郭春梅,吳 靜,王滄海,王亞丹,尹金淑
100038北京市,首都醫(yī)科大學(xué)附屬北京世紀(jì)壇醫(yī)院消化內(nèi)科
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·論著·
瞬時(shí)彈性測(cè)定儀測(cè)定受控衰減參數(shù)在脂肪性肝病中的應(yīng)用價(jià)值
郭春梅,吳 靜,王滄海,王亞丹,尹金淑
100038北京市,首都醫(yī)科大學(xué)附屬北京世紀(jì)壇醫(yī)院消化內(nèi)科
【摘要】目的探討瞬時(shí)彈性測(cè)定儀(FibroScan)測(cè)定受控衰減參數(shù)(CAP)在區(qū)分不同原因所致的脂肪性肝病(FLD)中的價(jià)值。方法選取2013年10月—2014年12月于首都醫(yī)科大學(xué)附屬北京世紀(jì)壇醫(yī)院行超聲檢查測(cè)定肝臟硬度及脂肪變,并確診為FLD的患者524例,根據(jù)病因?qū)⒒颊叻譃榉蔷凭灾拘愿尾?NAFLD)組406例,慢性乙型病毒性肝炎(CHB)合并NAFLD組69例,酒精性肝病(ALD)組49例。另選擇門診就診查抗線粒體抗體M2(AMA-M2)陽性患者48例為AMA-M2組?;颊呔?jīng)腹部超聲診斷為FLD。記錄患者的一般資料,并檢測(cè)肝功能、血脂等指標(biāo)。由經(jīng)過專門培訓(xùn)的醫(yī)師測(cè)定CAP,取右腋前線和腋中線第7、8肋間捕獲10次回波,取中位數(shù)(M)作為CAP。結(jié)果各組丙氨酸氨基轉(zhuǎn)移酶(ALT)、堿性磷酸酶(ALP)、三酰甘油(TG)、低密度脂蛋白膽固醇(LDL-C)及高密度脂蛋白膽固醇(HDL-C)水平比較,差異均無統(tǒng)計(jì)學(xué)意義(P>0.05)。各組性別、年齡、體質(zhì)指數(shù)(BMI)、天冬氨酸氨基轉(zhuǎn)移酶(AST)、γ-谷酰轉(zhuǎn)肽酶(GGT)、總膽固醇(TC)水平比較,差異均有統(tǒng)計(jì)學(xué)意義(P<0.05)。各組CAP比較,差異有統(tǒng)計(jì)學(xué)意義(P<0.05);其中,CHB合并NAFLD組、ALD組、AMA-M2組CAP低于NAFLD組,CHB合并NAFLD組CAP低于ALD組,差異均有統(tǒng)計(jì)學(xué)意義(P<0.05)。結(jié)論應(yīng)用FibroScan測(cè)定CAP有助于區(qū)分不同原因所致的FLD患者。
【關(guān)鍵詞】脂肪肝;受控衰減參數(shù);脂肪肝,酒精性;乙型肝炎,慢性;自身免疫性肝病
郭春梅,吳靜,王滄海,等.瞬時(shí)彈性測(cè)定儀測(cè)定受控衰減參數(shù)在脂肪性肝病中的應(yīng)用價(jià)值[J].中國(guó)全科醫(yī)學(xué),2016,19(14):1659-1662.[www.chinagp.net]
Guo CM,Wu J,Wang CH,et al.Value of FibroScan in the detection of controlled attenuation parameters for fatty liver disease[J].Chinese General Practice,2016,19(14):1659-1662.
