失代償期肝硬化患者低鈉血癥與肝損傷程度及并發(fā)癥的關(guān)系

武 健，尹 芳，羅貫虹，朱紹華，李 紅，張 靜，鄭洋洋，孫 菡，周新民

(第四軍醫(yī)大學(xué)第一附屬醫(yī)院 消化內(nèi)科，西安 710000)

失代償期肝硬化患者低鈉血癥與肝損傷程度及并發(fā)癥的關(guān)系

武 健，尹 芳，羅貫虹，朱紹華，李 紅，張 靜，鄭洋洋，孫 菡，周新民

(第四軍醫(yī)大學(xué)第一附屬醫(yī)院 消化內(nèi)科，西安 710000)

目的 分析失代償期肝硬化患者低鈉血癥與肝損傷程度及并發(fā)癥發(fā)生情況的相關(guān)性。方法 選取2015年7月-2016年7月第四軍醫(yī)大學(xué)西京醫(yī)院消化內(nèi)科收治的142例失代償期肝硬化合并低鈉血癥患者進(jìn)行回顧性分析。根據(jù)入院時(shí)血鈉濃度將所選患者分為輕度、中度、重度3組。比較不同分組的Child-Pugh評(píng)分、終末期肝病模型(MELD)評(píng)分及主要并發(fā)癥的發(fā)生情況。所有患者均隨訪3個(gè)月，研究并記錄隨訪時(shí)出現(xiàn)腹水、自發(fā)性腹膜炎、肝性腦病等并發(fā)癥及病死率與低鈉血癥的相關(guān)性。計(jì)量資料組間比較采用χ2檢驗(yàn)，相關(guān)性分析采用Spearman分析。結(jié)果 輕度低鈉組Child-Pugh A級(jí)患者比例較高(42.3%)，重度低鈉組Child-Pugh C級(jí)患者比例較高(72.4%)，3組患者的Child-Pugh評(píng)分差異有統(tǒng)計(jì)學(xué)意義(χ2=50.175，P=0.000 2)；血鈉水平隨Child-Pugh評(píng)分的上升而降低，差異有統(tǒng)計(jì)學(xué)意義(r=-0.464，P=0.002 3)。輕度低鈉組MELD評(píng)分≤9患者比例較高(50.7%)，重度低鈉組MELD評(píng)分≥30患者比例較高(62.1%)，3組患者的肝功能MELD評(píng)分的分布差異有統(tǒng)計(jì)學(xué)意義(χ2=75.106，P=0.000 8)。血鈉水平隨MELD評(píng)分的上升而降低，差異有統(tǒng)計(jì)學(xué)意義(r=-0.644，P=0.004 5)。輕度、中度、重度低鈉血癥的腹水發(fā)生率為71.8%、92.9%、100.0%；自發(fā)性腹膜炎為14.1%、31.0%、65.5%；肝性腦病發(fā)生率分別為14.1%、35.7%、55.2%；病死率分別為12.7%、33.3%、65.5%。3組的并發(fā)癥發(fā)生率和病死率比較，差異均有統(tǒng)計(jì)學(xué)意義(χ2值分別為14.127、24.467，P值均<0.05)。結(jié)論 血鈉可作為一個(gè)預(yù)測(cè)指標(biāo)判定失代償期肝硬化患者并發(fā)癥的發(fā)生率。

肝硬化; 低鈉血癥; 腹水; 腹膜炎; 肝性腦病

電解質(zhì)紊亂是失代償期肝硬化最常見的并發(fā)癥，其中低鈉血癥尤為常見。我國肝硬化患者低鈉血癥的發(fā)生率約62.4%，國外約為30%[1]。研究發(fā)現(xiàn)，血鈉水平能在一定程度上反映肝硬化患者的預(yù)后，且與肝性腦病、肝腎綜合征、自發(fā)性腹膜炎等其他并發(fā)癥的發(fā)生有關(guān)，血鈉水平越低，肝病患者預(yù)后越差。Child-Pugh評(píng)分及終末期肝病模型(MELD)是用于評(píng)價(jià)肝硬化患者病情進(jìn)展的重要指標(biāo)之一。本研究旨在通過探討失代償期肝硬化患者血鈉水平與Child-Pugh評(píng)分、MELD評(píng)分及其并發(fā)癥的相關(guān)性，以期更好地指導(dǎo)臨床工作，為評(píng)估肝硬化患者的病情及預(yù)后提供參考依據(jù)。

