炎癥性腸病面臨的問題與挑戰(zhàn)

1、炎癥性腸病：面臨的問題與挑戰(zhàn),,Increasing cumulative number of ulcerative colitis and Crohn’s disease patients in Japan during a 17-year period according to the national registry maintained by the Ministry of Health, Labor and Welfare

2、of the Japanese government,Yao T, Matsui T, et al. Dis Colon Rectum 2000;,Age- and sex-adjusted annual incidence ofCD and UC in the Songpa-Kangdongdistrict, Seoul, 1986–2005.,Yang SK, et al. Inflamm Bowel Dis 2008,New

3、Cases （香港）,Leong Inflamm Bowel Dis 2004,,,,,,,,,,,,,,,,,,,,,,,,,,,,,0,5,10,15,20,25,30,35,<85,86-89,90-92,93-95,96-98,99-01,Year,New Cases,Ulcerative colitisn= 121,Crohn’s diseasen = 80,,,,,,,,,,,,,,,,Annual Incide

4、nce of IBD in Hong Kong,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,0,0.2,0.4,0.6,0.8,1,1.2,1.4,<85,86-89,90-92,93-95,96-98,99-01,Year,Annual Incidence per 105,Ulcerative colitis: 1.2 per 100,000,Crohn’s disease: 1 per 10

5、0,000,,UC (3100 cases),Time trend (data from 7 hospitals),Endoscopy,Hospitalized,Yr,Cases,Patients in 2003 : patients in 1990: Patients diagnosed by endoscopy – 4.09 : 1.00 Hospitalized patients – 3.36:1.00,中華消化雜

6、志 2006; 26(6):368,,,,,,10,8,6,4,2,1930,1940,1950,1960,1970,1980,,,,,,Year of Diagnosis,Comparing East & West,1990,2000,Incidence per 105,IBD — 我國面臨的問題與挑戰(zhàn),流行病學(xué)：近年病例數(shù)增長很快，但缺乏基于社區(qū)人口的流行病學(xué)研究，缺乏確切的患病率、發(fā)病率中國處于一個流行病學(xué)研究的黃金時

7、期 生活模式發(fā)生巨大變化：冰箱（冷鏈學(xué)說） 食物解構(gòu)：西方化,East versus West…,GeneticsGut FloraDietOther Environmental factors,遺傳易感性 中國（亞洲）與西方明顯不同：NOD2 易感基因的篩選：高通量基因篩選或全基因組掃描,IBD — 我國面臨的問題與挑戰(zhàn),Genetics in the WestHugot et al. Nature 1996O

8、gura et al. Nature 2001Van Limbergen et al. Gut 2007Mathew et al. Nature Rev 2008Parkes et al. Nat Gen 2007,Crohn’s DiseaseCARD 15 (NOD 2 mutation) – 20% caucasian & JewishIL-23 receptor (IL-23R) 2 - 4 fol

9、d for Crohn’s diseaseATG16L1 (1st autophagy gene) 1.3 - 2.0 fold Crohn’s diseaseIRGM (2nd autophagy gene) only Crohn’s diseaseIBD-5 locus5p13.1 IL12B,Genetics in the WestFranke et al. Nat Genet 2008Silverberg e

10、t al. Nat Genet 2009,Ulcerative Colitis1p36 (OR 0.77)12q15 (OR 1.35)IL-10IL-2,Genetics in the EastYang et al. Am J Gastro 2008Yamazaki et al. Hum Mol Gen 2005Myung et al. Int J Colorectal Dis 2002Yoshita

11、ke et al. Tissue Antigens 1999,No CARD 15 (NOD 2 mutation) in China, Hong Kong, Japan (also no IL23R, ATG16L1, 5p13.1)Korea, Israeli Arabs, Turkey, India,TNF-SF15 Crohn’s DiseaseHLA-DRB1*1502 allele Ulcerativ

12、e ColitisIn Korea and Japan,Instead...,Disease LocationChow et al. Inflamm Bowel Dis, in press Louis et al. Gut 2001,Phenotype,Stricturing,Inflammatory,Penetrating,Evolution of disease behavior as determined by t

