可引起儿童急性肝衰竭的遗传代谢病

引起儿童急性肝衰竭(ALF)的病因较为复杂,其中遗传代谢病占比较高,特别是在婴幼儿时期。遗传代谢病是一类代谢相关基因突变导致的细胞生理功能破坏的先天性疾病,种类繁多,临床表现多样,ALF是其引起的严重并发症之一,由于部分缺乏特异性表现容易被忽视。应尽早识别这类病因引起的ALF,以期逆转ALF的进程,提高患者预后。本文对可引起儿童ALF的常见遗传代谢病予以归纳介绍,以期提高医生对此类病因的认识。     

重视儿童急性肝衰竭的诊治

儿童急性肝衰竭(PALF)临床上虽少见,但起病急,进展快,严重威胁着儿童的生命和健康。其病因多样,目前较多患儿最终仍未能明确病因。PALF的临床表现与成人有所不同,婴幼儿早期肝性脑病的判断有一定的难度。维持内环境的稳定及病因治疗对于PALF极为重要,应避免乱用药、滥用血制品,有指征的患儿可行血液净化治疗为自体肝功能恢复和肝移植赢得更多的时间。PALF的精准诊治需要受到更多的重视。     

儿童急性肝衰竭的病因及诊治

1 儿童肝衰竭的定义 肝衰竭是指多种因素引起的严重肝脏损害,导致其合成、解毒、排泄和生物转化等功能发生严重障碍或失代偿,出现以凝血机制障碍、黄疸、肝性脑病、腹水等为主要表现的一组临床症候群. 在国内,儿童肝衰竭又有儿童重症肝炎、小儿暴发性肝炎之称.儿童急性肝衰竭(pediatric acute liver failure,PALF)定义为原先无肝脏损害,8周内突发严重肝功能障碍,注射维生素K1无法纠正的凝血障碍,凝血酶原时间(PT)＞20 s或国际标准化比值(INR)＞2.0,可无肝性脑病;或肝性脑病合并凝血障碍,PT＞15 s或INR＞1.5.这一概念对儿童有不足之处,有些儿童代谢性疾病累及肝脏,平时无症状,可突然表现为急性肝衰竭(ALF),可有脑病症状,但和ALF无关.     

儿童急性肝衰竭的肝移植治疗

儿童急性肝衰竭(PALF)是一种罕见的综合征,致死率高。肝移植仍然是目前PALF唯一疗效肯定的治疗方法。近年来,我国儿童肝移植技术日趋成熟,已显著改善PALF预后。但PALF进行肝移植仍存在许多问题,充分讨论PALF患儿行肝移植术术前、术中和术后存在的客观问题,将进一步改善PALF患儿的整体预后。     

急性肝衰竭动物模型的研究进展

急性肝衰竭是一种严重而复杂的肝脏疾病,短期病死率高,其发病机制尚未明确,亦缺乏特效药物。动物模型制备对于深层次揭露急性肝衰竭发病和药物疗效机制具有重要意义,而实验动物和制备方式的选择是研究能否有效实施的关键保障。总结了近年来常用及新型急性肝衰竭动物模型和相应制备方式,大致将急性肝衰竭动物模型分为以下四大类:化学药物模型、手术模型、感染模型及其他模型。同时,结合Terblanche和Hickman等肝衰竭模型评价标准对上述模型进行评价,希望能为此病的基础研究提供模型选择及评价参考。     

急性肝衰竭的研究概况

肝衰竭(ALF)是临床具有较高病死率的严重疾病之一,也是临床医生面临的最具挑战性的问题.ALF是肝细胞死亡的发生和程度与肝细胞的再生不平衡所产生.肝细胞死亡有两种形式,凋亡和坏死,其中急性肝衰竭引起的细胞死亡是与线粒体损伤程度密切相关.后者足以使三磷酸腺苷的贮存耗尽而引起多器官衰竭.     

急性肝衰竭的治疗进展

急性肝衰竭(ALF)是一种罕见的危及生命的疾病,病情发展迅速并影响多个器官系统功能,生存率低。早期识别病因及保护重要脏器功能对生存至关重要。近年来,随着人工肝、干细胞移植及肝移植技术不断发展,ALF疗效有明显提高。主要从ALF的病因和累及的主要器官系统两大方面阐述了ALF的治疗,并介绍了人工肝及干细胞移植的最新进展。     

