今日の臨床サポート

ヘリコバクター・ピロリ感染症

著者: 塩田星児1) 大分大学医学部附属病院 総合内科・総合診療科

著者: 村上和成2) 大分大学医学部附属病院 消化器内科

監修: 上村直実 国立国際医療研究センター 国府台病院

著者校正/監修レビュー済:2021/10/27
参考ガイドライン:
  1. 日本ヘリコバクター学会H. pylori感染の診断と治療のガイドライン2016改訂版
  1. 日本消化器病学会:消化性潰瘍診療ガイドライン2020 改訂第3版
患者向け説明資料

概要・推奨   

  1. ピロリ菌感染症には除菌治療が勧められる(推奨度1)。
  1. 胃潰瘍・十二指腸潰瘍は、たとえ瘢痕期であっても除菌治療が勧められる(推奨度1)。
  1. 早期胃癌に対して内視鏡的治療を行った場合も除菌治療が勧められる(推奨度1)。
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要とな
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧に
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要と
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧に
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
塩田星児 : 特に申告事項無し[2021年]
村上和成 : 特に申告事項無し[2021年]
監修:上村直実 : 未申告[2021年]

改訂のポイント:
  1. 定期レビューを行った。
  1. 2021年5月に日本ヘリコバクター学会から発表された「血清抗体法を用いたヘリコバクター・ピロリ(ピロリ菌)感染診断に関する注意喚起」について記載した。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. ヘリコバクター・ピロリ(以下、ピロリ菌)は1982年オーストラリアのWarrenとMarshallによって分離され、その後消化性潰瘍との関連が証明された。
  1. ピロリ菌感染によってもたらされる萎縮性胃炎は胃癌の発生母地であることが明らかになり、1994年WHOの下部組織であるIARCにより胃癌の第一級の発癌因子であることが認定され、世界各国で除菌治療が行われるようになった。2014年にはIARCが胃癌予防としてピロリ菌除菌による対策を推奨した。
  1. わが国では2000年に日本ヘリコバクター学会から「H. pylori感染の診断と治療ガイドライン」が発表され、03年、09年、さらには2016年に改訂(以下、2016改訂版ガイドライン)された。また、胃潰瘍ガイドラインの適用と評価に関する研究班から07年に「EBMに基づく胃潰瘍診療ガイドライン」が、日本消化器病学会から09年に「消化性潰瘍診療ガイドライン」が発表され、ピロリ菌除菌治療についても記載されている。2015年、2020年には改訂版も発表された。
  1. 除菌治療の保険適用疾患が、胃潰瘍・十二指腸潰瘍のみから、2010年より胃MALTリンパ腫、免疫性(特発性)血小板減少性紫斑病(ITP)、早期胃癌に対する内視鏡的治療後が追加となった。
  1. さらに2013年2月には「ヘリコバクター・ピロリ感染胃炎」に対する除菌治療が保険適用となった。
  1. 現在、ピロリ菌除菌治療は一般臨床の場でも行われるようになってきたが、その一方でいくつかの問題点も指摘されている。
  1. 2018年に日本小児栄養消化器肝臓学会から、「小児期ヘリコバクター・ピロリ感染症の診療と管理ガイドライン2018(改訂2版)」が発表されているが、日本ヘリコバクター学会から提唱されている方針と異なる箇所があるためここでは言及していない。ただし、小児に対する診断や治療の際には一読することをお勧めする。
 
  1. 萎縮性胃炎に対する除菌により胃粘膜の萎縮が改善し、胃癌の発生抑制が期待できることから、除菌治療が勧められる(推奨度1)。
  1. まとめ:ピロリ菌除菌により組織学的胃炎が改善することは明らかであるが、組織学的胃粘膜の萎縮も改善する。腸上皮化生については結論が出ていない。
  1. 代表事例:わが国における大規模ランダム化臨床試験[1]では組織学的な萎縮スコアの改善を認め、メタ解析[2][3]でも胃粘膜の萎縮が除菌により改善されることが明らかとなっている。一方腸上皮化生についてはメタ解析では「除菌により腸上皮化生の改善傾向はあるものの、統計学的な有意な改善ではない」であった[2][3]。またわが国で10年間調査した研究では、除菌により胃体部大弯は半年後から、胃前庭部大弯、胃角部小弯、胃体部小弯は1年後から、胃前庭部小弯は6年後から、萎縮は有意に改善した[4]
  1. 結論:ピロリ菌除菌により組織学的胃粘膜の萎縮が改善する。
  1. 追記:2013年2月には「ヘリコバクター・ピロリ感染胃炎」に対する除菌治療が保険適用として追加され、その診断には内視鏡検査が必須とされている。
問診・診察のポイント  
  1. ピロリ菌の感染率は年齢ともに上昇する。日本においては第2次世界大戦後に生まれたものでは感染率が低く、以前に生まれたもので感染率が高い。ピロリ菌の感染経路はいまだ明らかとなっていないが、衛生状況、ならびに家族間での感染が最も考えられている。したがって、家族にピロリ菌感染者がいたことや、消化性潰瘍、胃癌の家族歴があることはピロリ菌感染を疑わせるものとなる。

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文献 

著者: Theodoros Rokkas, Dimitios Pistiolas, Panos Sechopoulos, Ioannis Robotis, Georgios Margantinis
雑誌名: Helicobacter. 2007 Nov;12 Suppl 2:32-8. doi: 10.1111/j.1523-5378.2007.00563.x.
Abstract/Text BACKGROUND: Helicobacter pylori infection is a crucial factor in the multistep carcinogenic process of gastric cancer. In this process the gastric mucosa evolves through the stages of acute gastritis, chronic gastritis, gastric atrophy (GA), and intestinal metaplasia (IM) before developing gastric adenocarcinoma.
AIMS: The main aim of this study was to systematically review the long-term effects of H. pylori eradication on gastric histology (i.e. effects on GA and IM for both antrum and corpus) by meta-analyzing all relevant studies.
METHODS: Extensive English-language medical literature searches for human studies were performed through October 2006, using suitable key words. Pooled estimates [odds ratio (OR) with 95% confidence intervals (CI)] were obtained using random-effects model.
RESULTS: For antrum GA the pooled OR with 95% CI was 0.554 (0.372-0.825), p=0.004. For corpus GA the pooled OR was 0.209 (0.081-0.538), p<0.001. For antrum IM the pooled OR was 0.795 (0.587-1.078), p=0.14. For corpus IM the pooled OR was 0.891 (0.663-1.253), p=0.506.
CONCLUSION: The results showed significant improvement of GA, whereas improvement was not shown for IM.

