来源：《世界华人消化杂志》2002年6月15日第10卷第6期(总第98期)

栏目：临床经验

幽门螺杆菌粪便抗原检测的评价

刘欣；郅敏；董蕾；畅碧霞

摘要　目的:对幽门螺杆菌粪便抗原（HpSA）检测诊断Hp感染的特异性、敏感性进行临床评价.方法:采用酶联免疫分析法检测55例因上消化道症状就诊患者的幽门螺杆菌粪便抗原（HpSA）. 同时进行14C-尿素呼气试验（14C-UBT），其中20例在接受胃镜检查时取胃窦部黏膜进行Hp的组织学检查.Hp SA分别与14C-UBT及组织学检查进行比较，以评价HpSA诊断Hp感染的特异性、敏感性、准确性.结果:HpSA与14C-UBT比较其特异性、敏行院妥既沸苑直鹞0.3%，95.8%和92.7%.HpSA与组织学检查比较其特异性、敏感性、准确性分别为80%,100%和90%.结论:HpSA检测是一种操作简便、准确、非侵入性的诊断Hp感染的方法.适合常规检查，尤其适合幼儿、孕妇等的Hp感染的诊断及Hp根除后的随访.

0 引言

随着幽门螺杆菌（Helicobacter pylori,Hp）感染在胃十二指肠疾病中作用认识的提高［1－17]，临床检查Hp感染的方法也日益增多［18－24].目前常用的方法分为侵入性和非侵入性两大类.如尿素酶试验，组织学检查、培养，血清学试验，尿素呼气试验等.但这些方法都因各自的局限作为临床常规检测Hp而受到了很大的限制.近年来国内外文献［24－41］报道了检测粪便Hp抗原（Hp stool antigen,Hp SA）的一种新的非侵入性方法.我们通过与14C-尿素呼气试验（14C-urea breath test,14C-UBT）及组织学检查进行比较，以评价HpSA检测Hp感染在临床应用的价值.

1 材料和方法

1.1 材料 2001－05/2001－10因上消化道症状在我院门诊及住院就诊的患者55例，其中男28例，女27例，年龄29～77（平均52±12）岁,4wk内未服用抗生素、铋剂和质子泵抑制剂等对Hp检测有影响者.胃镜检查慢性胃炎39例，消化性溃疡16例.其中有20例在胃镜检查时取胃窦部黏膜行Hp的组织学检查（甲基氯哌乐凝染色）.

1.2 方法

1.2.1 Hp SA检测 患者于胃镜检查当日早晨留取粪便标本，采用酶联免疫分析双抗体夹心法，行Hp抗原检测.检测试剂盒由协合药业有限公司提供（批号700101-002），参照试剂盒说明书进行操作，简要步骤如下：设阳性和阴性对照各一个，提取100mg粪便标本加入稀释液400μL并混匀，在已用抗体包被的微孔板中加入稀释的粪便100μL，再加入酶标抗体，震荡30s后在室温孵育1h，洗涤微孔板6次后加入底物溶液，震荡30s后在室温孵育10min，加入反应终止液后15min内在酶标仪波长450nm处读取吸光度.A值≥0.12为阳性.

1.2.2 14C-UBT 患者于胃镜检查后2h口服14C-尿素胶囊一粒，25min后收集呼气样本，于HTY1001Hp测试仪（深圳市海得威生物科技有限公司）上行样本14C放射性活度测定，14C-UBT（CO2）≥2KBq/mol为Hp阳性.

