摘要
目的 分析急性失代偿期肝硬化患者短期发生不良预后的独立危险因素，评估肝脏衰弱指数及联合CLIF-C AD评分对急性失代偿期肝硬化患者短期发生不良预后的预测能力。方法 选取2024年9月至2025年6月云南省第三人民医院住院的109例急性失代偿期肝硬化患者作为研究对象，比较不同病因肝硬化组之间一般资料、肝脏衰弱指数及每个子测试的差异性；并对入组患者进行3个月的随访，记录其生存状态，分为生存组和死亡组，分析急性失代偿期肝硬化患者短期发生不良预后影响因素，评估肝脏衰弱指数及联合CLIF-C AD评分对急性失代偿期肝硬化患者短期发生不良预后的预测能力。结果 不同病因肝硬化组间一般资料比较，研究结果显示：四组间年龄、性别、吸烟史、饮酒史、WBC、CTP评分、CTP分级、MELD评分、CLIF-C AD评分差异具有统计学意义（P＜0.05），其余指标比较差异均无统计学意义（P＞0.05）。不同病因肝硬化组间肝脏衰弱指数及其各子测试进行比较，研究结果显示：四组间握力差异具有统计学意义（P＜0.05），而坐立试验、平衡试验、LFI差异不具有统计学意义（P＞0.05）。生存组与死亡组一般资料比较，研究结果显示：两组间BMI、RBC、Hb、ChE、AST、TBIL、DBIL、Cr、CTP评分、CTP分级、MELD评分、CLIF-C AD评分差异具有统计学意义（P＜0.05），其余指标比较差异均无统计学意义（P＞0.05）。生存组与死亡组的肝脏衰弱指数及各项子测试的比较，结果显示：两组间握力、坐立试验、平衡试验、LFI比较差异均有统计学意义（P＜0.05）。单因素COX回归分析显示BMI、RBC、Hb、WBC、ALP、Cr、CTP评分、CTP分级、MELD评分、CLIF-C AD评分、握力、坐立试验、平衡试验、LFI是急性失代偿期肝硬化患者短期发生不良预后的影响因素（P＜0.05）。多因素COX回归分析显示Hb、ALP、LFI仍是急性失代偿期肝硬化患者短期发生死亡的独立影响因素（P＜0.05）。ROC曲线显示握力、坐立试验、平衡试验以及LFI预测急性失代偿期肝硬化患者短期发生死亡风险的AUC分别为0.746（95%CI 0.646～0.845）、0.804（95%CI 0.709～0.900）、0.784（95%CI 0.670～0.898）、0.869（95%CI 0.789～0.948），P值均＜0.05。LFI、CLIF-C AD评分及二者联合对急性失代偿期肝硬化患者短期发生死亡风险AUC分别为0.869（95%CI 0.789～0.948）、0.767（95%CI 0.659～0.875）、0.917（95%CI 0.789～0.948），P值均＜0.05。结论 LFI联合CLIF-C AD评分对急性失代偿期肝硬化患者短期发生死亡风险的预测效能最佳，二者相结合更全面地评估急性失代偿期肝硬化患者的病情严重程度及预后风险。
关键词： 肝硬化；衰弱；肝脏衰弱指数；全身炎症；CLIF-C AD评分；MELD评分
Abstract
Objective To analyze independent risk factors for short-term adverse outcomes in patients with acute decompensated cirrhosis and to evaluate the predictive ability of the Liver Frailty Index and combined CLIF-C AD score for short-term adverse outcomes in these patients. Methods A total of 109 patients with acute decompensated cirrhosis hospitalized at Yunnan Provincial Third People's Hospital from September 2024 to June 2025 were enrolled. The study compared differences in general characteristics, the Liver Frailty Index (LFI), and each subtest between cirrhosis groups with different etiologies. Patients underwent a 3-month follow-up to record survival status, categorizing them into survival and mortality groups. This study analyzed factors influencing short-term adverse outcomes in patients with acute decompensated cirrhosis and evaluated the predictive ability of the Liver Frailty Index and combined CLIF-C AD score for short-term adverse outcomes in this population. Results Comparisons of general characteristics among cirrhosis groups with different etiologies revealed statistically significant differences (P < 0.05) in age, gender, smoking history, drinking history, WBC, CTP score, CTP grade, MELD score, and CLIF-C AD score. while differences in the remaining indicators were not statistically significant (P > 0.05). Comparing the Liver Function Index (LFI) and its sub-tests among cirrhosis groups with different etiologies, the results showed statistically significant differences in grip strength among the four groups (P < 0.05), whereas differences in the sit-to-stand test, balance test, and LFI were not statistically significant (P > 0.05). Comparing general characteristics between the survival and mortality groups, the results showed statistically significant differences in BMI, RBC, Hb, ChE, AST, TBIL, DBIL, Cr, CTP score, CTP grade, MELD score, and CLIF-C AD score (P < 0.05). Differences in all other indicators were not statistically significant (P > 0.05). Comparison of the Liver Frailty Index and its sub-tests between the survival and mortality groups revealed statistically significant differences in grip strength, sit-to-stand test, balance test, and LFI (P < 0.05). Univariate Cox regression analysis identified BMI, RBC, Hb, WBC, ALP, Cr, CTP score, CTP classification, MELD score, CLIF-C AD score, grip strength, sit-to-stand test, balance test, and LFI as independent predictors of short-term adverse outcomes in patients with acute decompensated cirrhosis (P < 0.05). Multivariate Cox regression analysis confirmed Hb, ALP, and LFI as independent predictors of short-term mortality in patients with acute decompensated cirrhosis (P < 0.05). ROC curve analysis revealed the following AUC values for predicting short-term mortality risk: grip strength (0.746, 95% CI 0.646–0.845), sit-to-stand test (0.784, 95% CI 0.670–0.898), balance test (0.804, 95% CI 0.709–0.900), and LFI (0.864, 95% CI 0.709–0.900). 