PMID 17991174  Helicobacter. 2007 Nov;12 Suppl 2:32-8. doi: 10.1111/j.・・・
著者: Jin Wang, Lijuan Xu, Ruihua Shi, Xiayue Huang, Simon Wing Heng Li, Zuhu Huang, Guoxin Zhang
雑誌名: Digestion. 2011;83(4):253-60. doi: 10.1159/000280318. Epub 2011 Feb 1.
Abstract/Text OBJECTIVE: Whether gastric atrophy (GA) and intestinal metaplasia (IM) are reversible after the eradication of Helicobacter pylori remains controversial. The purpose of this meta-analysis was to systematically review histological alterations in GA and IM by comparing histological scores before and after H. pylori eradication.
METHODS: English-language articles in the medical literature containing information about the association between infection with H. pylori and gastric premalignant lesions (i.e. GA and IM) were identified by searching the Medline, PubMed, and EMBASE databases with suitable key words up to December 2009. Review Manager 4.2.8 was used for the meta-analysis.
RESULTS: Twelve studies containing a total of 2,658 patients were included in the first meta-analysis. Before treatment, 2,648 patients had antrum GA, 2,401 patients had corpus GA, 2,582 patients had antrum IM, and 2,460 patients had corpus IM. Comparing the histological alterations before and after H. pylori eradication, the pooled weighted mean difference (WMD) with 95% CI for antral GA was 0.12 (0.00-0.23), p = 0.06. For corpus GA, the pooled WMD was 0.32 (0.09-0.54), p = 0.006. For antral IM, the pooled WMD was 0.02 (-0.12-0.16), p = 0.76, and for corpus IM, the pooled WMD was -0.02 (-0.05-0.02), p = 0.42.
CONCLUSION: Our study shows that eradication of H. pylori results in significant improvement in GA in the corpus but not in the antrum; it also does not improve gastric mucous IM. Consequently, all patients with GA in the corpus should be tested for H. pylori infection, and eradication therapy should be prescribed for H. pylori-positive patients in those with GA in corpus.

Copyright © 2011 S. Karger AG, Basel.
PMID 21282951  Digestion. 2011;83(4):253-60. doi: 10.1159/000280318. E・・・
著者: Masaaki Kodama, Kazunari Murakami, Tadayoshi Okimoto, Ryugo Sato, Masahiro Uchida, Takashi Abe, Seiji Shiota, Yoshifumi Nakagawa, Kazuhiro Mizukami, Toshio Fujioka
雑誌名: J Gastroenterol. 2012 Apr;47(4):394-403. doi: 10.1007/s00535-011-0504-9. Epub 2011 Dec 6.
Abstract/Text BACKGROUND: Atrophic gastritis and intestinal metaplasia (IM) are well known as precancerous lesions of gastric cancer. The present study evaluated the gastric mucosa for 10 years after H. pylori eradication at five points of the stomach as recommended by the updated Sydney system to clarify the relationship between H. pylori eradication and gastric cancer prevention.
METHODS: Among the comprised 373 patients, 323 were H. pylori-positive while 50 patients were H. pylori-negative. Patients with successful eradication underwent follow-up endoscopic examination every year. Biopsy specimens were taken from five points of the stomach, as recommended by the updated Sydney system, and were evaluated for the degree of gastritis prospectively.
RESULTS: Two hundred ninety-four out of the 323 H. pylori-positive patients successfully achieved eradication. Of the 197 patients on whom five-point biopsy was performed, the courses of 30 patients were able to be observed every year for 10 years after successful eradication. Inflammation, activity, and atrophy score at all five points were significantly reduced half a year to 6 years after eradication. IM scores fluctuated intensely up and down during all observation periods; however, IM score of the lesser curvature of the corpus continued decreasing gradually and showed a significant decrease 6 years after (0.97 ± 0.09 to 0.42 ± 0.17, P < 0.05).
CONCLUSION: In 10 years after H. pylori eradication, atrophy at all sites and IM in the lesser curvature of the corpus gradually and significantly decreased. These results suggest that the improvement of gastric atrophy and IM might have association with the reduction of gastric cancer occurrence.

PMID 22138891  J Gastroenterol. 2012 Apr;47(4):394-403. doi: 10.1007/s・・・
著者: Kazunari Murakami, Tomoari Kamada, Hiroki Ishikawa, Hiroshi Imamura, Hiroshi Matsumoto, Minoru Fujita, Ken-Ichi Tarumi, Akiko Shiotani, Kazuhiro Mizukami, Seiji Shiota, Tadayoshi Okimoto, Masaaki Kodama, Ayako Akiyoshi, Tetsuya Oda, Atsunari Noda, Jiro Hata, Ken Haruma, Toshio Fujioka
雑誌名: Clin Lab. 2011;57(7-8):481-7.
Abstract/Text BACKGROUND: ODK-0702 is a stick-type urinary Helicobacter pylori (H. pylori) antibodies detection kit, developed to improve the original housing type urinary H. pylori antibodies detection kit "RAPIRUN H. pylori Antibody". This stick-type kit is designed for the efficient daily medical practice at hospital or clinic, public or school health checkup, to detect H. pylori infection. The aim of this study was to evaluate the performance and correlation of this kit with the original kit and the ELISA kit.
METHODS: Control kits were "RAPIRUN H. pylori Antibody" (Kit A) and "URINELISA H. pylori Antibody" (Kit B). Urine samples were obtained from 249 subjects scheduled for upper endoscopy, 99 subjects suspected of having upper gastrointestinal disease, and 150 subjects receiving health checkups. Rates of agreement in results between ODK-0702 and the control kits were investigated.
RESULTS: High agreement rates of 98.4% (245/249) and 88.8% (221/249) were found between ODK-0702 and the kits, Kit A and B, respectively. In patients, the agreement rates of ODK-0702 as compared to Kit A and B were 99.0% (98/99) and 88.9% (88/99), respectively. In control subjects, the agreement rates of ODK-0702 as compared to Kit A and B were 98.0% (147/150) and 88.7% (133/150), respectively.
CONCLUSIONS: ODK-0702 enabled rapid testing within 15 minutes and showed equivalent performance as control kits, being clinically very useful in the diagnosis of H. pylori infection.

PMID 21888011  Clin Lab. 2011;57(7-8):481-7.
著者: Masaaki Kodama, Kazunari Murakami, Tadayoshi Okimoto, Yoshihiro Fukuda, Tadashi Shimoyama, Masumi Okuda, Chieko Kato, Intetsu Kobayashi, Toshio Fujioka
雑誌名: World J Gastroenterol. 2012 Jan 7;18(1):44-8. doi: 10.3748/wjg.v18.i1.44.
Abstract/Text AIM: To investigate the effects of proton pump inhibitor (PPI) treatment on stool antigen test using the TestMate pylori enzyme immunoassay.
METHODS: This study assessed 28 patients [16 men and 12 women; mean age (63.1 ± 5.9) years; range, 25-84 years] who underwent stool antigen test and urea breath test (UBT) before and after PPI administration.
RESULTS: Using the UBT as the standard, the sensitivity, specificity and agreement of the stool antigen test in all 28 patients were 95.2%, 71.4%, and 89.3%, respectively, before PPI administration, and 88.9%, 90.9%, and 89.3%, respectively, after PPI treatment. Mean UBT values were 23.98% ± 5.33% before and 16.19% ± 4.75% after PPI treatment and, in 15 patients treated for ≥ 4 wk, were significantly lower after than before 4 wk of PPI treatment (12.58% ± 4.49% vs 24.53% ± 8.53%, P = 0.048). The mean optical density (A(450/630)) ratios on the stool antigen test were 1.16 ± 0.20 before and 1.17 ± 0.24 after PPI treatment (P = 0.989), and were 1.02 ± 0.26 and 0.69 ± 0.28, respectively, in the group treated for > 4 wk (P = 0.099).
CONCLUSION: The stool antigen test was equally sensitive to the UBT, making it a useful and reliable diagnostic method, even during PPI administration.

