慢性慢性肝衰竭：一种全球性疾病

StephenW

Acute-on-chronic liver failure: a global disease

    Martin Schulz1, http://orcid.org/0000-0002-7028-3881Jonel Trebicka1,2

    Translational Hepatology, Department of Internal Medicine I, Goethe University Frankfurt, Frankfurt am Main, Germany
    European Foundation for the Study of Chronic liver Failure, EFCLIF, Barcelona, Spain

    Correspondence to Dr Jonel Trebicka, Translational Hepatology Department of Internal Medicine I, Goethe University Frankfurt, Frankfurt am Main 7, 60590, Hessen, Germany; [email protected]

http://dx.doi.org/10.1136/gutjnl-2020-323973
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Acute-on-chronic liver failure (ACLF) is a frequent complication in hospitalised patients with liver cirrhosis. A large body of data has been published in recent years, demonstrating that acute decompensation constitutes a dramatic turning point in the course of cirrhosis, with development of ACLF being the most severe form of acute decompensation (AD).1 Within the last decades, heterogeneous definitions of ACLF have been proposed in different regions of the world, that is, the European European Association for the Study of the Liver - Chronic Liver Failure (EASL-CLIF) definition, the NASCELD definition in North American and the East Asian APASL criteria. Due to those, epidemiological data on ACLF are heterogenous and not easy to compare.

In Gut, Mezzano and colleagues have undertaken huge efforts to homogenise and compare the existing evidence.2 They present an extensive systematic review and meta-analysis on the burden of ACLF worldwide (figure 1A), which constitutes the largest epidemiological study on this subject to date.3 The authors were able to identify 30 prospective and retrospective cohort studies from around the world, which include 43 206 ACLF patients and 140 835 patients without ACLF. Strengths of this study are its scale and the robustness of data, which highlight the global significance of ACLF for patients and healthcare systems.

The authors chose the EASL-CLIF ACLF criteria as the more balanced between east and west. This meta-analysis demonstrated, that 35% of patients admitted with decompensated cirrhosis worldwide presented an ACLF at hospital admission, with a 60% mortality in the first 90 days. Interestingly, the 90-day mortality rates differed by region, showing the highest mortality in South America (73%) and South Asia (68%), rendering this study the first to map geographic differences in ACLF outcomes (figure 1B). As in the CANONIC study, kidney failure seems to be the most common with almost 50% worldwide, whereas respiratory failure was the least common organ failure reported with 11%. However, this may be under-represented due to the portion of patients followed by hepatologists, while intensive care physicians work less frequently in this field. Interestingly, alcohol was the most frequent aetiology of underlying cirrhosis with 45% worldwide, showing the highest prevalence in Europe. Importantly, this should again raise the awareness of the community to dedicate efforts and funds to this stigmatised and neglected population of patients. Regional differences were also reported in the prevalence of alcohol consumption as the precipitating event triggering ACLF with the highest in East Asia and North America with 30%, followed by Europe with 25%. Yet, the most frequent ACLF trigger events portrayed in this meta-analysis were bacterial infections in 35%, followed by gastrointestinal bleeding 22% and alcohol 19% globally. In Europe and South Asia, almost 50% of ACLF patients showed bacterial infection as ACLF precipitating event. This finding was also confirmed in a recent multicentric prospective study, Predicting Acute on Chronic Liver Failure (PREDICT).4 5 The large prospective PREDICT trial, which has not been included in this meta-analysis since its results have only been published recently, has classified and evaluated precipitating events prospectively and their role on outcomes.5 PREDICT included 1273 European patients, who were non-electively hospitalised with acute decompensation. It showed bacterial infection and severe alcoholic hepatitis, either alone or in combination, accounted for almost all (96%–97%) acute decompensations and ACLF in its cohort.5 Furthermore, it was able to show that the type of ACLF trigger did not influence patient’s outcome, whereas number of precipitating events did. Yet, objective criteria for the classification of precipitants in the studies included in this meta-analysis were missing. Therefore, it has to be stated, that the data are probably not entirely consistent with the PREDICT study and possibly reality.

Nevertheless, this systematic review and meta-analysis draws the attention to the global significance of ACLF. Recent concepts are, that ACLF is one form of acutely decompensated cirrhosis, but PREDICT could characterise the other forms.4 A very severe form is pre-ACLF, mainly driven by systemic inflammation, which has since been validated in Chinese cohorts.6 A different phenotype in AD is unstable decompensated cirrhosis, which is mainly driven by portal hypertension.7 8 In addition, stable decompensated cirrhosis patients constitute a major part of patients acute decompensation. These different courses of disease are not reflected in studies included in this meta-analysis. It will be a major challenge for investigations in the future to allow early identification of acute decompensation phenotypes and to stratify patients for individual risk for disease progression. One step in this direction was the introduction of the M10LS20 algorithm, which allows bed-side stratification of patients with advanced chronic liver disease based on Model for Endstage Liver Disease (MELD) and liver shear-wave elastography (L-SWE).9

In summary, this meta-analysis, conducted by Mezzano and colleagues, is the first study to gather worldwide epidemiological data on prevalence and mortality of ACLF to systematically evaluate the global burden of disease (see figure 1). Even though the authors chose to restrict study inclusion by EASL-CLIF definition of ACLF, the significance of the general conclusions drawn from this meta-analysis remain most relevant. ACLF is highly prevalent worldwide in hospitalised patients with acute decompensation and is associated with high short-term mortality. This fact urges for unified international criteria defining acute decompensation and recommendations on patient’s management.

