楊航 趙黎莉 韓萍 陳慶靈 文君 劉潔 程曉靜 李嘉
摘要:
目的 預(yù)測(cè)失代償事件以采取積極的預(yù)防措施,是提高肝硬化患者生存期的關(guān)鍵。本文旨在探索血清殼多糖酶3樣蛋白1(CHI3L1)對(duì)肝硬化患者發(fā)生失代償事件風(fēng)險(xiǎn)的預(yù)測(cè)價(jià)值。方法 納入2019年1月—2021年5月于天津市第二人民醫(yī)院診療的305例肝硬化患者,進(jìn)行病例對(duì)照研究。其中基線時(shí)處于代償期肝硬化的患者200例,處于失代償期肝硬化的患者105例。將305例肝硬化患者,以1年內(nèi)是否發(fā)生失代償事件進(jìn)行分組,其中發(fā)生失代償事件組79例,未發(fā)生失代償事件組226例;將200例代償期肝硬化患者,以1年內(nèi)是否發(fā)生首次失代償事件進(jìn)行分組,其中發(fā)生首次失代償事件組43例,未發(fā)生首次失代償事件組157例。符合正態(tài)分布的計(jì)量資料兩組間比較采用成組t檢驗(yàn)或Mann-Whitney U檢驗(yàn);計(jì)數(shù)資料兩組間比較采用Wilcoxon秩和檢驗(yàn)或χ2檢驗(yàn)。采用二分類Logistic回歸分析各變量與失代償事件之間的相關(guān)性;采用受試者工作特征曲線(ROC曲線)下面積(AUC)來(lái)評(píng)價(jià)各變量對(duì)失代償事件的預(yù)測(cè)價(jià)值,采用約登指數(shù)最大值來(lái)確定最佳臨界值。結(jié)果 1年內(nèi)發(fā)生失代償事件患者的基線血清CHI3L1水平高于未發(fā)生患者[243.00(136.00~372.00)ng/mL vs 117.50(67.75~205.25)ng/mL, U=4 720.500, P<0.001];1年內(nèi)發(fā)生首次失代償事件患者的基線血清CHI3L1水平高于未發(fā)生患者[227.98(110.00~314.00)ng/mL vs 90.00(58.00~168.50)ng/mL,U=1 681.500,P<0.001]?;€血清CHI3L1水平較高的肝硬化患者,1年內(nèi)發(fā)生失代償事件的風(fēng)險(xiǎn)增加(OR=1.004,95%CI:1.002~1.006,P<0.001);基線血清CHI3L1水平較高的代償期肝硬化患者,1年內(nèi)發(fā)生首次失代償事件的風(fēng)險(xiǎn)增加(OR=1.006,95%CI:1.003~1.008,P<0.001)。使用基線血清CHI3L1水平預(yù)測(cè)代償期肝硬化患者發(fā)生首次失代償事件風(fēng)險(xiǎn)的AUC為0.751,最佳臨界值為95.5 ng/mL,敏感度和特異度分別為90.7%和55.4%;聯(lián)合血清CHI3L1和Child-Pugh分級(jí)建立預(yù)測(cè)模型,AUC為0.809,約登指數(shù)最大時(shí)敏感度和特異度分別為72.1%和77.1%。結(jié)論 血清CHI3L1可做為代償期肝硬化患者發(fā)生首次失代償事件風(fēng)險(xiǎn)的有效預(yù)測(cè)因子,且在聯(lián)合Child-Pugh分級(jí)后具有更高的預(yù)測(cè)價(jià)值。
關(guān)鍵詞:肝硬化; 殼多糖酶3樣蛋白質(zhì)1; 危險(xiǎn)因素
基金項(xiàng)目:
天津市醫(yī)學(xué)重點(diǎn)學(xué)科(??疲┙ㄔO(shè)項(xiàng)目(TJYXZDXK-059B); 天津市自然科學(xué)基金(20JCYBJC01150); 天津市衛(wèi)生健康科技項(xiàng)目(TJWJ2021MS034)
Value of serum chitinase-3-like protein 1 in predicting the risk of decompensation events in patients with liver cirrhosis
YANG Hang1, ZHAO Lili2, HAN Ping1, CHEN Qingling1, WEN Jun2, LIU Jie2, CHENG Xiaojing2, LI Jia2. (1. Clinical School of The Second Peoples Hospital, Tianjin Medical University, Tianjin 300070, China; 2. Department of Hepatology, Tianjin Second Peoples Hospital, Tianjin 300192, China)
Corresponding author:LI Jia, 18622663700@163.com (ORCID:0000-0003-0100-417X)
Abstract:
