The Association Between Cholecystectomy, Metabolic Syndrome, and Nonalcoholic Fatty Liver Disease: A Population-Based Study

Carmen S S Latenstein, Louise J M Alferink, Sarwa Darwish Murad, Joost P H Drenth, Cornelis J H M van Laarhoven, Philip R de Reuver, Carmen S S Latenstein, Louise J M Alferink, Sarwa Darwish Murad, Joost P H Drenth, Cornelis J H M van Laarhoven, Philip R de Reuver

Abstract

Objectives: Obesity is a risk factor for several phenotypes such as gallstones, metabolic syndrome (MS), and nonalcoholic fatty liver disease (NAFLD). It has been suggested that cholecystectomy is a risk factor for metabolic abnormalities and NAFLD. We aimed to determine whether cholecystectomy is associated with MS or NAFLD in a Dutch population-based study.

Methods: The Rotterdam Study is an ongoing prospective population-based cohort. We included participants who underwent a liver ultrasound between 2009 and 2014 to assess steatosis. The prevalence of MS and NAFLD was calculated, and we performed regression analyses relating cholecystectomy with MS and NAFLD and adjusted for age, sex, study cohort, education level, physical activity, energy intake, time since cholecystectomy, body mass index, presence of hypertension, diabetes mellitus, and steatosis/MS.

Results: We included 4,307 participants (57.5% women, median age 66.0 years [interquartile range 58-74]). In total, 265 participants (6.2%) underwent a cholecystectomy. The median age at the time of cholecystectomy was 57.0 years (47.5-66.5), and the median time from cholecystectomy to imaging of the liver was 10.0 years (0.5-19.5). The prevalence of MS in participants with cholecystectomy was 67.2% and 51.9% in participants without cholecystectomy (P < 0.001). Ultrasound diagnosed moderate/severe NAFLD was present in, respectively, 42.7% and 34.2% of the participants (P = 0.008). After multivariable adjustments for metabolic factors, cholecystectomy was no longer associated with the presence of MS or NAFLD.

Discussion: The prevalence of MS and NAFLD is higher in participants after cholecystectomy. However, our trial shows that cholecystectomy may not be independently associated with the presence of MS and NAFLD after correction for metabolic factors.

Figures

Figure 1.
Figure 1.
Available data on time line. Participants in cohort I and cohort III of the Rotterdam Study were included. Participants in cohort I had their first visit to the study center between 1989 and 1993. We included data from visit 5 (2009–2011). Participants in cohort III had their first visit to the study center between 2006 and 2008. We included data from visit 2 (2012–2014).
Figure 2.
Figure 2.
Flowchart of inclusion. Participants were included from cohort I and cohort III. Participants with missing ultrasound or metabolic syndrome data were excluded. RS, Rotterdam Study.