StephenW

慢性慢性肝衰竭：一种全球性疾病

    Martin Schulz1，http：//orcid.org/0000-0002-7028-3881Jonel Trebicka1,2

    法兰克福歌德大学第一医学科内科转化性肝病，德国美因河畔法兰克福
    欧洲慢性肝衰竭研究基金会，EFCLIF，西班牙巴塞罗那

    通讯作者：德国歌德大学法兰克福歌德大学内科一内科转化性肝病学系Jonel Trebicka博士，德国黑森州60590；乔纳尔·特雷比卡（@ kgu.de）

http://dx.doi.org/10.1136/gutjnl-2020-323973
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慢性肝功能衰竭（ACLF）是住院肝硬化患者的常见并发症。近年来已发布了大量数据，表明急性代偿失调是肝硬化过程中的一个重大转折点，ACLF的发展是急性代偿失调（AD）的最严重形式。1在过去的几十年中，异质性在世界不同地区已经提出了ACLF的定义，即欧洲肝病-慢性肝衰竭研究协会（EASL-CLIF）定义，北美的NASCELD定义和东亚APASL标准。由于这些原因，ACLF的流行病学数据是异类的，不容易比较。

Mezzano及其同事在古特（Gut）方面进行了巨大的努力，以均质化和比较现有证据。2他们对全球ACLF的负担进行了广泛的系统综述和荟萃分析（图1A），构成了有关该主题的最大的流行病学研究。 date.3作者能够确定来自世界各地的30项前瞻性和回顾性队列研究，其中包括43至206位ACLF患者和140至835位无ACLF的患者。这项研究的优势在于其规模和数据的可靠性，突出了ACLF对患者和医疗系统的全球意义。

作者选择EASL-CLIF ACLF标准作为东西方之间的平衡点。这项荟萃分析表明，全球有35％的失代偿性肝硬化患者入院时出现ACLF，在最初90天内死亡率为60％。有趣的是，不同地区的90天死亡率不同，显示出南美（73％）和南亚（68％）的最高死亡率，这使该研究首次绘制了ACLF结果的地理差异（图1B）。就像在CANONIC研究中一样，肾脏衰竭似乎是最常见的，占全球的近50％，而呼吸衰竭是最不常见的器官衰竭，据报道为11％。但是，由于肝脏科医生紧随其后的部分患者，这可能不足以表示，而重症监护医师在该领域的工作频率较低。有趣的是，酒精是潜在的肝硬化最常见的病因，全球范围内为45％，显示出欧洲患病率最高。重要的是，这应该再次提高社区的意识，即为这种被污名化和被忽视的患者群体奉献努力和资金。据报道，酒精消费的流行程度也存在地区差异，因为该事件触发了ACLF，其在东亚和北美洲的比例最高，为30％，其次是欧洲的25％。然而，这项荟萃分析中最常见的ACLF触发事件是35％的细菌感染，其次是胃肠道出血22％和酒精19％。在欧洲和南亚，几乎有50％的ACLF患者显示细菌感染为ACLF沉淀事件。最近的一项多中心前瞻性研究《预测慢性肝衰竭的急性发作（PREDICT）》也证实了这一发现。45大型前瞻性PREDICT试验因其研究结果仅在最近发表，因此并未纳入该荟萃分析对前瞻性事件及其在结果中的作用进行分类和评估。5PREDICT包括1273名欧洲患者，他们因急性失代偿而在非自愿性的情况下住院。它表明细菌感染和严重酒精性肝炎，无论是单独还是联合使用，几乎都占其队列中所有急性失代偿的（96％–97％）和ACLF。5此外，它能够表明ACLF触发类型并没有影响患者的预后，而促发性事件的数量确实如此。然而，这项荟萃分析中所包括的研究中，对于沉淀剂分类的客观标准仍然缺失。因此，必須指出，這些數據可能與PREDICT的研究和現實情況並不完全一致。

然而，這種系統的綜述和薈萃分析吸引了人們對ACLF的全球意義的關注。最近的觀念是，ACLF是急性失代償性肝硬化的一種形式，但PREDICT可以作為其他形式的特徵。4ACLF前是一種非常嚴重的形式，主要由全身性炎症驅動，此現像已在中國隊列中得到驗證。6 AD的表型是不穩定的失代償性肝硬化，這主要是由門脈高壓引起的。78此外，穩定的失代償性肝硬化患者構成急性失代償患者的主要部分。這些不同的病程未反映在本薈萃分析中的研究中。允許早期識別急性代償表型和對患者進行疾病發展的個體風險分層將是未來研究的主要挑戰。朝此方向邁出的一步是，引入了M10LS20算法，該算法可根據晚期肝病模型（MELD）和肝切波彈性成像（L-SWE）9對晚期慢性肝病患者進行床旁分層。9

總而言之，由Mezzano及其同事進行的這項薈萃分析是第一項收集有關ACLF患病率和死亡率的全球流行病學數據以系統評估全球疾病負擔的研究（見圖1）。儘管作者選擇通過EASL-CLIF對ACLF的定義來限制研究的納入，但從該薈萃分析得出的一般結論的重要性仍然最重要。 ACLF在急性代償失調的住院患者中非常普遍，與短期死亡率高有關。這一事實敦促採用統一的國際標準來定義急性代償失調，並就患者管理提出建議。

StephenW

https://gut.bmj.com/content/gutj ... 020-323973.full.pdf