New opinion on the issue of proton pump inhibitor-refractory gastroesophageal reflux disease
Abstract
The aim of review. To present up-to-date data on the causes of proton pump inhibitor-refractory gastroesophageal reflux disease (GERD) development.
Summary. The prevalence of GERD reaches 20–30% of population, and approximately 40–50% of patients do not respond to standard treatment by proton pump inhibitors (PPI). There is a disorder of the immune response as a disbalance between cellular and humoral components of immunity at GERD, that can be determined as phenotype of macrophages (М1 or М2), and other immune and non-immune cells.
Conclusion. For the present moment it becomes clear, that low compliance of patients to PPI treatment, cytochrome Р450 isoenzyme CYP2C19 polymorphism and other known reasons are unable to explain growing number of refractory GERD cases. Therefore, studying of disease at cellular and tissue levels in relation to type of refluxate can disclose new mechanisms of refractory GERD and to increase treatment efficacy.
About the Authors
Yu. V. Yevsyutina
State educational government-financed institution of higher professional education «Sechenov First Moscow state medical university»
Russian Federation
Russian Federation
Yevsyutina Yuliya V — post-graduate student, Chair of internal diseases propedeutics, medical faculty
119991, Moscow, Pogodinskaya street, 1, bld 1
A. S. Trukhmanov
State educational government-financed institution of higher professional education «Sechenov First Moscow state medical university»
Russian Federation
Russian Federation
Trukhmanov Aleksander S — MD, PhD, professor, Chair of internal diseases propedeutics, medical faculty
119991, Moscow, Pogodinskaya street, 1, bld 1
References
1. Маев И.В., Вьючкова Е.С., Щекина М.И. Гастроэзофагеальная рефлюксная болезнь – болезнь XXI века. Лечащий врач 2004; 4:10-4.
2. Трухманов А.С. Гастроэзофагеальная рефлюксная болезнь: клинические варианты, прогноз, лечение: Автореф дис ... д-ра мед наук. М., 2008. 48 с.
3. Трухманов А.С., Джахая Н.Л., Кайбышева В.О., Сторонова О.А. Новые аспекты рекомендаций по лечению больных гастроэзофагеальной рефлюксной болезнью. Гастроэнтерол гепатол 2013; 1(4):1-9.
4. Шептулин А.А. Современные возможности и перспективы лечения резистентных форм гастроэзофагеальной рефлюксной болезни. Рос журн гастроэнтерол гепатол колопроктол 2010; 20 (6):81-5.
5. Bell N.J.V., Burget D., Howden C.W., et al. Appropriate acid suppression for the management of gastroesophageal reflux disease. Digestion 1992; 51 (suppl. 1):59-67.
6. Cheng L., Cao W., Behar J., Fiocchi C., Biancani P., Harnett K.M. Acid-induced release of platelet-activating factor by human esophageal mucosa induces inflammatory mediators in circular smooth muscle. J Pharmacol Exp Ther 2006; 319:117-26.
7. Cheng L., Cao W., Fiocchi C., Behar J., Biancani P., Harnett K.M. In vitro model of acute esophagitis in the cat. Am J Physiol Gastrointest Liver Physiol 2005; 289:860-9.
8. Cheng L., de la Monte S., Ma J., Hong J., Tong M., Cao W., Behar J., Biancani P., Harnett K.M. HClactivated neural and epithelial vanilloid receptors (TRPV1) in cat esophageal mucosa. Am J Physiol Gastrointest Liver Physiol 2009; 297:13-4.
9. Cheng L., Harnett K.M., Cao W., Liu F., Behar J., Fiocchi C., Biancani P. Hydrogen peroxide reduces lower esophageal sphincter tone in human esophagitis. Gastroenterology 2005; 129:1675-85.
10. Cicala M., Emerenziani S., Guarino M.P., Ribolsi M. Proton pump inhibitor resistance, the real challenge in gastroesophageal reflux disease. World J Gastroenterol 2013; 19 (39):6529-35.
11. El-Serag H.B., Sweet S., Winchester C.C., Dent J. Update on the epidemiology of gastroesophageal reflux disease: a systematic review. Gut 2014; 63 (6):871-8.