2 结果

2.1 HpSA与14C-UBT其特异性为90.3%（28/31例），敏感性为95.8%(23/24例)，阳性预测值为88.5%（23/26例），阴性预测值为96.6%（28/29例），准确性为92.7%（51/55例，表1）.

表1　HpSA检测与14C-UBT结果比较（n）

2.2　HpSA与胃黏膜Hp  其特异性为80%（8/10例），敏感性为100%（10/10例），阳性预测值83.3%（10/12例），阴性预测值为100%（8/8例），准确性为90%（18/20例，如表2）.

表2　HpSA检测与胃黏膜Hp组织学检测结果比较（n）

3 讨论

随着Hp的发现，与其相关的胃十二指肠疾病的研究已取得了很大进展，现已确认Hp是慢性胃炎和消化性溃疡的主要致病因子［1-16]，并且是胃腺癌与淋巴瘤的诱发因素之一［42]，国际癌症研究中心（IARC）已将其列为Ⅰ类致癌因子［1-16，43-46]. 因此，临床上对于有上消化道症状的患者常规行Hp检查是非常必要的.目前临床上用于诊断Hp感染的方法很多，分为侵入性和非侵入性两大类.如尿素酶试验，组织学检查、培养，血清学试验，尿素呼气试验，PCR等方法［18-24].侵入性检查如尿素酶试验，组织学检查、培养等必须在行胃镜检查的同时采集活检标本，且其结果受所采集标本的部位、数量等因素影响，该项检查对于不能耐受胃镜检查的患者及Hp根除后的随访患者难以接受.血清学检查虽为非侵入性检查，但由于Hp感染数周后血中才出现特异抗体，阴性者血中也可存在交叉反应性抗体（如空肠弯曲菌感染），且Hp根除后血中抗体可长时间维持在阳性水平，故血清学阳性不能完全肯定患者有活动性感染，阴性也不能排除初期的感染，因此，血清学抗体的检测只能用于流行病学筛检而不能用于临床诊断.14C-UBT及13C-UBT虽也为非侵入性检查方法，但因14C-UBT有放射性而使其应用受限，13C-UBT虽无放射性，但检测仪器太昂贵，不便于临床应用.近年来，国外开发出一种非侵入性的Hp粪便抗原检测方法，采用抗Hp多克隆抗体检测粪便中的Hp抗原，其检测结果具有很高的特异性和敏感性，分别为75.0～96.4%及90～98.2%，且可重复性好.目前国内也有用该方法对Hp检测的报道，而且认为对诊断Hp现症感染有高度的准确性和可靠性［47]，并在Hp根除后的随访方面也有很高的准确性,与14C-UBT相似.我们分别以14C-UBT及组织学检查为对照，以评价HpSA的临床应用价值，结果表明HpSA与14C-UBT相比其特异性、敏感性及准确性分别分别为90.3%，95.8%和92.7%，与组织学检测相比其特异性、敏感性及准确性分别为80%，100%和90%，与上述报道结果相似.该项检查留取标本容易，操作简便、省时、无创，适合常规检查，尤其适合幼儿、孕妇、年老体弱者的Hp感染的诊断及Hp根除后的随访，值得临床推广应用［26，34，35，48].

刘欣，郅敏，董蕾，畅碧霞，西安交通大学第二医院消化内科 陕西省西安市 710004

4 参考文献

1 Miehlke S, Kirsch C, Dragosics B, Gschwantler M, Oberhuber G, Antos D, Dite P, Luter J, Labenz J, Leodolter A, Malfertheiner P, Neubauer A, Ehninger G, Stolte M, Bayerd rffer E.Helicobacter pylori and gastric cancer: current status of the Austrain Czech German gastric cancer prevention trial (PRISMA-Study). World J Gastroenterol 2001;7:243-247

2 Huang MF,Zhu YQ,Zhang CX,Liu S,Huang X,Deng CS.Effect of Helicobacter pylori infection on gastric mucosa proliferation、DNA content and cancer genetic expression. Shijie Huaren Xiaohua Zazhi 2000;8：1057-1059

3 Liu GF, Yao XX, Feng LY, Song M, Cui DL. Relationship of type TH1/TH2 cytokines in Hp infected gastric diseases. Shijie Huaren Xiaohua Zazhi 2000;8:1105-1108

4 Li Y,Li JB,Chen J,Chen S. Relationship between epithelial cell apoptosis of gastric mucosa/proliferationand Fas/FasL expression in Hp+ peptic ulcer patients.Shijie Huaren Xiaohua Zazhi 2001;9:1404-1408

5 Zhang WD,Xu ZM. Present status and common opinion about Helicobacter pylori study. Shijie Huaren Xiaohua Zazhi 2000；8：1084-1088

6 Xu C，Jin ZD，Li ZS. Helicobacter pylori and Gastroesophageal reflux disease. Shijie Huaren Xiaohua Zazhi 2001；9：679-681

7 Yao YL,Zhang WD.The relationship of Helicobacter pylori and gastric carcinoma. Shijie Huaren Xiaohua Zazhi 2001；9：1045-1049

8 Chen SY, Wang JY, Ji Y, Zhang XD, Zhu CW.Effects of Helicobacter pylori and protein kinase C on gene mutation in gastric cancer and precancerous lesions. Shijie Huaren Xiaohua Zazhi 2001;9:302-307

9 Liu HF, Liu WW, Fang DC,Yang SM, Zhao L. Gastric epithelial apoptosis induced by Helicobacter pylori and its relationship with Bax protein expression. Shijie Huaren Xiaohua Zazhi 2000;8:860-862

10 Wang CD, Huang HH, Chen YL.Effect of Helicobacter pylori infection on antral G and D cells in patients with active duodenal ulcer. Shijie Huaren Xiaohua Zazhi 2000;8:847-850