0.804 (95% CI 0.709–0.900), 0.784 (95% CI 0.670–0.898), and 0.869 (95% CI 0.789–0.948), respectively, with all P values < 0.05. The AUCs for predicting short-term mortality risk in patients with acute decompensated cirrhosis were 0.869 (95% CI 0.789–0.948), 0.767 (95% CI 0.659–0.875), and 0.917 (95% CI 0.789–0.948) for LFI, CLIF-C AD score, and their combined assessment, respectively, all with P < 0.05. 0.917 (95% CI 0.789–0.948), respectively, with P values all <0.05. Conclusion : The combined LFI and CLIF-C AD scores demonstrated the highest predictive efficacy for short-term mortality risk in patients with acute decompensated cirrhosis. This integrated approach provides a more comprehensive assessment of disease severity and prognostic risk in this patient population. Conclusion The combined use of LFI and CLIF-C AD scores demonstrates the highest predictive efficacy for short-term mortality risk in patients with acute decompensated cirrhosis. This integrated approach provides a more comprehensive assessment of disease severity and prognostic risk in this patient population.
Key words： Cirrhosis; Frailty; Liver frailty index; Systemic inflammation; CLIF-C AD score; MELD score
参考文献 References
[1] Gustot T, Stadlbauer V, Laleman W, et al. Transition to decompensation and acute－on－chronic liver failure:Role of predisposing factors and precipitating events[J].J Hepatol,2021,75(Suppl 1):S36－S48.
[2] Cai YJ, Dong JJ, Dong JZ, et al. A nomogram for predicting prognostic value of inflammatory response biomarkers in decompensated cirrhotic patients without acute-on-chronic liver failure[J]. Aliment Pharmacol Ther, 2017,45(11): 1413–1426.
[3] 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]. Journal of hepatology, 2015, 62: 831-840.
[4] Shi Y, Shu Z, Sun W, et al. Risk stratification of decompensated cirrhosis patients by Chronic Liver Failure Consortium scores: classification and regression tree analysis[J]. Hepatology research, 2017, 47: 328-337.
[5] DENG Y,LIN L,FAN X F,et al.Incorporation of frailty estimated by gait speed within MELD-Na and the predictive potential for mortality in cirrhosis[J]. Therapeutic Advances in Chronic Disease, 2020,11: 2040622320922023.
[6] Tandon, Montano-Loza AJ, et al. Sarcopenia and frailty in decompensated cirrhosis[J]. Journal of hepatology,2021,75 Suppl 1(Suppl 1):S147-S162.
[7] Wang S, Whitlock R, Xu C, et al. Frailty is associated with increased risk of cirrhosis disease progression and death[J]. Hepatology,2022;75(3):600-609.
[8] Lai JC, Covinsky KE, Dodge JL, et al. Development of a novel frailty index to predict mortality in patients with end-stage liver disease[J]. Hepatology,2017;66(2):564-574
[9] Kardashian A, Ge J, McCulloch CE, et al. Identifying an Optimal Liver Frailty Index Cutoff to Predict Waitlist Mortality in Liver Transplant Candidates[J]. Hepatology, 2021;73(3):1132-1139.
[10] Lai JC, Rahimi RS, Verna EC, et al. Frailty Associated With Waitlist Mortality Independent of Ascites and Hepatic Encephalopathy in a Multicenter Study[J]. Gastroentero-logy, 2019, 156: 1675-1682.
[11] Haugen C E, Mcadams-Demarco M, Holscher C M, et al. Multicenter Study of Age, Frailty, and Waitlist Mortality Among Liver Transplant Candidates[J].Annals of surgery, 2020, 271: 1132-1136.
[12] 中华医学会消化病学分会. 中国肝硬化临床诊治共识意见[J].中华消化杂志,2023,43(04)：227-247.
[13] Pugh RN,Murray-Lyon IM,Dawson JL,et al.Transection of the oesophagus for bleeding oesophageal varices[J].Br J Surg,1973,60(8):646-649.
