Features of the course of gallstone disease in comorbid patients with non-alcoholic fatty liver disease

Objective: to improve diagnostic and therapeutic tactics in patients with cholelithiasis in combination with NAFLD, taking into account the impact of comorbidity. Materials and methods: We examined 180 people who applied to the Lotos Medical Center in Chelyabinsk in the period 2018-2020 with cholelithiasis and NAFLD at the age of 19 to 65 years. The study included 128 women (72%) and 52 men (28%). The mean age of the participants was 51.3±9 years. The work took into account anamnestic (comorbid pathology) anthropometric data (height, body weight, body mass index, waist circumference). All patients underwent general clinical, biochemical blood tests, ultrasound of the abdominal cavity, MSCT of the abdominal cavity with an assessment of the density of liver tissue, bile and gallbladder stones. Results of the study: The study showed that among patients with cholelithiasis in combination with NAFLD, 56% had comorbidity. Gallstones of low density were found in 41.6%, high density in 58.4%. Comorbid pathology was represented by obesity, cardiovascular diseases, pathology of the endocrine system, diseases of the gastrointestinal tract and diseases of the kidneys and urinary system. In the group of patients with gallstones with a density of more than 75 Hounsfield units, comorbid pathology was more common, and the degree of liver steatosis and fibrosis was higher. During treatment with UDCA 15 mg/kg, positive dynamics was observed in patients with low-density stones: a decrease in stone density and size (effective litholysis), normalization of liver density, normalization of cytolysis, cholestasis, and carbohydrate metabolism. In patients with gallstones over 75 Hounsfield units, there was a decrease in bile density without effective litholysis, normalization of cytolysis stigmas, cholestasis, correction of lipid and carbohydrate metabolism. Conclusion: in patients with cholelithiasis in combination with NAFLD, comorbid pathology is more common, which negatively affects the effectiveness of litholysis and worsens the prognosis in these patients. Medical litholysis in these patients is possible only at the initial stage of the disease in the presence of stones of low density and size. UDCA therapy makes it possible to control the density of bile and the size of gallbladder stones, the activity of the inflammatory process in the liver, preventing the progression and complications of NAFLD and cholelithiasis in comorbid patients.

Cholelithiasis, non-alcoholic fatty liver disease, litholysis, comorbidity

1. Fortin M., Bravo G., Hudon C., Vanasse A., Lapointe L. Prevalence of multimorbidity among adults seen in family practice. Ann Fam Med. 2005 May-Jun;3(3):223-8. doi: 10.1370/afm.272

2. Chowdhury M. Z.I., Anik A. M., Farhana Z., et al. Prevalence of metabolic syndrome in Bangladesh: a systematic review and meta-analysis of the studies. BMC Public Health. 2018 Mar 2;18(1):308. doi: 10.1186/s12889-018-5209-z

3. Osadchuk M. A., Kireeva N. V., Vasilieva I. N., Mironova E. D. The influence of the severity of metabolic disorders on the diameter of the stones in the gallbladder: clinical and instrumental and laboratory data. Therapy. 2019;5(3):55-59. (in Russ.) doi: 10.18565/therapy.2019.3.55-59 @@Осадчук М. А., Киреева Н. В., Васильева И. Н., Миронова Е. Д. Влияние степени выраженности метаболических нарушений на диаметр конкрементов в желчном пузыре: клинико-инструментальные илабораторные данные. Терапия. 2019; 5 (3): 55

4. ChenL-Y., Qiao Q-H., Zhang S-Cetal. Metabolic syndrome and gallstone disease. World J Gastroenterol. 2012 Aug 21;18(31):4215-20. doi: 10.3748/wjg.v18.i31.4215

5. Ata N., Kucukazman M., Yavuz B., et al. The metabolic syndrome is associated with complicated gallstone disease. Can J Gastroenterol. 2011 May;25(5):274-6. doi: 10.1155/2011/356761

6. Marques P., Collado A., Martinez-Hervás S., er al. Systemic Inflammation in Metabolic Syndrome: Increased Platelet and Leukocyte Activation, and Key Role of CX3CL1/CX3CR1 and CCL2/CCR2 Axes in Arterial Platelet-Proinflammatory Monocyte Adhesion. J Clin Med. 2019 May 18;8(5):708. doi: 10.3390/jcm8050708

7. Lin I. C., Yang Y. W., Wu M. F., Yeh Y. H., Liou J. C., Lin Y. L., Chiang C. H. The association of metabolic syndrome and its factors with gallstone disease. BMC Fam Pract. 2014 Jul 29;15:138. doi: 10.1186/1471-2296-15-138

8. Fairfield C. J., Wigmore S. J., Harrison E. M. Gallstone Disease and the Risk of Cardiovascular Disease. Sci Rep. 2019 Apr 9;9(1):5830. doi: 10.1038/s41598-019-42327-2

9. Uspensky Yu. P., Fominykh Yu. A., Sousova J. V., Gulunov Z. H., Niyazov R. M. Gastrointestinal manifestations of metabolic syndrome. Doctor. 2018;29(12): 3-8. doi:10.29296/25877305-2018-12-0

10. Smelt A. H. Triglycerides and gallstone formation. Clin Chim Acta. 2010 Nov 11;411(21-22):1625-31. doi: 10.1016/j.cca.2010.08.003

