中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Issue 7
Jul.  2014

Significance of serum cystatin C level for early diagnosis of acute kidney injury in patients with acute-on-chronic liver failure

DOI: 10.3969/j.issn.1001-5256.2014.07.024
Research funding:

 

  • Received Date: 2013-08-15
  • Published Date: 2014-07-20
  • Objective To investigate the significance of serum cystatin C (CysC) level for the early diagnosis of acute kidney injury (AKI) in patients with acute- on- chronic liver failure (ACLF) . Methods Sixty patients with chronic hepatitis B- related ACLF and 60 patients with CHB, as well as 60 healthy controls, were included in the study. The ACLF patients were followed up until discharge, and serum samples were collected during hospital stay. Serum CysC level was measured by latex- enhanced immunoturbidimetric assay. The receiver operating characteristic (ROC) curves of serum CysC, creatinine (Cr) , and sodium levels for the diagnosis of AKI were drawn, and the areas under the ROC curves (AUCs) and optimal cut- off values were determined. For normally distributed measurement data, comparison between groups was made by one- way analysis of variance, and multiple comparisons were made by two- sided t test; otherwise, comparison between groups was made by Mann- Whitney U test. Enumeration data were analyzed by chi- square test. The Pearson correlation test was used for correlation analysis. The AUCs and optimal cut- off values were calculated by Medcal 12. 7. 1. 0. Results The serum CysC level in ACLF patients was 1050 ± 444 ng /ml, which was significantly higher than those in healthy controls (638 ± 275 ng /ml, P = 0. 016) and CHB patients (661 ± 225 ng /ml, P = 0. 028) ; for ACLF patients, serum CysC level was not significantly correlated with serum Cr level (r =0.311, P >0.05) , but showed a significant positive correlation with MELD score (r =0. 529, P <0. 01) . During hospital stay, 8 (13.3%) of ACLF patients developed AKI. The multivariate logistic regression analysis indicated that serum CysC level was the independent risk factor for AKI development in ACLF patients (OR = 1. 008, P = 0. 021) . The cut- off value of serum CysC level for the early diagnosis of AKI in ACLF patients was 1210 ng /ml. Conclusion Elevated serum CysC level may provide an early prediction of AKI development in ACLF patients with a normal serum Cr level during hospital stay.

     

  • 肝脏疾病包括由于感染、免疫系统异常、遗传因素等病因导致的肝炎、肝硬化、肝肿瘤等一系列主要累及肝脏的消化系统疾病[1]。近年中国作者在学术期刊发表了大量肝脏疾病研究,并获国际引用,例如在欧洲肝病学会(EASL)2018年发布的《EASL临床实践指南: 肝细胞癌管理》[2]的参考文献中,77篇有来自中国的作者,其中40篇有来自中国的通信作者。

    文献计量分析是对出版物的内容和引用进行定量分析的研究方法[3]。近年已有一些对肝脏疾病研究进行的文献计量分析。Yang等[4]报道,2009年—2018年全球胃肠肝病学研究的8.9%来自中国,仅次于美国和日本。Hu等[5]报道在1964年—2014年中国作者在胃肠肝病学期刊发表的、被引频次前50的文章中,基础研究多于临床研究。马宏宇等[6]报道1991年—2017年肝癌队列研究的数量持续增长。Li等[7]报道在1973年—2018年,慢性乙型肝炎治疗相关研究中,来自中国的记录最多,达20.85%。Xu等[8]报道1980年—2020年被引频次前100的肝细胞癌管理研究有26篇来自中国,仅次于美国和意大利。但这些研究均未分析中国作者在不同类别期刊发表的肝脏疾病研究的变化趋势,对于高被引文章仅关注总被引频次,没有关注其被其他肝脏疾病研究引用的情况。

    有研究[9]报道国家自然科学基金资助与中国生物医学研究者发表文章的数量和期刊影响因子加权数量升高均相关。国家自然科学基金资助总额的上涨可促进中国作者完成并发表数量与质量更高的研究[10],但目前未见研究报道近年中国作者发表的肝脏疾病研究获国家自然科学基金资助情况。

    本研究旨在通过分析2016年—2020年中国(不含港澳台地区)作者在SCIE(Science Citation Index Expanded)数据库收录的胃肠肝病学期刊发表的肝脏疾病研究的题录数据与来源期刊的特征,评价中国作者发表的肝脏疾病研究出版物特征的变化趋势,了解中国学者在肝脏疾病研究领域的贡献;通过计算被中国与全球作者发表在胃肠肝病学期刊上的肝脏疾病研究引用频次,为评价中国作者发表的肝脏疾病研究的国际与国内影响力提供证据。

