邱正強(qiáng)
(四川省宜賓縣人民醫(yī)院,宜賓 644800)
血清CEA、AFP、CA199、CA125在肝炎及肝硬化患者中的檢測(cè)意義
邱正強(qiáng)
(四川省宜賓縣人民醫(yī)院,宜賓 644800)
目的:探析血清癌胚抗原(CEA)、甲胎蛋白(AFP)、糖鏈抗原199(CA199)及癌抗原125(CA125)在慢性病毒性肝炎及肝炎后肝硬化患者的早期診斷及治療中的檢測(cè)價(jià)值。方法:分析2014年11月~2016年9月在我院接受治療的109例肝病患者的臨床資料,其中慢性病毒性肝炎患者61例(慢性肝炎組),肝炎后肝硬化者48例(肝炎后肝硬化組)。另外選取同期在我院體檢的28例健康體檢者作為本次研究的健康對(duì)照組。比較各組間的一般資料、血清CEA、AFP、CA199、CA125水平及其陽(yáng)性率。結(jié)果:三組患者的一般資料無(wú)顯著差異性。慢性肝炎組者的血清AFP、CA199與CA125水平顯著較健康對(duì)照組高,中、重度患者顯著較健康對(duì)照組高,而CEA水平與健康對(duì)照組間無(wú)顯著差異性,且慢性肝炎組者的血清AFP與CA199、CA125水平隨著疾病病情的加重而升高。肝炎后肝硬化者的血清AFP、CA199與CA125水平顯著較健康對(duì)照組高,其中代償組患者的血清AFP、CA199與CA125水平顯著較失代償組低。慢性肝炎組的血清AFP、CA199與CA125的陽(yáng)性率均顯著較肝炎后肝硬化組低,但兩組的CEA陽(yáng)性率無(wú)顯著差異性。結(jié)論:動(dòng)態(tài)監(jiān)測(cè)慢性病毒性肝炎及肝炎后肝硬化患者血清AFP、CA199與CA125水平在肝癌、微量腹水的早期診斷及肝硬化代償期與失代償期的鑒別中具有重要的檢測(cè)意義,值得推廣。
癌胚抗原;甲胎蛋白;糖鏈抗原199;癌抗原125;肝炎;肝硬化
【[Key words] carcino-embryonic antigen (CEA); alpha fetoprotein (AFP); carbohydrate antigen 199(CA199); cancer antigen 125(CA125), hepatitis; liver cirrhosis
臨床上,腫瘤標(biāo)志物主要是指宿主對(duì)機(jī)體內(nèi)新生物發(fā)生反應(yīng)而形成并進(jìn)至組織或體液內(nèi)的物質(zhì)或者是惡性腫瘤細(xì)胞脫落或分泌至組織或體液內(nèi)的物質(zhì),該分泌過(guò)程及其機(jī)制較為復(fù)雜,主要受機(jī)體組織損傷或者修復(fù)再生狀態(tài)的影響,故在良性病變與部分正常組織情況下也可能形成[1,2]。癌胚抗原(CEA)主要在肝臟、胰腺、結(jié)腸癌及正常胚胎腸道內(nèi)表達(dá),屬于蛋白多糖復(fù)合物之一[3]。甲胎蛋白(AFP)在肝細(xì)胞性肝癌診斷中具有重要的臨床價(jià)值[4]。糖鏈抗原199(CA199)是臨床胰腺癌中的重要腫瘤標(biāo)志物之一,在膽管癌及肝癌患者中也呈高表達(dá)狀[5]。癌抗原125(CA125)屬于糖鏈抗原之一,是卵巢癌的重要腫瘤標(biāo)志物之一,在診斷卵巢癌及其預(yù)后判斷中發(fā)揮了重要作用,在肝硬化及肝炎中的表達(dá)呈上升狀[6,7]。本研究旨在通過(guò)檢測(cè)肝硬化及病毒性肝炎患者體內(nèi)的CEA、AFP、CA199及CA125的表達(dá)水平,探析上述腫瘤標(biāo)志物在肝硬化及肝炎診治及預(yù)后判斷中的臨床價(jià)值。
1.1 研究對(duì)象分析2014年11月~2016年9月在我院接受治療的109例肝病患者的臨床資料。包括慢性肝炎患者61例(包括輕度者26例,中度者22例,重度者13例);肝硬化者48例(包括代償期者25例和失代償期者23例)。臨床診斷符合2000年9月西安中華醫(yī)學(xué)會(huì)感染病與寄生蟲病學(xué)會(huì)和肝病學(xué)會(huì)修訂的《病毒性肝炎防治方案》。另外選取28例同期在我院體檢的健康體檢者作為本次研究的健康對(duì)照組。排除存在慢性疾患者。本研究經(jīng)我院醫(yī)學(xué)倫理委員會(huì)批準(zhǔn),患者知情同意此次研究并簽署相關(guān)知情同意書。
