朱婷,聶青和,李謹(jǐn)革,曹義戰(zhàn),趙保民,高祿化,王媛媛,李汨
·論著·
N-乙酰半胱氨酸治療重癥肝病的臨床療效研究
朱婷,聶青和,李謹(jǐn)革,曹義戰(zhàn),趙保民,高祿化,王媛媛,李汨
目的探討作為轉(zhuǎn)化醫(yī)學(xué)“華麗轉(zhuǎn)身”的典范——N-乙酰半胱氨酸(N-acetylcysteine,NAC)治療重癥肝病的臨床療效及安全性。方法選取HBV感染引起的重癥肝病266例,隨機(jī)分為治療組136例(其中肝硬化失代償期87例,肝衰竭49例)和對(duì)照組130例(其中肝硬化失代償期85例,肝衰竭45例)。對(duì)266例采取維護(hù)肝細(xì)胞膜穩(wěn)定性及肝細(xì)胞膜修復(fù)(保肝)、抗病毒、合理應(yīng)用抗生素、營(yíng)養(yǎng)支持及輸注新鮮血漿、全血或人血白蛋白等綜合治療措施,均未使用谷胱甘肽制劑。治療組加用NAC(8 g,1次/d),治療45 d為1個(gè)療程。45 d后觀察患者的肝功能、終末期肝病模型(model forend-stage liver disease, MELD)評(píng)分、Child-Pugh評(píng)分及藥物不良反應(yīng)。結(jié)果2組癥狀均有所改善,治療組治療45 d后肝功能(部分或全部)等均明顯改善,MELD及Child-Pugh評(píng)分均明顯下降,且改善幅度明顯優(yōu)于對(duì)照組(P<0.05)。治療期間無(wú)NAC嚴(yán)重藥物不良反應(yīng)事件。結(jié)論NAC可明顯改善重癥肝病患者的各項(xiàng)肝功能指標(biāo),且無(wú)嚴(yán)重不良反應(yīng),可在臨床上推廣應(yīng)用。
乙酰半胱氨酸;肝硬化;肝疾??;肝功能衰竭
N-乙酰半胱氨酸(N-acetylcysteine,NAC)為還原型谷胱甘肽(glutathione,GSH)的前體,最早應(yīng)用于20世紀(jì)60年代,主要用于呼吸系統(tǒng)疾病,是一種經(jīng)典的化痰藥物[1]。近年來(lái),國(guó)外學(xué)者經(jīng)研究證實(shí)NAC具有顯著保護(hù)肝細(xì)胞的作用,可最終降低多器官功能衰竭的發(fā)病率。2005年美國(guó)肝病研究學(xué)會(huì)(American Association for the Study of Liver Diseases, AASLD)發(fā)布的關(guān)于急性肝衰竭(acute liver failure, ALF)診療指南中推薦,NAC可用于治療明確或懷疑對(duì)乙酰氨基酚(acetamidophenol,APAP)過(guò)量導(dǎo)致的ALF[2]。2011年對(duì)其指南進(jìn)行更新,指出NAC除可用于APAP中毒引起的ALF外,對(duì)非APAP所致的ALF也有治療作用,還可用于治療藥物誘發(fā)性肝損傷[3]。2012年歐洲肝臟研究學(xué)會(huì)指出NAC和皮質(zhì)類(lèi)固醇具有協(xié)同效應(yīng),進(jìn)而改善重度酒精性肝炎[4]。2011年,NAC經(jīng)美國(guó)食品藥品監(jiān)督管理局批準(zhǔn)用于APAP中毒引起的ALF,其安全性和臨床療效已得到認(rèn)可[5]。我國(guó)最新《肝衰竭診治指南(2012年版)》[6]與AASLD指南一致,推薦NAC對(duì)藥物性肝損傷所致ALF有益,確診或疑似APAP過(guò)量引起的ALF和非APAP引起的ALF,應(yīng)用NAC亦可改善結(jié)局。最近國(guó)外研究發(fā)現(xiàn),NAC對(duì)其他原因引起的重癥肝病同樣有良好的臨床療效。
重癥肝病在臨床上常指肝硬化失代償期及肝衰竭等相關(guān)肝病的總稱(chēng)[7]。重癥肝病病情嚴(yán)重,變化較快,一旦確診應(yīng)立即救治,否則病死率極高[8]。目前尚缺乏治療重癥肝病的特效藥,且臨床療效欠佳。NAC成為肝病治療領(lǐng)域的閃亮點(diǎn),作為轉(zhuǎn)化醫(yī)學(xué)“華麗轉(zhuǎn)身”的典范,為重癥肝病提供了重要治療手段[9]。重癥肝病患者在維護(hù)肝細(xì)胞膜穩(wěn)定性及肝細(xì)胞膜修復(fù)(保肝)、抗病毒[10]、合理應(yīng)用抗生素、營(yíng)養(yǎng)支持及輸注新鮮血漿、全血或人血白蛋白等綜合內(nèi)科治療基礎(chǔ)上,聯(lián)合NAC,以期更高效率地改善臨床癥狀,降低病死率,提高生存質(zhì)量?,F(xiàn)將我院聯(lián)合NAC治療HBV感染引起的重癥肝病的療效及安全性分析如下。
