慢加急性肝衰竭疾病严重程度判断及临床分型:争鸣与探讨

慢加急性肝衰竭(ACLF)是在慢性肝病基础上发生的急性肝功能失代偿的临床综合征,特点是伴随多器官功能衰竭和短期高病死率[1].由于不同国家区域ACLF的病因、诱因及发病机制不同,不同学会对 ACLF的定义存在一些争议,包括是否将器官功能衰竭纳入ACLF的定义、慢性肝病基础是否包括非肝硬化的慢性肝炎,是否包括失代偿期肝硬...     

慢加急性肝衰竭研究的新视角:肝纤维化与损伤抵抗

慢加急性肝衰竭(acute-on-chronic liver failure, ACLF)是我国及亚太地区慢性肝病患者常见的危重急症,其发病机制尚未完全阐明,且目前缺乏有效的治疗方法.近年研究显示,与发生在无慢性肝病基础上的急性肝衰竭患者相比,有慢性肝病基础的患者抵抗后续急性打击的能力更强.该发现促使临床专家和基础研究者从慢性肝病基础上损伤抵抗这一新的角度出发来探讨ACLF的发病机制.本文就肝纤维化基础上损伤抵抗(模拟ACLF)现象及其细胞与分子机制的研究现状作一述评,以期为阐明ACLF的发病机制及寻找新的治疗靶点提供理论依据.     

慢加急性肝衰竭临床分型的再认识：从起病表现和动态转归的新视角重新定义

慢加急性肝衰竭（ACLF）是在慢性肝病基础上发生的急性肝功能失代偿,是以器官功能衰竭和短期高病死率为特点的复杂临床综合征。ACLF具有可逆转性,长期预后转归结局多样化。依据疾病特征进行ACLF临床分型,对优化疾病管理路径具有重要意义。本文结合东西方ACLF定义和临床特征,从起病表现和动态转归的新视角重新定义,提出ACLF新型临床分型。第一种是基于起病时肝内、外器官衰竭为特征的ACLF临床分型,包括：Ⅰ型ACLF,慢性肝病基础上的肝脏功能衰竭;Ⅱ型ACLF,慢性肝病基础上肝脏急性失代偿合并多脏器功能衰竭。第二种是基于临床转归的动态ACLF临床分型,包括A型：快速进展型,B型：快速恢复型,C型：缓慢进展型,D型：缓慢恢复型,E型：缓慢持续型。新视角ACLF临床分型的提出,期望东西方学者对ACLF疾病认识更具有包容性,缩小分歧,优化疾病管理路径,合理利用医疗资源,供临床医生借鉴。     

慢加急性肝衰竭：基于起病表现的新型临床分型特征及预后分析

目的 分析慢加急性肝衰竭(ACLF)起病时肝内、外器官衰竭特点,探索新型ACLF临床分型特征,为疾病诊治及转归提供依据。方法 回顾性收集2015年1月—2022年10月于首都医科大学附属北京佑安医院住院治疗的首次确诊为ACLF患者的临床资料。根据起病时肝内、外器官衰竭的情况,将患者分为Ⅰ型和Ⅱ型ACLF。Ⅰ型ACLF为慢性肝病基础上的肝功能衰竭;Ⅱ型ACLF为慢性肝病急性失代偿合并多脏器功能衰竭。分析Ⅰ型和Ⅱ型ACLF患者的临床特征,采用受试者工作特征曲线(ROC曲线)评估MELD、MELD-Na和CLIF-C ACLF评分系统对Ⅰ型和Ⅱ型ACLF患者90天预后的预测价值。符合正态分布的计量资料两组间比较采用成组t检验;非正态分布的计量资料两组间比较采用Wilcoxon秩和检验;计数资料两组间比较采用χ²检验或Fisher精确检验。结果 共纳入582例ACLF患者,其中Ⅰ型ACLF患者535例,Ⅱ型ACLF患者47例。两组患者的病因均以乙型肝炎和酒精性肝病为主,组间差异均无统计学意义(P值均>0.05)。Ⅰ型ACLF以慢性非肝硬化肝病(28.2%)和代偿性肝...     