13、he Montreal Classification over 10 years in Chinese patients with Crohn’s Disease.Chow et al. Inflamm Bowel Dis 2008,,(P = 0.025),(P = 0.005),,,Extra-intestinal manifestationsis uncommon,At least 1 EIM in 25% CD and

14、17% UC,CD與腸結(jié)核的鑒別—尚未解決的問題,腸結(jié)核與克羅恩病的鑒別(7ed內(nèi)科學(xué)),?,,,CD與TB的鑒別 TB依然常見 CD與TB臨床表現(xiàn)與內(nèi)鏡下表現(xiàn)相似 CD病人有時抗TB治療有效千萬不要忘記TB 仔細(xì)鑒別：PCR 應(yīng)用 有疑問時先抗結(jié)核 密切隨訪,IBD — 我國面臨的問題與挑戰(zhàn),Treatment,Chinese consensus on the diagnosis and management of

15、 inflammatory bowel disease 中華消化病學(xué)會 2007,Treatment of UC,Analysis of 3015 UC patients - Aminsalicylates: 66.8% - Corticosteroids: 26.2% - Immunopressants: 2.1% - Chinese medicine: 3.7%

16、- Adding/only topical treatment: 32.5% - Turn to operation: 3.1%,中華消化雜志 2006; 26(6):368,Treatment of UC,胡伏蓮: 中國新藥雜志 2001; 10(3):201,Efficacy and safety of mesalazine (Etiasa) Etiasa S

17、ASP p value N=52 n=34Symptom free(%) 57.7 50.0 >0.05Endoscopic healing 26.9 2.9 <0.05Side effect(%) 1.9 10.8

18、 <0.05* at week 6,,,,Treatment of UC,蔡建庭: 中華消化雜志 2001; 21(10):593,Efficacy and safety of Osalazine Osalazine SASP p value n=100

19、 n=30Marked effect(%) 39.0 13.3 >0.05Effect(%) 47.0 63.3No effect(%) 14.0 23.4 Adverse event(%) 20.0

20、 33.3 <0.05* at week 4,,,,Treatment of UC,劉占舉: 中華消化雜志 2007; 27(5):295,Efficacy and safety of Balsalazide Balsalazide SASP p value

21、 n=57 n=43Marked effect(%) 49.1 44.1 >0.05Effect(%) 35.1 32.6No effect(%) 15.8 23.3 Adver

22、se event(%) 8.8 30.2 <0.05* at week 8,,,,Treatment of CD,Analysis of 515 CD patients - Aminsalicylates: 57.67% - Corticosteroids: 28.74% - Immunopressants: 4.66% - Antibiotics: 4

23、5.63% - Chinese medicine: 14.25% - Surgical treatment: 33.2%,J Gastroenterol Hepatol 2006; 21:1009,治療 UC：5-ASA、皮質(zhì)激素、免疫調(diào)節(jié)劑療程、適應(yīng)癥、療效、副反應(yīng) CD： 生物制劑的應(yīng)用黏膜愈合作為新的療效標(biāo)準(zhǔn)？上階梯療法與下階梯療法 維持治療的方法？長期維持或過度到免疫抑制劑？ 長期治療的擔(dān)心：腫瘤發(fā)生率是否

24、升高？,IBD — 面臨的問題與挑戰(zhàn),中外有關(guān)IBD的共識意見,中國炎癥性腸病協(xié)作組. 對我國炎癥性腸病診斷治療規(guī)范的共識意見(2007)Carter M J，et al. Guidelines for the management of inflammatory bowel disease in adults. Gut,2004,53(9):V1-16(英國)Travis S P L, et al. European eviden

25、ce based consensus on the diagnosis and management of Crohn‘s disease: current management[J]. Gut,2006,55(suppe 1):i16-i35(歐洲)Lichtenstein G R, et al. American Gastroenterological Association Institute Medical Position

26、Statement on Corticosteroids, Immunomodulators,and Infliximab in Inflammatory Bowel Disease. Gastroenterol, 2006, 130(3):935-939；940-987(美國),最新的共識意見,Management of Crohn ’ s Disease in Adults Practice Parameters Committee