Savarino Vincenzo, Visaggi Pierfrancesco, Marabotto Elisa, Bertin Luisa, Pasta Andrea, Calabrese Francesco, Zentilin Patrizia, Ghisa Matteo, Ribolsi Mentore, Mari Amir, Tolone Salvatore, de Bortoli Nicola, Savarino Edoardo V
Department of Internal Medicine, Gastroenterology Unit, University of Genoa, Genoa.
Department of Translational Research and New Technologies in Medicine and Surgery, Gastroenterology Unit, University of Pisa, Pisa.
J Clin Gastroenterol. 2025 Mar 1;59(3):197-205. doi: 10.1097/MCG.0000000000002128.
Among the various factors implicated in the pathogenesis of gastroesophageal reflux disease (GERD), visceral hypersensitivity and mucosal resistance have been recently re-evaluated in relation to the increasing phenomenon of proton pump inhibitor failure, particularly in patients with nonerosive reflux disease (NERD). Intensive research has allowed us to understand that noxious substances contained in the refluxate are able to interact with esophageal epithelium and to induce the elicitation of symptoms. The frequent evidence of microscopic esophagitis able to increase the permeability of the mucosa, the proximity of sensory afferent nerve fibers to the esophageal lumen favoring the higher sensitivity to noxious substances and the possible activation of inflammatory pathways interacting with sensory nerve endings are pathophysiological alterations confirming that mucosal resistance is impaired in GERD patients. Accordingly, the reinforcement of protective mechanisms of esophageal mucosa by topical therapies has become a novel treatment target. Alginate, the combination of hyaluronic acid+chondroitin sulphate and Poliprotect have been shown to adhere to esophageal mucosa and to have good protective properties. Several placebo-controlled clinical trials have shown that these compounds, given alone or as add-on therapy for short periods, enable to relieve symptoms and to improve the quality of life in NERD patients. Further studies are needed to confirm the above results and to find new mucosal protectants in order to improve the management of NERD patients.
在胃食管反流病(GERD)发病机制涉及的各种因素中,内脏高敏感性和黏膜抵抗力最近因质子泵抑制剂失效现象增多,特别是在非糜烂性反流病(NERD)患者中,而得到重新评估。深入研究使我们明白,反流物中含有的有害物质能够与食管上皮相互作用并引发症状。微观食管炎频繁出现,可增加黏膜通透性;感觉传入神经纤维靠近食管腔,有利于对有害物质产生更高敏感性;炎症途径可能与感觉神经末梢相互作用而被激活,这些病理生理改变证实GERD患者的黏膜抵抗力受损。因此,通过局部治疗增强食管黏膜的保护机制已成为一个新的治疗靶点。海藻酸盐、透明质酸+硫酸软骨素组合以及Poliprotect已被证明可附着于食管黏膜并具有良好的保护特性。多项安慰剂对照临床试验表明,这些化合物单独使用或短期作为附加疗法,能够缓解NERD患者的症状并改善其生活质量。需要进一步研究来证实上述结果,并寻找新的黏膜保护剂,以改善NERD患者的治疗。