慢加急性肝衰竭研究最新进展——定义、发病机制及临床管理

正慢加急性肝衰竭(ACLF)是一组由慢性肝病为基础、急性肝内外损伤为诱因,伴有多器官功能衰竭和早期高死亡率为特点的临床综合征。多器官功能衰竭尤其是肝外器官衰竭是ACLF区别于急性肝衰竭的本质所在。ACLF病程急、病情复杂且危重等特点引发了学界对这一高病死率临床综合征的关注并开展一系列研究。一、定义与诊断标准目前ACLF被广泛认可的定义是:慢性肝病或肝硬化基础     

缓慢持续型慢加急性肝衰竭与慢性肝衰竭的甄别*

正肝衰竭是多种因素引起的严重肝脏合成和代谢功能紊乱,以黄疸、凝血功能障碍为主要表现的一组临床症候群。临床常见肝衰竭类型包括慢加急性肝衰竭(acute-on-chronic liver failure,ACLF)和慢性肝衰竭。缓慢持续型ACLF与慢性肝衰竭的临床表现类似,部分缓慢持续型ACLF患者可发展为慢性肝衰竭,两者容易发生混淆。现从疾病概念、慢性肝病基础、病理学特征、起病过程、肝功能损伤的主要指标,即总胆红素和凝血功能指标、对人工肝治疗反应和疾病预后转归等方面进行如下甄别。     

慢加急性肝衰竭临床评分及分型系统的演变进程

慢加急性肝衰竭（ACLF）发病机制复杂,临床治疗困难,预后差。由于不同国家地区慢性肝病分布的不同,在过去的几十年中,有超过十种ACLF评分及分型标准被提出,表明ACLF在定义、评分及分型方面存在较大分歧。通过梳理具有广泛影响的几种评分及分型的特点,探讨其演变进程及适用于我国的分型标准,为优化治疗方案提供参考。     

慢加急性肝衰竭：从病理生理到临床实践

慢加急性肝衰竭（ACLF）是在慢性肝病基础上出现的急剧肝功能失代偿的临床症候群,其临床特征是疾病进展快、常须要多器官支持治疗、近中期病死率可高达50%以上,因而该病在临床上受到广泛关注。由于发病机制复杂等原因,目前国内外对ACLF的定义尚未达成广泛一致。从对该病的认识着手,评述国内外对ACLF概念的认识过程及差异,分析ACLF重要病理生理变化和特点及提出以此为基础的新的治疗理念和方法。因此得出,未来建立在该病病理生理机制指导下的临床实践将会收到更好的治疗效果和获得更好的预后。     

CLIF-C OFs在乙型肝炎相关慢性肝病急性失代偿患者中鉴别慢加急性肝功能衰竭的临床研究

目的探究欧洲肝病学会提出的适用于以酒精为病因引起的慢加急性肝衰竭诊断标准(CLIF Consortium Organ Failure score,CLIF-C OF)是否适用于乙型肝炎相关的慢加急性肝衰竭。方法筛选并纳入2005年1月至2010年12月上海瑞金医院乙型肝炎相关慢性肝病急性失代偿患者854例,按CLIF-C OF标准分为ACLF组和非ACLF组。分析ACLF组和非ACLF组的临床和实验室指标、病情严重程度和短期病死率。结果 ACLF组262例和非ACLF组592例。ACLF组较非ACLF组年龄大,肝、肾、脑、凝血、循环、呼吸功能衰竭情况均显著高于入院非ACLF组(P0.01),28 d和90 d病死率均显著升高(27.1%比3.1%、39.6%比4.9%,P0.01),提示病情更重。结论欧洲肝病学会所提出的评分标准可从乙型肝炎相关慢性肝病合并急性失代偿患者中筛选出一组病情更为危重、病死率更高的慢加急性肝衰竭患者群体。乙型肝炎相关慢性肝病并发急性失代偿患者中确实存在一群疾病程度更严重的ACLF群体,CLIF-C OF标准可将ACLF患者从乙型肝炎相关慢性肝病并发急性失代偿患者中区分出来,以指导临床医生治疗决策。     

