进展性慢性肝病发生慢加急性肝衰竭的风险预测及分层管理

祁婷婷; 陈金军

doi:10.3969/j.issn.1001-5256.2023.10.005

进展性慢性肝病发生慢加急性肝衰竭的风险预测及分层管理

DOI: 10.3969/j.issn.1001-5256.2023.10.005

祁婷婷^{1, 2},
陈金军^{1, 2, 3, , ,}

1.
南方医科大学南方医院肝病中心，广州 510515
2.
广东省肝脏疾病研究所，广州 510515
3.
南方医科大学南方医院增城院区肝病科，广州 511300

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：祁婷婷负责查找文献及撰写文稿；陈金军确定文稿撰写思路及修改。

详细信息

通信作者:
陈金军， chjj@smu.edu.cn （ORCID： 0000－0003－4275－9149）

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出版历程
- 收稿日期: 2023-07-06
- 出版日期: 2023-10-30

Development of acute－on－chronic liver failure in progressive chronic liver diseases： Risk prediction and stratified management

Tingting QI^{1, 2},
Jinjun CHEN^{1, 2, 3
, ,
,}

1.
Liver Disease Center，Nanfang Hospital，Southern Medical University，Guangzhou 510515，China
2.
Guangdong Provincial Institute of Liver Diseases，Guangzhou 510515，China
3.
Department of Hepatology，Zengcheng Branch of Nanfang Hospital，Southern Medical University，Guangzhou 511300，China

More Information

Corresponding author: CHEN Jinjun， chjj@smu.edu.cn （ORCID： 0000－0003－4275－9149）

摘要

摘要: 进展性慢性肝病患者因肝炎活动、急性失代偿或肝衰竭及其并发症住院，病情严重程度不一，需要分层管理。慢加急性肝衰竭（ACLF）是进展性慢性肝病患者中短期病死率最高的群体，均应在三级医院诊治。未达到ACLF的患者虽然病死率相对较低，但存在进展至ACLF的风险，一旦进展到ACLF，病死率明显增加，需进行分层管理：其中进展率极低的患者转归良好，在基层医院救治即可；而有进展至ACLF风险的高危人群，应当密切监视病情变化，及时转诊。目前尚缺乏准确评估进展至ACLF风险的预测模型，需要进一步研究新的标志物或算法。
- 慢加急性肝功能衰竭 /
- 进展性慢性肝病 /
- 模型，统计学 /
- 生物标记
Abstract: Patients with advanced chronic liver disease （ACLD） are hospitalized due to hepatitis， acute decompensation or liver failure and its complications， and they often require stratified management due to different severities. The patients with acute－on－chronic liver failure （ACLF） have the highest short－term mortality rate among ACLD patients and should be treated in tertiary hospitals. Although non－ACLF patients tend to have a relatively low mortality rate， they still have the risk of progression to ACLF， and there is a significant increase in mortality rate after progression to ACLF， which requires stratified management. The patients with extremely low progression rates often have favorable clinical outcomes and can be administrated in primary hospitals， while the high－risk population should be closely monitored and timely transferred in case of disease progression. However， currently there is still a lack of accurate predictive models for evaluating the risk of progression to ACLF， and further studies are needed to find new biomarkers or algorithms.
- Acute－On－Chronic Liver Failure /
- Advanced Chronic Liver Disease /
- Models， Statistical /
- Biomarkers

HTML全文

表 1 Padua－AD模型^［20］

Table 1. Padua－AD model^［20］

表 2 ACLD住院患者发生ACLF的主要预测模型

Table 2. Major predictive models for developing ACLF among hospitalized patients with ACLD