    题录与引文数据来自SCIE数据库,期刊的学科分类与分区及其他期刊信息来自JCR(Journal Citation Reports)。

    2021年7月通过Web of Science平台检索SCIE与JCR数据库。在JCR数据库下载2020年胃肠肝病学(Gastroenterology & Hepatology)期刊的刊名、影响因子与JCR分区(根据影响因子的四分位数分为Q1~Q4区),期刊的特征均使用2020年数据。在SCIE数据库中检索题名获摘要包含Liver、Hepatocellular、Hepatitis、Cirrhosis或Hepatic,出版年为2016年—2020年,发表在胃肠肝病学期刊上,出版物类型为Article的期刊文章,导出题录信息与参考文献。从导出的题录信息排除临床指南,并筛选通信作者单位含有中国(不含港澳台地区)机构的记录。使用Microsoft Excel 2019进行汇总统计。

    使用R 4.1.0[11]运行package bibliometrix 3.1.4[12],利用SCIE数据库导出的题录与参考文献信息计算研究纳入的文献在2016年—2020年,被中国作者和全球作者在胃肠肝病学期刊发表的肝脏疾病研究引用的频次。构成比的变化使用R package DescTools 0.99.42[13]进行Cochran-Armitage检验,检验上升趋势,当P>0.5时检验下降趋势,单侧检验以P<0.025认为存在上升或下降趋势。

    表 1展示了2016年—2020年中国作者在胃肠肝病学期刊上发表的肝脏疾病研究的特征,92种胃肠肝病学期刊上共发表17091篇肝脏疾病研究,所有记录均有通信作者信息,其中2705篇(15.8%)含有来自中国机构的通信作者,并且中国作者在胃肠肝病学期刊上,年度发表的肝脏疾病研究数量和占比(Z=7.44,P<0.001) 也逐年增加,其中9.5%的研究发表在Q1胃肠肝病学期刊上,49.4%的研究被引频次大于5次。

    表  1  2016年—2020年在SCIE收录的胃肠肝病学期刊上发表的肝脏疾病研究特征
    Table  1.  Characteristics of liver diseases research published on Gastroenterology & Hepatology journals indexed in SCIE during 2016 to 2020
    项目 中国作者发文数量(篇) 全球作者发文数量(篇) 中国作者发文占比(%)
    出版年
    2016 446 3294 13.5
    2017 464 3324 14.0
    2018 474 3259 14.5
    2019 640 3618 17.7
    2020 681 3596 18.9
    期刊JCR分区
    Q1 473 4961 9.5
    Q2 984 5666 17.4
    Q3 799 3413 23.4
    Q4 449 3051 14.7
    开放获取 1283 8630 14.9
    被引频次
    0 302 1447 20.9
    1~5 1066 5840 18.3
    6~10 514 3187 16.1
    11~20 464 3142 14.8
    >20 359 3485 10.3
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    2020年JCR胃肠肝病学期刊中影响因子较高的且为Q1区的期刊有23种,其中包含两种主要发表综述文章的期刊(Nature Reviews Gastroenterology & HepatologySeminars in Liver Disease)与较少发表肝脏疾病研究的期刊。表 2展示了中国作者在2020年Q1区胃肠肝病学期刊发表肝脏疾病研究情况,期刊根据全球作者发表肝脏疾病研究的数量排序,在排名前10的期刊中,有3种期刊中国作者发表的研究占比超过10%。

    表  2  2016年—2020年中国作者在2020年Q1区胃肠肝病学期刊发表肝脏疾病研究情况
    Table  2.  Chinese authors published liver diseases research on Gastroenterology & Hepatology journals in the Q1 of 2020 during 2016-2020
    序号 期刊 中国作者发文数量(篇) 全球作者发文数量(篇) 中国作者发文占比(%)
    1 Hepatology 226 1382 16.4
    2 Journal of Hepatology 97 918 10.6
    3 Alimentary Pharmacology & Therapeutics 21 390 5.4
    4 Gastroenterology 20 365 5.5
    5 Clinical Gastroenterology and Hepatology 11 296 3.7
    6 Gut 38 270 14.1
    7 Clinics in Liver Disease 0 215 0
    8 Journal of Gastroenterology 5 183 2.7
    9 American Journal of Gastroenterology 8 178 4.5
    10 Journal of Hepato-Biliary-Pancreatic Sciences 6 151 4.0
    11 Liver Cancer 8 121 6.6
    12 Clinical and Molecular Hepatology 3 100 3.0
    13 Lancet Gastroenterology & Hepatology 6 89 6.7
    14 Hepatobiliary Surgery and Nutrition 8 75 10.7
    15 Cellular and Molecular Gastroenterology and Hepatology 4 60 6.7
    16 Gastrointestinal Endoscopy 0 48 0
    17 Gut Microbes 5 32 15.6
    18 Gastric Cancer 5 31 16.1
    19 Endoscopy 1 24 4.2
    20 Digestive Endoscopy 0 19 0
    21 Journal of Crohn’s & Colitis 1 9 11.1
    22 Nature Reviews Gastroenterology & Hepatology 0 5 0
    23 Seminars in Liver Disease 0 0 -
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    表 3展示了中国作者在不同分区胃肠肝病学期刊上发表的肝脏疾病研究占全球同分区比例的变化。2020年中国作者在各分区胃肠肝病学期刊发表的研究数量较2016年均有增加,中国作者在Q1区胃肠肝病学期刊发表的肝脏疾病研究占全球同分区的比例逐年上升(P<0.001),在Q3区胃肠肝病学期刊发表的肝脏疾病研究占全球Q3区的比例最高。