慢加急性肝衰竭的定义、预后评估及诊治进展

慢加急性肝衰竭(ACLF)是一种在慢性肝病基础上发生肝功能急性失代偿的临床综合征,目前全球尚无统一定义标准。其显著特征是肝病进展迅速,常伴发多器官功能衰竭,短期病死率高。慢性肝病以慢性病毒性肝炎和酒精性肝病最为常见。感染、酒精、肝毒性药物等是其发生的主要诱因,但有高达40%～50%的ACLF病例没有可识别的诱发因素。早期发现并准确评估病情对ACLF患者至关重要,但目前仍缺乏早期预警并准确评估病情的理想方法。目前的治疗方法主要为器官支持和并发症的治疗,肝移植是唯一能够改善预后的治疗手段,但如何选择合适的患者以及肝移植的时机仍存在一定争议。     

Acute-on-chronic liver failure in children

Although various complex definitions of acute-on-chronic liver failure(ACLF)have been suggested in relation to adult patients, there is currently no universal definition of the syndrome in pediatric patients. In simplified terms, ACLF is characterized by the acute deterioration of the liver functions due to the effects of a precipitating factor on the basis of a chronic liver disease. Acute events and underlying liver diseases are very different in children from those seen in adults.Moreover, acute events and underlying chronic liver diseases vary among geographical regions, although it seems that the most common such diseases and acute events are autoimmune hepatitis, Wilson's disease, and their flares. ACLF is associated with a poor prognosis. While no scoring systems have been developed to predict the prognosis for children with ACLF, modified versions of the Asian Pacific Association for the Study of the liver's acute-on-chronic liver failure scoring system and the Chronic Liver Failure-Sequential Organ Failure Assessment criteria can be used in children until specific and validated scoring systems are available. Aside from liver transplantation, there is no proven treatment for ACLF. Thus, the early recognition of ACLF prior to the development of extrahepatic organ failure is important.     

Acute-on-chronic liver failure:Pathogenesis,prognostic factors and management

Acute-on-chronic liver failure(ACLF) is increasingly recognized as a complex syndrome that is reversiblein many cases. It is characterized by an acute deterioration of liver function in the background of a pre-existing chronic liver disease often associated with a high short-term mortality rate. Organ failure(OF) is always associated, and plays a key role in determining the course, and the outcome of the disease. The definition of ACLF remains controversial due to its overall ambiguity, with several disparate criteria among various associations dedicated to the study of liver diseases. Although the precise pathogenesis needs to be clarified, it appears that an altered host response to injury might be a contributing factor caused by immune dysfunction, ultimately leading to a pro-inflammatory status, and eventually to OF. The PIRO concept(Predisposition, Insult, Response and Organ Failure) has been proposed to better approach the underlying mechanisms. It is accepted that ACLF is a different and specific form of liver failure, where a precipitating event is always involved, even though it cannot always be ascertained. According to several studies, infections and active alcoholism often trigger ACLF. Viral hepatitis, gastrointestinal haemorrhage, or drug induced liver injury, which can also provoke the syndrome. This review mainly focuses on the physiopathology and prognostic aspects. We believe these features are essential to further understanding and providing the rationale for improveddisease management strategies.     