1.1 對(duì)象選擇2013年3月—2014年3月我院收治的HBV感染引起的重癥肝病266例,按照隨機(jī)分組原則將其分為治療組和對(duì)照組。治療組136例,其中肝硬化失代償期87例(男47例,女40例),年齡(42.8±6.7)歲;肝衰竭49例(男22例,女27例),年齡(45.6±9.7)歲。對(duì)照組130例,其中肝硬化失代償期85例(男48例,女37例),年齡(42.2± 5.9)歲;肝衰竭45例(男24例,女21例),年齡(44.3±8.9)歲。2組在年齡、性別、病程及病情(臨床癥狀和實(shí)驗(yàn)室指標(biāo))方面比較均衡(P均<0.05)。入組患者未出現(xiàn)脫落現(xiàn)象。
1.2 診斷標(biāo)準(zhǔn)重癥肝病肝硬化失代償期診斷符合2000年《病毒性肝炎防治方案》[11]和2010年更新的《慢性乙型肝炎防治指南(2010年版)》[12]:①Child-Pugh評(píng)級(jí)一般為B、C級(jí);②實(shí)驗(yàn)室檢查如ALB<35 g/L、血清清蛋白與球蛋白比值<1.0、TBIL>35 μmol/L,ALT和AST升高,PTA<60%;③臨床表現(xiàn)有腹水、肝性腦病及門(mén)脈高壓癥引起的食管、胃底靜脈明顯曲張或破裂出血。肝衰竭診斷符合《肝衰竭診治指南(2012年版)》[6],分為臨床及病理學(xué)診斷標(biāo)準(zhǔn)。臨床診斷根據(jù)病史、臨床表現(xiàn)和輔助檢查等綜合評(píng)定將肝衰竭分為ALF、亞急性肝衰竭、慢加急性(亞急性)肝衰竭和慢性肝衰竭。
1.3 排除標(biāo)準(zhǔn)①同時(shí)合并2種或以上并發(fā)癥;②ALF;③肝衰竭晚期;④患者因其他原因拒絕入組。
1.4 治療方法按照相關(guān)指南推薦,2組均給予維護(hù)肝細(xì)胞膜穩(wěn)定性及肝細(xì)胞膜修復(fù)(如多烯磷脂酰膽堿、前列地爾和腺苷蛋氨酸等)、抗病毒、輸注新鮮血漿或人血白蛋白、合理應(yīng)用抗生素及營(yíng)養(yǎng)支持等綜合治療[13-14]。2組均未使用GSH制劑。治療組在對(duì)照組常規(guī)用藥的基礎(chǔ)上加用NAC 8 g,加入10%葡萄糖注射液250ml,緩慢滴注,1次/d,療程45 d。主要觀察指標(biāo):治療45 d后,2組ALT、AST、TBIL、ALB和PTA等水平的變化情況[15-16]。
1.5 統(tǒng)計(jì)學(xué)處理應(yīng)用SPSS 17.0軟件進(jìn)行數(shù)據(jù)處理,計(jì)量資料用±s表示,組內(nèi)治療前后比較采用自身配對(duì)t檢驗(yàn),組間治療前后差值比較采用成組t檢驗(yàn)。P<0.05表示差異有統(tǒng)計(jì)學(xué)意義。
2.1 2組肝硬化失代償期患者治療前后肝功能生化指標(biāo)比較治療45 d后,2組ALT、AST、TBIL和PTA較治療前均顯著改善(P均<0.05),ALB雖較治療前有所上升,但差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)。治療45 d后,治療組TBIL和PTA的改善情況明顯優(yōu)于對(duì)照組(P均<0.05)(表1);而ALT、AST和ALB與對(duì)照組相比,差異無(wú)統(tǒng)計(jì)學(xué)意義(P均>0.05)(表1)。
表1 2組肝硬化失代償期患者治療前后肝功能生化指標(biāo)變化(±s)Table 1 Comparison of variations of liver function parameters of decompensated cirrhotic patients before and after treatment between the treatment group and the control group(±s)
表1 2組肝硬化失代償期患者治療前后肝功能生化指標(biāo)變化(±s)Table 1 Comparison of variations of liver function parameters of decompensated cirrhotic patients before and after treatment between the treatment group and the control group(±s)
注:*2組之間差值d比較用成組t檢驗(yàn)。同組治療前后比較用自身配對(duì)t檢驗(yàn)。治療組:ALT,t=7.961,P=0.000;AST,t=13.548,P=0.000;TBIL,t=10.692,P=0.000;ALB,t=2.019,P=0.074;PTA,t=8.171,P=0.000。對(duì)照組:ALT,t=7.858,P=0.000;AST,t=17.632,P=0.000;TBIL,t= 12.330,P=0.000;ALB,t=1.908,P=0.089;PTA,t=4.397,P=0.002
