢性肝病患者和老年人等感染HEV后,肝损伤严重,甚至进展为急性或亚急性肝衰竭,病死率较高[121-124]。孕妇戊型肝炎易发生出血、子痫或急性或亚急性肝衰竭,可导致早产、流产和死胎等不良妊娠结局,病死率高达20%~25%[125-126]。慢性肝脏疾病如慢性乙型肝炎和肝硬化等患者感染HEV后,易发生急性、亚急性或慢加急性肝衰竭,病死率高[127-128]。
(三)慢性肝炎
慢性HEV感染是指HEV RNA持续阳性3个月以上[8,129]。免疫抑制患者如器官移植受者、人类免疫缺陷病毒(human immunodeficiency virus,HIV)感染者和接受化疗、造血干细胞移植或免疫抑制剂治疗的血液肿瘤患者等,感染HEV后,通常无法依靠自身免疫短期内清除体内HEV[129-131],易发展为慢性戊型肝炎。至今报告的慢性HEV感染多见于基因3型和4型HEV[9];也有基因7型HEV[22]和大鼠HEV致人类慢性戊型肝炎的报道[25-28]。
大多数慢性HEV感染者为无症状或轻微临床表现,但存在肝功能持续异常,主要为ALT、AST和GGT升高[132]。但部分患者可表现ALT、AST和GGT水平正常或仅轻度升高。部分慢性戊型肝炎可进展为肝硬化,且进展快,一般为2~3年[132-134]。少数慢性HEV感染者可表现为抗-HEV IgM和抗-HEV IgG持续阴性,需检测外周血和/或粪便HEV RNA或HEV抗原才能确诊[132]。
(四)HEV感染肝外表现
HEV感染可引起多种肝外表现,包括神经系统、血液系统、肾脏和其他免疫介导的临床表现[135-149],其确切的发病机制尚不清楚,可能与病毒表位与组织中自身抗原相互作用,以及HEV在肝外组织中复制有关。
神经系统表现最为常见,包括格林-巴利综合征、神经性肌肉萎缩、脑炎、脊髓炎、肌炎、前庭神经炎、周围神经炎和面神经麻痹等[143-150]。欧洲一项研究报告,16.5%戊型肝炎患者有神经系统临床表现,免疫正常患者较免疫抑制患者更常见(22.6%对比3.2%,P<0.001)。神经性肌肉萎缩和格林-巴利综合征是最常见的临床表现,多种基因型HEV急性和慢性感染后均可发生。
其次是肾脏表现,包括肾损伤、膜增生性肾小球肾炎和冷球蛋白血症等[151-152]。一项回顾性研究报告,感染HEV 3型的实质器官移植患者,其估算的肾小球滤过率(estimated glomerular filtration rate,eGFR)下降,组织学检查显示高蛋白尿、IgA肾病、膜增生性肾小球肾炎和冷球蛋白血症,随着HEV被清除而恢复[153]。
HEV可引起多种血液系统表现,如血小板减少症、自身免疫性溶血性贫血、再生障碍性贫血、溶血性贫血等[154-156]。此外,有HEV感染导致急性胰腺炎、关节炎和心肌炎等报道[157-158],但多为单个病例,尚缺乏系统性研究。
(五)无症状HEV感染
在免疫健全的供血员中,存在无症状HEV感染者,经随访,其中少数人可HEV RNA和/或HEV抗原持续阳性3个月以上[159-163]。
六
|治 疗|
(一)急性戊型肝炎
大部分急性戊型肝炎患者能自身清除病毒而康复;少部分患者可能进展为急性或亚急性肝衰竭。因此,治疗原则是以对症支持疗法为主,不需要抗病毒治疗[116],但需密切观察病情。
1. 一般治疗:(1)休息:急性戊型肝炎早期,应居家或住院隔离,并卧床休息。恢复期逐渐增加活动,活动程度以不感到疲劳,避免过劳和熬夜,以利康复。(2)营养:宜进食中等量蛋白质、低脂肪、高维生素类食物,通常碳水化合物摄入量不可过多。恢复期要避免过食和禁酒,不饮含有酒精的饮料。