模型或研究名称	模型或要素	国家或地区	纳入人群	ACLF 诊断标准	截断值	AUC	C－指数	参考文献
CLIF－C ACLF－D	［0.03×年龄+0.45×腹水+ 0.26×ln（白细胞计数）］－（0.37×白蛋白）+［0.57×ln（总胆红素）］+［1.72×ln（血肌酐）］+3×10	欧洲	肝硬化急性失代偿患者，酒精性肝病为主，（MELD：28±8）	EASL	NA	NA	90天：0.76 （0.72～0.80）	［10］
COSSH－onset－ACLF	0.101×ln（ALT）+0.819×ln（总胆红素）+2.820×ln（INR）+ 0.016×ln（铁蛋白）	中国	HBV相关慢性肝病，急性肝炎活动或急性失代偿（MELD：NA）	COSSH	6.3	7天：0.939 14天：0.939 28天：0.926	7天：0.928 （0.910～0.947） 14天：0.925 （0.908～0.943） 28天：0.913 （0.892～0.934）	［18］
CATCH－LIFE	－7.71+1.38×（HBV再激活合并急性肝损伤）+0.74×（自发性再燃伴有高HBV DNA载量）+1.50×（HAV或HEV重叠感染）+0.91×（细菌感染）+ 0.81×ln（总胆红素）+4.17×ln（INR）+0.63×ln（中性粒细胞与淋巴细胞比值）	中国	HBsAg阳性肝硬化急性失代偿［MELD：17（12～23）］	EASL	0.22	28天：0.902（0.874～0.930）	28天：0.902 （0.874～0.930）	［11］
Padua－AD模型	CLIF－C AD、Child－Pugh分级、CRP	意大利	肝硬化急性失代偿，酒精性肝病为主，［MELD：20（14~25）］	EASL	NA	1年：0.86 （0.80～0.92）	NA	［20］
PATA模型	0.341+3.111×凝血酶原时间+ 0.595×年龄+0.626×总胆红素－0.295×ALT	中国	慢性乙型肝炎急性加重患者（MELD：NA）	APASL	0.614	90天：0.959（0.941～0.977）	NA	［19］
注：NA，原文中未提供。

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参考文献(43)