項(xiàng)目nALT(U/L)AST(U/L)TBIL(μmol/L)ALB(g/L)PTA(%)治療組87治療前127.9±23.1108.7±19.268.9±15.633.8±5.644.3±8.1治療45 d50.6±10.852.7±14.526.6±5.535.1±7.368.3±13.8差值d77.3±9.756.0±4.142.3±4.01.3±0.624.0±3.0對(duì)照組85治療前125.4±21.5105.3±18.967.2±13.333.7±6.843.2±7.9治療45 d52.1±11.354.5±13.747.8±9.734.9±5.450.3±11.1差值d73.3±9.350.8±2.919.4±1.61.2±0.67.1±1.6 t值*0.3001.0455.3790.1095.038 P值0.7680.3100.0000.9140.000
2.2 2組肝硬化失代償期患者治療前后Child-Pugh評(píng)分比較治療45 d后,2組Child-Pugh評(píng)分均降低,差異有統(tǒng)計(jì)學(xué)意義(P<0.05)。治療組的療效顯著優(yōu)于對(duì)照組(P<0.05)。見(jiàn)表2。
表2 2組肝硬化失代償期患者治療前后Child-Pugh評(píng)分變化(±s)Table 2 Com parison of variations of Child-Pugh scores of decom pensated cirrhotic patients before and after treatment between the treatment group and the control group(±s)
表2 2組肝硬化失代償期患者治療前后Child-Pugh評(píng)分變化(±s)Table 2 Com parison of variations of Child-Pugh scores of decom pensated cirrhotic patients before and after treatment between the treatment group and the control group(±s)
注:*2組之間差值d比較用成組t檢驗(yàn)。同組治療前后比較用自身配對(duì)t檢驗(yàn)。治療組Child-Pugh評(píng)分:t=4.635,P=0.001;對(duì)照組Child-Pugh評(píng)分:t=2.670,P=0.026
項(xiàng)目nChild-Pugh評(píng)分(分)治療組87治療前11.8±3.5治療45 d6.2±1.5差值d5.6±1.2對(duì)照組85治療前11.6±3.2治療45 d9.3±2.7差值d2.3±0.9 t值*2.235 P值0.040
2.3 2組肝衰竭患者治療前后肝功能生化指標(biāo)比較治療45 d后,2組ALT、AST、TBIL、ALB和PTA較治療前均顯著改善(P均<0.05),且治療組TBIL和PTA改善情況顯著優(yōu)于對(duì)照組(P均<0.05)。治療組ALT、AST和ALB與對(duì)照組比較差異無(wú)統(tǒng)計(jì)意義(P均>0.05)。見(jiàn)表3。
2.4 2組肝衰竭患者治療前后終末期肝病模型(model for end-stage liver disease,MELD)和Child-Pugh評(píng)分比較治療45 d后,2組MELD和Child-Pugh評(píng)分較治療前明顯降低(P均<0.05),且治療組的變化幅度明顯高于對(duì)照組(P均<0.05)。見(jiàn)表4。
2.5 不良反應(yīng)應(yīng)用不良反應(yīng)觀察表記錄不良反應(yīng),本組未發(fā)生嚴(yán)重不良反應(yīng)事件。治療組出現(xiàn)皮疹和惡心嘔吐各1例,分別給予減緩輸液速度和抗酸藥物處理后好轉(zhuǎn),并繼續(xù)完成用藥療程。
表3 2組肝衰竭患者治療前后肝功能生化指標(biāo)變化(±s)Table 3 Comparison of variations of liver function parameters of patients w ith liver failure before and after treatment between the treatment group and the control group(±s)
表3 2組肝衰竭患者治療前后肝功能生化指標(biāo)變化(±s)Table 3 Comparison of variations of liver function parameters of patients w ith liver failure before and after treatment between the treatment group and the control group(±s)