PMID 22228969  World J Gastroenterol. 2012 Jan 7;18(1):44-8. doi: 10.3・・・
著者: Kentaro Sugano
雑誌名: Gastric Cancer. 2019 May;22(3):435-445. doi: 10.1007/s10120-018-0876-0. Epub 2018 Sep 11.
Abstract/Text BACKGROUND: Helicobacter pylori (H. pylori) is considered to be the most important risk factor for gastric cancer (GC). The International Agency for Research on Cancer reported that H. pylori eradication could reduce the risk of developing GC. Several clinical studies have investigated this relationship as well; however, their results are inconsistent owing to the varied inclusion criteria. To address the effect of H. pylori eradication on GC incidence, we conducted a comprehensive meta-analysis with several subgroup analyses to resolve these inconsistencies.
METHODS: We searched MEDLINE and Ichushi-Web to identify randomized control trial and cohort study articles (English or Japanese) through December 2016. Manual searches were also conducted to identify unlisted references in these databases. Eligible studies reported GC incidence as an outcome, with comparisons between H. pylori eradication and control groups. Subgroup analyses were conducted by country, conditions at baseline, and follow-up periods.
RESULTS: We selected 28 studies among 1583 references in the databases and 4 studies by manual searches. The H. pylori eradication group showed significantly lower risk of GC [odds ratio (OR) 0.46; 95% confidence interval 0.39-0.55]. The subgroup analyses indicated that the beneficial effect of eradication was greater in Japan (OR 0.39; 95% CI 0.31-0.49), particularly among those with benign conditions (OR 0.32; 95% CI 0.19-0.54), although none of them was statistically significant. However, reduction of gastric cancer after eradication was significantly greater (p = 0.01) in the groups with long-term (5 years or longer) follow-up (OR 0.32; 95% CI 0.24-0.43) as compared to those with shorter follow-up (less than 5 years) (OR 0.55; 95% CI 0.41-0.72).
CONCLUSION: Real world data showed that large-scale eradication therapy has been performed mostly for benign conditions in Japan. Since eradication effects in preventing gastric cancer are conceivably greater there, GC incidence may decline faster in Japan than expected from the previous meta-analyses data which were based on multi-national, mixed populations with differing screening quality and disease progression.

PMID 30206731  Gastric Cancer. 2019 May;22(3):435-445. doi: 10.1007/s1・・・
著者: Masahiro Asaka, Mototsugu Kato, Shin-ichi Takahashi, Yoshihiro Fukuda, Toshiro Sugiyama, Hiroyoshi Ota, Naomi Uemura, Kazunari Murakami, Kiichi Satoh, Kentaro Sugano, Japanese Society for Helicobacter Research
雑誌名: Helicobacter. 2010 Feb;15(1):1-20. doi: 10.1111/j.1523-5378.2009.00738.x.
Abstract/Text BACKGROUND: Over the past few years, the profile of Helicobacter pylori infection has changed in Japan. In particular, the relationship between H. pylori and gastric cancer has been demonstrated more clearly. Accordingly, the committee of the Japanese Society for Helicobacter Research has revised the guidelines for diagnosis and treatment of H. pylori infection in Japan.
MATERIALS AND METHODS: Four meetings of guidelines preparation committee were held from July 2007 to December 2008. In the new guidelines, recommendations for treatment have been classified into five grades according to the Minds Recommendation Grades, while the level of evidence has been classified into six grades. The Japanese national health insurance system was not taken into consideration when preparing these guidelines.
RESULTS: Helicobacter pylori eradication therapy achieved a Grade A recommendation, being useful for the treatment of gastric or duodenal ulcer, for the treatment and prevention of H. pylori-associated diseases such as gastric cancer, and for inhibiting the spread of H. pylori infection. Levels of evidence were determined for each disease associated with H. pylori infection. For the diagnosis of H. pylori infection, measurement of H. pylori antigen in the feces was added to the tests not requiring biopsy. One week of proton-pump inhibitor-based triple therapy (including amoxicillin and metronidazole) was recommended as second-line therapy after failure of first-line eradication therapy.
CONCLUSION: The revised Japanese guidelines for H. pylori are based on scientific evidence and avoid the administrative restraints that applied to earlier versions.

PMID 20302585  Helicobacter. 2010 Feb;15(1):1-20. doi: 10.1111/j.1523-・・・
著者: Masahiro Asaka, Mototsugu Kato, Toshiro Sugiyama, Kiichi Satoh, Hajime Kuwayama, Yoshihiro Fukuda, Toshio Fujioka, Tadayoshi Takemoto, Ken Kimura, Takashi Shimoyama, Kihachirou Shimizu, Shinichi Kobayashi, Japan Helicobacter pylori Eradication Study Group
雑誌名: J Gastroenterol. 2003;38(4):339-47. doi: 10.1007/s005350300061.
Abstract/Text BACKGROUND: To evaluate histopathological changes and effects on inhibition of ulcer recurrence, a follow-up survey was performed in Japanese patients with Helicobacter pylori-positive active peptic ulcers. These patients had previously participated in a large-scale multicenter trial of triple therapy with lansoprazole (LPZ)/amoxicillin (AMPC)/clarithromycin (CAM) for eradication of H. pylori.
METHODS: Patients who had been treated with LPZ only or a combination of LPZ, AMPC, and CAM for a period of 7 days and in whom ulcer healing had been confirmed after treatment were grouped according to successful or failed eradication of H. pylori. They were examined endoscopically to determine whether ulcers had recurred. The updated Sydney system was applied to study histological changes after H. pylori eradication therapy, compared with baseline.
RESULTS: Twelve months after treatment for H. pylorieradication, gastric ulcers had recurred in 11.4% of those with successful H. pylorieradication and in 64.5% of those with unsuccessful H. pylori eradication. Duodenal ulcers had recurred in 6.8% of patients for whom H. pylori eradication was successful and in 85.3% of patients in whom eradication failed. These findings proved that H. pylori eradication significantly reduced ulcer recurrence ( P < 0.0001 for both types of ulcers). Histopathological findings of inflammation and activity grade in both gastric and duodenal ulcers were more favorable in patients with successful eradication than in those with unsuccessful eradication.
CONCLUSIONS: H. pylori eradication significantly inhibited ulcer recurrence in Japanese peptic ulcer patients. Histopathological findings were also improved with regard to inflammation and activity (neutrophils) in patients in whom H. pylori eradication was successful.