11. Ata N, Kucukazman M, Yavuz B, et al. The metabolic syndrome is associated with complicated gallstone disease. Can J Gastroenterol. 2011 May;25(5):274-6. doi: 10.1155/2011/356761

12. Zhao S. F., Wang A. M., Yu X. J., Wang L. L., Xu X. N., Shi G. J. Association between gallstone and cardio-cerebrovascular disease: Systematic review and meta-analysis. Exp Ther Med. 2019 Apr;17(4):3092-3100. doi: 10.3892/etm.2019.7291

13. Bueverov A. O. Clinical and Pathogenetic Parallels of Nonalcoholic Fatty Liver Disease and Gallstone Disease.Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2019;29(1):17-23. (In Russ.) doi:10.22416/1382-4376-2019-29-1-17-23 @@Буеверов А. О. Клинико-патогенетические параллели НАЖБП ЖКБ. Российский Журнал гастроэнтерологии, гепатологии, колопроктологии. 2019;29(1):17-23

14. Komshilova K. A., Troshina E. A. Obesity and non-alcoholic fatty liver disease. Treatment and prevention. 2012;1:99-108. (in Russ.) @@Комшилова К. А., Трошина Е. А. Ожирение и неалкогольная жировая болезнь печени. Лечение и профилактика. 2012;1:99-108

15. Skvortsova T. E., Sitkin S. I., Radchenko V. G., Seliverstov P. V. Gallstone disease Modern approaches to diagnosis, treatment and prevention: a guide for doctors. Moscow: Forte print Publ., 2013. 32 P. (in Russ.) @@Скворцова Т. Э., Ситкин С. И., Радченко В. Г., Селиверстов П. В. Желчнокаменная болезнь Современные подходы к диагностике, лечению и профилактике: пособие для врачей. М.: Форте принт, 2013. 32с

16. Li X., Guo X., Ji H., Yu G., Gao P. Gallstones in Patients with Chronic Liver Diseases. Biomed Res Int. 2017;2017:9749802. doi: 10.1155/2017/9749802

17. Tint G. S., Salen G., Colalillo A., Graber D., Verga D., Speck J., Shefer S. Ursodeoxycholic acid: a safe and effective agent for dissolving cholesterol gallstones. Ann Intern Med. 1982 Sep;97(3):351-6. doi: 10.7326/0003-4819-97-3-351

18. Lee J. M., Hyun J. J., Choi I. Y., et al.Comparison on Response and Dissolution Rates Between Ursodeoxycholic Acid Alone or in Combination With Chenodeoxycholic Acid for Gallstone Dissolution According to Stone Density on CT Scan: Strobe Compliant Observation Study. Medicine (Baltimore). 2015 Dec;94(50): e2037. doi: 10.1097/MD.0000000000002037

19. Tomida S., Abei M., Yamaguchi T., Matsuzaki Y., Shoda J., Tanaka N., Osuga T. Long-term ursodeoxycholic acid therapy is associated with reduced risk of biliary pain and acute cholecystitis in patients with gallbladder stones: a cohort analysis. Hepatology. 1999 Jul;30(1):6-13. doi: 10.1002/hep.510300108

20. Ivashkin V. T., Mayevskaya M. V., Pavlov C. S., et al. Diagnostics and treatment of non-alcoholic fatty liver disease: clinical guidelines of the Russian Scientific Liver Society and the Russian gastroenterological association.Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2016;26(2):24-42. (In Russ.) doi: 10.22416/1382-4376-2016-26-2-24-42 @@Ивашкин В. Т., Маевская М. В., Павлов Ч. С., Тихонов И. Н., Широкова Е. Н., Буеверов А. О., Драпкина О. М., Шульпекова Ю. О., Цуканов В. В., Маммаев С. Н., Маев И. В., Пальгова Л. К. Клинические рекомендации по диагностике и лечению неалкогольной жировой болезни печени Российского общества по изучению печени и Российской гастроэнтерологической ассоциации. Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2016;26(2):24-41

21. Bueverov A. O. Clinical and Pathogenetic Parallels of Nonalcoholic Fatty Liver Disease and Gallstone Disease.Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2019;29(1):17-23. (In Russ.) doi:10.22416/1382-4376-2019-29-1-17-23 @@Буеверов А. О. Клинико-патогенетические параллели НАЖБП и ЖКБ. Российский Журнал гастроэнтерологии, гепатологии, колопроктологии. 2019;29(1):17-23

22. Mayevskaya M. V., Nadinskaia M. Yu., Lunkov V. D., et al. An Effect of Ursodeoxycholic Acid on Inflammation, Steatosis and Liver Fibrosis and Atherogenesis Factors in Patients with Non-Alcoholic Fatty Liver Disease: Results of the USPEH Study.Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2019;29(6):22-29. (In Russ.) doi:10.22416/1382-4376-2019-29-6-22-29 @@Маевская М. В., Надинская М. Ю., Луньков В. Д., Пирогова И. Ю., Чесноков Е. В., Кодзоева Х. Б., Ивашкин В. Т. Влияние урсодезоксихолевой кислоты на воспаление, стеатоз и фиброз печени и факторы атерогенеза у больных неалкогольной жировой болезнью печени: результаты исследования УСПЕХ. Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2019;29(6):22-29. doi:10.22416/1382-4376-2019-29-6-22-29