Non-alcoholic fatty liver disease associated with gallstones in females rather than males: a longitudinal cohort study in Chinese urban population

Jia Liu, Haiyan Lin, Chengqi Zhang, Lu Wang, Shuo Wu, Dongzhi Zhang, Fang Tang, Fuzhong Xue, Yanxun Liu, Jia Liu, Haiyan Lin, Chengqi Zhang, Lu Wang, Shuo Wu, Dongzhi Zhang, Fang Tang, Fuzhong Xue, Yanxun Liu

Abstract

Background: Whether non-alcoholic fatty liver disease (NAFLD) is a risk factor for gallstones remains uncertain. Few longitudinal or cohort studies have been used to identify this relationship. The aim of this study was to confirm the association between NAFLD and gallstones in a longitudinal cohort of urban dwellers in China.

Methods: To elucidate the association between NAFLD and gallstones, we fitted a generalized estimating equation (GEE) model in a large-scale longitudinal cohort over 6 years, which included 11,200 participants with at least three regular health check-ups.

Results: A total of 498 cases of gallstones occurred during the 6-year follow-up, which resulted in a total incidence density of 12.73 per 1000 person-years (498/39, 135.5 person-years). The GEE analyses confirmed and clarified the association between NAFLD and gallstones (relative risk (RR) = 1.2381, 95% confidence interval (CI) = 1.003-1.528, P = 0.047) after adjusting for other potential confounding factors, especially in females (RR = 1.707, 95% CI = 1.245-2.341, P = 0.001).

Conclusions: NAFLD is associated with gallstones in an urban Chinese population from the middle to upper socioeconomic strata. Moreover, this association is more strongly apparent in females than in males. Further cohort studies must be conducted to confirm this association in the general population.

Figures

Figure 1
Figure 1
The longitudinal cohort study sample for analysis of association between non-alcoholic fatty liver disease and gallstones.

