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Aliment Pharmacol Ther. 2015 Sep;42(6):649-63. doi: 10.1111/apt.13324. Epub 2015 Jul 16.

Systematic review: the effects of long-term proton pump inhibitor use on serum gastrin levels and gastric histology.

Author information

1
Gastrocentrum, Department of Clinical Sciences, Intervention and Technology (CLINTEC), Centre for Digestive Diseases, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
2
Institut für Pathologie, Klinikum Bayreuth GmbH, Bayreuth, Germany.
3
PharmaGenesis London, London, UK.
4
Global Medicines Development, AstraZeneca R&D, Mölndal, Sweden.
5
Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

Abstract

BACKGROUND:

Proton pump inhibitors (PPIs) have a well-established safety profile. However, concerns have been raised about a potential relationship between PPI-induced hypergastrinaemia and the development of enterochromaffin-like (ECL) cell hyperplasia, neuroendocrine tumours and gastric cancer during long-term therapy.

AIM:

To review the effects of long-term PPI use on serum gastrin levels and gastric histopathology.

METHODS:

A systematic literature search was conducted in PubMed on 21 April 2015 to identify studies reporting the effects of long-term (defined as >3 years) PPI use on gastrin levels and gastric histopathology.

RESULTS:

A total of 16 studies (1920 patients) met the inclusion criteria. During long-term PPI therapy, mean gastrin levels rose to one to three times the upper limit of the normal range (~100 pg/mL), and an increased prevalence of ECL cell hyperplasia was observed (+7.8-52.0%). Helicobacter pylori-positive patients had a significantly increased risk of developing ECL linear/micronodular hyperplasia compared with H. pylori-negative patients [OR: 2.45 (95% CI: 1.47-4.10), P = 0.0006]; however, no evidence of neoplastic changes was found. The risk of corpus atrophy was markedly higher in H. pylori-positive patients than in H. pylori-negative patients [OR: 11.45 (95% CI: 6.25-20.99), P < 0.00001]. Not a single case of gastric adenocarcinoma was found.

CONCLUSIONS:

Long-term PPI therapy induced moderate hypergastrinaemia in most patients and an increased prevalence of ECL cell hyperplasia. H. pylori-positive patients receiving long-term PPI therapy were exposed to a higher risk of corpus atrophy than H. pylori-negative patients. No neuroendocrine tumours or gastric cancers were found.

PMID:
26177572
DOI:
10.1111/apt.13324
[Indexed for MEDLINE]
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