    表  3  2016年—2020年中国作者在SCIE收录的不同分区胃肠肝病学期刊上发表的肝脏疾病研究占全球同分区胃肠肝病学期刊上发表的肝脏疾病研究比例变化
    Table  3.  The proportion of liver disease research published by Chinese authors in different divisions of Gastroenterology & Hepatology journals indexed in SCIE accounted for the change in the proportion of liver diseases research published in the same division in the world during 2016 to 2020
    项目 2016年 2017年 2018年 2019年 2020年 Z P
    Q1区(中国/全球) 6.0%(58/961) 8.0%(77/961) 9.6%(95/987) 11.5%(121/1052) 12.2%(122/1000) -0.05 <0.0011)
    Q2区(中国/全球) 16.7%(193/1154) 17.6%(196/1112) 14.3%(153/1069) 19.2%(232/1210) 18.7%(210/1121) -1.59 0.056
    Q3区(中国/全球) 19.9%(111/559) 22.5%(137/610) 23.6%(148/626) 25.6%(195/761) 24.3%(208/857) -2.20 0.0141)
    Q4区(中国/全球) 13.5%(84/620) 8.4%(54/641) 13.5%(78/577) 15.5%(92/595) 22.8%(141/618) -5.72 <0.0011)
    注:1)P<0.025。
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    表 4展示了中国作者在胃肠肝病学期刊上发表的肝脏疾病研究获国自然基金资助情况,2020年中国作者在各分区胃肠肝病学期刊发表的获国自然基金资助的研究数量较2016年均有增加,在Q1区胃肠肝病学期刊发表的肝脏疾病研究获国自然基金资助的比例最高,达79.7%。各分区胃肠肝病学期刊发表的获国自然基金资助的肝脏疾病研究在同分区的比例,在5年间无明显变化。

    表  4  2016年—2020年中国作者在SCIE收录的胃肠肝病学期刊上发表的肝脏疾病研究获国家自然科学基金资助情况
    Table  4.  The research on liver diseases published by Chinese authors in the Gastroenterology & Hepatology journals indexed in SCIE was funded by the National Natural Science Foundation of China during 2016 to 2020
    项目 2016年 2017年 2018年 2019年 2020年 Z P
    Q1区(资助/全部) 81.0%(47/58) 76.6%(59/77) 91.6%(87/95) 80.2%(97/121) 71.3%(87/122) 1.62 0.0521)
    Q2区(资助/全部) 46.1%(89/193) 49.5%(97/196) 53.6%(82/153) 52.6%(122/232) 53.8%(113/210) -1.65 0.0491)
    Q3区(资助/全部) 52.3%(58/111) 39.4%(54/137) 49.3%(73/148) 49.2%(96/195) 40.9%(85/208) 1.00 0.159
    Q4区(资助/全部) 35.7%(30/84) 46.3%(25/54) 32.1%(25/78) 35.9%(33/92) 38.3%(54/141) 0.04 0.4861)
    注:1)为对下降趋势进行的检验。
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    图 1展示了2016年—2020年中国作者在Q1区胃肠肝病学期刊发表肝脏疾病研究被引频次分布。截至2021年7月20日,中国作者在胃肠肝病学期刊上发表的肝脏疾病研究的总被引频次中位数为5次,第25、75百分位数为2和13次;被全球作者在胃肠肝病学期刊上发表的肝脏疾病研究引用频次的中位数为0,第25、75百分位数为0和1次;被中国作者在胃肠肝病学期刊上发表的肝脏疾病研究引用频次的中位数与第25、75百分位数均为0次。2016年—2020年中国作者在胃肠肝病学期刊发表的肝脏疾病研究的总被引频次(33 140次),6.7%(2222次)来自全球作者胃肠肝病学期刊发表的肝脏疾病研究,3.6%(1200次)来自中国作者在胃肠肝病学期刊发表的肝脏疾病研究。

