国王学院标准[48]O'Grady JG, Alexander GJ, Hayllar KM, et al. Early indicators of prognosis in fulminant hepatic failure. Gastroenterology. 1989;97:339-345.http://www.ncbi.nlm.nih.gov/pubmed/2490426?tool=bestpractice.com
为广泛接受的ALF患者的预后评估工具。该标准是通过对 1973-1987 年间由英国伦敦国王学院医院 (King's College Hospital) 肝病病房 (Liver Unit) 连续收治的 588 例 ALF 患者进行回顾性分析而确立的。[48]O'Grady JG, Alexander GJ, Hayllar KM, et al. Early indicators of prognosis in fulminant hepatic failure. Gastroenterology. 1989;97:339-345.http://www.ncbi.nlm.nih.gov/pubmed/2490426?tool=bestpractice.com针对预测值确定和评估了与死亡率相关的预后因素。值得注意的是,预后评估中使用的INR水平不同于被用作ALF特征性诊断的INR水平。
尽管符合全部指标对病死率的预测具有高特异性,但是敏感性和阴性预测值仍然很低。因此,没有达到这个标准的并不能确保其生存。[58]Pauwels A, Mostefa-Kara N, Florent C, et al. Emergency liver transplantation for acute liver failure. Evaluation of London and Clichy criteria. J Hepatol. 1993;17:124-127.http://www.ncbi.nlm.nih.gov/pubmed/8445211?tool=bestpractice.com[59]Anand AC, Nightingale P, Neuberger JM. Early indicators of prognosis in fulminant hepatic failure: an assessment of the King's criteria. J Hepatol. 1997;26:62-68.http://www.ncbi.nlm.nih.gov/pubmed/9148024?tool=bestpractice.com[60]Shakil AO, Kramer D, Mazariegos GV, et al. Acute liver failure: clinical features, outcome analysis, and applicability of prognostic criteria. Liver Transpl. 2000;6:163-169.http://onlinelibrary.wiley.com/doi/10.1002/lt.500060218/pdfhttp://www.ncbi.nlm.nih.gov/pubmed/10719014?tool=bestpractice.com[61]Bailey B, Amre DK, Gaudreault P. Fulminant hepatic failure secondary to acetaminophen poisoning: a systematic review and meta-analysis of prognostic criteria determining the need for liver transplantation. Crit Care Med. 2003;31:299-305.http://www.ncbi.nlm.nih.gov/pubmed/12545033?tool=bestpractice.com[62]McPhail MJ, Wendon JA, Bernal W. Meta-analysis of performance of Kings's College Hospital Criteria in prediction of outcome in non-paracetamol-induced acute liver failure. J Hepatol. 2010;53:492-499.http://www.ncbi.nlm.nih.gov/pubmed/20580460?tool=bestpractice.com国王学院标准的灵敏度为 68%-69%,特异性为 82%-92%。[63]American Association for the Study of Liver Diseases. AASLD position paper: the management of acute liver failure: update 2011. November 2011. http://www.aasld.org/ (last accessed 16 August 2017).https://www.aasld.org/sites/default/files/guideline_documents/AcuteLiverFailureUpdate201journalformat1.pdf尽管国王学院标准已经在成人ALF队列中得到验证,但是有数据表明,其可能无法可靠地预测儿童患者的结局。[64]Sundaram V, Shneider BL, Dhawan A, et al. King's College Hospital Criteria for non-acetaminophen induced acute liver failure in an international cohort of children. J Pediatr. 2013;162:319-323.e1.http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3504621/http://www.ncbi.nlm.nih.gov/pubmed/22906509?tool=bestpractice.com
总体来讲,这些标准有助于鉴别ALF高死亡风险患者。尽管如此,也存在局限性,美国肝病研究协会(AASLD)并不推荐使用预后评分系统来确定肝移植候选人。[63]American Association for the Study of Liver Diseases. AASLD position paper: the management of acute liver failure: update 2011. November 2011. http://www.aasld.org/ (last accessed 16 August 2017).https://www.aasld.org/sites/default/files/guideline_documents/AcuteLiverFailureUpdate201journalformat1.pdf
继发于扑热息痛过量的ALF:
非扑热息痛相关的ALF:
Clichy标准[52]Bernuau J, Samuel D, Durand F, et al. Criteria for emergency liver transplantation in patients with acute viral hepatitis and factor V below 50% of normal: a prospective study. Hepatology. 1991;14:49A.
