Development of plasma ghrelin level as a novel marker for gastric mucosal atrophy after <i>Helicobacter pylori</i> eradication

The severity of atrophic gastritis is significantly associated with the risk of gastric cancer. Although the current gold standard for assessing the gastric cancer risk is esophagogastroduodenoscopy with a pathological examination, the development of less-invasive biomarkers is warranted for efficient risk stratification of gastric cancer. Serum pepsinogens (PGs) are biomarkers used to predict the extent of gastric mucosal atrophy; however, they are not an accurate reflection of gastric mucosal atrophy after <i>Helicobacter pylori</i> eradication. The present study was conducted to investigate the usefulness of plasma ghrelin levels as a marker for gastric mucosal atrophy, and as a risk stratification marker for gastric cancer, even after <i>H. pylori</i> eradication. Patients who received <i>H. pylori</i> eradication treatment were enrolled in the study. The severity of gastric mucosal atrophy was evaluated both endoscopically and histologically. Serum pepsinogen and plasma ghrelin levels were measured before and at 1, 12, 24, and 48 weeks after treatment. The study was approved by the Research Ethics Committee of the Keio University School of Medicine (no. 20140102; 8 July 2014). Eighteen patients completed the study protocol. Total and acyl plasma ghrelin levels demonstrated no significant change from before treatment to 48 weeks after eradication; however, there was a significant difference between open-type and closed-type atrophic gastritis. The PG I/II ratio increased significantly from 48 weeks after <i>H. pylori</i> eradication. The severity of the histological intestinal metaplasia scores correlated inversely with plasma total ghrelin levels from before to 48 weeks after <i>H. pylori</i> eradication. Plasma levels of ghrelin correlate well with the level of gastric mucosal atrophy, even after <i>H. pylori</i> eradication.KEY MESSAGESGhrelin plasma levels are associated with the progression of endoscopic atrophic gastritis, even at 48 weeks after <i>H. pylori</i> eradication.Ghrelin plasma levels are also associated with increased severity of histological intestinal metaplasia 48 weeks after <i>H. pylori</i> eradication.Pepsinogen I/II ratios increased immediately after <i>H. pylori</i> eradication and are inappropriate for assessing atrophic gastritis after <i>H. pylori</i> eradication. Ghrelin plasma levels are associated with the progression of endoscopic atrophic gastritis, even at 48 weeks after <i>H. pylori</i> eradication. Ghrelin plasma levels are also associated with increased severity of histological intestinal metaplasia 48 weeks after <i>H. pylori</i> eradication. Pepsinogen I/II ratios increased immediately after <i>H. pylori</i> eradication and are inappropriate for assessing atrophic gastritis after <i>H. pylori</i> eradication.萎缩性胃炎的严重程度与胃癌风险显著相关。当前评估胃癌风险的金标准为联合病理检查的食管胃十二指肠镜检（esophagogastroduodenoscopy），但仍亟需开发低侵入性生物标志物，以实现高效的胃癌风险分层。血清胃蛋白酶原（serum pepsinogens, PGs）是用于预测胃黏膜萎缩程度的生物标志物，但在幽门螺杆菌（Helicobacter pylori）根除后，其无法准确反映胃黏膜萎缩情况。本研究旨在探讨血浆饥饿素（plasma ghrelin）水平作为胃黏膜萎缩标志物以及胃癌风险分层标志物的应用价值，即便在幽门螺杆菌根除后亦是如此。 本研究纳入接受幽门螺杆菌根除治疗的患者。通过内镜及组织学手段评估胃黏膜萎缩的严重程度。分别于治疗前、治疗后1、12、24及48周检测血清胃蛋白酶原与血浆饥饿素水平。本研究经庆应义塾大学医学院研究伦理委员会批准（编号：20140102；批准日期：2014年7月8日）。最终18名患者完成了全部研究方案。 血浆总饥饿素与酰化饥饿素水平在幽门螺杆菌根除治疗前至治疗后48周内无显著变化，但开放型与闭合型萎缩性胃炎患者的上述指标存在显著差异。PG I/II比值在幽门螺杆菌根除后48周时显著升高。组织学肠化生评分的严重程度与幽门螺杆菌根除前至根除后48周的血浆总饥饿素水平呈负相关。即便在幽门螺杆菌根除后，血浆饥饿素水平仍与胃黏膜萎缩程度密切相关。 KEY MESSAGES： 1. 即便在幽门螺杆菌根除后48周，血浆饥饿素水平仍与内镜下萎缩性胃炎的进展相关。 2. 血浆饥饿素水平也与幽门螺杆菌根除后48周时组织学肠化生的严重程度升高相关。 3. 胃蛋白酶原I/II比值在幽门螺杆菌根除后立即升高，因此不适用于评估幽门螺杆菌根除后的萎缩性胃炎。 即便在幽门螺杆菌根除后48周，血浆饥饿素水平仍与内镜下萎缩性胃炎的进展相关。血浆饥饿素水平也与幽门螺杆菌根除后48周时组织学肠化生的严重程度升高相关。胃蛋白酶原I/II比值在幽门螺杆菌根除后立即升高，因此不适用于评估幽门螺杆菌根除后的萎缩性胃炎。