登革热所致严重肝炎患者的急性肝衰竭及死亡预测因素
Acute liver failure and death predictors in patients with dengue-induced severe hepatitis.
作者信息
Teerasarntipan Tongluk, Chaiteerakij Roongruedee, Komolmit Piyawat, Tangkijvanich Pisit, Treeprasertsuk Sombat
机构信息
Department of Medicine, Division of Gastroenterology, Faculty of Medicine, Chulalongkorn University, and Thai Red Cross, Bangkok 10330, Thailand.
Department of Biochemistry, Center of Excellence in Hepatitis and Liver Cancer, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
出版信息
World J Gastroenterol. 2020 Sep 7;26(33):4983-4995. doi: 10.3748/wjg.v26.i33.4983.
BACKGROUND
Liver injury in patients with dengue infection is common. Most patients have mild and transient hepatitis. Acute liver failure (ALF) in dengue infection is rare but results in an extremely poor prognosis.
AIM
To identify prognostic predictors of ALF and death in patients with dengue-induced severe hepatitis (DISH).
METHODS
We retrospectively reviewed 2311 serologically confirmed adolescent and adult dengue patients who were hospitalized during a 12-year study period (between 2007 and 2019) at the university hospital of King Chulalongkorn Memorial Hospital, Bangkok, Thailand. Patients with DISH [ = 134 (5.80%)], defined as a baseline transaminase > 10 times the normal reference cut-off level, and DISH with subsequent ALF as defined by the American Association for the Study of the Liver Diseases 2011 criteria [ = 17 (0.74%)], were included. Predictors of ALF and in-hospital death were identified using logistic regression analysis.
RESULTS
Of the 151 dengue-infected patients with severe liver injury or ALF, 51% were female, with a mean age of 27.9 ± 14.5 years. Capillary leakage syndrome (CLS) occurred in 68.2% ( = 103) of DISH and 100% of ALF patients. The mortality rate was low in DISH patients (0.8%) but was remarkably high if ALF developed (58.8%). In univariate analysis, age, sex, hematocrit, white blood count, atypical lymphocyte count, platelet count, international normalized ratio (INR), bilirubin, serum glutamate-oxaloacetate transaminase, serum glutamate-pyruvate transaminase, alkaline phosphatase, albumin, creatinine, Model for End-Stage Liver Disease (MELD) score, presence of liver comorbidity and presence of CLS were identified as potential prognostic parameters for ALF or death. In multivariate analysis, the MELD score remained the only predictor of ALF with an adjusted odds ratio (aOR) of 1.3 [95% confidence interval (CI): 1.1-1.5; = < 0.001]. An initial MELD score ≥ 15 was associated with ALF from DISH with an area under the receiver operating characteristic (AUROC) of 0.91, 88.2% sensitivity and 87.3% specificity. Regarding mortality prediction, the deterioration of liver function to ALF was the most significant factor related to death in DISH patients (aOR 108.5, 95%CI: 5.5-2145.4, = 0.002). Other independent factors associated with death included baseline INR (aOR 10.4, 95%CI: 2.6-40.5, = 0.001). An INR ≥ 1.5 predicted death from DISH with an AUROC of 0.83 (81.8% sensitivity and 86.8% specificity).
CONCLUSION
The MELD score is the best predictor of ALF in DISH patients, a complication from dengue that is associated with high mortality. The presence of ALF and the baseline INR level are independent markers of death in DISH patients.
背景
登革热感染患者的肝损伤很常见。大多数患者有轻度和短暂性肝炎。登革热感染所致急性肝衰竭(ALF)虽罕见,但预后极差。
目的
确定登革热所致严重肝炎(DISH)患者发生ALF及死亡的预后预测因素。
方法
我们回顾性分析了2311例血清学确诊的青少年及成年登革热患者,这些患者于2007年至2019年这12年研究期间在泰国曼谷朱拉隆功国王纪念医院大学医院住院。纳入了DISH患者[ = 134例(5.80%)],定义为基线转氨酶>正常参考临界值的10倍,以及符合美国肝病研究协会2011年标准定义的继发ALF的DISH患者[ = 17例(0.74%)]。采用逻辑回归分析确定ALF及院内死亡的预测因素。
结果
在151例登革热感染所致严重肝损伤或ALF患者中,51%为女性,平均年龄27.9±14.5岁。68.2%( = 103例)的DISH患者及100%的ALF患者发生了毛细血管渗漏综合征(CLS)。DISH患者的死亡率较低(0.8%),但如果发展为ALF则死亡率显著升高(58.8%)。单因素分析中,年龄、性别、血细胞比容、白细胞计数、异型淋巴细胞计数、血小板计数、国际标准化比值(INR)、胆红素、血清谷草转氨酶、血清谷丙转氨酶、碱性磷酸酶、白蛋白、肌酐、终末期肝病模型(MELD)评分、肝脏合并症的存在及CLS的存在被确定为ALF或死亡的潜在预后参数。多因素分析中,MELD评分仍是ALF的唯一预测因素,校正比值比(aOR)为1.3[95%置信区间(CI):1.1 - 1.5; = < 0.001]。初始MELD评分≥15与DISH所致ALF相关,受试者工作特征曲线下面积(AUROC)为0.91,灵敏度为88.2%,特异度为87.3%。关于死亡率预测,肝功能恶化为ALF是DISH患者死亡的最显著相关因素(aOR 108.5,95%CI:5.5 - 2145.4, = 0.002)。其他与死亡相关的独立因素包括基线INR(aOR 10.4,95%CI:2.6 - 40.5, = 0.001)。INR≥1.5预测DISH患者死亡的AUROC为0.83(灵敏度81.8%,特异度86.8%)。
结论
MELD评分是DISH患者发生ALF的最佳预测因素,DISH是登革热的一种并发症,与高死亡率相关。ALF的存在及基线INR水平是DISH患者死亡的独立标志物。