11 Qiu JW, Hu JL, Wu KC, Peng DR, Shi BL, Ji WS， Fan DM.Relationship between cagA vacA genotypes and antibiotic resistance of Helicobacter pylori strains. Shijie Huaren Xiaohua Zazhi 2001;9:739-742

12 Wang DX, Fang DC, Li W, Du QX, Liu WW.A study on relationship between infection of Helicobacter pylori and inactivation of antioncogenes in cancer and pre-cancerous lesion.Shijie Huaren Xiaohua Zazhi 2001;9:984-987

13 Zhang LX, Zhang L, Liu YG, Zhang NX, Yan XJ, Han FC， Hou Y. A case-control study on the relationship between Helicobacter pylori expressed cytotoxin associated gene A (CagA) and gastroduodenal ulcer. Shijie Huaren Xiaohua Zazhi 2000;8:733-736

14 Hobsley M, Tovey F. Helicobacter pylori: the primary cause of duodenal ulceration or a secondary infection. World J Gastroenterol 2001;7:149-151

15 Hou P, Tu ZX, Xu GM, Gong YF, Ji XH, Li ZS. Helicobacter pylori vacA genotypes and cagA status and their relationship to associated diseases.World J Gastroenterol 2000;6:605-607

16 Williams CL.Helicobacter pylori and endoscopy.J Hosp Infect 1999;41:263-268

17 Fan XG,Peng XN. Helicobacter pylori and its related disease. Shijie Huaren Xiaohua Zazhi 2001;9:979-983

18 Xu JR, Zhang L, Yan XJ, Cui DX, Jiang H, Han FC.Cloning and sequence analysis of Helicobacter pylori ureC. Shijie Huaren Xiaohua Zazhi 2001;9:308-311

19 Wang XZ,Li D. The serodiagnosis of Helicobacter pylori.Shijie Huaren Xiaohua Zazhi 2000；8:550-551

20 Sun T,Ye JX,Ma GX,Cui LH,Liu CQ,Pu J,Fu SF,Jiang Y. Using 13C-urea breath test to diagnose Helicobacter pylori infection. Shijie Huaren Xiaohua Zazhi 2000;8:270

21 Li ZJ,Jiang T,Zhou WM. The value of detecting Helicobacter pylori antibody in saliva by enzyme-linked immuno-sorbent assay. Shijie Huaren Xiaohua Zazhi 2000;8:241-241

22 Wang CD,Lu XQ. Clinical application of Helicobacter pylori urea breath test. Shijie Huaren Xiaohua Zazhi 2000；8:789-792

23 Huang Y,Xu LN. The dependent test of Helicobacter pylori urea enzyme. Shijie Huaren Xiaohua Zazhi 2000；8:549-550

24 Metz DC, Furth EE, Faigel DO, Kroser JA, Alavi A, Barrett DM, Montone K. Realities of diagnosing Helicobacter pylori infection in clinical practice: a case for non-invasive indirect methodologies. Yale J Biol Med 1998;71:81-90

25 Shepherd AJ, Williams CL, Doherty CP, Hossack M, Preston T, McColl KE, Weaver Arch LT. Comparison of an enzyme immunoassay for the detection of Helicobacter pylori antigens in the faeces with the urea breath test.Dis Child 2000;83:268-270

26 Pilotto A, Malfertheiner P. An approach to Helicobacter pylori infection in the elderly.Aliment Pharmacol Ther 2002;16:683-691

27 Odaka T, Yamaguchi T, Koyama H, Saisho H, Nomura F. Evaluation of the Helicobacter pylori stool antigen test for monitoring eradication therapy. Am J Gastroenterol 2002;97:594-599

28 Kim PS, Lee JW, Pai SH, Kim YB, Cho JK, Lee JW, Jeong S, Lee DH, Kim HG, Kwon KS, Cho HG, Shin YW, Kim YS. Detection of Helicobacter pylori antigen in stool by enzyme immunoassay. Yonsei Med J 2002;43:7-13

29 Vaira D, Vakil N, Menegatti M, van't Hoff B, Ricci C, Gatta L, Gasbarrini G, Quina M, Pajares Garcia JM, van Der Ende A, van Der Hulst R, Anti M, Duarte C, Gisbert JP, Miglioli M, Tytgat G. The Stool Antigen Test for Detection of Helicobacter pylori after Eradication Therapy. Ann Intern Med 2002;136:280-287

30 Suzuki N, Wakasugi M, Nakaya S, Okada K, Mochida R, Sato M, Kajiyama H,Takahashi R, Hirata H, Ezure Y, Koga Y, Fukuda Y, Shimoyama T. Production and application of new monoclonal antibodies specific for a fecal Helicobacter pylori antigen. Clin Diagn Lab Immunol 2002;9:75-78

