药物性肝损伤致急性肝衰竭预测模型的比较研究

摘要/Abstract

摘要： 目的: 对比药物性肝损伤(DILI)致急性肝衰竭预测模型的预测效能。方法: 纳入2014年至2018年DILI患者298例,判断符合Hy’s法则、新Hy’s法则和Robles模型标准的DILI病例数以及发生肝衰竭病例数,分别计算每种模型的敏感度、特异度、阳性预测值和阴性预测值。结果: 298例患者中,女性211例(70.8%),平均年龄(54.7±14.7)岁;肝细胞损伤型230例(77.2%),胆汁淤积型为19例(6.4%),混合型49例(16.4%);13例(4.4%)出现急性肝衰竭,5例(1.7%)患者因肝脏原因死亡或行肝移植。符合Hy’s法则161例、新Hy’s法则208例和Robles模型73例,发展为急性肝衰竭的病例依次为:9例(5.8%)、12例(5.6%)和11例(15.1%)。符合Robles模型DILI患者发展为急性肝衰竭风险最高,其敏感度为84.6%,特异度为78.2%,阴性预测值为99.1%。与未达到Robles模型DILI 患者比较,达到Robles标准DILI患者1、3、12个月肝脏生化指标复常率显著减低(P<0.05)。结论: 与Hy’s 法则及新Hy’s法则比较,Robles模型预测DILI患者出现急性肝衰竭的特异度及阳性预测值最优,该模型还能更准确的预测患者1年内肝脏生化指标复常率。

关键词: 药物性肝损伤, 急性肝衰竭, 预测模型, 预后

Abstract: Objective To compare the efficacy of different models in the prediction of acute liver failure in drug-induced liver injury (DILI) patients. Methods We conducted a retrospective cohort study of patients diagnosed with DILI from 2014 to 2018. Data of liver biochemical tests of these DILI patients were collected and acute liver failure (ALF) cases were identified among those fulfilled the criterion of Hy's law, new Hy's law and Robles model, respectively. The sensitivity, specificity, positive predictive and negative predictive value were calculated, respectively. Results A total of 298 patients were enrolled, with an average age of 54.7 ± 14.7 years, including 211 female patients (70.8%). Most cases of DILI were hepatocellular injury (77.2%), followed by mixed injury (16.4%) and cholestatic injury (6.4%). Among all the patients, 13 (4.4%) cases progressed to ALF, 5 (1.7%) underwent liver transplantation or died of liver-related events. In this study, 161 DILI patients met the criterion of Hy’s law, 5.8% of them progressed to ALF, 208 cases met the criterion of new Hy’s law, 5.6% progressed to ALF, while 73 cases met the criterion of Robles model and 15.1% developed ALF. DILI patients fulfilled the Robles model had the highest risk of developing ALF, with the sensitivity of 84.6%, the specificity of 78.2%, and the positive predictive value of 99.1%. DILI patients who met the criterion of Robles model had significantly lower rate of liver biochemical normalization at 1, 3 and 12 months compared with DILI patients who did not (P<0.05). Conclusion When applied at DILI recognition, the Robles model provides the best specificity and positive predictive value in the prediction of ALF development, and most accurately predicts the normalization rate of liver biochemical indices within 1 year.

Key words: Drug-induced liver injury, Acute liver failure, Predictive model, Prognosis

杨瑞园, 刘立伟, 罗娟, 李轲鑫, 田秋菊, 王艳, 赵新颜, 贾继东. 药物性肝损伤致急性肝衰竭预测模型的比较研究[J]. 肝脏, 2020, 25(7): 671-675.

YANG Rui-yuan, LIU Li-wei, LUO Juan, LI Ke-xin, TIAN Qiu-ju, WANG Yan, ZHAO Xin-yan, JIA Ji-dong. A comparative study of predictive models for acute liver failure in drug-induced liver injury[J]. Chinese Hepatolgy, 2020, 25(7): 671-675.