2. 对症处理:患者有明显食欲不振、频繁呕吐并有黄疸时,除休息和营养外,可静脉滴注葡萄糖液、生理盐水和维生素C等。
(二)胆汁淤积型戊型肝炎
可选用熊去氧胆酸、S-腺苷蛋氨酸。胆汁瘀积严重者,可考虑应用糖皮质激素,必要时,可考虑行血浆置换或胆红素吸附等人工肝支持治疗[164]。
(三)重型戊型肝炎(肝衰竭)
以综合疗法为主,主要措施是加强护理,密切观察病情。加强支持疗法,维持水、电解质和能量平衡。改善肝脏微循环,降低内毒素血症,预防和治疗各种并发症。必要时,考虑人工肝支持治疗或肝移植[116]。
有研究报告,重型戊型肝炎(肝衰竭)患者接受利巴韦林治疗,可快速清除HEV和肝酶复常[165]。对肾移植患者的利巴韦林治疗剂量为200 mg隔日1次,疗程3个月[165];也有报告,利巴韦林治疗剂量为600~1 000 mg,疗程5个月[165]。有一些研究报告,皮质类固醇治疗重型戊型肝炎(肝衰竭)患者可减缓肝衰竭进展[129]。
(四)妊娠期戊型肝炎
对患急性戊型肝炎孕妇的治疗,以对症支持疗法和保护肝脏为主,密切随访肝功能,争取孕妇完成妊娠[166]。对有重型肝炎倾向的患者,积极对症支持治疗,包括人工肝支持治疗等;病情好转者可继续妊娠;如果积极对症支持治疗后,病情无好转,甚至加重者,可考虑终止妊娠。对于已经确诊重型肝炎(肝衰竭)者,则应及早终止妊娠,同时积极对症支持治疗,包括人工肝等支持治疗,必要时可行肝移植[167-168]。
(五)慢性乙型肝炎合并戊型肝炎
针对乙型肝炎病毒(hepatitis B virus,HBV)感染,依据《慢性乙型肝炎防治指南(2019版)》,采用一线核苷(酸)类似物如恩替卡韦、替诺福韦酯或富马酸丙酚替诺福韦治疗[169]。对重症患者应加强支持治疗,必要时考虑人工肝支持治疗或肝移植[116]。
(六)慢性戊型肝炎
1. 器官移植受者的慢性戊型肝炎的治疗:研究显示,减少免疫抑制剂剂量(以不发生排斥反应为准)可使近三分之一的慢性HEV感染者清除病毒[131]。
聚乙二醇干扰素α已成功用于治疗少数肝移植受者和1例血液透析患者[170-172]。但聚乙二醇干扰素α可刺激免疫系统,并增加急性排斥反应的风险,目前禁用于胰腺、心脏和肺移植受者[173]。
利巴韦林单药治疗在慢性HEV感染的器官移植受者中的研究较多[174-175]。单用利巴韦林3个月后,可获得持续病毒学应答(sustained viral response,SVR)。但利巴韦林可导致贫血、干咳等不良反应[175]。此外,部分患者可对利巴韦林产生无应答或不耐受[176]。
2. 其他免疫抑制人群的慢性戊型肝炎治疗:主要包括接受化疗的血液肿瘤患者和HIV感染患者。聚乙二醇干扰素α、利巴韦林或两者联合,可有效治疗血液肿瘤和HIV患者的慢性HEV感染[177-178]。有研究报道,利巴韦林治疗后,86%干细胞移植后的慢性HEV感染者能获得SVR[67]。
戊型肝炎治疗流程见图2[8,33,179-181]。
推荐意见6:急性戊型肝炎多为自限性,通常以对症支持治疗为主,不需要抗病毒治疗。(A1)
推荐意见7:诊断为慢性HEV感染的实体器官移植受者,可减少或调整免疫抑制剂治疗剂量(以不发生排斥反应为准),或用利巴韦林600 mg/d单药治疗3个月。(B1)如利巴韦林停药后复发,可再用利巴韦林单药治疗6个月。(B1)
七
|尚待研究和解决的问题|
1. 调查我国HEV感染率、发病率、基因型及亚型分布;
2. 研究重型戊型肝炎的发病机制、治疗和预防;