Objective To investigate the value of serum chitinase-3-like protein 1 (CHI3L1) in predicting the risk of decompensation events in patients with liver cirrhosis, since prediction of decompensation events and adoption of active preventive measures are the key to improving the survival time of patients with liver cirrhosis. Methods A case-control study was conducted for 305 patients with liver cirrhosis who were diagnosed and treated in Tianjin Second Peoples Hospital from January 2019 to May 2021, among whom there were 200 patients with compensated liver cirrhosis and 105 patients with decompensated liver cirrhosis at baseline. According to whether decompensation events occurred within 1 year, the 305 patients with liver cirrhosis were divided into decompensation group with 79 patients and non-decompensation group with 226 patients; according to whether decompensation events occurred for the first time within 1 year, the 200 patients with compensated liver cirrhosis were divided into first-time decompensation group with 43 patients and non-first-time decompensation group with 157 patients. The independent samples t-test or the Mann-Whitney U test was used for comparison of normally distributed continuous data between groups, and the Wilcoxon rank-sum test or the chi-square test was used for comparison of categorical data between groups. The binary logistic regression analysis was used to investigate the association between each variable and decompensation events; the receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC) were used to investigate the value of each variable in predicting decompensation events, and the maximum value of Youden index was used to determine the optimal cut-off value. Results The patients who experienced decompensation events within 1 year had a significantly higher baseline serum level of CHI3L1 than those who did not experience such events [243.00 (136.00-372.00) ng/mL vs 117.50 (67.75-205.25) ng/mL, U=4720.500, P<0.001], and the patients who experienced decompensation events for the first time within 1 year had a significantly higher baseline serum level of CHI3L1 than those who did not experience such events [227.98 (110.00-314.00) ng/mL vs 90.00 (58.00-168.50) ng/mL, U=1 681.500, P<0.001]. Patients with cirrhosis with higher baseline CHI3L1 levels had an increased risk of decompensation events within 1 year (OR=1.004,95%CI: 