12. Fiocchi C. Intestinal inflammation: a complex interplay of immune and nonimmune cell interactions. Am J Physiol Gastrointest Liver Physiol 1997; 273:769-75.
13. Fitzgerald R.C., Onwuegbusi B.A., Bajaj-Elliott M., Saeed I.T., Burnham W.R., Farthing M.J. Diversity in the esophageal phenotypic response to gastroesophageal reflux: immunological determinants. Gut 2002; 50:451-9.
14. Rieder F., Biancani P., Harnett K., Yerian L., Falk G.W. Inflammatory mediators in gastroesophageal reflux disease: impact on esophageal motility, fibrosis, and carcinogenesis. Am J Physiol Gastrointest Liver Physiol 2010; 298:571-81.
15. Fu X., Beer D.G., Behar J., Wands J., Lambeth D., Cao W. cAMP-response element-binding protein mediates acid-induced NADPH oxidase NOX5-S expression in Barrett esophageal adenocarcinoma cells. J Biol Chem 2006; 281:20368-82.
16. Furuta, et al. Effect of cytochrome P4502C19 genotypic differences on cure rates for gastroesophageal reflux disease by lansoprazole. Clin Pharmacol Ther 2002; 72 (4):453-60.
17. Hernandez-Quintero M., Kuri-Harcuch W., Gonzalez Robles A., Castro-Munozledo F. Interleukin-6 promotes human epidermal keratinocyte proliferation and keratin cytoskeleton reorganization in culture. Cell Tissue Res 2006; 325:77-90.
18. Ishizaki T., Horai Y. Review article: cytochrome P450 and the metabolism of proton pump inhibitors – emphasis on rabeprazole. Aliment Pharmacol Ther 1999; 13 (suppl. 3):27-36.
19. Isomoto H., Inoue K., Kohno S. Interleukin-8 levels in esophageal mucosa and long-term clinical outcome of patients with reflux esophagitis. Scand J Gastroenterol 2007; 42:410-1.
20. Itzkowitz S.H., Yio X. Inflammation and cancer IV. Colorectal cancer in inflammatory bowel disease: the role of inflammation. Am J Physiol Gastrointest Liver Physiol 2004; 287:7-17.
21. Kastelein F., Spaander M.C., Steyerberg E.W., et al. Proton pump inhibitors reduce the risk of neoplastic progression in patients with Barrett’s esophagus. Clin Gastroenterol Hepatol 2013; 11 (4):382-8.
22. Ken Ariizumi, et al. Therapeutic effects of 10 mg/ day rabeprazole administration on reflux esophagitis was not influenced by the CYP2C19 polymorphism. J Gastroenterol Hepatol 2006; 21:1428-34.
23. Kohata Y., Fujiwara Y., Machida H., Okazaki H., Yamagami H., Tanigawa T., Watanabe K., Watanabe T, Tominaga K., Wei M., Wanibuchi H., Arakawa T. Role of Th-2 cytokines in the development of Barrett’s esophagus in rats. J Gastroenterol 2011; 46 (7):883-93.
24. Kuo C.H., et al. Rabeprazole Can Overcome the Impact of CYP2C19 polymorphism on quadruple therapy. Helicobacter 2010; 15 (4):265-72.
25. McInnes I.B., Liew F.Y. Cytokine networks – towards new therapies for rheumatoid arthritis. Nat Clin Pract Rheumatol 2005; 1:31-9.
26. Ogawa R., Echizen H. Drug-drug interaction profiles of proton pump inhibitors. Clin Pharmacokinet 2010; 49 (8):509-33.
27. O’Riordan J.M., Abdel-Latif M.M., Ravi N., McNamara D., Byrne P.J., McDonald G.S., Keeling P.W., Kelleher D., Reynolds J.V. Proinflammatory cytokine and nuclear factor kappa-B expression along the inflammation-metaplasia-dysplasia-adenocarcinoma sequence in the esophagus. Am J Gastroenterol 2005; 100:1257-64.