根据法国对急性病毒性肝炎患者的前瞻性研究,不行肝移植者的生存率最低,包括肝性脑病及低V因子水平者。[52]Bernuau J, Samuel D, Durand F, et al. Criteria for emergency liver transplantation in patients with acute viral hepatitis and factor V below 50% of normal: a prospective study. Hepatology. 1991;14:49A.在这个队列研究中,这些标准预测死亡的阳性预测值为82%,阴性预测值为98%。尽管如此,随后的研究所报道,针对其他人群(包括对乙酰氨基酚和非对乙酰氨基酚 ALF 患者)的预测值更低,劣于国王学院标准。[58]Pauwels A, Mostefa-Kara N, Florent C, et al. Emergency liver transplantation for acute liver failure. Evaluation of London and Clichy criteria. J Hepatol. 1993;17:124-127.http://www.ncbi.nlm.nih.gov/pubmed/8445211?tool=bestpractice.com[65]Izumi S, Langley PG, Wendon J, et al. Coagulation factor V levels as a prognostic indicator in fulminant hepatic failure. Hepatology. 1996;23:1507-1511.http://www.ncbi.nlm.nih.gov/pubmed/8675171?tool=bestpractice.com
存在肝性脑病和V因子水平:
在<30岁的患者中,<20%正常值或者
在>30岁患者中,<30%正常值。
终末期肝病模型(MELD)[66]Kamath PS, Wiesner RH, Malinchoc M, et al. A model to predict survival in patients with end-stage liver disease. Hepatology. 2001;33:464-470.http://www.ncbi.nlm.nih.gov/pubmed/11172350?tool=bestpractice.com[67]Wiesner R, Edwards E, Freeman R, et al. Model for end-stage liver disease (MELD) and allocation of donor livers. Gastroenterology. 2003;124:91-96.http://www.ncbi.nlm.nih.gov/pubmed/12512033?tool=bestpractice.com
被美国器官共享网络(UNOS)与器官获取和移植网络(OPTN)组织采纳,MELD评分被确认为是肝硬化患者预测短期病死率的预测模型,并且当前在美国等待肝移植患者中用来分配供体器官。[66]Kamath PS, Wiesner RH, Malinchoc M, et al. A model to predict survival in patients with end-stage liver disease. Hepatology. 2001;33:464-470.http://www.ncbi.nlm.nih.gov/pubmed/11172350?tool=bestpractice.com[67]Wiesner R, Edwards E, Freeman R, et al. Model for end-stage liver disease (MELD) and allocation of donor livers. Gastroenterology. 2003;124:91-96.http://www.ncbi.nlm.nih.gov/pubmed/12512033?tool=bestpractice.com一些回顾性研究报道,在ALF相关病死率预测中,MELD评分与国王学院标准的预测价值基本相同。[68]Kremers WK, van IJperen M, Kim WR, et al. MELD score as a predictor of pretransplant and posttransplant survival in OPTN/UNOS status 1 patients. Hepatology. 2004;39:764-769.http://www.ncbi.nlm.nih.gov/pubmed/14999695?tool=bestpractice.com[69]Zaman MB, Hoti E, Qasim A, et al. MELD score as a prognostic model for listing acute liver failure patients for liver transplantation. Transplant Proc. 2006;38:2097-2098.http://www.ncbi.nlm.nih.gov/pubmed/16980011?tool=bestpractice.com[70]Katoonizadeh A, Decaestecker J, Wilmer A, et al. MELD score to predict outcome in adult patients with non-acetaminophen-induced acute liver failure. Liver Int. 2007;27:329-334.http://www.ncbi.nlm.nih.gov/pubmed/17355453?tool=bestpractice.com[71]Yantorno SE, Kremers WK, Ruf AE, et al. MELD is superior to King's College and Clichy's criteria to assess prognosis in fulminant hepatic failure. Liver Transpl. 2007;13:822-828.http://onlinelibrary.wiley.com/doi/10.1002/lt.21104/fullhttp://www.ncbi.nlm.nih.gov/pubmed/17539002?tool=bestpractice.com美国急性肝衰竭研究组的前瞻性数据显示,对乙酰氨基酚过量患者中,MELD 评分 ≥30 的阴性预测值较高,为 82%,因而 MELD 评分<30 者的生存概率较高。在非对乙酰氨基酚ALF患者中,MELD评分≥30的阳性预测值为81%,但这些值并不比国王学院标准准确。[63]American Association for the Study of Liver Diseases. AASLD position paper: the management of acute liver failure: update 2011. November 2011. http://www.aasld.org/ (last accessed 16 August 2017).https://www.aasld.org/sites/default/files/guideline_documents/AcuteLiverFailureUpdate201journalformat1.pdf[72]Rossaro L, Chambers CC, Polson J, et al. Performance of MELD in predicting outcome in acute liver failure (Abstract S1492). Gastroenterology. 