위장질환에 따른 H.pylori 감염빈도와 검사방법의 비교분석

김대현,조재현,금민수,최성곤,이창형,탁원형,권영오,김성국,최용환,정준모 慶北大學校 醫科大學 1997 慶北醫大誌 Vol.38 No.2

목적 : H. pylori가 위장관 질환의 병인에 깊은 관련이 있어 이의 적절한 진단 및 치료가 중요하게 대두되고 있다. 이에 저자들은 소화기 증상을 주소로 내원한 환자들을 대상으로 내시경 검사를 실시하여 H. pylori검출을 위한 CLO검사, IgG 항체검사 및 H&E 염색 등을 시행하여 각 질환별로 H. pylori 감염의 양성율을 알아보고 검사법에 따른 민감도 및 특이도를 그 유용성에 대하여 조사하였다. 대상 및 방법 : 1996 4월에서 8월까지 경북대학교병원에 소화기증상을 주소로 내원한 총 313명의 환자를 대상으로 내시경 검사를 실시하여 H. pylori 검출을 위한 CLO 검사, IgG 항체검사, 조직염색 검사를 실시하였다. 결과 : 전체 대상 환자수는 313명이었고 연령별 분포는 16세부터 80세 까지 다양하였으며 그중40대, 50대, 60대가 각각 69예(22%), 73예(23.3%), 65예(20.8%)로 전체 환자중 66%를 차지하였다. 남녀비는 2.07 대 1로 남자가 많았다. 대상환자의 평균나이는 52±15세였고, 전체 대상환자에서 H. pylori 양성군과 음성군의 평균나이는 각각 50±15세, 54±15세 였고, 궤양환자군에서 H. pylori 양성군과 음성군사이의 평균나이는 각각 49±14.8세, 55±13.8세로 나타났다. 각 질환별분포는 위염이 72명(23%), 십이지장 궤양이 85명(27.2%), 위궤양이 80명(25.6%), 위암이 20명(6.4%), 비궤양성 소화불량이 13명(4.2%), 기타가 43명(13.7%)이었으며, H. pylori 감염 양성율은 위염이 71%, 십이지장 궤양이 86.8%, 위궤양이 58.3%, 위암이 75%, 비궤양성 소화불량이 75%였으며 특히 유문륜 궤양에서는 100%의 양성율을 보였다. 소화성 궤양군과 비궤양군에서의 H. pylori 양성율을 비교해 본 결과 궤양군에서는 73.1%, 비궤양군에서는 72%로 통계학적으로 차이는 없었다(P=0.91). 소화성 궤양환자에서 출혈이 동반된 군과 동반되지 않은 군에서의 H. pylori 양성율을 비교해 본 결과 출혈이 동반된 군에서의 양성율은 54.5%였고, 출혈이 동반되지 않은 군에서는 77.5%의 양성율을 보여 출혈이동반되지 않은 군에서 통계학적으로 유의하게 높았다(P=0.014). 나이에 따른 양성율을 알아본 결과 50세 이하에서는 78.5%였고, 50세 이상에서는 67.5%로서 양성율이 낮았으나 통계학적으로 유의성은 없었다(P=0.052). 각 검사법에 따른 민감도 및 특이도는 전체 환자중에서는 CLO검사가 88.9%, 96.1%, IgG항체검사 90.8%, 58.5%, H&E 염색검사 86.9%, 79.2%로서 민감도는 비슷하게 나왔으나 CLO검사는 상대적으로 특이도가 다른 검사법에 비해 높았다. 궤양군에서의 CLO검사의 민감도와 특이도는 92.0%, 95.6%였고, 비궤양군에서의 민감도와 특이도는 84.3%, 96.8%로서 비궤양군에서는 CLO검사의 민감도는 약간 낮았다. 나이에 따른 CLO 검사의 민감도 및 특이도는 50세 이하에서는 91.5%, 93.1% 였고, 50세 이상에서는 86.3%, 97.9%로서 50세 이상에서는 상대적으로 CLO검사의 민감도가 낮았다. 결론 : 본 연구에서는 위장질환에 따른 H. pylori 양성율을 알아보았는데, 다른 보고에서 처럼 높게 나왔으며, 진단 방법으로 사용한 CLO검사, IgG항체 검사, 조직염색검사 등은 모두 비교적 높은 예민도를 나타냈고, 그중 CLO검사가 간편하고 경제적이라는 면에서 임상적으로 유용한 검사로 여겨지나 상대적으로 CLO검사의 민감도가 낮은 비궤양성 질환과 50세 이상의 환자군에서는 CLO검사 외에 다른 검사방법을 병행함으로써 H. pylori의 진단율을 높일 수 있을 것으로 사료된다. Background: Gastric colonization by Helicobacter. pylori is common among patients with peptic ulcer and gastritis. And various diagnostic tests are available in confirming H. pylori infection. The aim of this paper is to estimate the prevalence of H. pylori infection in Gastroduodenal disorders and compare the sensitivity and specificity of the most widely available tests. Methods: A total of 313 patients were tested for H. pylori infection by IgG Ab, CLO test and H&E stains. Results: The prevalence of H. pylori infection was significantly higher in duodenal ulcer(86.8%) than in gastric cancer(75%), gastritis(71%) and gastric ulcer(58.3%)(P=0.009). The sensitivity and specificity of each test was as follows: CLO test(88.9%, 96.1%), IgG Ab test(90.8%, 58.5%), H&E stain(86.9%, 79.2%). Sensitivity of CLO test in peptic group was 92.0%, whereas in non-peptic group, it was 86.3%. Sensitivity of CLO test in age under 50 was 91.5%, that over 50 it was 86.3%. Conculsions: There is a strong association between H. pylori and gastrointestinal disorders. CLO tests have relatively high sensitivity and specificity, especially in peptic group and younger age(below 50 yr)group. But in those patients in which CLO tests are less sensitive (age>50 or non-peptic group), more than one test may be necessary to diagnose the presence of the organism.