31 Yu FJ, Wu DC, Kuo CH, Lu CY, Su YC, Lee YC, Lin SR, Liu CS, Jan CM, Wang WM. Diagnosis of Helicobacter pylori infection by stool antigen test in southern Taiwan.Gaoxiong Yixue Kexue Zazhi 2001;17:344-350

32 Manes G, Balzano A, Iaquinto G, Ricci C, Piccirillo MM, Giardullo N, Todisco A, Lioniello M, Vaira D. Accuracy of stool antigen test in posteradication assessment of Helicobacter pylori infection.Dig Dis Sci 2001;46:2440-2444

33 Gisbert JP, Pajares JM. Diagnosis of Helicobacter pylori infection by stool antigen determination: a systematic review. Am J Gastroenterol 2001;96:2829-2838

34 van Doorn OJ, Bosman DK, van't Hoff BW, Taminiau JA, Kate FJ, van der Ende A. Helicobacter pylori Stool Antigen test: a reliable non-invasive test for the diagnosis of Helicobacter pylori infection in children. Eur J Gastroenterol Hepatol 2001;13:1061-1065

35 Koletzko S, Feydt-Schmidt A. Infants differ from teenagers: use of non-invasive tests for detection of Helicobacter pylori infection in children. Eur J Gastroenterol Hepatol 2001;13:1047-1052

36 Agha-Amiri K, Peitz U, Mainz D, Kahl S, Leodolter A, Malfertheiner P.A novel immunoassay based on monoclonal antibodies for the detection of Helicobacter pylori antigens in human stool. Z Gastroenterol 2001;39:555-560

37 Masoero G, Lombardo L, Della Monica P, Vicari S, Crocilla C, Duglio A, Pera A. Discrepancy between Helicobacter pylori stool antigen assay and urea breath test in the detection of Helicobacter pylori infection. Dig Liver Dis 2000;32:291-293

38 Leodolter A, Agha-Amiri K, Peitz U, Gerards C, Ebert MP, Malfertheiner P. Validity of a Helicobacter pylori stool antigen assay for the assessment of H.pylori status following eradication therapy. Eur J Gastroenterol Hepatol 2001;13:673-676

39 Wang YL, Sheu BS, Huang JJ, Yang HB. Noninvasive stool antigen assay can effectively screen Helicobacter pylori Infection and assess success of eradication therapy in hemodialysis patients. Am J Kidney Dis 2001;38:98-103

40 Roth DE, Taylor DN, Gilman RH, Meza R, Katz U, Bautista C, Cabrera L, Velapatino B, Lebron C, Razuri M, Watanabe J, Monath T. Posttreatment follow-up of Helicobacter pylori infection using a stool antigen immunoassay. Clin Diagn Lab Immunol 2001;8:718-723

41 Konstantopoulos N, Russmann H, Tasch C, Sauerwald T, Demmelmair H, Autenrieth I,Koletzko S. Evaluation of the Helicobacter pylori stool antigen test (HpSA) for detection of Helicobacter pylori infection in children. Am J Gastroenterol 2001;96:677-683

42 Agresta F,Trentin G,Mainente P,Della-Libera D,Bianco A,Salvagno L.Gastric MALT lymphomas:the value of an endoscopic follow-up evaluation.Surg Endosc 2000;14:1153-1155

43 Vu C,Ng YY.Prevalence of Helicobacter pylori in peptic ulcer disease in a Singapore hospital.Singapore Med J 2000;41:478-481

44 Kath R,Fiehler J，Schneider CP，Hoffken K.Gastric cancer in very young adult:apropos four patients and a review of the literature. J Cancer Res Clin Oncol 2000;126:233-237

45 Plummer M,Vivas J,Fauchere JL,Del Giudice G,Pena AS,Ponzetto A,Lopez G,Miki K,Oliver W,Munoz N. Helicobacter Pylori and stomach cancer:a case-control study in Venezuela.Cancer Epidemiol Biomarkers Prev 2000;9:961-965

46 Torrado J,Plummer M, Vivas J,Garay J,Lopez G,Peraza S,Carillo E ,Oliver W,Munoz N. Lewis antigen alterations in a population at high risk of stomach cancer.Cancer Epidemiol Biomakers Prev 2000;9:671-694

47 Hu FL,Cheng H,Li J,Gu Q,Wang WH.Evaluation and comparison of the Helicobacter pylori stool antigen test and the gastric mucosal antigen test.Zhonghua Yixue Zazhi 2000;80:820-822

48 Koletzko S, Feydt-Schmidt A. Infants differ from teenagers: use of non-invasive tests for detection of Helicobacter pylori infection in children.Eur J Gastroenterol Hepatol 2001;13:1047-1052