1.002-1.006, P<0.001); Patients with compensated cirrhosis with higher baseline serum CHI3L1 levels had an increased risk of first decompensated event within 1 year (OR=1.006,95%CI: 1.003-1.008, P<0.001). The baseline serum level of CHI3L1 had an AUC of 0.751 in predicting the risk of first-time decompensation events, with a sensitivity of 90.7% and a specificity of 55.4% at the optimal cut-off value of 95.5 ng/mL. The predictive model based on the combination of serum CHI3L1 level and Child-Pugh class had an AUC of 0.809, with a sensitivity of 72.1% and a specificity of 77.1% at the maximum value of Youden index. Conclusion Serum CHI3L1 level can be used as an effective predictive factor for the risk of first-time decompensation events in patients with compensated liver cirrhosis, and its combination with Child-Pugh class shows a higher predictive value.
Key words:Liver Cirrhosis;? Chitinase-3-Like Protein 1; Risk Factors
Research funding:
Tianjin Key Medical Subject Construction Project (TJYXZDXK-059B); Tianjin Natural Science Fund (20JCYBJC01150); Tianjin Health Science Project (TJWJ2021MS034)
慢性肝病的共同病理結(jié)局是肝纖維化/肝硬化。根據(jù)既往是否發(fā)生并發(fā)癥,肝硬化可分為代償期肝硬化和失代償期肝硬化,進(jìn)展至失代償期肝硬化后,患者死亡風(fēng)險(xiǎn)增加[1]。失代償事件中,食管胃底靜脈曲張破裂出血(esophageal variceal bleeding,EVB)尤為兇險(xiǎn)[2-3]。預(yù)測(cè)失代償事件以采取積極的預(yù)防措施,是提高肝硬化患者生存期的關(guān)鍵。血清殼多糖酶3樣蛋白1(chitinase-3-like protein 1,CHI3L1)是一種檢測(cè)纖維化進(jìn)展的無(wú)創(chuàng)指標(biāo),可預(yù)測(cè)ALT正常或輕度升高的患者中、重度肝纖維化[4]。本研究對(duì)CHI3L1預(yù)測(cè)肝硬化患者出現(xiàn)失代償事件和代償期肝硬化患者出現(xiàn)首次失代償事件風(fēng)險(xiǎn)的臨床價(jià)值進(jìn)行回顧性病例對(duì)照研究,探索CHI3L1對(duì)失代償事件發(fā)生風(fēng)險(xiǎn)的評(píng)估價(jià)值,以便合理指導(dǎo)治療,提高肝硬化患者生存期。
1 資料與方法
1.1 研究對(duì)象 收集2019年1月—2021年5月于天津市第二人民醫(yī)院診療的肝硬化患者中,符合納排標(biāo)準(zhǔn)的患者的人口學(xué)特征、臨床資料和隨訪1年內(nèi)失代償事件的發(fā)生情況。以隨訪1年內(nèi)失代償事件的發(fā)生情況進(jìn)行分組,進(jìn)行病例對(duì)照研究。失代償事件定義為顯性腹水、EVB或顯性肝性腦病[1]。納入標(biāo)準(zhǔn):(1)肝硬化診斷符合《肝硬化診治指南》[5];乙型肝炎診斷符合《慢性乙型肝炎防治指南(2019年版)》[5];丙型肝炎診斷符合《丙型肝炎防治指南(2019年版)》[6];非酒精性脂肪性肝病診斷符合《非酒精性脂肪性肝病防治指南(2018更新版》[7];酒精性肝病符合《酒精性肝病防治指南(2018更新版)》[8];自身免疫性肝炎診斷符合《自身免疫性肝炎診斷和治療指南(2021)》[9];原發(fā)性膽汁性膽管炎診斷符合《原發(fā)性膽汁性膽管炎的診斷和治療指南(2021)》[10];(2)隨訪時(shí)間>1年或隨訪期間發(fā)生終點(diǎn)事件。排除標(biāo)準(zhǔn):(1)ALT>2倍正常值上限;(2)合并惡性腫瘤;(3)有嚴(yán)重的肺心腎等系統(tǒng)疾?。唬?)接受過(guò)降低門靜脈高壓的預(yù)防手段(預(yù)防性內(nèi)鏡套扎或硬化劑、經(jīng)頸靜脈肝內(nèi)門體分流術(shù)或口服非選擇性β受體阻滯劑)。