    图  1  2016年—2020年中国作者在Q1区胃肠肝病学期刊发表肝脏疾病研究被引频次分布
    注:TC,总被引频次;LC,被中国作者在胃肠肝病学期刊上发表的肝脏疾病研究引用频次;GC, 被全球作者在胃肠肝病学期刊上发表的肝脏疾病研究引用频次;图中省略了被引频次>50的点。
    Figure  1.  The distribution of citation frequency of Chinese authors' published liver diseases research in Q1 Gastroenterology and Hepatology journals during 2016 to 2020

    筛选2016年—2020年,中国作者在胃肠肝病学期刊上发表的肝脏疾病研究被中国与全球作者在胃肠肝病学期刊上发表的肝脏疾病研究引用频次前10的研究,因存在排名同为前10的研究,因此各选取前9篇,表 5展示了这些研究。被中国作者在胃肠肝病学期刊上发表的肝脏疾病研究引用频次最高的9篇研究中,5篇为临床研究,4篇兼有临床与基础研究;临床研究的研究设计5篇为队列研究,2篇为随机对照试验,2篇为描述性研究;研究主题3篇为乙型肝炎,3篇为肝细胞癌,2篇为肝硬化,1篇为非酒精性脂肪性肝病。被全球作者在胃肠肝病学期刊上发表的肝脏疾病研究引用频次最高的9篇研究中,7篇为临床研究,1篇兼有临床与基础研究;临床研究的研究设计5篇为队列研究,2篇为随机对照试验,1篇为横断面研究;研究主题3篇为乙型肝炎,2篇为肝硬化,1篇为非酒精性脂肪性肝病,2篇为COVID-19,1篇为肝细胞癌。

    表  5  2016年—2020年中国作者在SCIE收录的胃肠肝病学期刊上发表的肝脏疾病研究被中国作者与全球作者在胃肠肝病学期刊上发表的肝脏疾病研究引用频次排名前9的研究
    Table  5.  The liver disease research published by Chinese authors in the Gastroenterology & Hepatology journals indexed in SCIE was the 9 most frequently cited studies of liver disease research published by Chinese authors and global authors in the Gastroenterology & Hepatology journals during 2016 to 2020
    题名 期刊 出版年 通信作者单位 TC(排名) GC(排名) LC(排名)
    Development of Diagnostic Criteria and A Prognostic Score for Hepatitis B Virus-Related Acute- On-Chronic Liver Failure GUT 2018 浙江大学医学院附属第一医院 74(54) 20(6) 20(1)
    Serum Hepatitis B Virus RNA is Encapsidated Pregenome RNA that may be Associated with Persistence of Viral Infection and Rebound J HEPATOL 2016 北京大学 191(13) 45(1) 19(2)
    New Classification of Liver Biopsy Assessment for Fibrosis in Chronic Hepatitis B Patients Before and After Treatment HEPATOLOGY 2017 首都医科大学附属北京友谊医院 59(76) 18(7) 13(3)
    Covered Tips Versus Endoscopic Band Ligation Plus Propranolol for The Prevention of Variceal Rebleeding in Cirrhotic Patients with Portal Vein Thrombosis: A Randomised Controlled Trial GUT 2018 空军军医大学西京医院 50(103) 16(9) 11(4)
    Targeting Hepatic Traf1-Ask1 Signaling to Improve Inflammation, Insulin Resistance, And Hepatic Steatosis J HEPATOL 2016 武汉大学 73(58) 14(12) 11(4)
    Liver Transplantation for Hepatocellular Carcinoma Beyond the Milan Criteria GUT 2016 浙江大学医学院附属第一医院 95(40) 21(5) 10(6)
    Targeting Traf3 Signaling Protects Against Hepatic Ischemia/Reperfusions Injury J HEPATOL 2016 武汉大学 59(76) 10(21) 10(6)
    Perioperative Blood Transfusion Does Not Influence Recurrence-Free and Overall Survivals After Curative Resection for Hepatocellular Carcinoma A Propensity Score Matching Analysis J HEPATOL 2016 海军军医大学附属东方肝胆外科医院 69(60) 13(15) 9(8)
    Circular RNA Circmto1 Acts as The Sponge of Microrna-9 To Suppress Hepatocellular Carcinoma Progression HEPATOLOGY 2017 浙江大学,海军军医大学 664(1) 10(22) 9(8)
    Eight Millimetre Covered Tips Does Not Compromise Shunt Function but Reduces Hepatic Encephalopathy in Preventing Variceal Rebleeding J HEPATOL 2017 空军军医大学西京医院 56(86) 22(4) 8(10)
    …… …… …… …… …… …… ……
    Comparison of Laboratory Tests, Ultrasound, or Magnetic Resonance Elastography to Detect Fibrosis in Patients with Nonalcoholic Fatty Liver Disease: A Meta-Analysis HEPATOLOGY 2017 华中科技大学同济医学院附属协和医院 238(9) 45(1) 7(12)
    …… …… …… …… …… …… ……
    COVID-19: Abnormal Liver Function Tests J HEPATOL 2020 南方科技大学第二附属医院 242(8) 26(3) 5(22)
    Clinical Features of COVID-19-Related Liver Functional Abnormality CLIN GASTROENTEROL HEPATOL 2020 复旦大学附属公共卫生临床中心 236(10) 17(8) 5(23)
    注:J HEPATOLJournal of HepatologyCLIN GASTROENTEROL HEPATOLClinical Gastroenterology and Hepatology
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    近年全球学者对肝脏疾病的流行病学、诊断、治疗等研究取得了诸多进展[14],使用直接抗病毒药物治疗丙型肝炎、纳武利尤单抗与瑞戈非尼等药物治疗肝细胞癌、超声弹性成像与磁共振弹性成像等无创评估肝纤维化的方法在诊疗中的应用已经改变了临床实践[15-18],了解近年中国学者在肝脏疾病研究领域的贡献及其影响力,对认识肝病学学科发展现状与前景具有直接价值。