한국에서 분리된 Helicobacter pylori 균주에서의 병리 인자 분포 및 이에 대한 숙주 방어 기전의 분자생물학적 연구

김정목(Jung Mogg Kim),정현채(Hyun Chae Jung),이주영(Joo Young Lee),이경미(Kyung Mee Lee),진영주(Young Joo Chin),김영전(Young Jeon Kim),송인성(In Sung Song),김정룡(Chung Yong Kim) 대한내과학회 1998 대한내과학회지 Vol.54 No.1

Objectives: CagA or cytotoxin-positive H. pylori may be associated with gastroduodenal diseases. However, controversies about this association also exist. Moreover, there could be geographic differences in the prevalence of virulence factors such as cagA or cytotoxin. In H. pylori infection, the gastric mucosa shows acute and chronic inflammation. However, the pathogenesis of such as an inflammation by H. pylori is not well elucidated. We performed this study 1) to determine prevalence of the genes of virulence factor such as cagA and cytotoxin in H. pylori, 2) to assess the correlation of their presence with clinical findings, and 3) to test whether the vacuolating cytotoxin of H. pylori could evoke proinflammatory cytokine gene expression in gastric epithelial cells. Methods: 1) The prevalence of the cagA, vacA and adhesin genes in H. pylori strains isolated from Koreans was determined by PCR analysis. 2) H. pylori was cultured in Brucella broth containing 10% fetal bovine serum for 3 days using a shaker in a microaerophilic condition. Cytotoxin assay was performed by determining whether addition of the concentrated culture supernatants is able to cause vacuolization of HeLa cells. 3) After human gastric epithelial cells, Hs746T and AGS were incubated with the culture supernatants containing vacuolating cytotoxin, each RNAs were extracted from the gastric epithelial cells. And then various cytokine gene expression were assessed using RT-PCR. The expressed cytokine transcripts were quantified by RT-PCR and standard synthetic RNA. Among cytokines, IL-8 proteins were also measured by ELISA. Results: 1) More than 95% of H. pylori isolates from Korean adults possessed cagA, vacA and adhesin genes. And 80.6% of H. pylori strains have expressed vacuolating cytotoxicity against HeLa cells within 24 hours. 2) There was no correlation between the virulence factors of H. pylori strains and clinical findings. 3) Cytotoxin-positive culture supernatants also caused vacuolization in gastric epithelial cells, both Hs746T and AGS. 4) Expression of mRNA for proinflammatory cytokines such as IL-1 α, IL-8, MCP-1 and GM-CSF was much more upregulated by vacuolating cytotoxin-positive culture supernatants than cytotoxin-negative ones in both Hs746T and AGS cells. Number of molecules of the expressed IL-8 transcripts was parallel to the amounts of IL-8 protein secreted from gastric epithelial cells. Conclusion : These results suggest that virulence factors of H. pylori may not be factors determining disease entitiy in Korean patients infected with H. pylori. In addition, vacuolating cytotoxin secreted from H. pylori could give rise to vacuolization in gastric epithelial cells as well as induce proinflammatory cytokines from the cells.