脂肪性肝病(FLD)是以彌漫性肝細(xì)胞大泡性脂肪變?yōu)橹饕卣鞯呐R床病理綜合征,正常人肝臟中脂肪含量為2%~4%,當(dāng)脂肪的積累超過肝臟濕重的5%,或肝臟中5%以上肝細(xì)胞發(fā)生脂肪沉積稱為肝脂肪變[1]。FLD主要包括酒精性肝病(ALD)和非酒精性脂肪性肝病(NAFLD),疾病譜包括單純性脂肪肝、脂肪性肝炎及其相關(guān)肝硬化[1],其不僅導(dǎo)致肝病并發(fā)癥和死亡風(fēng)險(xiǎn)增加,還與代謝綜合征密切相關(guān)[2]。因此,F(xiàn)LD特別是肝脂肪變的診斷及其嚴(yán)重程度的判斷在臨床實(shí)踐中至關(guān)重要。受控衰減參數(shù)(CAP)是在既往瞬時(shí)彈性測(cè)定儀(FibroScan)基礎(chǔ)上利用超聲衰減原理定義的一個(gè)新參數(shù),主要用于定量檢測(cè)人體內(nèi)肝脂肪變程度。CAP與超聲振幅在肝臟傳遞過程中的衰減有關(guān),脂肪變?cè)絿?yán)重,CAP越高,并可以對(duì)隨訪患者肝臟脂肪含量的變化趨勢(shì)進(jìn)行精確的定量分析。多項(xiàng)研究已經(jīng)證實(shí)了CAP的臨床應(yīng)用價(jià)值,顯示其與肝臟組織的脂肪變程度S0~S3均有高度的相關(guān)性[3-4]。但是對(duì)于CAP測(cè)定在慢性乙型病毒性肝炎(CHB)合并FLD、ALD及自身免疫性肝病患者中應(yīng)用研究較少。本研究旨在分析FibroScan測(cè)定CAP在不同病因FLD患者中的應(yīng)用價(jià)值。
1對(duì)象與方法
1.1研究對(duì)象選取2013年10月—2014年12月于首都醫(yī)科大學(xué)附屬北京世紀(jì)壇醫(yī)院行超聲檢查測(cè)定肝臟硬度及脂肪變,并確診為FLD的患者524例,其中根據(jù)《非酒精性脂肪性肝病診療指南(2010年修訂版)》[5]及《酒精性肝病診療指南》[6],將患者分為NAFLD組406例,CHB合并NAFLD組69例,ALD組49例。另選擇門診就診查抗線粒體抗體M2(AMA-M2)陽性患者48例為AMA-M2組。AMA-M2組排除慢性病毒性肝炎、大量飲酒史〔酒精量>40 g/d(男)或20 g/d(女)〕、遺傳性疾病史、藥物性肝病史、惡性腫瘤病史者。體質(zhì)指數(shù)(BMI)>30 kg/m2時(shí)使用M探頭檢測(cè)失敗率達(dá)22%~27%[7],因此選擇BMI≤30 kg/m2者為研究對(duì)象。
1.2方法
1.2.1一般情況及超聲檢查記錄患者性別、年齡、身高、體質(zhì)量,計(jì)算BMI。超聲診斷FLD需具備以下3項(xiàng)腹部超聲表現(xiàn)中的2項(xiàng)[8]:(1)肝臟近場(chǎng)回聲彌漫性增強(qiáng)(“明亮肝”),回聲強(qiáng)于腎臟;(2)肝內(nèi)管道結(jié)構(gòu)顯示不清;(3)肝臟遠(yuǎn)場(chǎng)回聲逐漸衰減。
1.2.2血清學(xué)指標(biāo)與CAP檢測(cè)采用全自動(dòng)生化分析儀檢測(cè)丙氨酸氨基轉(zhuǎn)移酶(ALT)、天冬氨酸氨基轉(zhuǎn)移酶(AST)、堿性磷酸酶(ALP)、γ-谷氨酰轉(zhuǎn)移酶(GGT)、總膽固醇(TC)、三酰甘油(TG)、低密度脂蛋白膽固醇(LDL-C)、高密度脂蛋白膽固醇(HDL-C)水平等。由經(jīng)過專門培訓(xùn)的醫(yī)師測(cè)量CAP。測(cè)量時(shí),患者取仰臥位,上舉右臂,充分暴露右側(cè)肋間隙,取右腋前線和腋中線第7、8肋間捕獲10次回波,取中位數(shù)(M)作為CAP,代表肝臟的脂肪含量及彈性,并要求四分位數(shù)間距(QR)小于M的30%,成功率≥60%以保證結(jié)果可靠。
2結(jié)果
2.1臨床資料比較各組ALT、ALP、TG、LDL-C及HDL-C水平比較,差異均無統(tǒng)計(jì)學(xué)意義(P>0.05)。各組性別、年齡、BMI、AST、GGT、TC水平比較,差異均有統(tǒng)計(jì)學(xué)意義(P<0.05);其中,AMA-M2組年齡高于NAFLD組、CHB合并NAFLD組、ALD組,BMI低于NAFLD組、CHB合并NAFLD組、ALD組;ALD組AST水平高于NAFLD組、CHB合并NAFLD組,AMA-M2組ALP水平高于NAFLD組、CHB合并NAFLD組,ALD組GGT水平高于NAFLD組、CHB合并NAFLD組和AMA-M2組,AMA-M2組GGT水平高于NAFLD組、CHB合并NAFLD組,CHB合并NAFLD組TC水平低于NAFLD組、ALD組和AMA-M2組,AMA-M2組LDL-C水平低于NAFLD組,差異均有統(tǒng)計(jì)學(xué)意義(P<0.05,見表1)。
2.2CAP比較各組CAP比較,差異有統(tǒng)計(jì)學(xué)意義(P<0.05);其中,CHB合并NAFLD組、ALD組、AMA-M2組CAP低于NAFLD組,CHB合并NAFLD組CAP低于ALD組,差異均有統(tǒng)計(jì)學(xué)意義(P<0.05,見表2)。
表1 各組臨床資料比較