1.2 檢測(cè)方法 血清CHI3L1水平檢驗(yàn)采用Microlab STAR IVD ELISA全自動(dòng)酶聯(lián)免疫分析儀(瑞士哈美頓博納圖斯有限公司)及CHI3L1酶聯(lián)免疫法檢測(cè)試劑盒(杭州普望生物技術(shù)有限公司)測(cè)定;肝生化指標(biāo)采用HITACHI全自動(dòng)生物化學(xué)儀-7180及配套試劑(日本東京日立有限公司)測(cè)定;血常規(guī)采用Sysmex XN-2000血液分析儀及配套試劑(日本希森美康有限公司)測(cè)定;凝血指標(biāo)采用STAGO Compact血凝儀及配套試劑(法國(guó)思塔高有限公司)測(cè)定。樣本測(cè)定均由專職人員按照規(guī)范流程進(jìn)行操作。
1.3 統(tǒng)計(jì)學(xué)方法 采用SPSS 28.0軟件對(duì)數(shù)據(jù)進(jìn)行描述和分析。采用Kolmogorov-Smirnov檢驗(yàn)和Shapiro-Wilk 檢驗(yàn)來(lái)檢驗(yàn)連續(xù)變量是否符合正態(tài)分布。符合正態(tài)分布的計(jì)量資料采用x±s表示,不符合正態(tài)分布采用M(P25~P75),兩組間比較采用成組t檢驗(yàn)或Mann-Whitney U檢驗(yàn);計(jì)數(shù)資料兩組間比較采用Wilcoxon秩和檢驗(yàn)或χ2檢驗(yàn)。采用二分類Logistic回歸分析各變量與失代償事件之間的相關(guān)性;采用受試者工作特征曲線(ROC曲線)下面積(AUC)來(lái)評(píng)價(jià)各變量對(duì)失代償事件的預(yù)測(cè)價(jià)值,采用約登指數(shù)最大值來(lái)確定最佳臨界值。P<0.05為差異有統(tǒng)計(jì)學(xué)意義。
2 結(jié)果
2.1 一般情況 本研究共納入305例肝硬化患者,其中男176例,女129例;年齡(55.15±11.32)歲;基線時(shí)處于代償期肝硬化患者200例,處于失代償期肝硬化患者105例。將305例肝硬化患者,以1年內(nèi)是否發(fā)生失代償事件進(jìn)行分組,發(fā)生失代償事件組79例,未發(fā)生失代償事件組226例;將200例代償期肝硬化患者,以1年內(nèi)是否發(fā)生首次失代償事件進(jìn)行分組,其中發(fā)生首次失代償事件組43例,未發(fā)生首次失代償事件組157例。兩組患者基線人口學(xué)特征和臨床資料均無(wú)缺失。
2.2 基線資料比較
2.2.1 1年內(nèi)發(fā)生與未發(fā)生失代償事件組間比較 發(fā)生失代償事件組的男性占比較高、年齡較大、基線Child-Pugh分級(jí)水平較高、基線MELD評(píng)分較高、基線Alb水平較低、基線TBil水平較高、基線CHI3L1水平較高、基線INR較高且基線PLT水平較低,差異均有統(tǒng)計(jì)學(xué)意義(P值均<0.05),兩組患者的病因、基線ALT水平差異均無(wú)統(tǒng)計(jì)學(xué)意義(表1)。
2.2.2 1年內(nèi)發(fā)生與未發(fā)生首次失代償事件組間比較 發(fā)生首次失代償事件組的基線年齡較大、基線Child-Pugh分級(jí)較高、基線MELD評(píng)分較高、基線Alb水平較低、基線TBil水平較高、基線CHI3L1水平較高、基線INR較高且基線PLT水平較低,差異均有統(tǒng)計(jì)學(xué)意義(P值均<0.001);兩組患者的性別、病因和基線ALT的差異均無(wú)統(tǒng)計(jì)學(xué)意義(表2)。
2.3 二分類Logistic回歸分析
2.3.1 以1年內(nèi)發(fā)生失代償事件為結(jié)局進(jìn)行二分類Logistic回歸分析 單因素回歸分析中,患者的年齡、性別、基線Child-Pugh分級(jí)、MELD評(píng)分、Alb水平、CHI3L1水平、INR和PLT水平是患者1年內(nèi)發(fā)生失代償事件的影響因素(P值均<0.05)(表3)。將以上因素納入多因素回歸分析,結(jié)果顯示基線Child-Pugh分級(jí)(OR=1.722,95%CI:1.151~2.577,P=0.008)和CHI3L1水平(OR=1.004,95%CI:1.002~1.006,P<0.001)均為患者1年內(nèi)發(fā)生失代償事件的獨(dú)立影響因素。
2.3.2 以1年內(nèi)發(fā)生首次失代償事件為結(jié)局進(jìn)行二分類Logistic回歸分析 單因素回歸分析中,患者的年齡、基線Child-Pugh分級(jí)、MELD評(píng)分、Alb水平、TBil水平、CHI3L1水平、INR和PLT水平是患者1年內(nèi)發(fā)生首次失代償事件的影響因素(P值均<0.05)(表4)。將以上因素納入多因素回歸分析,結(jié)果顯示基線Child-Pugh分級(jí)(OR=7.184,95%CI:2.573~20.056,P<0.001)和CHI3L1水平(OR=1.006,95%CI:1.003~1.008,P<0.001)均為患者1年內(nèi)發(fā)生首次失代償事件的獨(dú)立影響因素。