不同肝病基础的慢加急性肝衰竭患者临床特征和预后评分模型预测效能比较

目的 探讨不同肝病基础的慢加急性肝衰竭(ACLF)患者临床特征及其各预后评分模型对病情判断的价值。方法 采用回顾性队列研究分析2017年1月～2018年12月我院收治的262例ACLF患者的临床资料,排除70例,在纳入的192例患者中,其肝病基础分别为非肝硬化慢性肝病(A组,n=54)、代偿期肝硬化(B组,n=87)和失代偿期肝硬化(C组,n=51)。分别采用Child-Pugh评分、MELD评分、欧洲肝病学会慢性肝衰竭研究组CLIF-C ACLF评分模型和中国重型乙型肝炎研究组(COSSH)模型预测28 d和90 d生存情况。结果 三组性别、年龄和病因构成比相比,均无显著性差异(P>0.05);三组血清TBIL和INR均无显著性差异(P >0.05);C组腹水和细菌感染发生率分别为70.6%和47.1%,显著高于B组的62.1%和33.3%或A组的40.7%和22.2%(P <0.05);A组28 d和90 d生存率分别为63.0%和59.3%,与B组的69.0% 和57.5%或C组的56.9%和47.1%比,均无显著性差异(P >0.05);血清TBIL、Cr、INR和肝性脑病是ACLF患者90 d死亡的影响因素;MELD、CLIF-C ACLFs和COSSH-ACLFs模型预测生存的效能显著优于Child-Pugh评分,而以MELD评分的效能最优。结论 不同肝病基础的ACLF患者临床特征和并发症存在差异,预后也存在一定的差异,可能需要更长时间的观察。     

慢加急性肝衰竭的国际标准与临床管理优化

慢加急性肝衰竭(ACLF)是明显区别于急性肝衰竭和单纯肝硬化急性失代偿的一类临床群体。起病于慢性肝病基础上,急性进展可出现肝脏以及肝外多器官衰竭,短期死亡率高,已成为全球的经济卫生负担。近年来,几大国际性肝病学会提出了不同的ACLF诊断标准并相继发布了各自定义下的ACLF诊疗共识或综述,在慢性肝病、急性损伤、器官衰竭等方面的理解存在较大分歧。目前我国在ACLF管理各个关键环节,如肝移植、ICU和姑息治疗方面数据仍较为有限,在全球ACLF诊断尚未达成共识的背景下,需进一步加强国际已有标准和证据的借鉴运用以及国内循证医学证据的积累。     

Acute kidney injury in acute on chronic liver failure

Acute on chronic liver failure (ACLF) is a distinct clinical entity; however, there is still debate in the way it is defined in the East as compared to the West, especially with respect to incorporation of kidney dysfunction or failure in the definition of ACLF. Kidney dysfunction is defined as serum creatinine between 1.5 and 1.9 mg/dl and kidney failure as serum creatinine of more than 2 mg/dl or requirement of renal replacement therapy according to the EASL-CLIF Consortium. Kidney dysfunction or failure is universally present in patients with ACLF according to the definition by the EASL-CLIF Consortium while on the contrary the APASL definition of ACLF does not incorporate kidney dysfunction or failure in its definition. Recently, both the diagnosis and management of renal failure in patients with cirrhosis has changed with the advent of the acute kidney injury (AKI) criteria defined as an abrupt decline in renal functions, characterized by an absolute increase in serum creatinine of 0.3 mg/dl within 48 h or an increase of more than 50 % from baseline, which is known or presumed to have occurred in the previous 7 days. Further, recent studies in patients with cirrhosis have shown the utility of biomarkers for the diagnosis of AKI. The present review covers the pathogenetic mechanisms, diagnosis, prognosis as well as management of AKI in patients with ACLF from both a Western as well as an Eastern perspective. The review identifies an unmet need to diagnose AKI and prevent this ominous complication in patients with ACLF.     

慢加急性肝衰竭与慢性肝衰竭临床特征对比性分析

目的了解慢加急性肝衰竭(ACLF)与慢性肝衰竭(CLF)的临床特征及预后差异。方法 103例慢性重型肝炎患者按肝衰竭诊疗指南分为ACLF组(35例)和CLF组(68例),比较两组临床及实验室指标、常见并发症、MELD评分及预后。结果 CLF在慢性重型肝炎中占66.02%(68/103),患者年龄较大、病程较长;两组在血常规参数(WBC、HB、PLT、MPV)和凝血指标(PT、APTT、TT)均有差异(P<0.05,P<0.01);ACLF组肝功能AST、ALT、TBIL、ALB高于CLF组,GLO、TBA低于CLF组(P<0.05,P<0.01);两组腹水和肝性脑病发生率差异有统计学意义(P<0.01);ACLF组MELD分值低于CLF组,其预后优于CLF组(P<0.05,P<0.01)。结论 ACLF和CLF在好发年龄、病程、血常规参数、凝血功能、肝功能指标、并发症腹水和肝性脑病发生率、MELD评分及预后均有差异。肝衰竭指南符合国情,有重要的临床应用价值。     

Defining acute-on-chronic liver failure: East,West or Middle ground?

