中国全科医学 ›› 2023, Vol. 26 ›› Issue (30): 3801-3808.DOI: 10.12114/j.issn.1007-9572.2022.0879

• 论著 • 上一篇    下一篇

天冬氨酸氨基转移酶/丙氨酸氨基转移酶与儿童噬血细胞性淋巴组织细胞增生症预后的相关性研究

施晓琦1,2,3, 罗南都1,2, 黄娇娇1,2, 杜作晨1,2,3, 黄佩1,2,3, 曹秀丽1,2, 陈艳1,2,3,*(), 何志旭1,2,3,*()   

  1. 1.563000 贵州省遵义市,遵义医科大学附属医院小儿内科
    2.563000 贵州省遵义市,贵州省儿童医院小儿内科
    3.563000 贵州省遵义市,遵义医科大学组织损伤修复与再生医学省部共建协同创新中心
  • 收稿日期:2022-11-23 修回日期:2023-05-17 出版日期:2023-10-20 发布日期:2023-06-13
  • 通讯作者: 陈艳, 何志旭

  • 作者贡献:施晓琦进行文章的构思与设计、数据管理、统计学处理、结果的分析与解释、论文撰写;罗南都、黄娇娇、杜作晨、黄佩、曹秀丽进行数据收集、研究的实施和可行性分析;陈艳、何志旭负责文章的构思与设计、修订、质量控制及审校、监督管理,对文章整体负责。
  • 基金资助:
    国家自然科学基金资助项目(82260036); 贵州省科技计划项目(黔科合平台人才-CXTD[2021]010); 省部共建协同创新中心项目(教科技厅函[2020]39号); 贵州省研究生科研基金项目(黔教合YJSKYJJ[2021]178)

Correlation between Aspartate Aminotransferase/Alanine Aminotransferase and Prognosis of Hemophagocytic Lymphohistiocytosis in Children

SHI Xiaoqi1,2,3, LUO Nandu1,2, HUANG Jiaojiao1,2, DU Zuochen1,2,3, HUANG Pei1,2,3, CAO Xiuli1,2, CHEN Yan1,2,3,*(), HE Zhixu1,2,3,*()   

  1. 1. Department of Pediatrics, the Affiliated Hospital of Zunyi Medical University, Zunyi 563000, China
    2. Department of Pediatrics, Guizhou Children's Hospital, Zunyi 563000, China
    3. Collaborative Innovation Center for Tissue Injury Repair and Regenerative Medicine of Zunyi Medical University, Zunyi 563000, China
  • Received:2022-11-23 Revised:2023-05-17 Published:2023-10-20 Online:2023-06-13
  • Contact: CHEN Yan, HE Zhixu

摘要: 背景 天冬氨酸氨基转移酶(AST)/丙氨酸氨基转移酶(ALT)是近年来评估急危重症预后的新指标。目前AST/ALT仅报道可用于评估成人噬血细胞性淋巴组织细胞增生症(HLH)的预后,而儿童HLH尚未见相关研究。 目的 探讨HLH患儿AST/ALT与临床特征的关系及预后意义,为临床早期识别并诊断儿童HLH提供理论依据。 方法 选取2013年1月—2022年5月遵义医科大学附属医院确诊为HLH的128例住院患儿为研究对象,通过电子病历系统收集患儿的基线资料。将患儿按AST/ALT三分位数分为3组:T1组(AST/ALT≤1.57,n=43),T2组(1.57<AST/ALT<3.22,n=42),T3组(AST/ALT≥3.22,n=43)。采取门诊复查和电话随访形式对患儿进行随访。随访开始时间为患儿出院时间,每6个月随访1次,随访截至2022-06-01,终止事件为患儿死亡或失访。采用Spearman秩相关分析探讨AST/ALT与实验室检查结果的相关性。绘制实验室指标预测HLH患儿死亡的受试者工作特征曲线(ROC曲线),计算ROC曲线下面积(AUC)并计算最佳截断值。采用Kaplan-Meier法绘制生存曲线分析不同AST/ALT分组对患者总生存期的影响,并用Log-rank检验进行比较。采用Cox比例风险回归分析探讨HLH患儿死亡的影响因素。 结果 3组患儿性别、进入儿童重症监护室(PICU)情况、治疗方式比较,差异有统计学意义(P<0.05)。3组患儿呼吸衰竭、休克发生率比较,差异有统计学意义(P<0.05)。T3组患儿乳酸脱氢酶、肌酸激酶同工酶、血清铁蛋白和活化部分凝血活酶时间高于T1、T2组,白蛋白、纤维蛋白原水平低于T1、T2组(P<0.05);T2、T3组Na+水平低于T1组,C反应蛋白水平高于T1组(P<0.05)。相关性分析结果显示,AST/ALT与中性粒细胞绝对值(rs=0.182,P=0.040)、C反应蛋白(rs=0.419,P<0.001)、总胆红素(rs=0.182,P=0.040)、肌酸激酶同工酶(rs=0.310,P<0.001)、乳酸脱氢酶(rs=0.474,P<0.001)、活化部分凝血活酶时间(rs=0.316,P<0.001)、血清铁蛋白(rs=0.311,P<0.001)呈正相关,与白蛋白(rs=-0.352,P<0.001)、纤维蛋白原(rs=-0.179,P=0.043)、Ca2+(rs=-0.259,P=0.003)、Na+(rs=-0.244,P=0.006)呈负相关。ROC曲线结果显示,C反应蛋白、乳酸脱氢酶、活化部分凝血活酶时间、血清铁蛋白、纤维蛋白原预测患儿死亡的AUC分别为0.560〔95%CI(0.451,0.669)〕、0.666〔95%CI(0.560,0.772)〕、0.605〔95%CI(0.499,0.710)〕、0.724〔95%CI(0.626,0.822)〕、0.648〔95%CI(0.551,0.745)〕、0.715〔95%CI(0.624,0.807)〕,最佳截断值分别为82.08 mg/L、40.5 U/L、927.5 U/L、53.95 s、1 897 μg/L、1.45 g/L。随访过程中T1、T2、T3组患儿死亡率分别为14.0%(6/43)、33.3%(14/42)、44.2%(19/43),差异有统计学意义(χ2=9.518,P=0.009)。多因素Cox比例风险回归分析结果显示,发生休克〔HR=4.24,95%CI(2.09,8.61),P<0.001〕、活化部分凝血活酶时间≥53.95 s〔HR=2.44,95%CI(1.24,4.81),P=0.010〕、血清铁蛋白≥1 897 μg/L〔HR=3.05,95%CI(1.02,9.09),P=0.046〕是HLH患儿死亡的影响因素。 结论 HLH患儿的AST/ALT更高,其预后不良的发生率更高,且其总生存期更短,患儿预后更差,早期关注AST/ALT变化对HLH患儿预后具有重要临床意义。