2.4 預(yù)測(cè)效能評(píng)估 對(duì)于肝硬化患者,以1年內(nèi)失代償事件的發(fā)生情況為狀態(tài)變量,以CHI3L1為檢驗(yàn)變量,繪制ROC曲線。結(jié)果顯示AUC為0.736(95%CI:0.673~0.798,P<0.001),最佳臨界值為206.5 ng/mL時(shí),敏感度和特異度分別為62.0%和76.1%(圖1a)。以CHI3L1為檢驗(yàn)變量,分別預(yù)測(cè)1年內(nèi)腹水、EVB和顯性肝性腦病發(fā)生風(fēng)險(xiǎn)的AUC(表5)。
對(duì)于代償期肝硬化患者,以1年內(nèi)首次失代償事件的發(fā)生情況為狀態(tài)變量,以血清CHI3L1水平為檢驗(yàn)變量,繪制ROC曲線。結(jié)果顯示AUC為0.751(95%CI:0.671~0.831,P<0.001),最佳臨界值為95.5 ng/mL時(shí),敏感度和特異度分別為90.7%和55.4%;以Child-Pugh分級(jí)為檢驗(yàn)變量,繪制ROC曲線。結(jié)果顯示AUC為0.643(95%CI:0.538~0.746,P=0.004)。聯(lián)合Child-Pugh分級(jí)和CHI3L1為檢驗(yàn)變量建立預(yù)測(cè)模型,Logit(P)=-4.492+0.006×CHI3L1+1.972×Child-Pugh分級(jí),得到的Logit模型具有統(tǒng)計(jì)學(xué)意義(χ2=36.855,P<0.001);繪制ROC曲線,結(jié)果顯示AUC為0.809(95%CI:0.737~0.882,P<0.001),該模型能夠正確分類82.0%的研究對(duì)象,約登指數(shù)最大時(shí)敏感度和特異度分別為72.1%和77.1%(圖1b)。
3 討論
CHI3L1是一種含383個(gè)氨基酸的單體糖基化蛋白,分子量約40 kD。編碼CHI3L1的基因位于人染色體1q32.1的一個(gè)8 kb的DNA上。CHI3L1由包括肝巨噬細(xì)胞在內(nèi)的多種類型的細(xì)胞以不同模式分泌,與血管生成、炎癥反應(yīng)、組織重塑和纖維化進(jìn)展等多種病理過(guò)程有關(guān),可通過(guò)激活TGF-β1、MAPK、ERK和PI3K/AKT等信號(hào)通路來(lái)發(fā)揮作用,但其在疾病進(jìn)展中確切的作用機(jī)制暫未完全明確[11]。CHI3L1在肝硬化的病程中可通過(guò)抑制肝巨噬細(xì)胞的凋亡來(lái)加劇肝硬化的進(jìn)程,在肝病領(lǐng)域,現(xiàn)階段針對(duì)CHI3L1的研究主要集中在對(duì)肝纖維化/肝硬化程度和對(duì)肝癌發(fā)生風(fēng)險(xiǎn)的預(yù)測(cè)[12],這一指標(biāo)還未被用于對(duì)肝硬化患者失代償事件發(fā)生風(fēng)險(xiǎn)的預(yù)測(cè)。本研究嘗試使用CHI3L1對(duì)代償期肝硬化患者發(fā)生失代償事件的風(fēng)險(xiǎn)和對(duì)代償期肝硬化患者發(fā)生首次失代償事件的風(fēng)險(xiǎn)進(jìn)行預(yù)測(cè)。
肝硬化患者的中位生存期約12年,發(fā)生首次失代償事件后,中位生存期約2年[13]。為提高肝硬化患者的生存期,需要預(yù)測(cè)失代償事件以采取積極的預(yù)防措施。筆者團(tuán)隊(duì)[14]聯(lián)合血小板和使用瞬時(shí)彈性成像檢查測(cè)得的肝硬度數(shù)據(jù)建立了預(yù)測(cè)首次失代償事件發(fā)生風(fēng)險(xiǎn)的模型,但是這一模型涉及的瞬時(shí)彈性成像檢查在很多地區(qū)暫未開展,這一模型還未在臨床普及應(yīng)用。本研究發(fā)現(xiàn),將患者血清CHI3L1用于對(duì)首次失代償事件的預(yù)測(cè)時(shí),AUC為0.751;反映肝臟儲(chǔ)備功能的Child-Pugh分級(jí)所包含的多項(xiàng)指標(biāo)是肝硬化患者發(fā)生失代償事件的重要影響因素,將血清CHI3L1與Child-Pugh分級(jí)進(jìn)行聯(lián)合建立的預(yù)測(cè)模型,AUC可達(dá)0.809,具有一定的臨床應(yīng)用價(jià)值,為預(yù)測(cè)首次失代償事件提供了新的可選手段。