参考文献

[1] Stravitz R T, Lee W M. Acute liver failure. Lancet, 2019,394: 869-881.
[2] Reuben A, Tillman H, Fontana R J, et al. Outcomes in Adults With Acute Liver Failure Between 1998 and 2013: An Observational Cohort Study. Ann Intern Med, 2016,164: 724-732.
[3] Khandelwal N, James L P, Sanders C, et al. Unrecognized acetaminophen toxicity as a cause of indeterminate acute liver failure. Hepatology, 2011,53: 567-576.
[4] Andrade R J, Aithal G P, Bj?rnsson E S, et al. EASL Clinical Practice Guidelines: Drug-induced liver injury. J Hepatol, 2019,70: 1222-1261.
[5] Vega M, Verma M, Beswick D, et al. The Incidence of Drug- and Herbal and Dietary Supplement-Induced Liver Injury: Preliminary Findings from Gastroenterologist-Based Surveillance in the Population of the State of Delaware. Drug Saf, 2017,40: 783-787.
[6] Suk K T, Kim D J, Kim C H, et al. A prospective nationwide study of drug-induced liver injury in Korea. Am J Gastroenterol, 2012,107: 1380-1387.
[7] Shen T, Liu Y, Shang J, et al. Incidence and Etiology of Drug-Induced Liver Injury in Mainland China. Gastroenterology, 2019,156: 2230-2241.
[8] Tujios S R, Lee W M. Acute liver failure induced by idiosyncratic reaction to drugs: Challenges in diagnosis and therapy. Liver International, 2018,38: 6-14.
[9] Thomas A M, Lewis J H. Nonacetaminophen Drug-Induced Acute Liver Failure. Clin Liver Dis, 2018,22: 301-324.
[10] Robles Diaz M, Lucena M I, Kaplowitz N, et al. Use of Hy's Law and a New Composite Algorithm to Predict Acute Liver Failure in Patients With Drug-Induced Liver Injury. Gastroenterology, 2014,147: 109-118.
[11] Danan G, Benichou C. Causality assessment of adverse reactions to drugs--I. A novel method based on the conclusions of international consensus meetings: application to drug-induced liver injuries. J Clin Epidemiol, 1993,46: 1323-1330.
[12] Danan G, Teschke R. RUCAM in Drug and Herb Induced Liver Injury: The Update. International J Mol Sci, 2016,17: 14.
[13] Aithal G P, Watkins P B, Andrade R J, et al. Case definition and phenotype standardization in drug-induced liver injury. Clin Pharmacol Ther, 2011,89: 806-815.
[14] Chalasani N P, Hayashi P H, Bonkovsky H L, et al. ACG Clinical Guideline: the diagnosis and management of idiosyncratic drug-induced liver injury. The American journal of gastroenterology, 2014,109: 950-966.
[15] Yu Y, Mao Y, Chen C, et al. CSH guidelines for the diagnosis and treatment of drug-induced liver injury. Hepatol Int, 2017,11: 221-241.
[16] William M, Lee M, Larson A M, et al. AASLD position paper: The management of acute liver failure: Update. Hepatology, 2011,55.
[17] Robles Diaz M, Lucena M I, Kaplowitz N, et al. Use of Hy's Law and a New Composite Algorithm to Predict Acute Liver Failure in Patients With Drug-Induced Liver Injury. Gastroenterology, 2014,147: 109-118.
[18] Wang Y, Wang L, Saxena R, et al. Clinicopathological features of He Shou Wu-induced liver injury: This ancient anti-aging therapy is not liver-friendly. Liver Int, 2019,39: 389-400.
[19] 韩琳, 杨曌, 梁庆升, 等. 药物性肝衰竭100例临床特征分析. 肝脏, 2019,24: 229-233.
[20] Bjornsson E, Olsson R. Outcome and prognostic markers in severe drug-induced liver disease. Hepatology, 2005,42: 481-489.
[21] Mack C L, Adams D, Assis D N, et al. Diagnosis and management of autoimmune hepatitis in adults and children: 2019 practice guidance and guidelines from the American Association for the study of liver diseases. Hepatology, 2019.
[22] Tian Q, Zhao X, Wang Y, et al. Histologic pattern is better correlated with clinical outcomes than biochemical classification in patients with drug-induced liver injury. Modern Pathol, 2019,32: 1795-1805.