PMID 12743773  J Gastroenterol. 2003;38(4):339-47. doi: 10.1007/s00535・・・
著者: Alexander C Ford, Brendan C Delaney, David Forman, Paul Moayyedi
雑誌名: Am J Gastroenterol. 2004 Sep;99(9):1833-55. doi: 10.1111/j.1572-0241.2004.40014.x.
Abstract/Text BACKGROUND AND AIM: We conducted a systematic review and economic analysis to ascertain the efficacy of eradication therapy in the treatment of H. pylori positive peptic ulcer disease.
METHODS: Comprehensive search of electronic databases, bibliographies of retrieved articles, contact with pharmaceutical companies, and experts in the field to identify published and unpublished literature from 1966 to the present. The data were incorporated into a Monte Carlo simulation Markov model that incorporated all the uncertainty in the estimates to evaluate cost-effectiveness.
RESULTS: Fifty-two trials were included in the final metaanalysis. In duodenal ulcer healing, H. pylori eradication therapy was superior to ulcer healing drug (relative risk (RR) of ulcer persisting = 0.66; 95% confidence interval (CI) = 0.58 to 0.76) and no treatment (RR = 0.37; 95% CI 0.26 to 0.53). In gastric ulcer healing, H. pylori eradication therapy was not statistically superior to ulcer healing drug (RR = 1.32; 95% CI = 0.92 to 1.90). In preventing duodenal ulcer recurrence, H. pylori eradication therapy was not statistically superior to maintenance therapy with ulcer healing drug (RR of ulcer recurring = 0.73; 95% CI = 0.42 to 1.25), but was superior to no treatment (RR = 0.19; 95% CI = 0.15 to 0.26). In preventing gastric ulcer recurrence, H. pylori eradication was superior to no treatment (RR = 0.31; 95% CI 0.19 to 0.48). The Markov model suggested H. pylori eradication is cost-effective for duodenal ulcer over 1 year and gastric ulcer over 2 years with over 95% confidence despite the uncertainty in the data.
CONCLUSIONS: H. pylori eradication therapy reduces the recurrence of peptic ulcer disease and is cost-effective.

PMID 15330927  Am J Gastroenterol. 2004 Sep;99(9):1833-55. doi: 10.111・・・
著者: A C Ford, B C Delaney, D Forman, P Moayyedi
雑誌名: Cochrane Database Syst Rev. 2006 Apr 19;(2):CD003840. doi: 10.1002/14651858.CD003840.pub4. Epub 2006 Apr 19.
Abstract/Text BACKGROUND: Peptic ulcer disease is the cause for dyspepsia in about 10% of patients. 95% of duodenal and 70% of gastric ulcers are associated with Helicobacter pylori. Eradication of H pylori reduces the relapse rate of ulcers but the magnitude of this effect is uncertain.
OBJECTIVES: The primary outcomes were the proportion of peptic ulcers healed initially and proportion of patients free from relapse following successful healing. Eradication therapy was compared to placebo or pharmacological therapies in H. pylori positive patients. Secondary aims included symptom relief and adverse effects.
SEARCH STRATEGY: Searches were conducted on the Cochrane Central register of Controlled Trials - CENTRAL (which includes the Cochrane Upper Gastrointestinal and Pancreatic Diseases Group Trials Register) on The Cochrane Library (Issue 3 2002) MEDLINE (1966 to July 2002) and EMBASE (1980 to July 2002). Reference lists from trials selected by electronic searching were handsearched to identify further relevant trials. Published abstracts from conference proceedings from the United European Gastroenterology Week (published in Gut) and Digestive Disease Week (published in Gastroenterology) were handsearched. The search was updated in September 2003, November 2004 and November 2005. Members of the Cochrane UGPD Group, and experts in the field were contacted and asked to provide details of outstanding clinical trials and any relevant unpublished materials
SELECTION CRITERIA: Randomised controlled trials of short and long-term treatment of peptic ulcer disease in H. pylori positive adults were analysed. Patients received at least one week of H pylori eradication compared with ulcer healing drug, placebo or not treatment. Trials were included if they reported assessment from 2 weeks onwards.
DATA COLLECTION AND ANALYSIS: Data were collected on ulcer healing, recurrence, relief of symptoms and adverse effects.
MAIN RESULTS: 63 trials were eligible. Data extraction was not possible in 7 trials, and 56 trials were included. In duodenal ulcer healing, eradication therapy was superior to ulcer healing drug (UHD) (34 trials, 3910 patients, relative risk [RR] of ulcer persisting = 0.66; 95% confidence interval [CI] = 0.58, 0.76) and no treatment (2 trials, 207 patients, RR = 0.37; 95% CI 0.26, 0.53). In gastric ulcer healing, no significant differences were detected between eradication therapy and UHD (14 trials, 1572 patients, RR = 1.25; 95% CI = 0.88, 1.76). In preventing duodenal ulcer recurrence no significant differences were detected between eradication therapy and maintenance therapy with UHD (4 trials, 319 patients, relative risk [RR] of ulcer recurring = 0.73; 95% CI = 0.42, 1.25), but eradication therapy was superior to no treatment (27 trials 2509 patients, RR = 0.20; 95% CI = 0.15, 0.26). In preventing gastric ulcer recurrence, eradication therapy was superior to no treatment (11 trials, 1104 patients, RR = 0.29; 95% CI 0.20, 0.42).
AUTHORS' CONCLUSIONS: A 1 to 2 weeks course of H. pylori eradication therapy is an effective treatment for H. pylori positive peptic ulcer disease.

PMID 16625592  Cochrane Database Syst Rev. 2006 Apr 19;(2):CD003840. d・・・
著者: N Uemura, T Mukai, S Okamoto, S Yamaguchi, H Mashiba, K Taniyama, N Sasaki, K Haruma, K Sumii, G Kajiyama
雑誌名: Cancer Epidemiol Biomarkers Prev. 1997 Aug;6(8):639-42.
Abstract/Text Although epidemiological studies strongly suggest an association between gastric cancer and Helicobacter pylori infection, there has been no clinical report indicating that cure of the infection prevents cancer. We conducted a nonrandomized H. pylori eradication trial in patients whose gastric cancer was removed by endoscopic resection (ER). We investigated the effect of treatment on the histopathology of the gastric mucosa, as well as on the incidence of metachronous gastric cancer during the long-term clinical and endoscopic follow-up. One hundred and thirty-two patients with early gastric cancer underwent ER and had H. pylori infection. Sixty-five (group A) were treated with omeprazole and antibiotics to eradicate the infection, and 67 (group B) were not. All patients were followed for 2 years post ER. After eradication treatment in group A, the disappearance of neutrophil infiltration in the antrum and body of the stomach was observed as was a decrease of the severity of intestinal metaplasia. Endoscopy after ER detected no new gastric cancers in these patients. After 3 years of follow-up, 6 (9%) of the 67 patients in group B had a new early-stage, intestinal-type gastric cancer endoscopically diagnosed. The above results suggest that H. pylori eradication may improve neutrophil infiltration and intestinal metaplasia in the gastric mucosa and inhibit the development of new carcinomas. This finding should be confirmed in a randomized, controlled trial.