[1]	de FRANCHIS R, FACULTY BV. Expanding consensus in portal hypertension: Report of the Baveno VI Consensus Workshop: Stratifying risk and individualizing care for portal hypertension[J]. J Hepatol, 2015, 63( 3): 743－ 752. DOI: 10.1016/j.jhep.2015.05.022.
[2]	de FRANCHIS R, BOSCH J, GARCIA－TSAO G, et al. Baveno VII－Renewing consensus in portal hypertension[J]. J Hepatol, 2022, 76( 4): 959－ 974. DOI: 10.1016/j.jhep.2021.12.022.
[3]	JALAN R, D’AMICO G, TREBICKA J, et al. New clinical and pathophysiological perspectives defining the trajectory of cirrhosis[J]. J Hepatol, 2021, 75( Suppl 1): S14－S26. DOI: 10.1016/j.jhep.2021.01.018.
[4]	MOREAU R, JALAN R, GINES P, et al. Acute－on－chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis[J]. Gastroenterology, 2013, 144( 7): 1426－ 1437, e1－ 1437.e 9. DOI: 10.1053/j.gastro.2013.02.042.
[5]	BAJAJ JS, O’LEARY JG, REDDY KR, et al. Survival in infection－related acute－on－chronic liver failure is defined by extrahepatic organ failures[J]. Hepatology, 2014, 60( 1): 250－ 256. DOI: 10.1002/hep.27077.
[6]	SARIN SK, CHOUDHURY A, SHARMA MK, et al. Acute－on－chronic liver failure: Consensus recommendations of the Asian Pacific Association for the Study of the Liver(APASL): An update[J]. Hepatol Int, 2019, 13( 4): 353－ 390. DOI: 10.1007/s12072－019－09946－3.
[7]	WU TZ, LI J, SHAO L, et al. Development of diagnostic criteria and a prognostic score for hepatitis B virus－related acute－on－chronic liver failure[J]. Gut, 2018, 67( 12): 2181－ 2191. DOI: 10.1136/gutjnl－2017－314641.
[8]	Liver Failure and Artificial Liver Group, Chinese Society of Infectious Diseases, Chinese Medical Association; Severe Liver Disease and Artificial Liver Group, Chinese Society of Hepatology, Chinese Medical Association. Guideline for diagnosis and treatment of liver failure(2018)[J]. J Clin Hepatol, 2019, 35( 1): 38－ 44. DOI: 10.3969/j.issn.1001－5256.2019.01.007. 中华医学会感染病学分会肝衰竭与人工肝学组, 中华医学会肝病学分会重型肝病与人工肝学组. 肝衰竭诊治指南(2018年版)[J]. 临床肝胆病杂志, 2019, 35( 1): 38－ 44. DOI: 10.3969/j.issn.1001－5256.2019.01.007.
[9]	European Association for the Study of the Liver. EASL clinical practice guidelines on acute－on－chronic liver failure[J]. J Hepatol, 2023, 79( 2): 461－ 491. DOI: 10.1016/j.jhep.2023.04.021.
[10]	TREBICKA J, FERNANDEZ J, PAPP M, et al. The PREDICT study uncovers three clinical courses of acutely decompensated cirrhosis that have distinct pathophysiology[J]. J Hepatol, 2020, 73( 4): 842－ 854. DOI: 10.1016/j.jhep.2020.06.013.
[11]	WANG TY, TAN WT, WANG XB, et al. Role of precipitants in transition of acute decompensation to acute－on－chronic liver failure in patients with HBV－related cirrhosis[J]. JHEP Rep, 2022, 4( 10): 100529. DOI: 10.1016/j.jhepr.2022.100529.
[12]	TANG XT, QI TT, LI BL, et al. Pre－acute－on－chronic liver failure in hepatitis B－related patients[J]. J Hepatol, 2021, 74( 2): 479－ 480. DOI: 10.1016/j.jhep.2020.09.001.
[13]	LI H, CHEN LY, ZHANG NN, et al. Characteristics, diagnosis and prognosis of acute－on－chronic liver failure in cirrhosis associated to hepatitis B[J]. Sci Rep, 2016, 6: 25487. DOI: 10.1038/srep25487.
[14]	SHI Y, YANG Y, HU YR, et al. Acute－on－chronic liver failure precipitated by hepatic injury is distinct from that precipitated by extrahepatic insults[J]. Hepatology, 2015, 62( 1): 232－ 242. DOI: 10.1002/hep.27795.
[15]	QI TT, ZHU CY, WANG JP, et al. MELD score<18 rule out 28－day ACLF development among inpatients with hepatitis B－related previous compensated liver disease[J]. J Viral Hepat, 2022, 29( 12): 1089－ 1098. DOI: 10.1111/jvh.13747.
