Journal of Gastroenterology

, Volume 54, Issue 6, pp 492–500 | Cite as

Proton pump inhibitor monotherapy is effective to attenuate dyspepsia symptoms associated with gastroesophageal reflux disease: a multicenter prospective observational study

  • Kimio IsshiEmail author
  • Nobuyuki Matsuhashi
  • Takashi Joh
  • Kazuhide Higuchi
  • Katsuhiko Iwakiri
  • Takeshi Kamiya
  • Noriaki Manabe
  • Maiko Ogawa
  • Seiji Arihiro
  • Ken Haruma
  • Koji Nakada
Original Article—Alimentary Tract


Background and aim

Gastroesophageal reflux disease (GERD) and functional dyspepsia (FD) are frequently overlapped. However, no treatment strategies have been established yet for such patients. This study compared the effects of proton pump inhibitor (PPI) treatment in patients with GERD-associated FD among three groups with varying severity levels of GERD symptoms.


The patients with GERD and FD symptoms received PPI treatment for 4 weeks after endoscopy, and the severity of the symptoms and responses to treatment were evaluated at before and after 4 weeks of treatment using the Gastroesophageal Reflux and Dyspepsia Therapeutic Efficacy and Satisfaction Test (GERD-TEST). The patients were divided into three groups in accordance with the severity of the GERD symptoms as assessed by the GERD symptom subscale (SS) scores of pre-treatment.


Data from 233 cases of 40 mild, 151 moderate and 42 severe symptoms were analyzed. Analysis of the pre-treatment scores for each symptom revealed that a higher GERD-SS score was significantly associated with higher scores on any kind of FD score. Four weeks of PPI treatment significantly and markedly alleviated any of GERD/FD symptoms. Most importantly, change in the score for each symptom after 4 weeks of treatment relative to the pre-treatment score was significantly greater in the groups with more severe GERD-SS.


FD symptoms associated with more severe GERD symptoms are supposed to be acid-related dyspepsia, and PPI monotherapy is recommended as the treatment of first choice in such patients.


Gastroesophageal reflux disease Functional dyspepsia (FD) Proton pump inhibitor Acid-related dyspepsia 



This study was conducted by the GERD Society and registered to UMIN-CTR #000006614. Financial support for this clinical study was provided by GERD Society (Osaka, Japan). This study was completed by 29 institutions in Japan. The authors thank all physicians who participated in this study and the patients whose cooperation made this study possible. The contributor of each institution is listed below.

Nobuyuki Matsuhashi, NTT Medical Center Tokyo; Mineo Kudo, Sapporo Hokuyu Hospital; Norimasa Yoshida and Takahiro Suzuki, Japanese Red Cross Kyoto Daiichi Hospital; Kazunari Murakami and Seiji Shiota, Oita University Faculty of Medicine; Mototsugu Kato and Katsuhiro Mabe, Hokkaido University Hospital; Tsuyoshi Sanuki and Junko Hori, Kita Harima Medical Center; Noriaki Manabe and Ken Haruma, Kawasaki Medical School; Yuji Naito and Osamu Handa, Kyoto Prefectural University of Medicine; Syuuji Inoue, National Hospital Organization Kochi Hospital; Hirokazu Oyamada and Yutaka Isozaki, Matsushita Memorial Hospital; Shuichi Muto, Tomakomai City Hospital; Kenji Furuta and Shunji Ohara, Shimane University Faculty of Medicine; Tadayuki Oshima and Hiroto Miwa, Hyogo College of Medicine; Yasuhiro Fujiwara and Yukie Kohata, Osaka City University Graduate School of Medicine; Kazuhiro Maeda and Yuji Sakai, Tenjin Clinic, Medical Corporation Shinai; Yugo Iwaya and Sadahisa Okuhara, Shinshu University School of Medicine; Takashi Abe and Yongmin Kim, Takarazuka Municipal Hospital; Hideki Mizuno, Toyama City Hospital;

Kimio Isshi, Isshi Gastro-Intestinal Clinic; Hiroshi Seno and Tsutomu Chiba, Kyoto University Hospital; Fukunori Kinjo and Manabu Nakamoto, University Hospital, University of the Ryukyus; Toshiro Sugiyama and Haruka Fujinami, University of Toyama; Keiko Utsumi, Aichi Medical University Medical Clinic; Hiroyuki Kuwano and Tatsuya Miyazaki, Gunma University Hospital; Noriko Watanabe, National Hospital Organization Mie Chuo Medical Center; Fumihiko Kinekawa and Kita Yuko, Sanuki Municipal Hospital; Tomonori Imaoka and Hirohumi Fujishiro, Shimane Prefectural Central Hospital; Takatsugu Yamamoto and Yasushi Kuyama, Teikyo University School of Medicine; Yasuaki Nakajima and Kenro Kawada, Tokyo Medical and Dental University.

Compliance with ethical standards

Conflict of interest

Kazuhide Higuchi received a research grants and lecture fees from Takeda Pharmaceutical Company Limited (Takeda), Daiichi Sankyo Company Limited (Daiichi Sankyo), Otsuka Pharmaceutical Company Limited (Otsuka), EA Pharma Company Limited (EA Pharma), Astellas Pharmaceutical Company Limited (Astellas) and Astra Zeneca Company Limited (Astra Zeneca). Takeshi Kamiya received research grants from AstraZeneca, Astellas, Daiichi Sankyo, Mylan EPD. Noriaki Manabe received research grants and lecture fees from Astellas, Mylan EPD. Ken Haruma received research grants and lecture fees from Astellas, AstraZeneca, Daiichi Sankyo, Otsuka and Takeda. The other authors declare that they have no conflict of interest.


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Copyright information

© Japanese Society of Gastroenterology 2019

Authors and Affiliations

  • Kimio Isshi
    • 1
    • 2
    Email author
  • Nobuyuki Matsuhashi
    • 3
  • Takashi Joh
    • 4
  • Kazuhide Higuchi
    • 5
  • Katsuhiko Iwakiri
    • 6
  • Takeshi Kamiya
    • 7
  • Noriaki Manabe
    • 8
  • Maiko Ogawa
    • 9
  • Seiji Arihiro
    • 9
  • Ken Haruma
    • 10
  • Koji Nakada
    • 11
  1. 1.Isshi Gastro-Intestinal ClinicTokyoJapan
  2. 2.Department of EndoscopyJikei University School of MedicineTokyoJapan
  3. 3.Department of GastroenterologyNTT Medical Center TokyoTokyoJapan
  4. 4.Gamagori City HospitalGamagori-City, AichiJapan
  5. 5.Second Department of Internal MedicineOsaka Medical CollegeTakatsukiJapan
  6. 6.Department of GastroenterologyNippon Medical School Graduate School of MedicineTokyoJapan
  7. 7.Department of Medical InnovationNagoya City University Graduate School Medical SciencesNagoyaJapan
  8. 8.Division of Endoscopy and Ultrasonography, Department of Laboratory MedicineKawasaki Medical School General Medical CenterOkayama-CityJapan
  9. 9.Division of Gastroenterology and Hepatology, Department of Internal MedicineKatsushika Medical Center Jikei University School of MedicineTokyoJapan
  10. 10.Department of General Internal Medicine 2Kawasaki Medical School Kawasaki HospitalKurashikiJapan
  11. 11.Department of Laboratory MedicineThe Jikei University Daisan HospitalTokyoJapan

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