PMID 9264278  Cancer Epidemiol Biomarkers Prev. 1997 Aug;6(8):639-42.・・・
著者: Motosugu Kato, Masahiro Asaka, Shouko Ono, Manabu Nakagawa, Souichi Nakagawa, Yuichi Shimizu, Makoto Chuma, Hiroshi Kawakami, Yoshito Komatsu, Shuhei Hige, Hiroshi Takeda
雑誌名: J Gastroenterol. 2007 Jan;42 Suppl 17:16-20. doi: 10.1007/s00535-006-1928-5.
Abstract/Text Because most gastric cancers develop from a background of Helicobacter pylori-infected gastric mucosa, H. pylori plays an important role in gastric carcinogenesis. Therefore, eradication of H. pylori may inhibit the incidence of gastric cancers. In experimental studies, H. pylori eradication has proved to act as a prophylaxis against gastric cancer. However, the results of recent randomized controlled studies are absolutely contradictory. In Japan, mucosal gastric cancer is usually resected by endoscopic treatment. As only a small part of the gastric mucosa is resected, secondary gastric cancer after endoscopic resection of the primary gastric cancer often develops at another site in the stomach. A nonrandomized Japanese study involving 132 early gastric cancer patients reported that eradication of H. pylori after endoscopic resection tended to reduce the development of secondary gastric cancer. Also, a retrospective multicenter survey indicated that the incidence rate of secondary gastric cancer in H. pylori-eradicated patients was about one-third that among patients in the non eradication group. We conducted a large-scale multicenter randomized trial to confirm the effect of H. pylori eradication on secondary and residual gastric cancer after endoscopic resection. This study was begun in 2003 and is ongoing at present. Diagnosis of a new carcinoma at another site of the stomach is defined as the primary end point, and recurrence of tumors at the resection site as a secondary end point. A total of 542 subjects have been enrolled in the study. This study will have the statistical power to demonstrate whether H. pylori eradication decreases the incidence and recurrence of gastric cancer.

PMID 17238020  J Gastroenterol. 2007 Jan;42 Suppl 17:16-20. doi: 10.10・・・
著者: Kazutoshi Fukase, Mototsugu Kato, Shogo Kikuchi, Kazuhiko Inoue, Naomi Uemura, Shiro Okamoto, Shuichi Terao, Kenji Amagai, Shunji Hayashi, Masahiro Asaka, Japan Gast Study Group
雑誌名: Lancet. 2008 Aug 2;372(9636):392-7. doi: 10.1016/S0140-6736(08)61159-9.
Abstract/Text BACKGROUND: The relation between Helicobacter pylori infection and gastric cancer has been proven in epidemiological studies and animal experiments. Our aim was to investigate the prophylactic effect of H pylori eradication on the development of metachronous gastric carcinoma after endoscopic resection for early gastric cancer.
METHODS: In this multi-centre, open-label, randomised controlled trial, 544 patients with early gastric cancer, either newly diagnosed and planning to have endoscopic treatment or in post-resection follow-up after endoscopic treatment, were randomly assigned to receive an H pylori eradication regimen (n=272) or control (n=272). Randomisation was done by a computer-generated randomisation list and was stratified by whether the patient was newly diagnosed or post-resection. Patients in the eradication group received lansoprazole 30 mg twice daily, amoxicillin 750 mg twice daily, and clarithromycin 200 mg twice daily for a week; those in the control group received standard care, but no treatment for H pylori. Patients were examined endoscopically at 6, 12, 24, and 36 months after allocation. The primary endpoint was diagnosis of new carcinoma at another site in the stomach. Analyses were by intention to treat. This trial is registered with the UMIN Clinical Trials Registry, number UMIN000001169.
FINDINGS: At 3-year follow-up, metachronous gastric carcinoma had developed in nine patients in the eradication group and 24 in the control group. In the full intention-to-treat population, including all patients irrespective of length of follow-up (272 patients in each group), the odds ratio for metachronous gastric carcinoma was 0.353 (95% CI 0.161-0.775; p=0.009); in the modified intention-to-treat population, including patients with at least one post-randomisation assessment of tumour status and adjusting for loss to follow-up (255 patients in the eradication group, 250 in the control group), the hazard ratio for metachronous gastric carcinoma was 0.339 (95% CI 0.157-0.729; p=0.003). In the eradication group, 19 (7%) patients had diarrhoea and 32 (12%) had soft stools.
INTERPRETATION: Prophylactic eradication of H pylori after endoscopic resection of early gastric cancer should be used to prevent the development of metachronous gastric carcinoma.
FUNDING: Hiroshima Cancer Seminar Foundation.

PMID 18675689  Lancet. 2008 Aug 2;372(9636):392-7. doi: 10.1016/S0140-・・・
著者: M Asaka, T Sugiyama, M Kato, K Satoh, H Kuwayama, Y Fukuda, T Fujioka, T Takemoto, K Kimura, T Shimoyama, K Shimizu, S Kobayashi
雑誌名: Helicobacter. 2001 Sep;6(3):254-61.
Abstract/Text BACKGROUND: Two triple therapies with lansoprazole (LPZ)/amoxicillin (AMPC)/clarithromycin (CAM) for eradication of Helicobacter pylori were studied in multicenter, double-blind fashion to evaluate the eradication rate of H. pylori and safety of eradiation treatment in Japanese patients with H. pylori-positive active gastric ulcers or duodenal ulcers.
METHODS: Patients were randomly chosen for the control treatment of LPZ 30 mg twice a day (b.i.d.; Group A-LPZ-only) or the test treatments of LPZ 30 mg plus AMPC 750 mg and CAM 200 mg b.i.d. (Group B-LAC200) and LPZ 30 mg, AMPC 750 mg and CAM 400 mg b.i.d. (Group C-LAC400). All eradication treatments lasted for a period of 7 days. Successful eradication was assessed by culture and gastric histology 1 month after completion of the ulcer treatment.
RESULTS: The eradication rates of H. pylori in the full analysis set were 0% in Group A-LPZ-only, 87.5% in Group B-LAC200 and 89.2% in Group C-LAC400 for gastric ulcer and, 4.4% in Group A-LPZ-only, 91.1% in Group B-LAC200 and 83.7% in Group C-LAC400 for duodenal ulcer. The eradication rates of Group B-LAC200 and Group C-LAC400 were 89.2% (95% CI: 84.8-93.7%) and 86.4% (95%CI: 81.5-91.3%) in total in the full analysis set, 89% (95% CI: 84.3-93.7%) and 85.3% (95%CI: 80.1-90.5%) in the per protocol set. The eradication rates in Groups B-LAC200 and group C-LAC400 were statistically significantly higher than the rate in Group A-LPZ-only for both gastric ulcer and duodenal ulcer patients (p <.0001 for both).
CONCLUSION: A satisfactorily high H. pylori eradication rate was obtained in Japanese ulcer patients with the triple therapy regimen consisting of LPZ 30 mg, AMPC 750 mg, and CAM 200 mg b.i.d.