1.2 研究方法采集血樣:清晨空腹采集3mL肘靜脈血,離心處理后送檢。
血清CEA、AFP、CA 199及CA 125的檢測(cè)方法:通過(guò)微粒子酶免疫分析法(MEIA)上化學(xué)發(fā)光儀CentaurCP(西門子公司,德國(guó))檢測(cè)。CEA參考值范圍:0~5μg/L,AFP:>20μg/L為陽(yáng)性;CA199:0~30.9U/mL;CA125:0~30.2 U/mL。
1.3 統(tǒng)計(jì)學(xué)方法本研究中的數(shù)據(jù)均采用SPSS19.0軟件進(jìn)行分析。數(shù)據(jù)計(jì)量以均數(shù)±標(biāo)準(zhǔn)差(±s)形式表示,比較采用t檢驗(yàn)和卡方(χ2)檢驗(yàn)。我們定義P<0.05為差異具有統(tǒng)計(jì)學(xué)意義。
2.1 一般資料本研究共納入137例研究對(duì)象,其中慢性肝炎組61例,肝炎后肝硬化組48例,健康對(duì)照組28例。三組患者的一般資料無(wú)顯著差異性(P>0.05)。
表1 各組患者一般資料比較
表2 各組患者腫瘤標(biāo)記物比較
2.2 各組患者腫瘤標(biāo)記物比較表2結(jié)果提示,慢性肝炎組者的血清AFP、CA199與CA125水平顯著較健康對(duì)照組高(P<0.05),中、重度患者顯著較健康對(duì)照組高(P<0.05),而CEA水平與健康對(duì)照組間無(wú)顯著差異性(P>0.05),且慢性肝炎組者的血清AFP與CA199、CA125水平隨著疾病病情的加重而升高(P<0.05)。肝炎后肝硬化者的血清AFP、CA199與CA125水平顯著較健康對(duì)照組高(P<0.05),其中代償組患者的血清AFP、CA199與CA125水平顯著較失代償組低(P<0.05)。
2.3 各組患者腫瘤標(biāo)記物陽(yáng)性率比較表3可見(jiàn),慢性肝炎組的血清AFP、CA199與CA125的陽(yáng)性率均顯著較肝炎后肝硬化組低(P<0.05),但兩組的CEA陽(yáng)性率無(wú)顯著差異性(P>0.05)。
表3 各組患者腫瘤標(biāo)記物陽(yáng)性率比較
目前大量學(xué)者一致認(rèn)為,血清甲胎蛋白(AFP)是原發(fā)性肝癌患者的重要診斷指標(biāo),陽(yáng)性表達(dá)率高達(dá)70%-90%,在肝硬化及病毒性肝炎患者體內(nèi)呈暫時(shí)性上升狀或者中低水平狀[8]。據(jù)報(bào)道,慢性病毒性肝炎者體內(nèi)的血清AFP水平隨著其炎性反應(yīng)分級(jí)的增高而不斷上升[9],考慮可能與肝細(xì)胞損傷嚴(yán)重及過(guò)度增生相關(guān),再生的大量肝細(xì)胞由于不成熟而形成AFP。本研究發(fā)現(xiàn),慢性肝炎者的AFP陽(yáng)性表達(dá)率(9.8%)顯著較肝硬化者(27.1%)低,且肝硬化代償期患者的AFP水平顯著低于失代償期者。有學(xué)者發(fā)現(xiàn),血小板下降、肝硬化、AFP水平上升均是原發(fā)性肝癌患者的危險(xiǎn)因子[10]。且大部分肝癌患者存在持續(xù)性乙或丙型肝炎病毒感染,大部分肝硬化的發(fā)生基于肝細(xì)胞癌,故對(duì)于血清AFP呈持續(xù)上升狀的肝硬化及病毒性肝炎者進(jìn)行AFP水平的動(dòng)態(tài)監(jiān)測(cè)可以幫助臨床醫(yī)師及早發(fā)現(xiàn)肝癌。
血清癌胚抗原(CEA)這種特異性抗原對(duì)慢性肝病者意義不大,僅個(gè)別肝硬化及肝炎患者體內(nèi)血清CEA呈上升狀[11]。據(jù)報(bào)道,CA125水平與患者肝硬化的病情關(guān)系密切,且與其腹水量呈一定的正相關(guān)性[12],考慮與CA125主要在體腔組織的上皮細(xì)胞中出現(xiàn)相關(guān),如果腹膜被非特異性刺激時(shí)而出現(xiàn)肝組織結(jié)構(gòu)遭破壞或者腹水現(xiàn)象,微循環(huán)受障致使肝臟無(wú)法處理抗原,導(dǎo)致血清CA125水平上升[13]。本研究發(fā)現(xiàn),一旦肝炎患者進(jìn)展為肝硬化時(shí),其體內(nèi)CA125陽(yáng)性表達(dá)率顯著增加,肝硬化失代償期患者的血清CA125水平明顯較代償期者高,尤其是腹水患者,此結(jié)果與以往的相關(guān)研究結(jié)果相吻合[14]。