[16]	JALAN R, PAVESI M, SALIBA F, et al. The CLIF Consortium Acute Decompensation score(CLIF－C ADs) for prognosis of hospitalised cirrhotic patients without acute－on－chronic liver failure[J]. J Hepatol, 2015, 62( 4): 831－ 840. DOI: 10.1016/j.jhep.2014.11.012.
[17]	LUO JJ, LIANG X, XIN JJ, et al. Serum ferritin diagnosis and prediction of hepatitis B virus－related acute－on－chronic liver failure[J]. J Med Virol, 2023, 95( 1): e28183. DOI: 10.1002/jmv.28183.
[18]	LUO JJ, LIANG X, XIN JJ, et al. Predicting the onset of hepatitis B virus－related acute－on－chronic liver failure[J]. Clin Gastroenterol Hepatol, 2023, 21( 3): 681－ 693. DOI: 10.1016/j.cgh.2022.03.016.
[19]	YU MX, LI XY, LU YX, et al. Development and validation of a novel risk prediction model using recursive feature elimination algorithm for acute－on－chronic liver failure in chronic hepatitis B patients with severe acute exacerbation[J]. Front Med, 2021, 8: 748915. DOI: 10.3389/fmed.2021.748915.
[20]	ZANETTO A, PELIZZARO F, CAMPELLO E, et al. Severity of systemic inflammation is the main predictor of ACLF and bleeding in individuals with acutely decompensated cirrhosis[J]. J Hepatol, 2023, 78( 2): 301－ 311. DOI: 10.1016/j.jhep.2022.09.005.
[21]	TANG XT, LI H, DENG GH, et al. New algorithm rules out acute－on－chronic liver failure development within 28 days from acute decompensation of cirrhosis[J]. J Clin Transl Hepatol, 2023, 11( 3): 550－ 559. DOI: 10.14218/JCTH.2022.00196.
[22]	ARROYO V, ANGELI P, MOREAU R, et al. The systemic inflammation hypothesis: Towards a new paradigm of acute decompensation and multiorgan failure in cirrhosis[J]. J Hepatol, 2021, 74( 3): 670－ 685. DOI: 10.1016/j.jhep.2020.11.048.
[23]	WANG Y, XU Y, SUN W, et al. Value of interleukin－6 combined with Model for End－Stage Liver Disease score in predicting the prognosis of hepa－titis B virus－related acute－on－chronic liver failure[J]. J Clin Hepatol, 2022, 38( 8): 1774－ 1779. DOI: 10.3969/j.issn.1001－5256.2022.08.011. 王艳, 徐英, 孙蔚, 等. IL－6联合终末期肝病模型评分对HBV相关慢加急性肝衰竭预后的预测价值[J]. 临床肝胆病杂志, 2022, 38( 8): 1774－ 1779. DOI: 10.3969/j.issn.1001－5256.2022.08.011.
[24]	MURAKAMI S, IMAMURA M, UCHIDA T, et al. Correction to: Serum interleukin－6 level predicts the prognosis for patients with alcohol－related acute－on－chronic liver failure[J]. Hepatol Int, 2023. DOI: 10.1007/s12072－023－10555－4.[ Online ahead of print]
[25]	SCHWARZKOPF K, RÜSCHENBAUM S, BARAT S, et al. IL－22 and IL－22－binding protein are associated with development of and mortality from acute－on－chronic liver failure[J]. Hepatol Commun, 2019, 3( 3): 392－ 405. DOI: 10.1002/hep4.1303.
[26]	YUAN W, MEI X, ZHANG YY, et al. High expression of interleukin－33/ST2 predicts the progression and poor prognosis in chronic hepatitis B patients with hepatic flare[J]. Am J Med Sci, 2020, 360( 6): 656－ 661. DOI: 10.1016/j.amjms.2020.06.023.
[27]	GRØNBÆK H, RØDGAARD－HANSEN S, AAGAARD NK, et al. Macrophage activation markers predict mortality in patients with liver cirrhosis without or with acute－on－chronic liver failure(ACLF)[J]. J Hepatol, 2016, 64( 4): 813－ 822. DOI: 10.1016/j.jhep.2015.11.021.
[28]	ZHAO RH, WU W, ZHOU ZB, et al. Prognostic utility of novel biomarkers in acute－on－chronic liver failure(ACLF) associated with hepatitis B: A multicenter prospective study[J]. Hepatol Res, 2019, 49( 1): 42－ 50. DOI: 10.1111/hepr.13251.
[29]	KERBERT AJC, VERSPAGET HW, ÀA NAVARRO, et al. Copeptin in acute decompensation of liver cirrhosis: Relationship with acute－on－chronic liver failure and short－term survival[J]. Crit Care, 2017, 21( 1): 321. DOI: 10.1186/s13054－017－1894－8.
