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The problem of comorbidity with a high risk of polypragmasia is relevant in a large group of patients with diseases in the digestive system. Currently, the problem of comorbidity in patients with gastroesophageal reflux disease (GERD) attracts the attention of specialists due to the high disease prevalence and data indicating its association with other digestive system diseases, primarily of the hepatobiliary system. The article presents the results of clinical and experimental studies revealing the pathogenetic connections of GERD and hepatobiliary pathology accompanied by biliary dyskinesia, factors leading to an impairment of the duodenal propulsive activity. It is noted that the most important components of the esophageal mucosa lesion in duodenogastroesophageal reflux are bile acids, lysolecithin and pancreatic enzymes. The relevance of prescribing drugs that can affect the course of pathogenetically related diseases, which can significantly reduce the risk of polypragmasia, is justified. Such drugs include ursodeoxycholic acid, which, in the conditions of the GERD and hepatobiliary pathology association, contributes to the functional state normalization of the liver and biliary tract, reduces biliary dyskinesia, the severity of duodenal hypertension and duodenogastroesophageal reflux. The next example is the rebamipide cytoprotector, which has a multilateral protective effect against the mucous membrane of the GIT, including the esophagus, gastroduodenal zone, small intestine, as well as liver. The expediency of prescribing rebamipide to patients who are refractory to therapy with proton pump inhibitors is justified. KEYWORDS: comorbidity, hepatobiliary pathology, gastroesophageal reflux disease, ursodeoxycholic acid, rebamipid, proton pump inhibitors. FOR CITATION: Kazyulin A.N., Goncharenko A.Yu., Kalyagin I.E. Association of hepatobiliary pathology and gastroesophageal reflux disease. Russian Medical Inquiry. 2021;5(6):404–412 (in Russ.). DOI: 10.32364/2587-6821-2021-5-6-404-412.