有學(xué)者發(fā)現(xiàn),血清CA125是一種常規(guī)監(jiān)控腹水的指標(biāo)[15],說(shuō)明在微量腹水早期診斷中CA125具有一定地檢測(cè)意義。糖鏈抗原199(CA199)是臨床胰腺癌患者的重要腫瘤標(biāo)志物之一,有資料研究結(jié)果顯示,肝硬化者血清CA199呈明顯高表達(dá)狀[16]。本研究發(fā)現(xiàn),慢性肝炎及肝炎后肝硬化患者病情越嚴(yán)重,其血清CA199水平及其陽(yáng)性率則越高,提示CA199可以用于肝臟受損程度評(píng)判的一種無(wú)創(chuàng)性指標(biāo),動(dòng)態(tài)監(jiān)測(cè)CA199水平可以有效判斷肝病患者的病情及其活躍期。肝臟受損程度越重,血清AFP、CA125與CA199水平則越高,上述三個(gè)無(wú)創(chuàng)性指標(biāo)均可用于肝臟受損程度的評(píng)判。
總之,動(dòng)態(tài)監(jiān)測(cè)慢性病毒性肝炎及肝炎后肝硬化患者血清AFP、CA199與CA125水平在肝癌、微量腹水的早期診斷及肝硬化代償期與失代償期的鑒別中具有重要的檢測(cè)意義,值得推廣。
[1] Tong MJ, Huynh TT, Siripongsakun S, et al. Predicting clinical outcomes in patients with HBsAg-positive chronic hepatitis[J]. Hepatol Int, 2015, 9(4): 567-77.
[2] 周珣, 李浩, 吳皖, 等. 乙型肝炎病毒前 S1抗原檢測(cè)的臨床價(jià)值分析[J]. 湖南師范大學(xué)學(xué)報(bào) (醫(yī)學(xué)版), 2015, 12(2): 60-62.
[3] Jeng JE, Wu HF, Tsai MF, et al. Independent and additive interaction between tumor necrosis factor β +252 polymorphisms and chronic hepatitis B and C virus infection on risk and prognosis of hepatocellular carcinoma: a case-control study[J]. Asian Pac J Cancer Prev, 2014, 15(23): 10209-10215.
[4] Poh Z, Goh BB, Chang PE, et al. Rates of cirrhosis and hepatocellular carcinoma in chronic hepatitis B and the role of surveillance: a 10-year follow-up of 673 patients[J]. Eur J Gastroenterol Hepatol, 2015, 27(6): 638-643.
[5] Montagnana M, Danese E, Lippi G. Squamous cell carcinoma antigen in hepatocellular carcinoma: Ready for the prime time[J]. Clin Chim Acta, 2015, 20(5): 161-166.
[6] Sinn DH, Yi J, Choi MS, et al. Serum alpha-fetoprotein may have a significant role in the surveillance of hepatocellular carcinoma in hepatitis B endemic areas[J]. Hepatogastroenterology, 2015, 62(138): 327-332.
[7] 楊澤安. CEA、CA125及CA153在乳腺癌中的檢測(cè)價(jià)值[J]. 湖南師范大學(xué)學(xué)報(bào) (醫(yī)學(xué)版), 2016, 13(3): 83-84.