1 資料與方法

1.1 研究對(duì)象 選擇2015年7月-2016年7月在本院消化內(nèi)科收治的首次診斷為失代償期肝硬化合并低鈉血癥患者142例，其中男96例，女46例，年齡29～75歲，平均(45.8±8.6)歲。其中乙型肝炎肝硬化87例，丙型肝炎肝硬化31例，酒精性肝硬化8例，自身免疫性肝硬化12例，不明原因肝硬化4例。所有入選患者診斷均符合第8版《內(nèi)科學(xué)》肝硬化失代償期的診斷標(biāo)準(zhǔn)[2]。排除標(biāo)準(zhǔn)：(1)合并原發(fā)性肝癌；(2)臨床資料不全者；(3)重復(fù)入院者；(4)合并其他器官衰竭；(5)回訪丟失者；(6)死于其他原因者。

1.2 判定標(biāo)準(zhǔn) 記錄142例首次確診失代償期肝硬化合并低鈉血癥患者的血鈉水平，血鈉濃度<135 mmol/L診斷為低鈉血癥，依據(jù)血鈉濃度分為輕度低鈉、中度低鈉及重度低鈉。輕度低鈉：131～135 mmol/L，71例；中度低鈉：121～130 mmol/L，42例；重度低鈉：≤120 mmol/L，29例。142例患者均不合并其他系統(tǒng)性疾病。Child-Pugh評(píng)分A級(jí)：37例，B級(jí)65例，C級(jí)：40例。

1.3 觀察指標(biāo) 所有患者入院后當(dāng)日或次日常規(guī)檢測(cè)血生化、血常規(guī)、PT，國際標(biāo)準(zhǔn)化比值(INR)，并行心電圖及超聲檢查。所有患者均隨訪3個(gè)月，記錄患者肝性腦病、肝腎綜合征的發(fā)病率。記錄隨訪時(shí)出現(xiàn)腹水、自發(fā)性腹膜炎、肝性腦病等并發(fā)癥，分析病死率與低鈉血癥的關(guān)系。Child-Pugh評(píng)分計(jì)算參考相關(guān)文獻(xiàn)[3];MELD評(píng)分=3.8×ln(膽紅素mol/L×0.058)+11.2×ln(INR)+9.6×ln(肌酐mol/L×0.011)+6.4×(病因?qū)W:膽汁淤積型或酒精性肝硬化為0,其他原因?yàn)?);1.4 統(tǒng)計(jì)學(xué)方法 采用SPSS18.0軟件進(jìn)行數(shù)據(jù)分析。計(jì)數(shù)資料組間比較采用χ2檢驗(yàn)，相關(guān)性分析采用Spearman分析。P<0.05為差異有統(tǒng)計(jì)學(xué)意義。

2 結(jié)果

2.1 不同程度低鈉血癥患者Child-Pugh分級(jí)比例比較 輕度低鈉組Child-Pugh A級(jí)患者比例較高，重度低鈉組Child-Pugh C級(jí)患者比例較高，3組患者的Child-Pugh評(píng)分差異有統(tǒng)計(jì)學(xué)意義(χ2=50.175，P=0.000 2)(表1)。血鈉水平隨Child-Pugh評(píng)分的上升而降低，差異有統(tǒng)計(jì)學(xué)意義(r=-0.464，P=0.002 3)。

表1 血清鈉水平與Child-Pugh評(píng)分的關(guān)系[例(%)]

2.2 不同程度低鈉血癥程度間MELD評(píng)分比例比較輕度低鈉組MELD評(píng)分≤9患者比例較高，重度低鈉組MELD評(píng)分≥30患者比例較高，3組患者的肝功能MELD評(píng)分的分布差異有統(tǒng)計(jì)學(xué)意義(χ2=75.106，P=0.000 8)(表2)。血鈉水平隨MELD評(píng)分的上升而降低，差異有統(tǒng)計(jì)學(xué)意義(r=-0.644，P=0.004 5)。

表2 血清鈉水平與MELD評(píng)分的關(guān)系[例(%)]