[30]	PONZIANI FR, SANTOPAOLO F, GASBARRINI A, et al. From coagulation imbalance to prediction of advanced chronic liver disease decompensation: The wind of change?[J]. J Hepatol, 2023, 79( 1): e25－e27. DOI: 10.1016/j.jhep.2022.12.027.
[31]	SCHEINER B, BALCAR L, NUSSBAUMER RJ, et al. Factor VIII/protein C ratio independently predicts liver－related events but does not indicate a hypercoagulable state in ACLD[J]. J Hepatol, 2022, 76( 5): 1090－ 1099. DOI: 10.1016/j.jhep.2021.12.038.
[32]	ENOMOTO M, TAKAYA H, NAMISAKI T, et al. Ratio of von Willebrand factor antigen to ADAMTS13 activity is a useful biomarker for acute－on－chronic liver failure development and prognosis in patients with liver cirrhosis[J]. Hepatol Res, 2022, 52( 4): 390－ 400. DOI: 10.1111/hepr.13743.
[33]	TAKAYA H, NAMISAKI T, ASADA S, et al. ADAMTS13, VWF, and endotoxin are interrelated and associated with the severity of liver cirrhosis via hypercoagulability[J]. J Clin Med, 2022, 11( 7): 1835. DOI: 10.3390/jcm11071835.
[34]	JACHS M, HARTL L, SIMBRUNNER B, et al. Decreasing von willebrand factor levels upon nonselective beta blocker therapy indicate a decreased risk of further decompensation, acute－on－chronic liver failure, and death[J]. Clin Gastroenterol Hepatol, 2022, 20( 6): 1362－ 1373.e 6. DOI: 10.1016/j.cgh.2021.07.012.
[35]	ARIZA X, GRAUPERA I, COLL M, et al. Neutrophil gelatinase－associated lipocalin is a biomarker of acute－on－chronic liver failure and prognosis in cirrhosis[J]. J Hepatol, 2016, 65( 1): 57－ 65. DOI: 10.1016/j.jhep.2016.03.002.
[36]	MARKWARDT D, HOLDT L, STEIB C, et al. Plasma cystatin C is a predictor of renal dysfunction, acute－on－chronic liver failure, and mortality in patients with acutely decompensated liver cirrhosis[J]. Hepatology, 2017, 66( 4): 1232－ 1241. DOI: 10.1002/hep.29290.
[37]	JUANOLA A, GRAUPERA I, ELIA C, et al. Urinary L－FABP is a promising prognostic biomarker of ACLF and mortality in patients with decompensated cirrhosis[J]. J Hepatol, 2022, 76( 1): 107－ 114. DOI: 10.1016/j.jhep.2021.08.031.
[38]	LI J, LIANG X, JIANG J, et al. PBMC transcriptomics identifies immune－metabolism disorder during the development of HBV－ACLF[J]. Gut, 2022, 71( 1): 163－ 175. DOI: 10.1136/gutjnl－2020－323395.
[39]	SUN ZY, LIU XL, WU DX, et al. Circulating proteomic panels for diagnosis and risk stratification of acute－on－chronic liver failure in patients with viral hepatitis B[J]. Theranostics, 2019, 9( 4): 1200－ 1214. DOI: 10.7150/thno.31991.
[40]	WEISS E, DE LA PEÑA－RAMIREZ C, AGUILAR F, et al. Sympathetic nervous activation, mitochondrial dysfunction and outcome in acutely decompensated cirrhosis: The metabolomic prognostic models(CLIF－C MET)[J]. Gut, 2023, 72( 8): 1581－ 1591. DOI: 10.1136/gutjnl－2022－328708.
[41]	ZHANG Y, TAN WT, WANG XB, et al. Metabolic biomarkers significantly enhance the prediction of HBV－related acute－on－chronic liver failure prognosis[J]. J Hepatol, 2023: S0168－8278(23) 04991. DOI: 10.1016/j.jhep.2023.07.011.
[42]	GARY PJ, LAL A, SIMONETTO DA, et al. Acute on chronic liver failure: Prognostic models and artificial intelligence applications[J]. Hepatol Commun, 2023, 7( 4): e0095. DOI: 10.1097/HC9.0000000000000095.
[43]	VERMA N, CHOUDHURY A, SINGH V, et al. APASL－ACLF Research Consortium－Artificial Intelligence(AARC－AI) model precisely predicts outcomes in acute－on－chronic liver failure patients[J]. Liver Int, 2023, 43( 2): 442－ 451. DOI: 10.1111/liv.15361.