References

    1. Ruhl CE, Everhart JE. Relationship of non-alcoholic fatty liver disease with cholecystectomy in the US population. Am J Gastroenterol 2013;108(6):952–8.
    1. Amigo L, Husche C, Zanlungo S, et al. Cholecystectomy increases hepatic triglyceride content and very-low-density lipoproteins production in mice. Liver Int 2011;31(1):52–64.
    1. Estes C, Razavi H, Loomba R, et al. Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease. Hepatology 2018;67(1):123–33.
    1. Buzzetti E, Pinzani M, Tsochatzis EA. The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD). Metabolism 2016;65(8):1038–48.
    1. Friedman SL, Neuschwander-Tetri BA, Rinella M, et al. Mechanisms of NAFLD development and therapeutic strategies. Nat Med 2018;24(7):908–22.
    1. Di Ciaula A, Garruti G, Wang DQ, et al. Cholecystectomy and risk of metabolic syndrome. Eur J Intern Med 2018;53:3–11.
    1. Chen Y, Wu S, Tian Y. Cholecystectomy as a risk factor of metabolic syndrome: From epidemiologic clues to biochemical mechanisms. Lab Invest 2018;98(1):7–14.
    1. Zweers SJ, Booij KA, Komuta M, et al. The human gallbladder secretes fibroblast growth factor 19 into bile: Towards defining the role of fibroblast growth factor 19 in the enterobiliary tract. Hepatology 2012;55(2):575–83.
    1. Thijs C, Knipschild P, van Engelshoven J. The prevalence of gallstone disease in a Dutch population. Scand J Gastroenterol 1990;25(2):155–60.
    1. van den Berg EH, Amini M, Schreuder TC, et al. Prevalence and determinants of non-alcoholic fatty liver disease in lifelines: A large Dutch population cohort. PLoS One 2017;12(2):e0171502.
    1. Bos MB, de Vries JH, Wolffenbuttel BH, et al. The prevalence of the metabolic syndrome in the Netherlands: Increased risk of cardiovascular diseases and diabetes mellitus type 2 in one quarter of persons under 60 [in Dutch]. Ned Tijdschr Geneeskd 2007;151(43):2382–8.
    1. Portincasa P, Moschetta A, Palasciano G. Cholesterol gallstone disease. Lancet 2006;368(9531):230–9.
    1. Bedogni G, Miglioli L, Masutti F, et al. Prevalence of and risk factors for nonalcoholic fatty liver disease: The dionysos nutrition and liver study. Hepatology 2005;42(1):44–52.
    1. Shaffer EA. Epidemiology and risk factors for gallstone disease: Has the paradigm changed in the 21st century? Curr Gastroenterol Rep 2005;7(2):132–40.
    1. Ikram MA, Brusselle GGO, Murad SD, et al. The Rotterdam Study: 2018 update on objectives, design and main results. Eur J Epidemiol 2017;32(9):807–50.
    1. Hamaguchi M, Kojima T, Itoh Y, et al. The severity of ultrasonographic findings in nonalcoholic fatty liver disease reflects the metabolic syndrome and visceral fat accumulation. Am J Gastroenterol 2007;102(12):2708–15.
    1. Alberti KG, Eckel RH, Grundy SM, et al. Harmonizing the metabolic syndrome: A joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 2009;120(16):1640–5.
    1. Goldbohm RA, van den Brandt PA, Brants HA, et al. Validation of a dietary questionnaire used in a large-scale prospective cohort study on diet and cancer. Eur J Clin Nutr 1994;48(4):253–65.
    1. Jaruvongvanich V, Sanguankeo A, Upala S. Significant Association between gallstone disease and nonalcoholic fatty liver disease: A systematic review and meta-analysis. Dig Dis Sci 2016;61(8):2389–96.
    1. Lu SN, Chang WY, Wang LY, et al. Risk factors for gallstones among Chinese in Taiwan. A community sonographic survey. J Clin Gastroenterol 1990;12(5):542–6.
    1. Chen JY, Hsu CT, Liu JH, et al. Clinical predictors of incident gallstone disease in a Chinese population in Taipei, Taiwan. BMC Gastroenterol 2014;14(1):83.
    1. Zhu L, Aili A, Zhang C, et al. Prevalence of and risk factors for gallstones in Uighur and Han Chinese. World J Gastroenterol 2014;20(40):14942–9.
    1. Koller T, Kollerova J, Hlavaty T, et al. Cholelithiasis and markers of nonalcoholic fatty liver disease in patients with metabolic risk factors. Scand J Gastroenterol 2012;47(2):197–203.