3. 研究妊娠期妇女感染HEV的发病机制、治疗和预防;
4. 研究我国慢性戊型肝炎发病人群、治疗和预防;
5. 研究HEV感染的肝外表现、治疗及预防;
6. 研究我国戊型肝炎疫苗最佳免疫策略;
7. 研发抗HEV新药。
编写组专家:
王麟 (北京大学基础医学院);窦晓光 (中国医科大学附属盛京医院);赵景民 (解放军总医院第五医学中心);周乙华 (南京大学医学院附属鼓楼医院);夏宁邵 (厦门大学公共卫生学院);李彤 (北京大学基础医学院);南月敏 (河北医科大学第三医院);王佑春 (中国食品药品检定研究院);王玲 (北京大学基础医学院);徐小元 (北京大学第一医院);庄辉 (北京大学基础医学院)
讨论组专家(按汉语拼音排序):
安纪红 (内蒙古自治区人民医院);陈红松 (北京大学人民医院);陈煜 (首都医科大学附属北京佑安医院);迟雁 (北京大学第一医院);邓国宏 (陆军军医大学西南医院);丁惠国 (首都医科大学附属北京佑安医院);段钟平 (首都医科大学附属北京佑安医院);范建高 (上海交通大学医学院附属新华医院);高沿航(吉林大学第一医院);韩涛 (天津市第三中心医院);韩英(空军军医大学第一附属医院);何剑峰 (广东省疾病预防控制中心);侯金林 (南方医科大学南方医院);胡鹏 (重庆医科大学附属第二医院);黄燕 (中南大学湘雅医院);黄缘(清华大学附属北京清华长庚医院);贾继东 (首都医科大学附属北京友谊医院);江应安 (武汉大学人民医院);李杰(北京大学基础医学院);李军 (南京医科大学附属第一医院);李君 (浙江大学医学院附属第一医院);李荣宽 (大连医科大学附属第二医院);李树臣 (哈尔滨医科大学附属第二医院);李文刚 (解放军总医院第五医学中心);李懿璇(北京大学第一医院);李玉芳 (宁夏医科大学总医院);蔺淑梅 (西安交通大学医学院第一附属医院);刘景丰 (福建省肿瘤医院);刘晓清 (北京协和医院);陆伦根 (上海交通大学医学院附属第一人民医院);罗新华 (贵州省人民医院);马雄 (上海交通大学医学院附属仁济医院);茅益民 (上海交通大学医学院附属仁济医院);饶慧瑛 (北京大学人民医院);任万华 (山东大学附属省立医院);尚佳 (河南省人民医院);石荔 (西藏自治区人民医院);苏明华 (广西医科大学第一附属医院);孙晓冬 (上海市疾病预防控制中心);孙亚朦 (首都医科大学附属北京友谊医院);王磊 (山东大学第二医院);魏来 (清华大学附属北京清华长庚医院);温志立 (南昌大学第二附属医院);吴彪 (海南省人民医院);吴超 (南京大学医学院附属鼓楼医院);谢尧 (首都医科大学附属北京地坛医院);辛绍杰 (解放军总医院第五医学中心);邢卉春 (首都医科大学附属北京地坛医院);徐爱强 (山东省疾病预防控制中心);徐京杭 (北京大学第一医院);杨东亮 (华中科技大学同济医学院附属协和医院);杨积明 (天津市第二人民医院);杨晋辉 (昆明医科大学第二附属医院);杨丽 (四川大学华西医院);杨永峰 (东南大学附属南京市第二医院);尤红 (首都医科大学附属北京友谊医院);于岩岩 (北京大学第一医院);张缭云 (山西医科大学第一医院);张岭漪 (兰州大学第二医院);张欣欣 (上海交通大学医学院附属瑞金医院);张跃新 (新疆医科大学第一附属医院);赵守松 (蚌埠医学院第一附属医院);周永健 (广州市第一人民医院);祖红梅 (青海省第四人民医院);左维泽 (石河子大学医学院第一附属医院)
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