注:NAFLD=非酒精性脂肪性肝病,CHB=慢性乙型病毒性肝炎,ALD=酒精性肝病,AMA-M2=抗線粒體抗體M2,BMI=體質(zhì)指數(shù),ALT=丙氨酸氨基轉(zhuǎn)移酶,AST=天冬氨酸氨基轉(zhuǎn)移酶,ALP=堿性磷酸酶,GGT=γ-谷氨酰轉(zhuǎn)移酶,TC=總膽固醇,TG=三酰甘油,LDL-C=低密度脂蛋白膽固醇,HDL-C=高密度脂蛋白膽固醇;與NAFLD組比較,aP<0.05;與CHB合并NAFLD組比較,bP<0.05;與ALD組比較,cP<0.05;d為χ2值,e為F值,余檢驗(yàn)統(tǒng)計(jì)量值為H值
表2 各組CAP比較
注:CAP=受控衰減參數(shù);與NAFLD組比較,aP<0.05;與CHB合并NAFLD組比較,bP<0.05
3討論
隨著生活水平的提高,NAFLD發(fā)病率逐漸升高,其不僅是糖尿病、冠心病等的危險(xiǎn)因素[2],而且NAFLD本身可進(jìn)展為脂肪性肝炎甚至肝硬化。據(jù)研究,在發(fā)展中國(guó)家,約1/3人口患有NAFLD,其中70%~90%為脂肪性肝炎,又有10%~30%可進(jìn)展為肝硬化[9]。目前,肝穿刺活檢仍然是診斷FLD的“金標(biāo)準(zhǔn)”[10]。然而,肝穿刺活檢存在內(nèi)出血、膽汁滲漏、血腫及感染等嚴(yán)重并發(fā)癥風(fēng)險(xiǎn),因此不適合作為FLD的篩查手段。目前,臨床多采用超聲檢查或CT診斷FLD,但超聲檢查的準(zhǔn)確率僅有30%[11],且受檢查者主觀因素影響較大。研究已證實(shí),F(xiàn)ibroScan測(cè)量受操作者主觀影響較少,既往對(duì)于肝臟硬度測(cè)定值的穩(wěn)定性評(píng)價(jià)提示其具有良好的重復(fù)性[12]。沈峰等[13]對(duì)于CAP穩(wěn)定性的評(píng)價(jià)結(jié)果顯示,同一操作者兩次CAP測(cè)定的組內(nèi)相關(guān)系數(shù)(ICC)為0.848,不同操作者ICC為0.718,提示CAP具有較高的穩(wěn)定性。
除NAFLD外,ALD、病毒性肝炎等均可出現(xiàn)FLD。尤其是我國(guó)作為肝炎大國(guó),慢性病毒性肝炎合并FLD的患者數(shù)量龐大。但對(duì)于不同疾病合并肝脂肪變的研究較少,且各研究結(jié)果不盡一致。2010年,法國(guó)Sasso等[14]首先開展一項(xiàng)多中心臨床研究,納入了115例慢性肝病患者,其中慢性丙型病毒性肝炎(CHC)、CHB、ALD、NAFLD患者分別為42、17、39、17例,患者在1周內(nèi)接受了肝穿刺活檢和CAP檢測(cè),根據(jù)肝穿刺活檢結(jié)果進(jìn)行肝脂肪變分級(jí):S0≤10%,S1:11%~33%,S2:34%~66%,S3>66%,結(jié)果發(fā)現(xiàn)各級(jí)CAP平均值分別為205、245、299、321 dB/m;不同程度脂肪變患者CAP有差異,CAP與肝脂肪變程度顯著相關(guān)(r=0.81,P=0.016)。沈峰等[15]對(duì)納入5個(gè)中心經(jīng)肝穿刺活檢證實(shí)的成年人(>18歲)NAFLD及CHB患者332例進(jìn)行研究發(fā)現(xiàn),BMI<25 kg/m2時(shí),CAP診斷大于5%脂肪變的ROC曲線下面積為0.853,最佳臨界值為244.5 dB/m;BMI≥25 kg/m2時(shí),CAP診斷大于5%脂肪變的ROC曲線下面積為0.835,最佳臨界值為269.5 dB/m。朱夢(mèng)飛等[16]對(duì)624例NAFLD、579例CHB及124例CHB合并NAFLD患者進(jìn)行CAP測(cè)定,結(jié)果發(fā)現(xiàn)CHB患者CAP為(218.90±56.40) dB/m,顯著低于NAFLD患者的(290.85±61.46) dB/m,也低于CHB合并NAFLD患者的(284.93±64.70) dB/m,而CHB合并NAFLD與NAFLD患者間CAP無差異;因此,作者認(rèn)為乙型肝炎病毒感染不影響CAP。Ahn等[17]對(duì)108例NAFLD及80例ALD患者進(jìn)行比較發(fā)現(xiàn),兩組CAP均明顯升高,尤其是B超診斷中到重度FLD(S2、S3)患者,但兩組比較CAP無差異。而本研究發(fā)現(xiàn),NAFLD組患者CAP顯著高于CHB合并NAFLD組、ALD組及AMA-M2組,而CHB合并NAFLD組CAP低于ALD組,提示對(duì)于超聲診斷為“NAFLD”的患者,應(yīng)進(jìn)行進(jìn)一步甄別,完善肝炎篩查及自身免疫抗體檢查。
總之,應(yīng)用FibroScan測(cè)定CAP可廣泛應(yīng)用于各類FLD患者,有助于區(qū)分不同病因所致的FLD。但本研究尚存在以下不足:(1)入選樣本未進(jìn)行肝組織活檢,而以超聲作為診斷FLD的標(biāo)準(zhǔn),在一定程度上可能影響結(jié)論;(2)鑒別NAFLD及ALD,主要依據(jù)患者病史,無飲酒量的量化指標(biāo);(3)非多中心研究,難以避免選擇偏倚。