PMID 11683930  Helicobacter. 2001 Sep;6(3):254-61.
著者: Kazuhide Higuchi, Takama Maekawa, Koichiro Nakagawa, Shinji Chouno, Takanobu Hayakumo, Naomi Tomono, Akio Orino, Hirohisa Tanimura, Kan Asahina, Naotaka Matsuura, Motohiko Endo, Masanori Hirano, Choitsu Sakamoto, Tsutomu Inomoto, Tetsuo Arakawa
雑誌名: Clin Drug Investig. 2006;26(7):403-14.
Abstract/Text OBJECTIVE: Seven-day administration of omeprazole 40 mg/day + amoxicillin 1500 mg/day + clarithromycin 800 mg/day is currently approved in Japan for the eradication of Helicobacter pylori infection. We investigated the efficacy and safety of an omeprazole-based triple therapy regimen in combination with amoxicillin and low-dose clarithromycin in Japanese patients.
METHODS: Patients were randomly assigned to either the low-dose group (omeprazole 40 mg/day + amoxicillin 1500 mg/day + clarithromycin 400 mg/day) or the high-dose group (omeprazole 40 mg/day + amoxicillin 1500 mg/day + clarithromycin 800 mg/day). A total of 288 patients were allocated to the low-dose (143) and high-dose (145) groups and were treated twice daily for 1 week.
RESULTS: For the full-analysis set, H. pylori eradication rates were 81.1% (116/143 patients, 90% confidence interval [CI] 74.9, 86.3) in the low-dose group and 80.0% (116/145 patients, 90% CI 73.7, 85.3) in the high-dose group. Per-protocol eradication rates were 81.7% (103/126 patients, 90% CI 75.1, 87.2) and 84.1% (90/107 patients, 90% CI 77.1, 89.6), respectively. When patients with non-susceptibility to clarithromycin were excluded, eradication rates were >80% for both gastric and duodenal ulcers in the two groups. The results suggested that eradication rates were affected more by susceptibility to clarithromycin than to amoxicillin. Both regimens were well tolerated.
CONCLUSION: This study demonstrated that an omeprazole-based triple-therapy regimen with clarithromycin 400 mg/day was as effective as that with clarithromycin 800 mg/day for H. pylori eradication.

PMID 17163273  Clin Drug Investig. 2006;26(7):403-14.
著者: Toshio Fujioka, Nobuo Aoyama, Kyoko Sakai, Yoshiyuki Miwa, Mineo Kudo, Junichi Kawashima, Yasuo Matsubara, Jun Miwa, Koji Yakabi
雑誌名: J Gastroenterol. 2012 Mar;47(3):276-83. doi: 10.1007/s00535-011-0487-6. Epub 2011 Nov 9.
Abstract/Text BACKGROUND: In recent years in Japan, the rate of clarithromycin (CAM) resistance in Helicobacter pylori has risen to around 30%, and the eradication rate with triple therapy [proton pump inhibitor + amoxicillin (AMPC) + CAM] has been trending downward to around 70%. In 2007, rabeprazole (RPZ)-based triple therapy (RPZ + AMPC + CAM: RAC therapy) was approved in Japan, and a large-scale nationwide study was therefore initiated to evaluate the efficacy and safety of RAC therapy in clinical practice.
METHODS: Patients with H. pylori-positive gastric/duodenal ulcer (including ulcer scars) were administered triple therapy comprising RPZ 10 mg, AMPC 750 mg, and CAM 200 mg (or 400 mg), twice daily for 7 days.
RESULTS: The eradication rate was 80.7% (2,551/3,162). The results of multivariate analysis indicated the following as factors affecting the eradication rate: sex, treatment compliance, history of H. pylori treatment, presence of urologic disease, presence of respiratory disease, and year of starting treatment. The incidence of adverse drug reactions (such as diarrhea and dysgeusia) was 4.4% (166/3,789). The results of multivariate analysis indicated the following as factors affecting the incidence of adverse drug reactions: sex, daily CAM dose, and history of allergies.
CONCLUSION: In a large-scale nationwide study of use in clinical practice, RAC therapy was confirmed to be effective and safe.

PMID 22065160  J Gastroenterol. 2012 Mar;47(3):276-83. doi: 10.1007/s0・・・
著者: Kazunari Murakami, Yuuichi Sakurai, Madoka Shiino, Nobuo Funao, Akira Nishimura, Masahiro Asaka
雑誌名: Gut. 2016 Sep;65(9):1439-46. doi: 10.1136/gutjnl-2015-311304. Epub 2016 Mar 2.
Abstract/Text OBJECTIVE: The objective of this study was to assess the efficacy, safety and tolerability of vonoprazan, a novel potassium-competitive acid blocker, as a component of Helicobacter pylori eradication therapy.
DESIGN: A randomised, double-blind, multicentre, parallel-group study was conducted to verify the non-inferiority of vonoprazan 20 mg to lansoprazole 30 mg as part of first-line triple therapy (with amoxicillin 750 mg and clarithromycin 200 or 400 mg) in H pylori-positive patients with gastric or duodenal ulcer history. The first 50 patients failing first-line therapy with good compliance also received second-line vonoprazan-based triple therapy (with amoxicillin 750 mg and metronidazole 250 mg) as an open-label treatment.
RESULTS: Of the 650 subjects randomly allocated to either first-line triple therapy, 641 subjects completed first-line therapy and 50 subjects completed second-line therapy. The first-line eradication rate (primary end point) was 92.6% (95% CI 89.2% to 95.2%) with vonoprazan versus 75.9% (95% CI 70.9% to 80.5%) with lansoprazole, with the difference being 16.7% (95% CI 11.2% to 22.1%) in favour of vonoprazan, thus confirming the non-inferiority of vonoprazan (p<0.0001). The second-line eradication rate (secondary end point) was also high (98.0%; 95% CI 89.4% to 99.9%) in those who received second-line therapy (n=50). Both first-line triple therapies were well tolerated with no notable differences. Second-line triple therapy was also well tolerated.
CONCLUSION: Vonoprazan is effective as part of first-line triple therapy and as part of second-line triple therapy in H pylori-positive patients with a history of gastric or duodenal ulcer.
TRIAL REGISTRATION NUMBER: NCT01505127.

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PMID 26935876  Gut. 2016 Sep;65(9):1439-46. doi: 10.1136/gutjnl-2015-3・・・
著者: Yuko Akazawa, Daisuke Fukuda, Yutaka Fukuda
雑誌名: Therap Adv Gastroenterol. 2016 Nov;9(6):845-852. doi: 10.1177/1756283X16668093. Epub 2016 Sep 22.
Abstract/Text Stable suppression of gastric acid secretion is a crucial factor in Helicobacter pylori eradication. Vonoprazan is a potassium-competitive acid blocker recently approved for use in Japan. As vonoprazan has a long duration of action and causes rapid and strong inhibition of gastric acid secretion, it has gained clinical attention for treating erosive oesophagitis, peptic ulcers, and H. pylori infection. In this review, we discuss the recent knowledge regarding the safety and efficacy of vonoprazan, focusing on its use in H. pylori eradication. The latest literature and our clinical experience have shown that vonoprazan-based therapies have satisfactory eradication rates. Additionally, vonoprazan-based therapies are associated with similar rates of adverse events as standard triple therapies with conventional proton-pump inhibitors.