注:*2組之間差值d比較用成組t檢驗(yàn)。同組治療前后比較用自身配對(duì)t檢驗(yàn)。治療組:ALT,t=6.972,P=0.000;AST,t=7.005,P=0.000;TBIL,t=20.638,P=0.000;ALB,t=4.220,P=0.002;PTA,t=5.750,P=0.000。對(duì)照組:ALT,t=6.752,P=0.000;AST,t=8.788,P=0.000;TBIL,t= 9.215,P=0.000;ALB,t=2.852,P=0.019;PTA,t=4.562,P=0.001
項(xiàng)目nALT(U/L)AST(U/L)TBIL(μmol/L)ALB(g/L)PTA(%)治療組49治療前238.5±47.1220.7±23.5402.3±35.933.1±2.332.5±8.2治療45 d112.8±23.8147.4±14.0178.2±13.536.9±1.563.5±16.7差值d125.7±18.073.3±10.5224.0±10.93.8±0.931.0±5.4對(duì)照組45治療前241.3±48.5238.5±24.9410.4±52.733.8±2.534.4±7.9治療45 d120.7±24.6149.2±13.3253.7±19.836.5±1.450.3±15.2差值d120.6±17.989.3±10.2156.7±17.02.7±0.916.0±3.5 t值*0.201-1.0943.3370.8422.342 P值0.8430.2880.0040.4110.031
表4 2組肝衰竭患者治療前后MELD和Child-Pugh評(píng)分比較(±s)Table 4 Comparison of variations of MELD and Child-Pugh scores of patients w ith liver failure before and after treatment between the treatment group and the control group(±s)
表4 2組肝衰竭患者治療前后MELD和Child-Pugh評(píng)分比較(±s)Table 4 Comparison of variations of MELD and Child-Pugh scores of patients w ith liver failure before and after treatment between the treatment group and the control group(±s)
注:*2組之間差值d比較用成組t檢驗(yàn)。同組治療前后比較用自身配對(duì)t檢驗(yàn)。治療組:MELD評(píng)分,t=5.841,P=0.000;Child-Pugh評(píng)分,t=5.751,P=0.000。對(duì)照組:MELD評(píng)分,t=5.411,P=0.016;Child-Pugh評(píng)分,t=8.788,P=0.000
項(xiàng)目nMELD評(píng)分(分)Child-Pugh評(píng)分(分)治療組49治療前22.8±5.812.4±3.1治療45 d10.5±2.96.3±1.3差值d12.3±2.16.1±1.1對(duì)照組45治療前21.9±4.412.6±2.8治療45 d16.6±3.39.2±1.7差值d5.3±1.83.4±0.6 t值*2.5282.190 P值0.0210.042
肝病是我國(guó)的常見(jiàn)病及多發(fā)病,嚴(yán)重威脅人類(lèi)健康,應(yīng)早發(fā)現(xiàn)、早診斷、早治療。肝病患者早期如未能立即診治,最終會(huì)發(fā)展為肝硬化失代償期及肝衰竭等重癥肝病。重癥肝病目前主要以?xún)?nèi)科藥物綜合治療為主,聯(lián)合手術(shù)和人工肝等療法[13,16]。然而,目前重癥肝病的內(nèi)科綜合治療因缺乏特效藥,加之病情的復(fù)雜性和多變性,患者臨床癥狀不能得到有效改善。隨著肝損傷程度的加重,逐漸發(fā)生感染、上消化道出血、肝性腦病及肝腎綜合征等多種并發(fā)癥,加速病情惡化,病死率上升[17]。因此,積極尋求有效治療重癥肝病的藥物至關(guān)重要,以期改善臨床癥狀,降低病死率,提高患者生活質(zhì)量。
NAC為單肽小分子,由L-半胱氨酸加乙?;纬蒣18]。截至目前為止,NAC仍然是治療呼吸系統(tǒng)疾病的重要藥物,在慢性阻塞性肺疾?。╟hronic obstructive pulmonary disease,COPD)、肺間質(zhì)纖維化、急性肺損傷及急性呼吸窘迫綜合征(acute respiratory distress syndrome,ARDS)的治療中發(fā)揮著關(guān)鍵作用[19]。NAC在COPD中的作用機(jī)制是通過(guò)降低血清/血漿中的中性粒細(xì)胞髓過(guò)氧化物酶,使外周多形核白細(xì)胞H2O2的釋放減少,從而抑制肺泡巨噬細(xì)胞氧離子的產(chǎn)生,最終降低超氧化物歧化酶的含量,使氧化/抗氧化系統(tǒng)趨于動(dòng)態(tài)平衡[20]。NAC還可應(yīng)用于支氣管哮喘的治療,通過(guò)減少核轉(zhuǎn)錄因子-κB的合成,降低腫瘤壞死因子的產(chǎn)生,從而減輕肺組織的炎癥反應(yīng)。此外,NAC治療急性肺損傷和ARDS時(shí)主要通過(guò)激活粒細(xì)胞內(nèi)GSH的水平,減少氧自由基的產(chǎn)生,減輕氧自由基對(duì)肺組織的損傷,發(fā)揮輔助治療作用。