    1. Nervi F, Miquel JF, Alvarez M, et al. Gallbladder disease is associated with insulin resistance in a high risk Hispanic population. J Hepatol 2006;45(2):299–305.
    1. Chen CH, Huang MH, Yang JC, et al. Prevalence and risk factors of gallstone disease in an adult population of Taiwan: An epidemiological survey. J Gastroenterol Hepatol 2006;21(11):1737–43.
    1. Wang HG, Wang LZ, Fu HJ, et al. Cholecystectomy does not significantly increase the risk of fatty liver disease. World J Gastroenterol 2015;21(12):3614–8.
    1. Shen C, Wu X, Xu C, et al. Association of cholecystectomy with metabolic syndrome in a Chinese population. PLoS One 2014;9(2):e88189.
    1. Su PY, Hsu YC, Cheng YF, et al. Strong association between metabolically-abnormal obesity and gallstone disease in adults under 50 years. BMC Gastroenterol 2019;19(1):117.
    1. Mendez-Sanchez N, Bahena-Aponte J, Chavez-Tapia NC, et al. Strong association between gallstones and cardiovascular disease. Am J Gastroenterol 2005;100(4):827–30.
    1. Barrera F, Azocar L, Molina H, et al. Effect of cholecystectomy on bile acid synthesis and circulating levels of fibroblast growth factor 19. Ann Hepatol 2015;14(5):710–21.
    1. Gastaldelli A. Fatty liver disease: The hepatic manifestation of metabolic syndrome. Hypertens Res 2010;33(6):546–7.
    1. Lizardi-Cervera J, Aguilar-Zapata D. Nonalcoholic fatty liver disease and its association with cardiovascular disease. Ann Hepatol 2009;8:S40–S43.
    1. van Dijk AH, Wennmacker SZ, de Reuver PR, et al. Restrictive strategy versus usual care for cholecystectomy in patients with gallstones and abdominal pain (SECURE): A multicentre, randomised, parallel-arm, non-inferiority trial. Lancet 2019;393(10188):2322–30.
    1. Mantovani A, Byrne CD, Bonora E, et al. Nonalcoholic fatty liver disease and risk of incident type 2 diabetes: A meta-analysis. Diabetes Care 2018;41(2):372–82.
    1. Utzschneider KM, Kahn SE. The role of insulin resistance in nonalcoholic fatty liver disease. J Clin Endocrinol Metab 2006;91(12):4753–61.
    1. Kitade H, Chen G, Ni Y, et al. Nonalcoholic fatty liver disease and insulin resistance: New Insights and potential new treatments. Nutrients 2017;9(4):E387.
    1. Khan RS, Bril F, Cusi K, et al. Modulation of insulin resistance in nonalcoholic fatty liver disease. Hepatology 2019;70(2):711–24.
    1. Ko CW, Beresford SA, Schulte SJ, et al. Insulin resistance and incident gallbladder disease in pregnancy. Clin Gastroenterol Hepatol 2008;6(1):76–81.
    1. Pihlajamaki J, Gylling H, Miettinen TA, et al. Insulin resistance is associated with increased cholesterol synthesis and decreased cholesterol absorption in normoglycemic men. J Lipid Res 2004;45(3):507–12.
    1. Adiels M, Olofsson SO, Taskinen MR, et al. Overproduction of very low-density lipoproteins is the hallmark of the dyslipidemia in the metabolic syndrome. Arterioscler Thromb Vasc Biol 2008;28(7):1225–36.
    1. Biddinger SB, Haas JT, Yu BB, et al. Hepatic insulin resistance directly promotes formation of cholesterol gallstones. Nat Med 2008;14(7):778–82.
    1. Nakeeb A, Comuzzie AG, Al-Azzawi H, et al. Insulin resistance causes human gallbladder dysmotility. J Gastrointest Surg 2006;10(7):940–8; discussion 948–9.
    1. Kullak-Ublick GA, Paumgartner G, Berr F. Long-term effects of cholecystectomy on bile acid metabolism. Hepatology 1995;21(1):41–5.
    1. Almond HR, Vlahcevic ZR, Bell CC, Jr, et al. Bile acid pools, kinetics and biliary lipid composition before and after cholecystectomy. N Engl J Med 1973;289(23):1213–6.
    1. Schwenzer NF, Springer F, Schraml C, et al. Non-invasive assessment and quantification of liver steatosis by ultrasound, computed tomography and magnetic resonance. J Hepatol 2009;51(3):433–45.

Source: PubMed

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