失代償事件中,EVB可危及生命。我國(guó)的《肝硬化門靜脈高壓食管胃靜脈曲張出血的防治指南》[15]建議結(jié)合胃鏡和Child-Pugh分級(jí)來(lái)判斷肝硬化患者EVB的風(fēng)險(xiǎn),以決定進(jìn)一步的預(yù)防和治療方案。但胃鏡屬于侵入性檢查,患者接受程度較差,且長(zhǎng)期隨訪困難。作為現(xiàn)階段臨床關(guān)注的焦點(diǎn),很多研究在探索可用于對(duì)肝硬化患者發(fā)生EVB風(fēng)險(xiǎn)進(jìn)行預(yù)測(cè)的模型,但現(xiàn)有的模型存在應(yīng)用病因范圍狹窄和涉及的侵入性檢查難以用于隨訪等諸多問(wèn)題,仍有必要進(jìn)行進(jìn)一步研究[16-17]。血清學(xué)指標(biāo)相對(duì)易獲得,本研究使用血清CHI3L1對(duì)肝硬化患者發(fā)生EVB的風(fēng)險(xiǎn)進(jìn)行預(yù)測(cè)時(shí),AUC為0.824,可用于對(duì)肝硬化患者發(fā)生EVB風(fēng)險(xiǎn)進(jìn)行非侵入性的評(píng)估,以便針對(duì)性地指導(dǎo)肝硬化患者的預(yù)防和治療方案。
綜上,本研究納入了多種病因?qū)е赂斡不幕颊吖?05例,結(jié)合患者1年的隨訪數(shù)據(jù),發(fā)現(xiàn)血清CHI3L1擁有無(wú)創(chuàng)評(píng)估肝硬化患者發(fā)生首次失代償事件這一顯著影響生存期事件的風(fēng)險(xiǎn)的前景,可作為針對(duì)代償期肝硬化患者預(yù)測(cè)首次失代償事件的預(yù)測(cè)因子。且對(duì)于代償期肝硬化人群發(fā)生EVB的風(fēng)險(xiǎn)已具有較好的預(yù)測(cè)價(jià)值,具有較好的臨床應(yīng)用前景。本研究為單中心回顧性研究,由于回顧性和病因構(gòu)成復(fù)雜而存在偏倚問(wèn)題,需要進(jìn)一步在外部隊(duì)列中進(jìn)行驗(yàn)證。但是本研究所使用的血清學(xué)指標(biāo)方便獲得,可重復(fù)性強(qiáng),且避免了影像學(xué)檢查所存在的主觀因素影響。同時(shí)作為使用試劑盒即可進(jìn)行檢測(cè)的方案,成本較低,易于推廣。尤其在瞬時(shí)彈性成像檢查還未開展的地區(qū),迫切需要一些利于隨訪的血清學(xué)指標(biāo)[18]。門靜脈高壓是肝硬化患者發(fā)生失代償事件的主要驅(qū)動(dòng)因素[19],新生血管的生成在門靜脈高壓的發(fā)生和發(fā)展中起至關(guān)重要的作用[20]。CHI3L1參與血管生成的病理進(jìn)程[10],考慮其血清學(xué)水平可能反映了肝硬化患者門靜脈高壓的進(jìn)展程度,進(jìn)而實(shí)現(xiàn)了對(duì)患者發(fā)生失代償事件風(fēng)險(xiǎn)的預(yù)測(cè)效能,但具體機(jī)制仍待基礎(chǔ)實(shí)驗(yàn)和進(jìn)一步臨床研究探索。
倫理學(xué)聲明:本研究方案于2021年10月13日經(jīng)由天津市第二人民醫(yī)院倫理委員會(huì)審批,批號(hào):津二人民倫審字[2021]54號(hào),患者均簽署知情同意書。
利益沖突聲明:本文不存在任何利益沖突。
作者貢獻(xiàn)聲明:李嘉、趙黎莉?qū)ρ芯康乃悸坊蛟O(shè)計(jì)有關(guān)鍵貢獻(xiàn);楊航、韓萍、文君、劉潔、程曉靜參與了研究數(shù)據(jù)的獲取、分析和解釋過(guò)程;楊航、陳慶靈參與起草或修改文章的關(guān)鍵內(nèi)容。
參考文獻(xiàn):
[1]
de FRANCHIS R, BOSCH J, GARCIA-TSAO G, et al. Baveno VII - Renewing consensus in portal hypertension[J]. J Hepatol, 2022, 76(4): 959-974. DOI: 10.1016/j.jhep.2021.12.022.
[2]GINS P, KRAG A, ABRALDES JG, et al. Liver cirrhosis[J]. Lancet, 2021, 398(10308): 1359-1376. DOI: 10.1016/S0140-6736(21)01374-X.
[3]KOUANDA A, BINMOELLER K, HAMERSKI C, et al. Safety and efficacy of EUS-guided coil and glue injection for the primary prophylaxis of gastric variceal hemorrhage[J]. Gastrointest Endosc, 2021, 94(2): 291-296. DOI: 10.1016/j.gie.2021.01.025.
[4]Chinese Society of Hepatology, Chinese Medical Association. Chinese guidelinesonthe management of liver cirrhosis[J]. J Clin Hepatol, 2019, 35(11): 2408-2425. DOI:? 10.3969/j.issn.1001-5256.2019.11.006.
中華醫(yī)學(xué)會(huì)肝病學(xué)分會(huì). 肝硬化診治指南[J]. 臨床肝膽病雜志, 2019, 35(11): 2408-2425. DOI: 10.3969/j.issn.1001-5256.2019.11.006.
