Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland.
Division of Gastroenterology and Hepatology, The National University Hospital of Iceland, 101 Reykjavik, Iceland.
Int J Mol Sci. 2019 Nov 2;20(21):5469. doi: 10.3390/ijms20215469.
Proton pump inhibitors (PPIs) are recommended as a first-line treatment for gastroesophageal reflux disease (GERD) and other acid related disorders. In recent years, concerns have been raised about the increasing prevalence of patients on long-term PPI therapy and inappropriate PPI use. It is well known that short-term PPI therapy is generally well tolerated and safe; however, their extensive long-term use is a major global issue. One of these long-standing concerns is PPI-induced gastrin elevation secondary to hypoacidity. Hypergastrinemia is believed to play a role in rebound hyperacidity when PPIs are discontinued resulting in induced dyspeptic symptoms that might result in the reinstitution of therapy. Gastrin exerts tropic effects in the stomach, especially on enterochromaffin-like (ECL) cells, and concerns have also been raised regarding the potential progression to dysplasia or tumor formation following long-term therapy. It is well known that a substantial number of patients on long-term PPI therapy can discontinue PPIs without recurrence of symptoms in deprescribing trials. What is unknown is how sustainable deprescribing should be undertaken in practice and how effective it is in terms of reducing long-term outcomes like adverse drug events, morbidity and mortality. Moreover, there is no clear consensus on when and how deprescribing strategies should be attempted in practice. This review sought to summarize the harms and benefits of long-term PPI therapy with special focus on gastrin elevation and its relation to deprescribing studies and future interventions that may improve PPI use.
质子泵抑制剂 (PPIs) 被推荐作为胃食管反流病 (GERD) 和其他酸相关疾病的一线治疗药物。近年来，人们对长期接受 PPI 治疗和不适当使用 PPI 的患者的发病率增加表示担忧。众所周知，短期 PPI 治疗通常耐受性良好且安全；然而，它们的广泛长期使用是一个全球性的主要问题。其中一个长期存在的问题是 PPI 引起的胃酸减少导致的胃泌素升高。人们认为，当停止使用 PPI 时，高胃泌素血症会导致反弹性胃酸过多，从而导致诱导性消化不良症状，这可能导致重新开始治疗。胃泌素在胃中发挥营养作用，特别是对肠嗜铬样 (ECL) 细胞，人们还担心长期治疗后可能会发展为异型增生或肿瘤形成。众所周知，在停药试验中，相当数量的长期接受 PPI 治疗的患者可以在没有症状复发的情况下停止使用 PPI。目前尚不清楚在实践中应该如何可持续地进行停药，以及在减少不良反应、发病率和死亡率等长期结局方面的效果如何。此外，关于何时以及如何在实践中尝试停药策略还没有明确的共识。本综述旨在总结长期 PPI 治疗的危害和益处，特别关注胃泌素升高及其与停药研究和未来可能改善 PPI 使用的干预措施的关系。