作者貢獻(xiàn):郭春梅進(jìn)行課題設(shè)計(jì)與實(shí)施、資料收集整理、撰寫論文、成文并對(duì)文章負(fù)責(zé);王滄海、王亞丹進(jìn)行課題實(shí)施、評(píng)估、資料收集;吳靜、尹金淑進(jìn)行質(zhì)量控制及審校。
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(本文編輯:吳立波)
Value of FibroScan in the Detection of Controlled Attenuation Parameters for Fatty Liver Disease
GUOChun-mei,WUJing,WANGCang-hai,etal.
DepartmentofGastroenterology,BeijingShijitanHospital,CapitalMedicalUniversity,Beijing100038,China
【Abstract】Objective To investigate the value of FibroScan in the detection of controlled attenuation parameters (CAP)for distinguishing fatty liver disease (FLD) patients with different etiological factors.MethodsFrom October 2013 to December 2014,we enrolled 524 patients who received ultrasonic examination of liver stiffness and fatty change and were definitely diagnosed as FLD in Beijing Shijitan Hospital,Capital Medical University.According to etiological factors,the patients were divided into three groups:NAFLD group (n=406),CHB+NAFLD group(n=69) and ALD group(n=49).We also enrolled 48 patients with AMA-M2 positive as AMA-M2 group.All the patients were diagnosed as FLD by abdominal ultrasound.The general data of the patients were recorded,and the detection of liver function and blood lipid were also conducted.Doctors who had received special training measured CAP value.They captured echos for 10 times between the 7th and 8th rib of the right axillary front and the right midaxillary line,and took the median as CAP.ResultsDifferent groups were not significantly different in the levels of ALT,ALP,TG,LDL-C and HDL-C(P>0.05).Different groups were significantly different in gender,age,BMI,AST,GGT and TC(P<0.05).Different groups were significantly different in CAP(P<0.05);CHB+NAFLD group,ALD group and AMA-M2 group were lower than NAFLD group in CAP,and CHB+NAFLD group was lower than ALD group in CAP(P<0.05).Conclusion The application of FibroScan in the determination of CAP could help distinguish FLD patients with different etiological factors.
【Key words】Fatty liver;Controlled attenuation parameter;Fatty liver,alcoholic;Hepatitis B,chronic;Autoimmune liver disease
基金項(xiàng)目:鐵道部科技研究開發(fā)計(jì)劃課題(2011Z004-F)
通信作者:吳靜,100038北京市,首都醫(yī)科大學(xué)附屬北京世紀(jì)壇醫(yī)院消化內(nèi)科;E-mail:wujing36@163.com
【中圖分類號(hào)】R 575.5
【文獻(xiàn)標(biāo)識(shí)碼】A
doi:10.3969/j.issn.1007-9572.2016.14.011
(收稿日期:2015-12-16;修回日期:2016-03-28)