2.3 不同程度低鈉血癥與肝硬化并發(fā)癥發(fā)生率的關(guān)系 重度低鈉患者出現(xiàn)肝性腦病、腹水、自發(fā)性腹膜炎的發(fā)生率與中度、輕度低鈉組相比明顯增高，差異有統(tǒng)計(jì)學(xué)意義(χ2=14.127，P=0.042)(表3)。重度低鈉患者的病死率(9/71,12.67%)與中度、輕度低鈉組(14/42,33.33%和19/29,65.52%)相比明顯增高，差異有統(tǒng)計(jì)學(xué)意義(χ2=24.467，P=0.031)。

表3 血清鈉水平與肝硬化并發(fā)癥發(fā)生率的關(guān)系[例(%)]

3 討論

低鈉血癥是肝硬化最常見的并發(fā)癥，發(fā)生低鈉血癥的肝硬化患者往往無明顯的特異性癥狀如嘔吐、惡心等，因此很難通過臨床表現(xiàn)來判斷病情，只有對(duì)血鈉水平的監(jiān)測(cè)能夠從一定程度上反映病情的嚴(yán)重程度及預(yù)后[3-4]。肝硬化并發(fā)低鈉血癥的原因較復(fù)雜，目前認(rèn)為可能有以下幾方面因素：(1)鈉攝入減少及排出的增加：鈉鹽攝入的嚴(yán)格控制及大劑量利尿劑的使用；(2)鈉泵衰竭：失代償期肝硬化患者體內(nèi)高能磷酸鍵及鈉泵的活性降低，致使Na+蓄積，腎小管、集合管對(duì)Na+重吸收降低；(3)血容量相對(duì)不足、水潴留導(dǎo)致稀釋性低鈉血癥；(4)低蛋白血癥致使血漿滲透壓下降[5-7]。

Child-Pugh、MELD評(píng)分是臨床上最常用的評(píng)價(jià)肝硬化終末期肝功能的指標(biāo)。本研究分析了血鈉濃度與Child-Pugh評(píng)分的關(guān)系，隨著Child-Pugh評(píng)分的逐漸增高，血清鈉水平逐漸降低，表明失代償期肝硬化患者血鈉濃度與Child-Pugh評(píng)分間有密切的相關(guān)性，間接反映了血鈉水平對(duì)失代償期肝硬化患者病情嚴(yán)重程度的評(píng)估作用。而MELD評(píng)分主要分析PT、肌酐、膽紅素、肝性腦病等指標(biāo)[8]，MELD評(píng)分值越高，平均血鈉水平越低，肝功能越差，腹水頑固難消，并發(fā)癥的發(fā)生率及病死率越高。本研究發(fā)現(xiàn)，在低鈉血癥患者中，重度低鈉患者出現(xiàn)肝性腦病、腹水、自發(fā)性腹膜炎的發(fā)生率與輕度低鈉組相比明顯增高。

失代償期肝硬化患者易發(fā)生上消化道出血、肝性腦病、肝腎綜合征等多種并發(fā)癥，常常危及患者生命。本研究表明，隨著血鈉濃度的升高，肝性腦病、自發(fā)性腹膜炎的發(fā)生率明顯升高，同時(shí)對(duì)患者的生存有較大影響。氨代謝異常以及神經(jīng)毒素所造成的谷胺酰鹽含量增加，致使腦星形膠質(zhì)細(xì)胞低度水腫，加之低鈉血癥滲透壓的改變?cè)斐赡X細(xì)胞水腫，形成低滲性腦病，加劇了腦星形細(xì)胞對(duì)血氨和其他毒物的敏感性，增加了肝性腦病的患病率[9-10]。失代償期肝硬化患者門靜脈高壓導(dǎo)致食管胃底靜脈曲張破裂，增加上消化道出血的風(fēng)險(xiǎn)，同時(shí)出血時(shí)鈉離子的大量丟失，擴(kuò)容后血鈉水平相對(duì)更低。