[5]Chinese Society of Infectious Diseases,Chinese Medical Association;Chinese Society of Hepatology, Chinese Medical Association. Guidelines for the prevention and treatment of chronic hepatitis B(version 2019)[J]. J Clin Hepatol, 2019,? 35(12):? 2648-2669. DOI: 10.3969/j.issn.1001-5256.2019.12.007.
中華醫(yī)學(xué)會(huì)感染病學(xué)分會(huì), 中華醫(yī)學(xué)會(huì)肝病學(xué)分會(huì).慢性乙型肝炎防治指南(2019年版)[J]. 臨床肝膽病雜志, 2019, 35(12): 2648-2669. DOI: 10.3969/j.issn.1001-5256.2019.12.007.
[6]Chinese Society of Hepatology and Chinese Society of Infectious Diseases, Chinese Medical Association. The guideline of prevention and treatment for hepatitis C (2019 version)[J]. J Clin Hepatol, 2019, 35(12): 2670-2686. DOI: 10.3969/j.issn.1001-5256.2019.12.008.
中華醫(yī)學(xué)會(huì)肝病學(xué)分會(huì), 中華醫(yī)學(xué)會(huì)感染病學(xué)分會(huì). 丙型肝炎防治指南(2019年版)[J]. 臨床肝膽病雜志, 2019, 35(12): 2670-2686. DOI: 10.3969/j.issn.1001-5256.2019.12.008.
[7]National Workshop on Fatty Liver and Alcoholic Liver Disease, Chinese Society of Hepatology, Chinese Medical Association: Fatty Liver Expert Committee, Chinese Medical Doctor Association. Guidelines of prevention and treatment for nonalcoholic fatty liver disease: a 2018 update[J]. J Clin Hepatol, 2018, 34(5): 947-957. DOI: 10.3969/j.issn.1001-5256.2018.05.007.
中華醫(yī)學(xué)會(huì)肝病學(xué)分會(huì)脂肪肝和酒精性肝病學(xué)組, 中國(guó)醫(yī)師協(xié)會(huì)脂肪性肝病專家委員會(huì). 非酒精性脂肪性肝病防治指南(2018年更新版)[J]. 臨床肝膽病雜志, 2018, 34(5): 947-957. DOI:?? 10.3969/j.issn.1001-5256.2018.05.007.
[8]Fatty Liver Expert Committee, Chinese Medical Doctor Association; National Workshop on Fatty Liver and Alcoholic Liver Disease,Chinese Society of Hepatology,Chinese Medical Association. Guidelines of prevention and treatment for alcoholic liver disease:a 2018 update[J]. J Clin Hepatol, 2018, 34(5): 939-946. DOI: 10.3969/j.issn.1001-5256.2018.05.006.
中國(guó)醫(yī)師協(xié)會(huì)脂肪性肝病專家委員會(huì), 中華醫(yī)學(xué)會(huì)肝病學(xué)分會(huì)脂肪肝和酒精性肝病學(xué)組. 酒精性肝病防治指南(2018年更新版)[J]. 臨床肝膽病雜志, 2018, 34(5): 939-946. DOI: 10.3969/j.issn.1001-5256.2018.05.006.
[9]Chinese Society of Hepatology,? Chinese Medical Association. Guidelines on the diagnosis and management of autoimmune hepatitis (2021)[J]. J Clin Hepatol, 2022,?? 38(1):? 42-49. DOI: 10.3969/j.issn.1001-5256.2022.01.008.
中華醫(yī)學(xué)會(huì)肝病學(xué)分會(huì).自身免疫性肝炎診斷和治療指南(2021)[J]. 臨床肝膽病雜志, 2022, 38(1): 42-49. DOI: 10.3969/j.issn.1001-5256.2022.01.008.
[10]Chinese Society of Hepatology, Chinese Medical Association. Guidelines on the diagnosis and management of primary biliary cholangitis(2021)[J]. J Clin Hepatol,? 2022, 38(1):? 35 -41. DOI: 10.3969/j.issn.1001-5256.2022.01.007.
中華醫(yī)學(xué)會(huì)肝病學(xué)分會(huì). 原發(fā)性膽汁性膽管炎的診斷和治療指南(2021)[J]. 臨床肝膽病雜志, 2022, 38(1): 35-41. DOI: 10.3969/j.issn.1001-5256.2022.01.007.