[14] Malinchoc M,Kamath PS,Gordon FD,et al.A model to predict poor survival in patients undergoing transjugular intrahepatic portosystemic shunts[J].Hepatology, 2000, 31(4):864-871.
[15] Engelmann C, Clària J, Szabo G, et al. Pathophysiology of decompensated cirrhosis: Portal hypertension, circulatory dysfunction, inflammation, metabolism and mitochondrial dysfunction[J]. J Hepatol,2021,75 Suppl 1(Suppl 1):S49-S66.
[16] GBD 2017 Cirrhosis Collaborators. The global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017[J]. Lancet Gastroenterol Hepatol, 2020,5(3):245-266.
[17] Hoogendijk EO, Afilalo J, Ensrud KE, et al. Frailty: implications for clinical practice and public health[J]. Lancet. 2019;394(10206):1365-1375.
[18] Deng Y, Hui Y, et al. Accumulating awareness on the clinical significance and relevance of frailty in cirrhosis: Time to dig deeper into mechanistic basis![J]. Liver international: official journal of the International Association for the Study of the Liver ,2023;43(8):1629-1643.
[19] CronDC, FriedmanJF, WinderGS, et al. Depression and frailty in patients with end-stage liver disease referred for transplant evaluation[J]. American journal of transplantation, 2016, 16(6): 1805-1811.
[20] TandonP, TangriN, ThomasL, et al. A rapid bedside screen to predict unplanned hospitalization and death in outpatients with cirrhosis: a prospective evaluation of the clinical frailty scale[J]. The American journal of gastroenterology, 2016, 111(12): 1759-1767.
[21] SerperM, TaoSY, KentDS, et al. Inpatient frailty assessment is feasible and predicts nonhome discharge and mortality in decompensated cirrhosis[J]. Liver transplantation, 2021, 27(12): 1711-1722.
[22] SchleicherEM, KremerWM, KalampokaV, et al. Frailty as tested by the clinical frailty scale Is a risk factor for hepatorenal syndrome in patients with liver cirrhosis[J]. Clinical and translational gastroenterology, 2022, 13(7): e00512.
[23] Xu CQ, Mohamad Y, Kappus MR, et al. The relationship between frailty and cirrhosis etiology: From the Functional Assessment in Liver Transplantation (FrAILT) Study[J]. Liver Int,2021,41(10):2467-2473.
[24] Scheiner B., Semmler G., Maurer F., et al. Prevalence of and risk factors for anaemia in patients with advanced chronic liver disease[J]. Liver Int. 2020;40:194–204.
[25] Singh S., Manrai M., Parvathi V.S., et al. Association of liver cirrhosis severity with anemia: does it matter? [J].Ann Gastroenterol. 2020;33:272–276.
[26] Parker R., Armstrong M.J., Bruns T., Hodson J., Rowe I.A., Corbett C.D., et al. Reticulocyte count and hemoglobin concentration predict survival in candidates for liver transplantation[J]. Transplantation. 2014;97:463–469.
[27] Shi Y., Zheng M.H., Yang Y., Wei W., Yang Q., Hu A., et al. Increased delayed mortality in patients with acute-on-chronic liver failure who have prior decompensation[J]. J Gastroenterol Hepatol. 2015;30:712–718.
[28] Bothou C., Ruschenbaum S., Kubesch A., Quenstedt L., Schwarzkopf K., Welsch C., et al. Anemia and systemic inflammation rather than arterial circulatory dysfunction predict decompensation of liver cirrhosis[J]. J Clin Med. 2020;9:1263.
[29] European Association for the Study of the Liver. EASL Clinical Practice Guidelines: management of cholestatic liver diseases[J]. J Hepatol, 2009,51(2):237-267.
[30] Lai JC, Tandon P, Bernal W, et al. Malnutrition, frailty, and sarcopenia in patients with cirrhosis: 2021 Practice Guidance by the American Association for the Study of Liver Diseases[J].Hepatology,2021,74(3):1611-1644.
[31] Zhang Y, Chen P, et al. Derivation and Validation of a Prognostic Model for Acute Decompensated Cirrhosis Patients[J]. Patient preference and adherence, 2023, 17:1293-1302.
[32] Al Kaabi H, Al Alawi AM, et al. Clinical Characteristics, Etiology, and Prognostic Scores in Patients with Acute Decompensated Liver Cirrhosis[J]. Journal of clinical medicine, 2023,12(17):5756.
[33] Baldin C, Piedade J, Guimarães L, et al. CLIF-C AD score predicts development of acute decompensations and survival in hospitalized cirrhotic patients[J]. Dig Dis Sci. 2021; 66: 4525-4535.
[34] Wang M, Shui AM, Huang CY,et al. The Liver Frailty Index enhances mortality risk prediction above and beyond MELD 3.0 alone[J]. Liver Transpl, 2024,30(12):1326-1329.