[8] Lee SD, Park SJ, Han SS, et al. Clinicopathological features and prognosis of combined hepatocellular carcinoma and cholangiocarcinoma after surgery[J]. Hepatobiliary Pancreat Dis Int, 2014, 13(6): 594-601.
[9] Yamasaki K, Tateyama M, Abiru S, et al. Elevated serum levels of Wisteria floribunda agglutinin-positive human Mac-2 binding protein predict the development of hepatocellular carcinoma in hepatitis C patients[J]. Hepatology, 2014, 60(5): 1563-1570.
[10] Jun CH, Hong HJ, Chung MW, et al. Risk factors for hepatocellular carcinoma in patients with drug-resistant chronic hepatitis B[J]. WorldJ Gastroenterol, 2013, 19(40): 6834-6841.
[11] 郭佳. 血清IL-6、CRP、CA19-9和CEA在胃癌患者中的檢測(cè)意義[J].湖南師范大學(xué)學(xué)報(bào) (醫(yī)學(xué)版), 2016, 13(5): 63-65.
[12] Hou Y, Xu P, Lou X, et al. Serum decoy receptor 3 is a useful predictor for the active status of chronic hepatitis B in hepatitis B e antigennegative patients[J]. Tohoku J Exp Med, 2013, 230(4): 227-232.
[13] Hshieh TT, Sundaram V, Najarian RM, et al. Hepatitis B surface antigen as a marker for recurrent, metastatic hepatocellular carcinoma after liver transplantation[J]. Liver Transpl, 2012, 18(8): 995-998.
[14] Shin HS, Kim SU, Park JY, et al. Antiviral efficacy of lamivudine versus entecavir in patients with hepatitis B virus-related advanced hepatocellular carcinoma[J]. J Gastroenterol Hepatol, 2012, 27(9): 1528-1534.
[15] Lederle FA, Pocha C. Screening for liver cancer: the rush to judgment[J]. Ann Intern Med, 2012, 156(5): 387-389.
[16] Park Y, Park Y, Lim HS, et al. Soluble human leukocyte antigen-G expression in hepatitis B virus infection and hepatocellular carcinoma[J]. Tissue Antigens, 2012, 79(2): 97-103.
The detective significance of the serum CEA, AFP, CA199 and CA125 in patients w ith hepatitis and liver cirrhosis
Qiu Zheng-qiang
(Yibin People’s Hospital, Yibin 644800, China)
Objective Our retrospective study was aimed toanalyze the detective value of the serum CEA, AFP, CA199 and CA125 in diagnosis and treatment of patients with chronic viral hepatitis and liver cirrhosis. M ethods Clinical data of 109 patients with hepatosis
treatment at our hospitalfrom November, 2014 to September, 2016 was retrospectivelyanalyzed, including 61 patients with chronic viral hepatitis (chronic hepatitis group) and 48 patients with liver cirrhosis (liver cirrhosis group).28 healthy persons at the same time at our hospital were chosen as the control group. The general information, the levels and the positive expression rate of the serum CEA, AFP, CA199 and CA125 in groups were compared. Results The general information in three groups had no statistical difference . The levels of the serum AFP, CA199 and CA125 in chronic hepatitis group were obviously higher than those in control group, and they in moderate, severe group were obviously higher than those in control group. The levels of CEA in groups had no statistical difference. The levels of the serum AFP, CA199 and CA125 in chronic hepatitis group were increasing as the the degree of severity. The levels of the serum AFP, CA199 and CA125 in liver cirrhosis group were obviously higher than those in control group, and the levels in compensatory cirrhosis group were obviously lower than those in discompensatory cirrhosis group . The positive expression rate of the serumAFP, CA199 and CA125 in chronic hepatitis group were obviously lower than those in liver cirrhosis group, and the positive expression rate of the serum CEA in two groups had no statistical difference. Conclusion The dynamic monitoring of the levels of the serum AFP, CA199 and CA125 in patients with chronic viral hepatitis and liver cirrhosis play important roles in early diagnosis and treatment of liver cancer and trace ascites and the identification between compensatory cirrhosis patients and discompensatory cirrhosis patients, which is worth promoting.
R575.1
A
1673-016X(2017)03-0171-04
2017-01-12
邱正強(qiáng),E-mail:arder123@126.com
湖南師范大學(xué)學(xué)報(bào)(醫(yī)學(xué)版)2017年3期