2005;128:A-705.根据一项大型 meta 分析的发现,MELD 评分在预测医院死亡率方面可能有一定的作用,尤其是对于非对乙酰氨基酚性 ALF。[73]McPhail MJ, Farne H, Senvar N, et al. Ability of King's College criteria and Model for End-stage Liver Disease scores to predict mortality of patients with acute liver failure: a meta-analysis. Clin Gastroenterol Hepatol. 2016;14:516-525.e5.http://www.cghjournal.org/article/S1542-3565(15)01403-2/fulltexthttp://www.ncbi.nlm.nih.gov/pubmed/26499930?tool=bestpractice.com
急性生理和慢性健康评估(APACHE)II[74]Knaus WA, Draper EA, Wagner DP, et al. APACHE II: a severity of disease classification system. Crit Care Med. 1985;13:818-829.http://www.ncbi.nlm.nih.gov/pubmed/3928249?tool=bestpractice.com
APACHE II评分系统是为了预测重症监护病房所有疾病患者病死率而设计的。评分系统包含12个常见的生理和实验室参数,调整了患者的年龄和潜在的慢性健康问题。[74]Knaus WA, Draper EA, Wagner DP, et al. APACHE II: a severity of disease classification system. Crit Care Med. 1985;13:818-829.http://www.ncbi.nlm.nih.gov/pubmed/3928249?tool=bestpractice.com一项对乙酰氨基酚过量患者的前瞻性研究发现,APACHE II 评分>15 与高死亡率相关,与国王学院标准的预测值类似,而另一项研究发现,评分≥20 更能预测死亡率及更需要进行肝移植。[11]Larson AM, Polson J, Fontana RJ, et al. Acetaminophen-induced acute liver failure: results of a United States multicenter, prospective study. Hepatology. 2005;42:1364-1372.http://www.ncbi.nlm.nih.gov/pubmed/16317692?tool=bestpractice.com[75]Mitchell I, Bihari D, Chang R, et al. Earlier identification of patients at risk from acetaminophen-induced acute liver failure. Crit Care Med. 1998;26:279-284.http://www.ncbi.nlm.nih.gov/pubmed/9468165?tool=bestpractice.com
急性肝衰竭研究组 (ALFSG) 指数[76]Rutherford A, King LY, Hynan LS, et al; ALF Study Group. Development of an accurate index for predicting outcomes of patients with acute liver failure. Gastroenterology. 2012;143:1237-1243.http://www.gastrojournal.org/article/S0016-5085%2812%2901155-9/fulltexthttp://www.ncbi.nlm.nih.gov/pubmed/22885329?tool=bestpractice.com[77]Koch DG, Tillman H, Durkalski V, et al. Development of a model to predict transplant-free survival of patients with acute liver failure. Clin Gastroenterol Hepatol. 2016;14:1199-1206.e2.http://www.ncbi.nlm.nih.gov/pubmed/27085756?tool=bestpractice.com
根据ALFSG入组的250例患者确定了预后指数,之后在另外250例患者中验证。与病死率或肝移植强相关的起始变量包括晚期昏迷等级、胆红素、INR、高血磷和M30抗原的高血清水平(肝细胞凋亡性细胞死亡的标志物)。这个指数的总体敏感性为85.6%,特异性为64.7%,并且在对乙酰氨基酚和非对乙酰氨基酚相关ALF患者之间的差异不显著。虽然这个预测指数明显优于国王学院标准和终末期肝病模型(MELD)评分,但是M30抗原的评估需要基于ELISA实验并且在大多数中心可能不容易获取。[76]Rutherford A, King LY, Hynan LS, et al; ALF Study Group. Development of an accurate index for predicting outcomes of patients with acute liver failure. Gastroenterology. 2012;143:1237-1243.http://www.gastrojournal.org/article/S0016-5085%2812%2901155-9/fulltexthttp://www.ncbi.nlm.nih.gov/pubmed/22885329?tool=bestpractice.com
根据 ALFSG 数据库开发了另一种预测无移植生存率的模型,涉及 878 例患者,然后在包含 885 例患者的队列中进行了验证。预测无移植生存率的变量包括肝性脑病的严重程度、ALF 的病因、对血管加压药的需求、胆红素和国际标准化比值 (INR)。在该模型中被认为有利的 ALF 病因包括对乙酰氨基酚过量、妊娠、缺血或甲型肝炎。依据该模型,得出验证队列的无移植生存率为 80%,敏感性为 37%,特异性为 95%。[77]Koch DG, Tillman H, Durkalski V, et al. Development of a model to predict transplant-free survival of patients with acute liver failure. Clin Gastroenterol Hepatol. 2016;14:1199-1206.e2.http://www.ncbi.nlm.nih.gov/pubmed/27085756?tool=bestpractice.com