PMID 27803739  Therap Adv Gastroenterol. 2016 Nov;9(6):845-852. doi: 1・・・
著者: Intetsu Kobayashi, Kazunari Murakami, Mototsugu Kato, Seiichi Kato, Takeshi Azuma, Shin'ichi Takahashi, Naomi Uemura, Tsutomu Katsuyama, Yoshihiro Fukuda, Ken Haruma, Masaru Nasu, Toshio Fujioka
雑誌名: J Clin Microbiol. 2007 Dec;45(12):4006-10. doi: 10.1128/JCM.00740-07. Epub 2007 Oct 17.
Abstract/Text Surveillance of Helicobacter pylori antimicrobial susceptibility reflecting the general population in Japan is limited. The antimicrobial susceptibilities of 3,707 H. pylori strains isolated from gastric mucosa samples of previously untreated patients diagnosed with gastroduodenal diseases at 36 medical facilities located throughout Japan between October 2002 and September 2005 were evaluated. Using an agar dilution method for antimicrobial susceptibility testing of H. pylori, the MIC distributions and trends during the study period for clarithromycin, amoxicillin, and metronidazole were studied. While the MIC(50) and MIC(90) for clarithromycin did not change during the 3-year period, the MIC(80) showed a 128-fold increase. Furthermore, the rate of resistance increased yearly from 18.9% (2002 to 2003) to 21.1% (2003 to 2004) and 27.7% (2004 to 2005). With a resistance rate of 19.2% among males compared to 27.0% among females, a significant gender difference was observed (P < 0.0001). Our study shows that in Japan, there is an evolving trend towards increased resistance to clarithromycin with geographical and gender differences as well as between clinical disease conditions. No significant changes in resistance were observed for amoxicillin and metronidazole during the period. While the benefit of H. pylori antimicrobial susceptibility testing has been debated in Japan, current empirical regimens are not based on susceptibility data representative of the general population. The development of an effective H. pylori eradication regimen in Japan will require continued resistance surveillance as well as a better understanding of the epidemiology of resistance.

PMID 17942652  J Clin Microbiol. 2007 Dec;45(12):4006-10. doi: 10.1128・・・
著者: Peter Malfertheiner, Francis Megraud, Colm A O'Morain, John Atherton, Anthony T R Axon, Franco Bazzoli, Gian Franco Gensini, Javier P Gisbert, David Y Graham, Theodore Rokkas, Emad M El-Omar, Ernst J Kuipers, European Helicobacter Study Group
雑誌名: Gut. 2012 May;61(5):646-64. doi: 10.1136/gutjnl-2012-302084.
Abstract/Text Management of Helicobacter pylori infection is evolving and in this 4th edition of the Maastricht consensus report aspects related to the clinical role of H pylori were looked at again in 2010. In the 4th Maastricht/Florence Consensus Conference 44 experts from 24 countries took active part and examined key clinical aspects in three subdivided workshops: (1) Indications and contraindications for diagnosis and treatment, focusing on dyspepsia, non-steroidal anti-inflammatory drugs or aspirin use, gastro-oesophageal reflux disease and extraintestinal manifestations of the infection. (2) Diagnostic tests and treatment of infection. (3) Prevention of gastric cancer and other complications. The results of the individual workshops were submitted to a final consensus voting to all participants. Recommendations are provided on the basis of the best current evidence and plausibility to guide doctors involved in the management of this infection associated with various clinical conditions.

PMID 22491499  Gut. 2012 May;61(5):646-64. doi: 10.1136/gutjnl-2012-30・・・
著者: T Furuta, N Shirai, M Kodaira, M Sugimoto, A Nogaki, S Kuriyama, M Iwaizumi, M Yamade, I Terakawa, K Ohashi, T Ishizaki, A Hishida
雑誌名: Clin Pharmacol Ther. 2007 Apr;81(4):521-8. doi: 10.1038/sj.clpt.6100043. Epub 2007 Jan 10.
Abstract/Text Helicobacter pylori eradication rates by triple therapy with a proton pump inhibitor, amoxicillin, and clarithromycin at standard doses depend on bacterial susceptibility to clarithromycin and patient CYP2C19 genotypes. We examined the usefulness of a personalized therapy for H. pylori infection based on these factors as determined by genetic testing. First, optimal lansoprazole dosing schedules that would achieve sufficient acid inhibition to allow H. pylori eradication therapy in each of different CYP2C19 genotype groups were determined by a 24-h intragastric pH monitoring. Next, 300 H. pylori-positive patients were randomly assigned to the standard regimen group (lansoprazole 30 mg twice daily (b.i.d.)), clarithromycin 400 mg b.i.d., and amoxicillin 750 mg b.i.d. for 1 week) or the tailored regimen group based on CYP2C19 status and bacterial susceptibility to clarithromycin assessed by genetic testing. Patients with failure of eradication underwent the second-line regimen. The per-patient cost required for successful eradication was calculated for each of the groups. In the first-line therapy, the intention-to-treat eradication rate in the tailored regimen group was 96.0% (95% CI=91.5-98.2%, 144/150), significantly higher than that in the standard regimen group (70.0%: 95% CI=62.2-77.2%, 105/150) (P<0.001). Final costs per successful eradication in the tailored and standard regimen groups were $669 and $657, respectively. In conclusion, the pharmacogenomics-based tailored treatment for H. pylori infection allowed a higher eradication rate by the initial treatment without an increase of the final per-patient cost for successful eradication. However, the precise cost-effectiveness of this strategy remains to be determined.

PMID 17215846  Clin Pharmacol Ther. 2007 Apr;81(4):521-8. doi: 10.1038・・・
著者: Kazunari Murakami, Tadayoshi Okimoto, Masaaki Kodama, Ryugo Sato, Koichiro Watanabe, Toshio Fujioka
雑誌名: J Clin Gastroenterol. 2008 Feb;42(2):139-42. doi: 10.1097/MCG.0b013e31802cbc1a.
Abstract/Text GOALS: We compared the eradication results of retreatment of eradication with proton pump inhibitor (PPI) plus amoxicillin and metronidazole for patients with Helicobacter pylori infection not eradicated by initial treatment with PPI plus amoxicillin and clarithromycin.
BACKGROUND: In Japan, the guideline proposes that the use of metronidazole in a triple therapy containing PPI, PPI plus amoxicillin and metronidazole is desirable in retreatment. However, there are no reports comparing various retreatment using different PPIs.
METHODS: After initial treatment failure with a PPI plus amoxicillin and clarithromycin, 169 patients were randomized to a PPI (rabeprazole, lansoprazole, or omeprazole) plus amoxicillin and metronidazole given b.i.d. for 7 days.
RESULTS: Pretreatment susceptibility testing showed a high level of clarithromycin resistance (78%). The over all eradication rates were similar with the 3 PPIs, 91.1% range 90.1 to 91.4 with intention-to-treat analysis. The presence of metronidazole resistance reduced the eradication rate by approximately 40% (from 96.6% to 57.1%, P<0.05).
CONCLUSIONS: In Japan, the combination of a PPI plus amoxicillin and metronidazole provide excellent eradication rates after initial treatment failure with a PPI plus amoxicillin and clarithromycin. The results with metronidazole resistant strains are less satisfactory and pretreatment susceptibility testing may become needed if the prevalence of metronidazole resistant H. pylori increase.