近年來(lái),國(guó)外學(xué)者提出“轉(zhuǎn)化醫(yī)學(xué)”一詞,在臨床醫(yī)學(xué)中得到逐漸認(rèn)可,其中一個(gè)成功案例是阿司匹林由鎮(zhèn)痛藥發(fā)展到心血管疾病的應(yīng)用。NAC也由呼吸系統(tǒng)的廣泛應(yīng)用發(fā)展到消化系統(tǒng)疾病,尤其是重癥肝病的應(yīng)用中,國(guó)外學(xué)者將其稱(chēng)之為肝病轉(zhuǎn)化醫(yī)學(xué)“華麗轉(zhuǎn)身”的典范[21]。大量基礎(chǔ)研究證實(shí),NAC除了作用于肺泡上皮細(xì)胞和紅細(xì)胞外,還可作用于肝細(xì)胞、肝臟內(nèi)皮細(xì)胞和庫(kù)普弗細(xì)胞。NAC用于重癥肝病的機(jī)制為:①NAC可提高機(jī)體內(nèi)GSH的含量,GSH具有抗氧化、解毒等功能,分子中發(fā)揮活性作用的基團(tuán)是半胱氨酸,而NAC因其分子量小可自由進(jìn)入細(xì)胞,經(jīng)脫乙?;纬蒐-半胱氨酸GSH合成的前體,增加肝細(xì)胞內(nèi)GSH的貯存,防止肝細(xì)胞壞死,減輕肝損傷[22];②NAC有增加NO的生物利用度和降低NO水平的雙重作用,NAC作為NO的載體可提高NO的生物利用度,發(fā)揮其擴(kuò)張微血管、增加氧的輸送和釋放、防止肝細(xì)胞損傷的作用;③NAC通過(guò)抑制誘導(dǎo)型一氧化氮合成酶,糾正過(guò)量NO生成保護(hù)肝細(xì)胞[23]。
基于美國(guó)研究組對(duì)173例NAC治療非APAP引起的ALF的隨機(jī)對(duì)照試驗(yàn)[24]和英國(guó)170例非APAP引起ALF兒童的回顧性研究[25],結(jié)果均提示NAC可提高患者生存率,藥物不良反應(yīng)少。本研究通過(guò)對(duì)266例重癥肝?。òǜ斡不Т鷥斊诤透嗡ソ撸┎扇【S護(hù)肝細(xì)胞膜穩(wěn)定性及肝細(xì)胞膜修復(fù)、抗病毒、合理應(yīng)用抗生素、營(yíng)養(yǎng)支持及輸注新鮮血漿、全血或人血白蛋白等綜合治療,未使用GSH制劑,觀察患者用藥45 d(1個(gè)療程)后的各項(xiàng)肝功能指標(biāo)。研究結(jié)果顯示,重癥肝病治療組和對(duì)照組的癥狀均有所改善,且治療組改善情況明顯優(yōu)于對(duì)照組,差異有統(tǒng)計(jì)學(xué)意義。NAC治療肝硬化失代償期,可明顯改善各項(xiàng)指標(biāo),其中TBIL、PTA和Child-Pugh評(píng)分這3項(xiàng)指標(biāo)的變化幅度與對(duì)照組相比,差異有統(tǒng)計(jì)學(xué)意義。NAC治療肝衰竭,TBIL、PTA、MELD及Child-Pugh評(píng)分指標(biāo)的變化與對(duì)照組相比,差異有統(tǒng)計(jì)學(xué)意義。在治療過(guò)程中雖然有極少數(shù)患者表現(xiàn)為皮疹和消化系統(tǒng)不良反應(yīng),但通過(guò)減慢滴速和抗酸藥物治療,不良反應(yīng)消失[26]。
總之,目前重癥肝病的治療尚缺乏特效藥和手段,其并發(fā)癥的復(fù)雜性和多樣性使肝衰竭臨床表現(xiàn)變化多端,病情迅速惡化,病死率極高。在臨床工作中應(yīng)堅(jiān)持早診斷、早治療,強(qiáng)調(diào)綜合治療的重要性[27]。NAC作為重癥肝病綜合治療方案中興起的一種藥物,仍須不斷探索,以期達(dá)到更好的治療效果,為循證醫(yī)學(xué)尋找更多的臨床研究證據(jù)。
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(2014-06-13收稿 2014-07-03修回)
(責(zé)任編委 張玲霞 本文編輯 陳玉琪)
Therapeutic efficacy of N-acetylcysteine in treatment of patientsw ith severe liver diseases
ZHU Ting,NIE Qing-he*,LIJin-ge,CAO Yi-zhan,ZHAO Bao-min,GAO Lu-hua,WANG Yuan-yuan,LIMi
