Tags

Type your tag names separated by a space and hit enter

Insights into Effects/Risks of Chronic Hypergastrinemia and Lifelong PPI Treatment in Man Based on Studies of Patients with Zollinger-Ellison Syndrome.
Int J Mol Sci. 2019 Oct 16; 20(20)IJ

Abstract

The use of proton pump inhibitors (PPIs) over the last 30 years has rapidly increased both in the United States and worldwide. PPIs are not only very widely used both for approved indications (peptic ulcer disease, gastroesophageal reflux disease (GERD), Helicobacter pylori eradication regimens, stress ulcer prevention), but are also one of the most frequently off-label used drugs (25-70% of total). An increasing number of patients with moderate to advanced gastroesophageal reflux disease are remaining on PPI indefinitely. Whereas numerous studies show PPIs remain effective and safe, most of these studies are <5 years of duration and little data exist for >10 years of treatment. Recently, based primarily on observational/epidemiological studies, there have been an increasing number of reports raising issues about safety and side-effects with very long-term chronic treatment. Some of these safety issues are related to the possible long-term effects of chronic hypergastrinemia, which occurs in all patients taking chronic PPIs, others are related to the hypo-/achlorhydria that frequently occurs with chronic PPI treatment, and in others the mechanisms are unclear. These issues have raised considerable controversy in large part because of lack of long-term PPI treatment data (>10-20 years). Zollinger-Ellison syndrome (ZES) is caused by ectopic secretion of gastrin from a neuroendocrine tumor resulting in severe acid hypersecretion requiring life-long antisecretory treatment with PPIs, which are the drugs of choice. Because in <30% of patients with ZES, a long-term cure is not possible, these patients have life-long hypergastrinemia and require life-long treatment with PPIs. Therefore, ZES patients have been proposed as a good model of the long-term effects of hypergastrinemia in man as well as the effects/side-effects of very long-term PPI treatment. In this article, the insights from studies on ZES into these controversial issues with pertinence to chronic PPI use in non-ZES patients is reviewed, primarily concentrating on data from the prospective long-term studies of ZES patients at NIH.

Authors+Show Affiliations

Digestive Diseases Branch, NIDDK, NIH, Bethesda, MD 20892-1804, USA. frkn505@gmail.com. Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582, Japan. frkn505@gmail.com.Digestive Diseases Branch, NIDDK, NIH, Bethesda, MD 20892-1804, USA. irene.ramosalvarez@nih.gov.Neuroendocrine Tumor Centra, Fukuoka Sanno Hospital, International University of Health and Welfare 3-6-45 Momochihama, Sawara-Ku, Fukuoka 814-0001, Japan. itopapa@kouhoukai.or.jp.Digestive Diseases Branch, NIDDK, NIH, Bethesda, MD 20892-1804, USA. robertj@bdg10.niddk.nih.gov.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

31623145

Citation

Lee, Lingaku, et al. "Insights Into Effects/Risks of Chronic Hypergastrinemia and Lifelong PPI Treatment in Man Based On Studies of Patients With Zollinger-Ellison Syndrome." International Journal of Molecular Sciences, vol. 20, no. 20, 2019.
Lee L, Ramos-Alvarez I, Ito T, et al. Insights into Effects/Risks of Chronic Hypergastrinemia and Lifelong PPI Treatment in Man Based on Studies of Patients with Zollinger-Ellison Syndrome. Int J Mol Sci. 2019;20(20).
Lee, L., Ramos-Alvarez, I., Ito, T., & Jensen, R. T. (2019). Insights into Effects/Risks of Chronic Hypergastrinemia and Lifelong PPI Treatment in Man Based on Studies of Patients with Zollinger-Ellison Syndrome. International Journal of Molecular Sciences, 20(20). https://doi.org/10.3390/ijms20205128
Lee L, et al. Insights Into Effects/Risks of Chronic Hypergastrinemia and Lifelong PPI Treatment in Man Based On Studies of Patients With Zollinger-Ellison Syndrome. Int J Mol Sci. 2019 Oct 16;20(20) PubMed PMID: 31623145.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Insights into Effects/Risks of Chronic Hypergastrinemia and Lifelong PPI Treatment in Man Based on Studies of Patients with Zollinger-Ellison Syndrome. AU - Lee,Lingaku, AU - Ramos-Alvarez,Irene, AU - Ito,Tetsuhide, AU - Jensen,Robert T, Y1 - 2019/10/16/ PY - 2019/09/19/received PY - 2019/10/08/revised PY - 2019/10/13/accepted PY - 2019/10/19/entrez PY - 2019/10/19/pubmed PY - 2020/2/27/medline KW - MEN1 KW - PPI KW - gastric carcinoid KW - gastrinoma KW - hypergastrinemia KW - neuroendocrine tumor JF - International journal of molecular sciences JO - Int J Mol Sci VL - 20 IS - 20 N2 - The use of proton pump inhibitors (PPIs) over the last 30 years has rapidly increased both in the United States and worldwide. PPIs are not only very widely used both for approved indications (peptic ulcer disease, gastroesophageal reflux disease (GERD), Helicobacter pylori eradication regimens, stress ulcer prevention), but are also one of the most frequently off-label used drugs (25-70% of total). An increasing number of patients with moderate to advanced gastroesophageal reflux disease are remaining on PPI indefinitely. Whereas numerous studies show PPIs remain effective and safe, most of these studies are <5 years of duration and little data exist for >10 years of treatment. Recently, based primarily on observational/epidemiological studies, there have been an increasing number of reports raising issues about safety and side-effects with very long-term chronic treatment. Some of these safety issues are related to the possible long-term effects of chronic hypergastrinemia, which occurs in all patients taking chronic PPIs, others are related to the hypo-/achlorhydria that frequently occurs with chronic PPI treatment, and in others the mechanisms are unclear. These issues have raised considerable controversy in large part because of lack of long-term PPI treatment data (>10-20 years). Zollinger-Ellison syndrome (ZES) is caused by ectopic secretion of gastrin from a neuroendocrine tumor resulting in severe acid hypersecretion requiring life-long antisecretory treatment with PPIs, which are the drugs of choice. Because in <30% of patients with ZES, a long-term cure is not possible, these patients have life-long hypergastrinemia and require life-long treatment with PPIs. Therefore, ZES patients have been proposed as a good model of the long-term effects of hypergastrinemia in man as well as the effects/side-effects of very long-term PPI treatment. In this article, the insights from studies on ZES into these controversial issues with pertinence to chronic PPI use in non-ZES patients is reviewed, primarily concentrating on data from the prospective long-term studies of ZES patients at NIH. SN - 1422-0067 UR - https://www.unboundmedicine.com/medline/citation/31623145/Insights_into_Effects/Risks_of_Chronic_Hypergastrinemia_and_Lifelong_PPI_Treatment_in_Man_Based_on_Studies_of_Patients_with_Zollinger-Ellison_Syndrome L2 - https://www.mdpi.com/resolver?pii=ijms20205128 DB - PRIME DP - Unbound Medicine ER -