急性/亚急性肝衰竭合并急性肾损伤的临床特征分析

目的初步明确急/亚急性肝衰竭(ALF/SALF)合并急性肾损伤(AKI)患者的临床特征。方法回顾性分析解放军第三〇二医院2015年1月-2016年12月收治的115例ALF/SALF患者临床资料,根据是否发生AKI分为AKI组(n=36)和无AKI组(n=79)。比较两组患者的年龄、性别、肝功能、外周血WBC水平、凝血功能、MELD评分及并发症发生情况等,观察发生AKI患者的预后情况。计量资料组间比较采用t检验,计数资料组间比较采用χ2检验。结果导致ALF/SALF的病因以药物性最为多见(49.57%),其次为不明原因(28.70%)。115例ALF/SALF患者中共36例合并AKI,AKI发生率为31.3%,其中1、2及3期发生率分别为11.30%、14.78%、5.22%。与未发生AKI的患者相比,AKI组患者年龄、WBC、中性粒细胞比值、腹水、腹腔和肺部感染率以及MELD评分均显著增高,血清Alb水平显著降低(P值均<0.05)。发生AKI的患者无效/死亡率明显高于无AKI患者(69.4%vs38.0%,χ2=9.815,P=0.002),且随AKI严重程度的增高,病死率升高,1、2及3期AKI患者无效/死亡的比例分别为61.5%、70.6%和83.3%。结论肝衰竭患者发生AKI时多存在感染或炎症反应,且AKI的发生与肝衰竭患者的病死率相关。     

急性肝衰竭的并发症

肝脏是机体的代谢中心，也是单核巨噬细胞系统重要组成部分。急性肝功能衰竭时，不但可引起氨基酸、糖及脂类代谢异常，而且由于TNF和IL-6过量产生和枯否细胞功能障碍，使内毒素和其他肝坏死毒性物质未经处理而进入血流，导致脑水肿、弥漫性血管内凝血(DIC)、消化道出血、肾功能衰竭、呼吸功能衰竭以及循环和胰腺功能障碍等一系列     

慢加急性肝衰竭并发急性肾损伤的诊治进展

慢加急性肝衰竭(ACLF)是国内最常见的肝衰竭类型,临床表现复杂,病死率高。ACLF并发急性肾损伤(AKI)时患者住院时间延长,多器官衰竭风险更高,常提示预后不良。简述了近年来ACLF并发AKI的定义、诱因、预后判断、诊断标志物、治疗等方面取得的进展,认为早期识别诊断AKI,并予以干预,有助于逆转肾损伤,避免发生重症AKI。     

新生儿急性肝衰竭的病因、诊断及治疗

新生儿急性肝衰竭是发生在新生儿期的急性肝功能完全或大部分丧失、危及生命的一种少见疾病,出生后即可有肝硬化表现,病死率高。主要病因包括妊娠期自身免疫性肝病、病毒感染、血液病、代谢性疾病和缺血性损伤及其他罕见原因等。治疗手段主要为对因治疗,病因不明或既定治疗无反应患者,肝移植仍然是其一项重要的治疗选择。目前新生儿急性肝衰竭相关研究较少,因此需要对影响治疗和预后的因素进行前瞻性研究。     

人工肝支持系统治疗慢加急性肝衰竭效果的网状Meta分析

目的采用网状Meta分析系统评价不同人工肝支持系统治疗慢加急性肝衰竭（ACLF）的疗效。方法计算机检索PubMed、EMBASE、Cochrane library、Clinical Trial、CNKI、SinoMed和万方数据库中关于不同形式人工肝治疗ACLF患者的随机对照试验。根据纳入排除标准进行文献筛选、资料提取及方法学质量评价,采用Stata15.1及R4.1.0软件进行网状Meta分析。结果共纳入14篇文献,共计1141例患者。网状Meta分析结果显示:不同干预方式交叉对比降低病死率差异均无统计学意义（P值均>0.05）,排序概率图显示降低30 d病死率血浆置换（PE）最优,其他依次为体外细胞疗法（ELAD）、分级血浆分离吸附（Prometheus）、分子吸附再循环系统（MARS）、Biologic-DT肝脏透析设备、PE+MARS。降低90 d病死率PE最优,其他依次为Prometheus、ELAD、MARS。改善肝性脑病方面,Biologic-DT最优,其他依次为MARS、PE+MARS、ELAD。出血风险最低者为ELAD,与标准医学治疗（SMT）相比Biologi...     