Department of Infectious Diseases,PLA Center for Infectious Diseases Diagnosis and Treatment, Tangdu Hospital,Fourth Military Medical University,Xi'an,Shaanxi710038,China
*Corresponding author,E-mail:nieqinghe@163.com
Objective To investigate the therapeutic efficacy and safety of N-acetylcysteine(NAC),which is regarded as the model of“gorgeous turn”of translationalmedicine,in treatment of patients with severe liver diseases.M ethods A total of 266 patients with severe liver diseases due to HBV infection were enrolled in the study,and randomized into a treatment group(n=136, 87 with decompensated liver cirrhosis,and 49 with liver failure)and a control group(n=130,85 with decompensated liver cirrhosis, and 45 with liver failure).All of the 266 patients were given the comprehensive treatmentmeasures,such asmaintaining hepatocyte membrane stable and hepatocyte membrane repair,antiviral therapy,rational use of antibiotics,nutritional support and the transfusion of fresh plasma,whole blood or albumin.Neither the treatment group nor the control group was treated with glutathione preparation.Additionally,the treatment group was given a daily dose of 8 g NAC for 45 days.Liver function parameters,model for endstage liver disease(MELD)and Child-Pugh scoresand adverse reactionswere observed after 45 days of treatment.Results The symptoms were improved both in the treatment group and in the control group.In the treatment group,some or all of the liver function parameters were markedly improved,and the MELD and Child-Pugh scores decreased markedly after 45 days of treatment.The improvement of the treatment group was significantly greater than that of the control group(P<0.05).There were no severe adverse reactions associated with NAC during treatment.Conclusions NAC can improve liver function parameters of patients with severe liver diseasesmarkedly,and has no severe adverse reactions during treatment.NAC injection can be widely used in clinical practice.
acetylcysteine;liver cirrhosis;liver diseases;liver failure
R341.1;R575.2
A
1007-8134(2014)04-0209-05
710038西安,第四軍醫(yī)大學(xué)唐都醫(yī)院傳染病科全軍感染病診療中心(朱婷、聶青和、李謹(jǐn)革、高祿化、王媛媛、李汨),急診科(曹義戰(zhàn)),消化內(nèi)科(趙保民)
聶青和,E-mail:nieqinghe@163.com