PMID 18209581  J Clin Gastroenterol. 2008 Feb;42(2):139-42. doi: 10.10・・・
著者: Susumu Take, Motowo Mizuno, Kuniharu Ishiki, Tomowo Yoshida, Nobuya Ohara, Kenji Yokota, Keiji Oguma, Hiroyuki Okada, Kazuhide Yamamoto
雑誌名: J Gastroenterol. 2011 Mar;46(3):318-24. doi: 10.1007/s00535-010-0347-9. Epub 2010 Nov 20.
Abstract/Text BACKGROUND: We previously reported that eradication of Helicobacter pylori reduced the risk of developing gastric cancer in patients with peptic ulcer diseases. In the present study, we further followed up our patient group to investigate the occurrence and clinical features of gastric cancers that developed after cure of the infection.
METHODS: Prospective post-eradication evaluations were conducted on 1674 consecutive patients who had received successful H. pylori eradication therapy. The patients had undergone endoscopic examination before eradication therapy to evaluate peptic ulcers, background gastric mucosal atrophy, and H. pylori infection. After confirmation of cure of the infection, follow-up endoscopy was performed yearly.
RESULTS: The patients were followed for up to 14.1 years (a mean of 5.6 years). During the follow-up, gastric cancer developed in 28 of the 1674 patients as long as 13.7 years after the cure of H. pylori infection. The risk of developing gastric cancer was 0.30% per year. Histologically, 16 of the gastric cancers were the intestinal type and 12 were the diffuse type; the risk of each cancer type was 0.17 and 0.13% per year, respectively. There was no significant inflammatory cell infiltration in the background gastric mucosa at the time the cancers were recognized.
CONCLUSION: There is a risk of developing gastric cancer of both the intestinal and diffuse types even after the cure of H. pylori infection and extinction of gastric inflammation. It is important to inform patients about the risk of gastric cancer after eradication therapy and offer them surveillance endoscopy.

PMID 21103997  J Gastroenterol. 2011 Mar;46(3):318-24. doi: 10.1007/s0・・・
著者: Masahiro Asaka, Mototsugu Kato, David Y Graham
雑誌名: Helicobacter. 2010 Dec;15(6):486-90. doi: 10.1111/j.1523-5378.2010.00799.x.
Abstract/Text A study conducted by the Japan Gast Study Group showed that eradication of Helicobacter pylori reduced the risk of gastric cancer by about one-third. However, it did not completely prevent the onset of latent gastric cancer among those at high risk (i.e., with atrophic gastritis). To prevent deaths from gastric cancer, it is necessary to eradicate H. pylori infection. We propose a program of risk stratification based on the presence of H. pylori infection with or without atrophic gastritis followed by targeted interventions. Those at no risk for gastric cancer (no H. pylori, no atrophic gastritis) need no therapy or follow-up. Those at low risk (H. pylori infected, nonatrophic gastritis) need only H. pylori eradication therapy. The smaller groups at high or very high risk need eradication and cancer surveillance. We estimated the costs and the benefits of this strategy. Gastric cancer screening by simultaneous measurement of serum pepsinogen and H. pylori antibody combined with eradication of H. pylori in all individuals at risk would initially increase national healthcare expenditure, but this would be offset by markedly reducing the cost of treating gastric cancer. The proposed strategy should prevent about 150,000 deaths from gastric cancer during the 5 years after its adoption. If the loss caused by these deaths is also taken into account, the economic effect of this strategy becomes enormous. It would probably reduce the incidence of gastric cancer by more than 80-90% within 10 years. The Japanese government should take the initiative to implement this strategy as soon as possible.

© 2010 Blackwell Publishing Ltd.
PMID 21073603  Helicobacter. 2010 Dec;15(6):486-90. doi: 10.1111/j.152・・・
著者: Susumu Take, Motowo Mizuno, Kuniharu Ishiki, Takayuki Imada, Tetsuji Okuno, Tomowo Yoshida, Kenji Yokota, Keiji Oguma, Masahide Kita, Hiroyuki Okada, Kazuhide Yamamoto
雑誌名: J Gastroenterol. 2012 Jun;47(6):641-6. doi: 10.1007/s00535-012-0536-9. Epub 2012 Feb 17.
Abstract/Text BACKGROUND: We previously reported that the reinfection rate with Helicobacter pylori in Japan was low despite a high prevalence of infection. In the present study, we extended our previous work to more accurately determine the reinfection rate.
METHODS: We enrolled 1625 patients (219 women and 1406 men, mean age 50.8 years) who had received H. pylori eradication therapy. After documentation of eradication, bacterial culture and urea breath test were carried out yearly. H. pylori strains were analyzed by using random amplification of polymorphic DNA fingerprinting.
RESULTS: A total of 1609 patients were followed for up to 12.5 years (mean 4.7 years); H. pylori became re-positive in 26 patients. In 13 of the 26 patients, H. pylori became positive at the first-year follow up. Stored H. pylori isolates were available for analysis from ten of the 13 patients; four of the isolates were genetically different from the initial strain, but the other six were identical to the initial strain. In the other 13 patients, H. pylori became positive at later follow up (mean 4.8 years; range 1.8-8.0 years). In all of the four of these patients whose isolates could be analyzed, the H. pylori strains were different from the initial strain. Assuming that reinfection occurred in the four patients positive for different strains of H. pylori at the first-year follow up and in the 13 positive at later follow up, the reinfection rate was 0.22% per year.
CONCLUSIONS: When probable recrudescence (H. pylori positivity with identical strains) was excluded, the reinfection rate of H. pylori in this Japanese population was very low, but we note that reinfection can occur over many years.

PMID 22350696  J Gastroenterol. 2012 Jun;47(6):641-6. doi: 10.1007/s00・・・
著者: Y Hu, J-H Wan, X-Y Li, Y Zhu, D Y Graham, N-H Lu
雑誌名: Aliment Pharmacol Ther. 2017 Nov;46(9):773-779. doi: 10.1111/apt.14319. Epub 2017 Sep 11.
Abstract/Text BACKGROUND: Up-to-date information regarding the recurrence rate of Helicobacter pylori (H. pylori) after eradication therapy is not available.
AIM: To evaluate the global recurrence rate following H. pylori eradication therapy and confirm its association with socioeconomic and sanitary conditions.
METHODS: A systematic search of PubMed, EMBASE and the Cochrane library was performed to identify potentially relevant publications using the following keywords: "Helicobacter pylori" or "H. pylori" or "Hp" and "recurrence" or "recrudescence" or "reinfection" or "recurrent" or "recurred" or "re-infect*" or "relapse*."
RESULTS: A total of 132 studies (53 934 patient-years) were analysed. Each study was weighted according to the duration of patient-years. The global annual recurrence, reinfection and recrudescence rate of H. pylori were 4.3% (95% CI, 4-5), 3.1% (95% CI, 2-5) and 2.2% (95% CI, 1-3), respectively. The H. pylori recurrence rate was inversely related to the human development index (HDI) (ie, 3.1% [95% CI, 2-4], 6.2% [95% CI, 4-8] and 10.9% [95% CI, 6-18] in countries with a very high, high and medium or low HDI) (P <.01) and directly related to H. pylori prevalence (10.9% [95% CI, 7-16], 3.7% [95% CI, 3-5], 3.4% [95% CI, 2-5] and 1.6% [95% CI, 0.5-3] in countries with a very high, high, medium or low local H. pylori prevalence) (P <.01). Global recurrence rates remained relatively stable between 1990s, 2000s and 2010s but varied across different regions (P <.05).
CONCLUSIONS: H. pylori recurrence remains a problem closely associated with socioeconomic and sanitary conditions. Methods to reduce recurrence in developing countries are needed.

© 2017 John Wiley & Sons Ltd.
PMID 28892184  Aliment Pharmacol Ther. 2017 Nov;46(9):773-779. doi: 10・・・

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