关键词: 淋巴组织细胞增多症,噬血细胞性, 肝功能不全, 儿童, 天冬氨酸氨基转移酶类, 丙氨酸转氨酶, 预后, 影响因素分析

Abstract:

Background

Aspartate aminotransferase (AST) /alanine aminotransferase (ALT) is a novel indicator to evaluate the prognosis of acute critical illness in recent years. At present, AST/ALT has only been reported to evaluate the prognosis of hemophagocytic lymphohistiocytosis (HLH) in adults, while HLH in children has not been studied.

Objective

To explore the relationship between AST/ALT and clinical characteristics and its prognostic significance in children with HLH, so as to provide a theoretical basis for early clinical recognition and diagnosis of HLH in children.

Methods

A total of 128 hospitalized children diagnosed with HLH in the Affiliated Hospital of Zunyi Medical University from January 2013 to May 2022 were selected as the research objects, and the baseline data of children were collected through the electronic medical record system. The children were divided into the T1 group (AST/ALT≤1.57, n=43), T2 group (1.57<AST/ALT<3.22, n=42), and T3 group (AST/ALT≥3.22, n=43) according to the AST/ALT quantiles, and followed up by outpatient review and telephone follow-up once every 6 months from the time of discharge to 2022-06-01, with the termination event of death or loss of follow-up. Spearman rank correlation analysis was used to explore the correlation between AST/ALT and laboratory test results. The receiver operating characteristic (ROC) curve of laboratory indicators for predicting death in children with HLHwas plotted, the area under ROC curve (AUC) and optimal cut-off value were calculated. Kaplan-Meier method was used to plot survival curves to analyze the effect of different AST/ALT groupings on overall survival, and Log-rank test was used for comparison. Cox proportional risk model was used to explore the influencing factors of death in children with HLH.

Results

There were statistically significant differences in gender, PICU admission, treatment methods, incidence of respiratory failure and shock among the 3 groups (P<0.05). Lactate dehydrogenase, creatine kinase isoenzyme, serum ferritin and activated partial thromboplastin time in the T3 group were higher than those in the T1 and T2 groups, while the levels of albumin and fibrinogen in the T3 group were lower than those in the T1 and T2 groups (P<0.05). Na+ level in the T2 and T3 groups was lower than that in the T1 group, while C-reactive protein level was higher than that in the T1 group (P<0.05). Correlation analysis showed that AST/ALT was positively correlated with absolute neutrophil count (rs=0.182, P=0.040), C-reactive protein (rs=0.419, P<0.001), total bilirubin (rs=0.182, P=0.040), creatine kinase isoenzyme (rs=0.310, P<0.001), lactate dehydrogenase (rs=0.474, P<0.001), activated partial thromboplastin time (rs=0.316, P<0.001), serum ferritin (rs=0.311, P<0.001), and negatively correlated with albumin (rs=-0.352, P<0.001), fibrinogen (rs=-0.179, P=0.043), Ca2+ (rs=-0.259, P=0.003), Na+ (rs=-0.244, P=0.006). ROC curve results showed that the AUCs of C-reactive protein, lactate dehydrogenase, activated partial thromboplastin time, serum ferritin and fibrinogen were 0.560〔95%CI (0.451, 0.669) 〕, 0.666〔95%CI (0.560, 0.772) 〕, 0.605〔95%CI (0.499, 0.710) 〕, 0.724〔95%CI (0.626, 0.822) 〕, 0.648〔95%CI (0.551, 0.745) 〕 and 0.715〔95%CI (0.624, 0.807) 〕, respectively, with the optimal cutoff values of 82.08 mg/L, 40.5 U/L, 927.5 U/L, 53.95 s, 1 897 μg/L, and 1.45 g/L, respectively. The mortality rate in the T1, T2 and T3 groups was 14.0% (6/43), 33.3% (14/42) and 44.2% (19/43), respectively, with statistically significant differences (χ2=9.518, P=0.009). Multivariate Cox proportional hazard regression analysis showed that shock〔HR=4.24, 95%CI (2.09, 8.61), P<0.001〕, activated partial thromboplastin time ≥53.95 s〔HR=2.44, 95%CI (1.24, 4.81), P=0.010〕and serum ferritin ≥1 897 μg/L〔HR=3.05, 95%CI (1.02, 9.09), P=0.046〕were the risk factors for death in children.

Conclusion

HLH patients in children with higher AST/ALT have higher incidence of poor prognosis, shorter overall survival, and worse prognosis.

Key words: Lymphohistiocytosis, hemophagocytic, Hepatic insufficiency, Child, Aspartate aminotransferases, Alanine transaminase, Prognosis, Root cause analysis