[11]OBER C, TAN Z, SUN Y, et al. Effect of variation in CHI3L1 on serum YKL-40 level, risk of asthma, and lung function[J]. N Engl J Med, 2008, 358(16): 1682-1691. DOI: 10.1056/NEJMoa0708801.
[12]HUANG X, ZHUANG J, YANG Y, et al. Diagnostic value of serum chitinase-3-like protein 1 for liver fibrosis: A Meta-analysis[J]. Biomed Res Int, 2022, 2022: 3227957. DOI: 10.1155/2022/3227957.
[13]GARCIA-TSAO G, ABRALDES JG. Nonselective beta-blockers in compensated cirrhosis: Preventing variceal hemorrhage or preventing decompensation?[J]. Gastroenterology, 2021, 161(3): 770-773. DOI: 10.1053/j.gastro.2021.04.077.
[14]LIU Y, LIU C, LI J, et al. Risk stratification of decompensation using liver stiffness and platelet counts in compensated advanced chronic liver disease (CHESS2102)[J]. J Hepatol, 2022, 76(1): 248-250. DOI: 10.1016/j.jhep.2021.10.006.
[15]Chinese Society of Hepatology. Chinese Medical Association; Chinese Socie ty of Gastroenterology, Chinese Medical Association; Chinese Society of Endoscopy. Chinese Medical Association Guidelines for the diagnosis and treatment of esophageal and gastric variceal bleeding in cirrhotic portal hypertensio[J]. J Clin Hepatol, 2016, 32(2): 203-219. DOI: 10.3969/j.issn.1001-5256.2016.02.002.
中華醫(yī)學(xué)會(huì)肝病學(xué)分會(huì),中華醫(yī)學(xué)會(huì)消化病學(xué)分會(huì), 中華醫(yī)學(xué)會(huì)內(nèi)鏡學(xué)分會(huì). 肝硬化門靜脈高壓食管胃靜脈曲張出血的防治指南[J]. 臨床肝膽病雜志, 2016, 32(2): 203-219. DOI: 10.3969/j.issn.1001-5256.2016.02.002.
[16]LIU H, SUN J, LIU G, et al. Establishment of a non-invasive prediction model for the risk of oesophageal variceal bleeding using radiomics based on CT[J]. Clin Radiol, 2022, 77(5): 368-376. DOI: 10.1016/j.crad.2022.01.046.
[17]ZHAO L, WANG T, GUO C, et al. Modified and alternative Baveno VI criteria based on age for ruling out high-risk varices in patients with compensated cirrhosis[J]. Hepatol Int, 2022, 16(4): 936-943. DOI: 10.1007/s12072-022-10359-y.
[18]LUO YX, ZHOU T. Value of systemic immune inflammatory index on predicting the proanosis of patients with decompensated liver cirrhosis[J/CD].? Chin J Liver Dis(Electronic Version) 2021, 13(1): 52-58. DOI: 10.3969/j.issn.1674-7380.2021.01.009.
羅永祥, 周濤. 全身免疫炎癥指數(shù)對(duì)失代償期肝硬化患者預(yù)后的評(píng)估價(jià)值[J/CD]. 中國(guó)肝臟病雜志(電子版), 2021, 13(1): 52-58. DOI: 10.3969/j.issn.1674-7380.2021.01.009.
[19]COSTA D, SIMBRUNNER B, JACHS M, et al. Systemic inflammation increases across distinct stages of advanced chronic liver disease and correlates with decompensation and mortality[J]. J Hepatol, 2021, 74(4): 819-828. DOI: 10.1016/j.jhep.2020.10.004.
[20]COULON S, HEINDRYCKX F, GEERTS A, et al. Angiogenesis in chronic liver disease and its complications[J]. Liver Int, 2011, 31(2): 146-162. DOI: 10.1111/j.1478-3231.2010.02369.x.
收稿日期:
2022-11-11;錄用日期:2023-01-02
本文編輯:王亞南
引證本文:
YANG H, ZHAO LL, HAN P, et al.
Value of serum chitinase-3-like protein 1 in predicting the risk of decompensation events in patients with liver cirrhosis
[J]. J Clin Hepatol, 2023, 39(7): 1578-1585.
楊航, 趙黎莉, 韓萍,? 等.
血清殼多糖酶3樣蛋白1(CHI3L1)對(duì)肝硬化患者發(fā)生失代償事件風(fēng)險(xiǎn)的預(yù)測(cè)價(jià)值[J]. 臨床肝膽病雜志, 2023, 39(7): 1578-1585.