Helicobacter pylori의 병독성 유전자 및 운동성이 인체 위점막 염증 반응의 병태 생리에 미치는 영향 (I) - 병독 인자 보유 유무에 따른 친염증성 cytokine의 발현능

정현채,김정목,진영주,이경미,김우호,송인성,김정룡 大韓消化器病學會 1997 大韓消化器病學會誌 Vol.29 No.5

상부위장관질환 환자에서 H . pylori 감염에 의한 위점막의 조직학적 변화와 혈청 Gastrin 및 혈청 IgG항체가의 상관관계

손호상(Ho Sang Shon),최정윤(Jung Yoon Choe),김지희(Chi Hui Kim),김태석(Tae Sug Kim),김채기(Chae Gi Kim),김이근(Ih Geun Kim),안기성(Ki Sung Ahn),김호각(Ho Gak Kim),오훈규(Hoon Kyu Oh),김용진(Yong Jin Kim),배정동(Jung Dong Bae) 대한소화기학회 1996 대한소화기학회지 Vol.28 No.3

Background/Aims: This study was performed to investigate the relationship between Helicobacter pylori infection and degree of gastric mucosal inflammation, IgG antibody titer against H. pylori, and fasting serum gastrin level. Methods: Patients were divided into 2 groups(H. pylori positive and negative) by identification of H. pylori in biopsied specimens with special staining. In H. pylori positive group, the density of gastric K. pylori colonization was further graded semiquantitatively from 1 to 3. The severity of gastritis in each group was scored according to the Sydney system from 0 to 3. Serum IgG antibody titer against H. pylori was detected by second-generation antigen based enzyme immunoassay(Cobas Core Anti-Helicobacter pylori EIA). Fasting serum gastrin level was measured by standard radioimmunoassay technique. Results: The severity of gastritis in H. pylori positive group was significantly higher than H. pylori negative group in mononuclear cell infiltration(pC0.001), activity of PMNL(pC0.001), and glandular atrophy(pC0.01). In H. pylori positive group, the density of H. pylori colonization was significantly correlated with mononuclear cell infiltration(r=0.67, p0.001), activity of PMNL(r=0.70, p0.001), and grandular atrophy (r=0.38, pC0.001). Neither density of H. pylori colonization nor severity of gastritis was correlated with fasting gastrin level and IgG antibody titer against H. pylori. Conclusions: H. pylori infection results in localized inflammatory reaction in gastric mucosa with relation to density of H. pylori colonization, but serum H. pylori IgG antibody titer does not reflect the severity of gastritis. Fasting serum gastrin level also has no relation with the density of H. pylori colonization and severity of gastritis. These findings suggest that the factor which cause inflammation in gastric mucosa may be different from that cause gastrin secretion or formation of IgG antibody. (Korean J Gastroenterol 1996; 28:311 - 319)