Acute-on-chronic liver failure(ACLF),a newly recognized clinical entity seen in hospitalized patients with chronic liver disease including cirrhosis,is associated with high short- and medium term morbidity and mortality.Noneof the definitions of ACLF proposed so far have been universally accepted,the two most commonly used being those proposed by the Asia-Pacific Association for the Study of Liver(APASL) and the European Association for the Study of Liver- Chronic Liver Failure(EASL-CLIF) consortium.On paper both definitions and diagnostic criteria appear to be different from each other,reflecting the differences in cut-off values for individual parameters used in diagnosis,the acute insult or precipitating event and the underlying chronic liver disease.Data directly comparing these two criteria are limited,and available studies reveal different outcomes when the two are applied to the same set of patients.However a review of the literature suggests that both definitions do not seem to identify the same set of patients.The definition given by the APASL consortium is easier to apply in day-to-day practice but the EASLCLIF criteria appear to better predict mortality in ACLF.The World Gastroenterology Organization working party have proposed a working definition of ACLF which will identify patients from whom relevant data can be collected so that the similarities and the differences between the two regions,if any,can be clearly defined.     

Acute-on-chronic liver failure: Controversies and consensus

Acute-on-chronic liver failure (ACLF) is a poorly defined syndrome characterised by rapid clinical deterioration in patients with chronic liver disease. Consequences include high short-term morbidity, mortality, and healthcare resource utilisation. ACLF encompasses a dysregulated, systemic inflammatory response, which can precipitate extra hepatic organ failures. Common precipitants include infection, alcoholic hepatitis, and reactivation of viral hepatitis although frequently no cause is identified. Heterogenous definitions, diagnostic criteria, and treatment guidelines, have been proposed by international hepatology societies. This can result in delayed or missed diagnoses of ACLF, significant variability in clinical management, and under-estimation of disease burden. Liver transplantation may be considered but the mainstay of treatment is organ support, often in the intensive care unit. This review will provide clarity around where are the controversies and consensus in ACLF including: Epidemiology and resource utilisation, key clinical and diagnostic features, strategies for management, and research gaps.     

Prognostic factors in acute-on-chronic liver failure: A prospective study from western India

The profile of acute-on-chronic liver failure (ACLF) has not been reported from western India. This study was undertaken to analyze the etiology and clinical profile of patients with ACLF and correlate these with outcome. Fifty-four consecutive cases of ACLF were investigated for underlying chronic liver disease (CLD) and acute insult and followed up for 6 months. Mortality, Child–Pugh score, and model for end-stage liver disease (MELD) score were recorded. The most common etiologies of CLD were hepatitis B (29.6 %) and cryptogenic (27.7 %). Prognosis was worse in patients with hepatitis B or alcohol as cause of CLD (mortality 79 %). Acute viral hepatitis A or E was the commonest cause of acute insult (33.3 %) and with statistically better outcome (60 % survival) as compared to sepsis, gastrointestinal bleed, or flare of HBV (survival 5 %, p < 0.05). On univariate analysis age, past history of decompensation, leukocytosis, serum bilirubin and creatinine, international normalized ratio, presence of spontaneous bacterial peritonitis, Child–Pugh score and hepatorenal syndrome were significant predictors of mortality. Multivariate analysis revealed a MELD score of >27 and presence of encephalopathy as independent predictors of mortality. Patients with ACLF had high mortality especially when they had underlying chronic hepatitis B or alcoholic liver disease. Presence of encephalopathy and MELD score were independent baseline predictors of mortality. Child–Pugh score was helpful for prognostication.