以亚急性肝衰竭为首发表现的IgG4相关性自身免疫性肝炎1例报告

<正>自身免疫性肝炎(AIH)是一种自身免疫反应介导的慢性进行性肝脏炎症性疾病,其临床特征为不同程度的血清转氨酶升高,IgG球蛋白增高、自身抗体阳性,组织学特征为以淋巴细胞、浆细胞浸润为主的界面性肝炎。IgG4相关性自身免疫性肝炎(immunoglobulin G4 -associated autoimmune hepatitis, IgG4-AIH)除了符合经典AIH的表现,     

慢加急性肝衰竭的发病机制和治疗进展

慢加急性肝衰竭(ACLF)是一类在慢性肝病基础上发生的以急性肝功能失代偿、肝外器官损伤和高短期死亡率为主要临床特征的严重临床综合征。欧美国家慢性肝病基础疾病以酒精性肝炎和慢性丙型肝炎为主,而我国及亚太地区以慢性乙型肝炎为主。尽管东西方肝脏基础疾病存在差异,但大多数ACLF患者发病的共同病理基础通常以长期慢性肝损伤导致的肝纤维化或肝硬化为主。目前,关于ACLF的研究正在世界各地广泛开展,但由于地域、患病人群及疾病诱因等多方面的差异,在ACLF定义、诊断标准及疾病管理等方面始终没有达成东西方共识。旨在从ACLF的定义、发病机制和疾病管理等方面展开阐述,以期为临床工作者提供能改善患者预后的新治疗策略。     

Epidemiology and outcomes of acute liver failure in Australia

BACKGROUND Acute liver failure(ALF) is a life-threatening syndrome with varying aetiologies requiring complex care and multidisciplinary management. Its changing incidence, aetiology and outcomes over the last 16 years in the Australian context remain uncertain.AIM To describe the changing incidence, aetiology and outcomes of ALF in South Eastern Australia.METHODS The database of the Victorian Liver Transplant Unit was interrogated to identify all cases of ALF in adults( 16 years) in adults hospitalised between January 2002 and December 2017. Overall, 169 patients meeting criteria for ALF were identified. Demographics, aetiology of ALF, rates of transplantation and outcomes were collected for all patients. Transplant free survival and overall survival(OS) were assessed based on survival to discharge from hospital. Results were compared to data from a historical cohort from the same unit from 1988-2001.RESULTS Paracetamol was the most common aetiology of acute liver failure, accounting for50% of cases, with an increased incidence compared with the historical cohort(P= 0.046). Viral hepatitis and non-paracetamol drug or toxin induced liver injury accounted for 15% and 10% of cases respectively. Transplant free survival(TFS)improved significantly compared to the historical cohort(52% vs 38%, P = 0.032).TFS was highest in paracetamol toxicity with spontaneous recovery in 72% of cases compared to 31% of non-paracetamol ALF(P 0.001). Fifty-nine patients were waitlisted for emergency liver transplantation. Nine of these died while waiting for an organ to become available. Forty-two patients(25%) underwent emergency liver transplantation with a 1, 3 and 5 year survival of 81%, 78% and72% respectively.CONCLUSION Paracetamol toxicity is the most common aetiology of ALF in South-Eastern Australia with a rising incidence over 30 years. TFS has improved, however it remains low in non-paracetamol ALF.     

Current concepts in acute liver failure

Acute liver failure (ALF) is a severe condition secondary to a myriad of causes associated with poor outcomes. The prompt diagnosis and identification of the aetiology allow the administration of specific treatments plus supportive strategies and to define the overall prognosis, the probability of developing complications and the need for liver transplantation. Pivotal issues are adequate monitoring and the institution of prophylactic strategies to reduce the risk of complications, such as progressive liver failure, cerebral oedema, renal failure, coagulopathies or infections. In this article, we review the main aspects of ALF, including the definition, diagnosis and complications. Also, we describe the standard-of-care strategies and recent advances in the treatment of ALF. Finally, we include our experience of care patients with ALF.     

Advances in the management of acute liver failure

Acute liver failure(ALF)is an uncommon but dramatic clinical syndrome characterized by hepatic encephalopathy and a bleeding tendency due to abrupt loss of liver function caused by massive or submassive liver necrosis in a patient with a previously healthy liver.The causes of ALF encompass a wide variety of toxic,viral,metabolic,vascular and autoimmune insults to the liver,and identifying the correct cause can be difficult or even impossible.Many patients with ALF develop a cascade of serious complications involving almost every organ system,and death is mostly due to multi-organ failure,hemorrhage,infection,and intracranial hypertension.Fortunately,the outcome of ALF has been improved in the last 3 decades through the specific treatment for the disease of certain etiology,and the advanced intensive care management.For most severely affected patients who fail to recover after treatment,rapid evaluation for transfer to a transplantation center and consideration for liver transplantation is mandatory so that transplantation can be applied before contraindications develop.This review focuses on the recent advances in the understanding of various contributing etiologies,the administration of etiology-specific treatment to alleviate the liver injury,and the management of complications(e.g.,encephalopathy,coagulopathy,cardiovascular instability,respiratory failure,renal failure,sepsis and metabolic disturbance)in patients with ALF.Assessment of the need for liver transplantation is also presented.