소아 H. pylori 감염 박멸후 재감염에 관한 연구

고재성,최연호,서정기 大韓消化器病學會 1997 大韓消化器病學會誌 Vol.30 No.5

위점막 조직에서 Helicobacter pylori 감염과 PCNA 발현 및 림프여포의 형성과의 관계

이옥재,최종상,이대일 大韓消化器病學會 1997 大韓消化器病學會誌 Vol.29 No.1

소화효소가 Helicobacter pylori의 증식과 공포화독소 생성에 미치는 영향

홍대식,강경희,장명웅 고신대학교(의대) 고신대학교 의과대학 학술지 2001 고신대학교 의과대학 학술지 Vol.16 No.1

Background : Global high prevalence rate of Helicobacter pylori infection is well-known fact. However, a large discrepancies exist between the diagnostic data obtained by the PCR and culture method, because the coccoid form of H.pylori which represent the majority form in the biological samples are not viable in the standard BHI broth with 5% horse serum. The component parts of saliva and gastric juice acted as neither stimulator nor inhibitor to the growth of H.pylori remain unclear. Objective : The purpose of this study was to evaluate the influence of amylase, pepsin, mucin, and lysozyme on the growth and vacuolating toxin production and titer of H.pylori in vitro. Materials and Methods : H.pylori 13,39,46,59,72,94,98 and 125 strains were isolated from patients with gastric disease. The digestive enzymes were inoculated in the 5% horse serum-BHI broth following final concentration of amylase (A; 0.20ug/ml), pepsin (P; 0.25ug/ml), mucin (M; 2,5ug/ml), and lysozyme (L; 1.5ug/ml). The vacuolating toxin titers of the culture supernatant were evaluated in the monolayer culture of RK-13 cells. Results : The morphologic conversion from bacillary to horse-shoe to coccoid forms of H.pylori was observed in the BHI broth containing 5% horse serum on day 5 culture. Half of H.pylori was changed from bacillary to coccoidal form on day 7 culture, most population of H.pylori was changed to coccoidal form on day 10 culture, and almost all H.pylori was changed to coccoidal form on day 14 culture. The growth of H.pylori 72, and 94 strains was increased in BHI broth containing each enzyme such as amylase, pepsin, mucin and mixture of two or three enzymes on day 5 and 7 culture. The growth of H.pylori 94 strains was increased in BHI broth containing each enzyme such as amylase, pepsin, mucin, and mixture of two or three enzymes on day 10 and 14 culture. The vacuolating toxin production of H.pylori strains was not influenced by the addition of amylase, pepsin, mucin, and lysozye or mixture of two or three enzymes. The neutralization of vacuolating toxin of H.pylori was not affected by the addition of amylase, pepsin, mucin, and lysozyme or mixture of two or three enzymes. Conclusion : We found that coccoid forms of H.pylori were viable in the standard 5% horse serum BHI media in the presence of amylase, pepsin, mucin, and lysozyme. The present study demonstrates that gastric juice of the stomach supports the viability of H.pylori and that oral route of infection is a plausible hypothesis. This work also demonstrates that gastric environment may not provide a selective advantage for the toxigenic strains of H.pylori.

소화효소가 Helicobater pylori의 증식과 공포화독소 생성에 미치는 영향

홍대식,강경희,장명웅 고신대학교 의학부 2001 高神大學校 醫學部 論文集 Vol.16 No.1

Background Global high prevalence rate of Helicobacter pylori infection is well-known fact. However, a large discrepancies exist between the diagnostic data obtained by the PCR and culture method, because the coccoid form of H. pylori which represent the majority form in the biological samples are not viable in the standard BHI broth with 5% horse serum. The component parts of saliva and gastric juice acted as neither stimulator nor inhibitor to the growth of H. pylori remain unclear. Objective The purpose of this study was to evaluate the influence of amylase. pepsin, mucin, and lysozyme on the growth and vacuolating toxin production and titer of H. pylori in vitro. Materials and Methods H pylori 13, 39, 46, 59, 72, 94, 98, and 125 strains were isolated from patients with gastric diseases. The digestive enzymes were inoculated in the 5% horse serum-BHI broth following final concentration of amylase (A: 0.25㎍/㎖), pepsin(P: 0.25㎍/㎖), mucin(M: 2.5㎍/㎖), and lysozyme(L: 1.5㎍/㎖). The vacuo-lating toxin titers of the culture supernatant were evaluated in the monolayer culture of RK-13 cells. Results The morphologic conversion from bacillary to horse-shoe to coccoid forms of H pylori was observed in the BHI broth containing 5% horse serum on day 5 culture. Half of H. pylori was evaluated from bacillary to coccoidal form on day 7 culture, most population of H. pylori was changed to coccoidal form on day 10 culture, and almost all H. pylori was changed to coccoidal form on day 14 culture. The growth of H. pylori 72, and 94 strains was increased in BHI broth containing each enzyme such as amylase, pepsin, mucin and mixture of two or three enzymes on day 5 and 7 culture. The growth of H. pylori 94 stains was increased in BHI broth containing each enzyme such as amylase, pepsin, mucin, and mixture of two or three enzymes on day 10 and 14 culture. The vacuolating toxin production of H. pylori strains was not influenced by the addition of amylase, pepsin, mucin and lysozyme or mixture of two or three enzymes. The neutralization of vacuolating toxin of H. pylori was not affected by the addition of amylase, pepsin mucin and lysozyme or mixture of two or three enzymes. Conclusion We found that coccoid forms of H. pylori were viable in the standard 5% horse serum BHI media in the presence of amylase, pepsin, mucin, and lysozyme. The present study demonstrates that gastric juice of the stomach supports the viability of H. pylori and that oral route of infection is a plausible hypothesis. This work also demonstrates that gastric environment may not provide a selective advantage for the toxigenic strains of H pylori.