    总被引频次可以用于评估出版物的影响力,但它假定所有引用的权重相同,具有明显的局限性。为了提高引文分析的可解释性,可以为引用加权,或者对施引文章和引用本身的特征进行限定[19]。胃肠肝病学期刊包括了肝病学专业期刊与消化病学专业期刊,其中Journal of HepatologyGutGastroenterology等高影响力期刊在全球享有盛誉。尽管中国作者也会在内科学期刊、医学综合期刊甚至多学科期刊发表肝脏疾病研究,但基本可以认为中国作者在专业期刊发表的肝脏疾病研究对于评价专科研究水平具有代表性,将来源期刊限定于胃肠肝病学期刊进行引文分析,有利于为认识肝脏疾病研究的影响力提供更加深入和巧妙的见解。

    中国作者在不同的Q1区胃肠肝病学期刊上发表的肝脏疾病研究占全球作者发表的肝脏疾病研究的比例存在明显差异,可能的原因包括部分期刊本身发表的肝脏疾病研究较少,且期刊出版文章时存在母国偏倚等现象[20]。在Q1区胃肠肝病学期刊,中国作者在Hepatology上发表的肝脏疾病研究占全球比例最高,为16.4%。中国作者在SCIE收录的Q1区胃肠肝病学期刊上发表的肝脏疾病研究数量不断增加,占全球同分区的比例不断上升,表明有更多的高质量研究获得国际学界认可,并得以在高影响力胃肠肝病学期刊发表。2016年—2020年在Q1区胃肠肝病学期刊发表的肝脏疾病研究获国自然基金资助的比例达71.3%~91.6%,明显高于发表在Q2/Q3/Q4区胃肠肝病学期刊上的肝脏疾病研究,表明获国自然基金资助是研究得以发表在高影响力胃肠肝病学期刊上的重要支撑。

    中国作者在胃肠肝病学期刊上发表的肝脏疾病研究被中国与全球作者在胃肠肝病学期刊上发表的肝脏疾病研究引用频次的排序存在差异,在各自排名前9的文章中有5篇相同,其中4篇兼被中外作者在胃肠肝病学期刊上发表的肝脏疾病研究引用,表明Wang等[21]对血清HBV RNA与HBV感染的持续性与反弹的关联的研究,Xu等[22]对修改中国人群肝细胞癌肝移植的标准的研究,Sun等[23]对慢性乙型肝炎患者肝纤维化状态进行重新分类的研究,以及Lv等[24]在肝硬化门静脉血栓形成患者中,应用改良术式联合普萘洛尔预防静脉曲张再出血的研究在国内和国际学界均具有一定影响。

    综上所述,近年中国作者在SCIE收录的高影响力胃肠肝病学期刊发表的肝脏疾病研究的数量不断增加,其中大部分研究获国自然基金资助。比较研究被中国与全球作者在胃肠肝病学期刊上发表的肝脏疾病研究引用频次,显示了中国作者发表的在国内和国际学界均具有较高影响的肝脏疾病研究。

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