失代償期肝硬化患者并發(fā)自發(fā)性腹膜炎大多起病隱匿，臨床表現(xiàn)不典型，易漏診、誤診。多因素logistic回歸分析[11]顯示，血鈉水平是失代償期肝硬化患者并發(fā)自發(fā)性腹膜炎的獨(dú)立危險(xiǎn)因素。其發(fā)生機(jī)制復(fù)雜，患者出現(xiàn)腹水后，腸壁水腫，通透性增加，使腸道細(xì)菌直接透過腸壁進(jìn)入腹腔形成感染。Child-Pugh C級(jí)發(fā)生自發(fā)性腹膜炎的比例明顯高于Child-Pugh A級(jí)，提示隨著肝損傷的加重，發(fā)生腹腔感染的幾率也隨之增加，這與肝功能Child-Pugh C級(jí)患者抵抗力降低、腸道屏障功能減退、腸道內(nèi)細(xì)菌跨膜易位感染、肝臟Kupffer細(xì)胞吞噬能力低下以及內(nèi)毒素血癥密切相關(guān)[12-13]。

綜上，血鈉水平能夠從一定程度上反映失代償期肝硬化患者的病情及預(yù)后，血鈉水平可作為判斷失代償期肝硬化病情嚴(yán)重程度的重要指標(biāo)之一。

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引證本文：WU J,YIN F,LUO GH,et al.Association of hyponatremia with degree of liver injury and complications in patients with decompensated liver cirrhosis[J].J Clin Hepatol,2017,33(2):277-280.(in Chinese)

武健，尹芳，羅貫虹，等.失代償期肝硬化患者低鈉血癥與肝損傷程度及并發(fā)癥的關(guān)系[J].臨床肝膽病雜志,2017,33(2):277-280.

(本文編輯：王 瑩)

Association of hyponatremia with degree of liver injury and complications in patients with decompensated liver cirrhosis

WUJian,YINFang,LUOGuanhong,etal.

(DepartmentofGastroenterology,XijingHospital,FourthMilitaryMedicalUniversity,Xi′an710000,China)

Objective To investigate the association of hyponatremia with the degree of liver injury and complications in patients with decompensated liver cirrhosis.Methods A retrospective analysis was performed for the clinical data of 142 patients with decompensated liver cirrhosis complicated by hyponatremia who were admitted to Department of Gastroenterology,Xijing Hospital of Fourth Military Medical University from July 2015 to July 2016.The patients were divided into mild group,moderate group,and severe group according to serum sodium concentration on admission.The Child-Pugh score,Model for End-Stage Liver Disease (MELD) score,and major complications were compared between groups.All the patients were followed up for 3 months,and the complications such as ascites,spontaneous bacterial peritonitis,and hepatic encephalopathy were recorded.The association of hyponatremia with complications and mortality was investigated.The chi-square test was used for comparison of categorical data between groups,and the Spearman corretation analysis was also performed.Results The mild group had a high proportion of Child-Pugh class A patients (42.3%) and the severe group had a high proportion of Child-Pugh class C patients (72.4%).There was a significant difference in Child-Pugh score between the mild,moderate,and severe groups (χ2=50.175,P=0.000 2).The serum sodium level decreased with the increasing Child-Pugh score (r=-0.464,P=0.002 3).The mild group had a high proportion of patients with an MELD score of ≤9 (50.7%) and the severe group had a high proportion of patients with an MELD score of ≥30 (62.1%).There was a significant difference in the distribution of MELD scores between the mild,moderate,and severe groups (χ2=75.106,P=0.000 8).The serum sodium level decreased with the increasing MELD score (r=-0.644,P=0.004 5).The incidence rates of ascites,spontaneous bacterial peritonitis,and hepatic encephalopathy were 71.8%/92.9%/100.0%,14.1%/31.0%/65.5%,and 14.1%/35.7%/55.2%,respectively,in the mild,moderate,and severe groups.The mortality rate was 12.7%,33.3%,and 65.5% in these three groups,respectively.There were significant differences in the incidence rate of complications and mortality rate between the three groups (χ2=14.127 and 24.467,bothP<0.05).Conclusion Serum sodium level can be used as a predictor for the incidence rate of complications in patients with decompensated liver cirrhosis.

liver cirrhosis; hyponatremia; ascites; peritonitis; hepatic encephalopathy

10.3969/j.issn.1001-5256.2017.02.014

2016-09-09；

2016-10-26。

武健(1987-)，男，主要從事肝病的基礎(chǔ)與臨床研究。

周新民，電子信箱：zhouxmm@fmmu.edu.cn。

R575.2

A

1001-5256(2017)02-0277-04