Helicobacter pylori 제균치료-1주치료로 충분한가?

양창헌 東國大學校醫學硏究所 2004 東國醫學 Vol.11 No.1

Warren과 Marshall이 1982년 위 생검 조직을 배양, 만성 위염의 원인균으로 Helicobacter pylori(H. pylori)를 동정한 이후 H. pylori는 만성 활동성 위염, 십이지장 궤양, 위 궤양, 위 림프종 및 위암의 발생에 중요한 역할을 하는 것으로 알려져 있다. H. pylori는 한번 인체 위장에 감염이 되면 수년 또는 평생 동안 감염이 지속될 수 있으며 자연 치유되는 경우는 드문 것으로 알려져 있다. 특히 한국은 위암 발병률과 사망률이 전 세계적으로 상당히 높은 편이며, H. pylori 감염률이 성인의 경우 69%~75%로 역시 전 세계적으로 상당히 높은 편이다. H. pylori 감염의 치료방법으로 과거에는 bismuth 제제 포함 병합요법이 이용되었으나 근래에는 프로톤 펌프 억제제(proton pump inhibitor, PPI)와 두 가지 항생제를 병용하는 삼제 병합요법이 H. pylori 감염의 1차 치료로 추천되고 있다. H. pylori의 제균치료 시 가장 기본적인 목표는 성공적인 박멸에 있다. PPI 포함 3제요법은 부작용이 적고 순응도가 좋으면서 제균율도 높기 때문에 1차 약제로 선호되고 있으나 한국의 경우 최근 PPI 포함 삼제요법의 1주일 치료성적의 다수가 60~70%로 낮은 편이며 7일 투여에 비하여 14일 투여의 제균율이 의미있게 높다는 국내외의 메타분석결과와 최근 항생제에 대한 내성균주 증가로 인한 제균율 감소를 고려하여 새로운 약제와 투여방법 및 기간에 대한 연구뿐만이 아니라 제균율을 높이기 위하여 probiotics, 동반 치료약물 및 항생제내성 등을 극복하기 위한 연구가 필요한 실정이다. 따라서 우리나라에서도 치료기간의 연장, 새로운 가이드라인 등의 제정이 필요한 시점이라고 생각되어 진다. Ever since Warren and Marshall discovered H. pylori to be the cause of chronic gastritis by culture of gastric biopsy in 1982, H. pylori has also been discovered to play an important role in the development of chronic active gastritis, duodenal ulcer, gastric ulcer, gastric lymphoma and gastric cancer. Once the gastric mucosa is infected with H. pylori, the infection may persist for years or lifelong and spontaneous resolution is rare. In South Korea, not only is there a relatively high prevalence and mortality rate of gastric cancer, but there is also a high colonization rate of H. pylori in adults, 65-75%, compared worldwide. In the past, H. pylon infection was treated with a combination drug regimen including a bismuth agent, but recently triple combination regimens including a proton pump inhibitor (PPI) and two antimicrobial agents are recommended as first line therapy. The most basic aim in the treatment of H. pylori is successful eradication. A triple drug regimen including a PPI is preferred as first-line therapy due to it's few side effects, good compliance and high eradication rate. Considering the relatively poor success rate of 60-70% with a PPI including triple therapy for 7 days in South Korea, meta-analysis reports of a significantly higher eradication rate with 14-day therapy compared to 7-day therapy, and the recent decrease in eradication rates due to the increase in antibiotic resistance, not only is more research needed on new drugs, treatment methods and durations but also on additional therapeutic measures, such as probiotics, that may increase eradication rates and conquer antibiotic resistance. Also it seem to be the time to establish a new guideline in the treatment of H. pylori in South Korea.

십이지장궤양 환자에서 혈액형 및 흡연과 Helicobacter pylori 감염과의 상관 관계

김명식,이돈행,김범수,최원,장재남,권계숙,조현근,신용문,김영수 大韓消化器病學會 1998 大韓消化器病學會誌 Vol.32 No.6