28. O’Shaughnessy A., Kelloff J., Gordon B., Dannenberg J., Hong K., Fabian J., Sigman C., Bertagnolli M., Stratton P., Lam S., Nelson G., Meyskens L., Alberts S., Follen M., Rustgi K., Papadimitrakopoulou V., Scardino T., Gazdar F., Wattenberg W., Sporn B., Sakr A., Lippman M., von Hoff D. Treatment and prevention of intraepithelial neoplasia: an important target for accelerated new agent development. Clin Cancer Res 2002; 8:314-46.
29. Philip O. Katz, Lauren B. Gerson, Marcelo F. Vela. Diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol 2013; 108:308-28.
30. Pietrzak A.T., Zalewska A., Chodorowska G., Krasowska D., Michalak-Stoma A., Nockowski P., Osemlak P., Paszkowski T., Rolinski J.M. Cytokines and anticytokines in psoriasis. Clin Chim Acta 2008; 394:7-21.
31. Pohl H., Welch H.G. The role of overdiagnosis and reclassification in the marked increase of esophageal adenocarcinoma incidence. J Natl Cancer Inst 2005; 97:142-6.
32. Rieder F., Cheng L., Harnett M., Chak A., Cooper S., Isenberg G., Ray M., Katz A., Catanzaro A., O’Shea R., Post B., Wong R., Sivak V., McCormick T., Phillips M., West A., Willis E., Biancani P., Fiocchi C. Gastroesophageal reflux disease-associated esophagitis induces endogenous cytokine production leading to motor abnormalities. Gastroenterology 2007; 132:154-65.
33. Saitoh T., et al. Influences of CYP2C19 polymorphism on recurrence of reflux esophagitis during proton pump inhibitor maintenance therapy. Hepatogastroenterology 2009; 56:703-6.
34. Samer C.F., Lorenzini K. Ing, Rollason V., Daali Y., Desmeules J.A. Applications of CYP450 testing in the clinical setting. Mol Diagn Ther 2013; 17:165-84.
35. Schmitz T., Chew L.J. Cytokines and myelination in the central nervous system. Sci World J 2008; 8:1119-47.
36. Seril D.N., Liao J., Yang G.Y., Yang C.S. Oxidative stress and ulcerative colitis-associated carcinogenesis: studies in humans and animal models. Carcinogenesis 2003; 24:353-62.
37. Souza R.F., Huo X., Mittal V., Schuler C.M., Carmack S.W., Zhang H.Y., Zhang X., Yu C., HormiCarver K., Genta R.M., Spechler S.J. Gastroesophageal reflux may cause esophagitis through a cytokine-mediated mechanism, not by caustic (acid) injury. Gastroenterology 2009; 137:1776-84.
38. Vakil N., van Zanten S.V., Kahrilas P., Dent J., Jones R. and the Global Consensus Group. Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol 2006; 101:1900-20.
39. Vogel J.D., West G.A., Danese S., de la Motte C., Phillips M.H., Strong S.A., Willis J., Fiocchi C. CD40-mediated immune-nonimmune cell interactions induce mucosal fibroblast chemokines leading to T-cell transmigration. Gastroenterology 2004; 126:63-80.
40. Williams I.R., Kupper T.S. Immunity at the surface: homeostatic mechanisms of the skin immune system. Life Sci 1996; 58:1485-507.
41. Xu X., Rivkind A., Pikarsky A., Pappo O., Bischoff C., Levi-Schaffer F. Mast cells and eosinophils have a potential profibrogenic role in Crohn disease. Scand J Gastroenterol 200; 39:440-7.
42. Zhong Y.Q., Lin Y., Xu Z. Expression of IFN-γ and IL-4 in the esophageal mucosa of patients with reflux esophagitis and Barrett’s esophagus and their relationship with endoscopic and histologic grading. Dig Dis Sci 2011;
43. (10):2865-70.
Review
For citations:
Yevsyutina Yu.V., Trukhmanov A.S. New opinion on the issue of proton pump inhibitor-refractory gastroesophageal reflux disease. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2014;24(5):4-10. (In Russ.)
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