References

    1. Everhart JE, Khare M, Hill M, Maurer KR. Prevalence and ethnic differences in gallbladder disease in the United States. Gastroenterology. 1999;117:632–639. doi: 10.1016/S0016-5085(99)70456-7.
    1. Zeng Q, He Y, Qiang DC, Wu LX. Prevalence and epidemiological pattern of gallstones in urban residents in China. Eur J Gastroenterol Hepatol. 2012;24:1459–1460. doi: 10.1097/MEG.0b013e3283583d13.
    1. Shaffer EA. Gallstone disease: epidemiology of gallbladder stone disease. Best Pract Res Clin Gastroenterol. 2006;20:981–996. doi: 10.1016/j.bpg.2006.05.004.
    1. Kosters A, Jirsa M, Groen AK. Genetic background of cholesterol gallstone disease. Biochim Biophys Acta. 2003;1637:1–19. doi: 10.1016/S0925-4439(02)00173-4.
    1. Everhart JE. Contributions of obesity and weight loss to gallstone disease. Ann Intern Med. 1993;119:1029–1035. doi: 10.7326/0003-4819-119-10-199311150-00010.
    1. Tsai CJ, Leitzmann MF, Willett WC, Giovannucci EL. Macronutrients and insulin resistance in cholesterol gallstone disease. Am J Gastroenterol. 2008;103:2932–2939. doi: 10.1111/j.1572-0241.2008.02189.x.
    1. Pagliarulo M, Fornari F, Fraquelli M, Zoli M, Giangregorio F, Grigolon A, Peracchi M, Conte D. Gallstone disease and related risk factors in a large cohort of diabetic patients. Dig Liver Dis. 2004;36:130–134. doi: 10.1016/j.dld.2003.10.007.
    1. De Alwis NM, Day CP. Non-alcoholic fatty liver disease: the mist gradually clears. J Hepatol. 2008;48(Suppl 1):S104–S112. doi: 10.1016/j.jhep.2008.01.009.
    1. Fracanzani AL, Valenti L, Russello M, Miele L, Bertelli C, Bellia A, Masetti C, Cefalo C, Grieco A, Marchesini G, Fargion S. Gallstone disease is associated with more severe liver damage in patients with non-alcoholic fatty liver disease. Plos One. 2012;7:e41183. doi: 10.1371/journal.pone.0041183.
    1. Loria P, Lonardo A, Lombardini S, Carulli L, Verrone A, Ganazzi D, Rudilosso A, D'Amico R, Bertolotti M, Carulli N. Gallstone disease in non-alcoholic fatty liver: prevalence and associated factors. J Gastroenterol Hepatol. 2005;20:1176–1184. doi: 10.1111/j.1440-1746.2005.03924.x.
    1. Koller T, Kollerova J, Hlavaty T, Huorka M, Payer J. Cholelithiasis and markers of nonalcoholic fatty liver disease in patients with metabolic risk factors. Scand J Gastroenterol. 2012;47:197–203. doi: 10.3109/00365521.2011.643481.
    1. Chen CH, Huang MH, Yang JC, Nien CK, Etheredge GD, Yang CC, Yeh YH, Wu HS, Chou DA, Yueh SK. Prevalence and risk factors of gallstone disease in an adult population of Taiwan: an epidemiological survey. J Gastroenterol Hepatol. 2006;21:1737–1743. doi: 10.1111/j.1440-1746.2006.04381.x.
    1. Nomura H, Kashiwagi S, Hayashi J, Kajiyama W, Ikematsu H, Noguchi A, Tani S, Goto M. Prevalence of gallstone disease in a general population of Okinawa, Japan. Am J Epidemiol. 1988;128:598–605.
    1. Hsing AW, Gao YT, McGlynn KA, Niwa S, Zhang M, Han TQ, Wang BS, Chen J, Sakoda LC, Shen MC, Zhang BH, Deng J, Rashid A. Biliary tract cancer and stones in relation to chronic liver conditions: a population-based study in Shanghai, China. Int J Cancer. 2007;120:1981–1985. doi: 10.1002/ijc.22375.
    1. Zeng MD, Fan JG, Lu LG, Li YM, Chen CW, Wang BY, Mao YM. Guidelines for the diagnosis and treatment of nonalcoholic fatty liver diseases. J Dig Dis. 2008;9:108–112. doi: 10.1111/j.1751-2980.2008.00331.x.
    1. Schafer JL. Multiple imputation: a primer. Stat Methods Med Res. 1999;8:3–15. doi: 10.1191/096228099671525676.
    1. Hubbard AE, Ahern J, Fleischer NL, Van der Laan M, Lippman SA, Jewell N, Bruckner T, Satariano WA. To GEE or not to GEE: comparing population average and mixed models for estimating the associations between neighborhood risk factors and health. Epidemiology. 2010;21:467–474. doi: 10.1097/EDE.0b013e3181caeb90.
    1. Ruhl CE, Everhart JE. Relationship of non-alcoholic fatty liver disease with cholecystectomy in the US Population. Am J Gastroenterol. 2013;108:952–958. doi: 10.1038/ajg.2013.70.
    1. Stinton LM, Shaffer EA. Epidemiology of gallbladder disease: cholelithiasis and cancer. Gut Liver. 2012;6:172–187. doi: 10.5009/gnl.2012.6.2.172.
    1. Hashimoto E, Tokushige K. Prevalence, gender, ethnic variations, and prognosis of NASH. J Gastroenterol. 2011;46(Suppl 1):63–69. doi: 10.1007/s00535-010-0311-8.
    1. Lonardo A, Trande P. Are there any sex differences in fatty liver? A study of glucose metabolism and body fat distribution. J Gastroenterol Hepatol. 2000;15:775–782. doi: 10.1046/j.1440-1746.2000.02226.x.
    1. Xie Y, Wang M, Zhang Y, Zhang S, Tan A, Gao Y, Liang Z, Shi D, Huang Z, Zhang H, Yang X, Lu Z, Wu C, Liao M, Sun Y, Qin X, Hu Y, Li L, Peng T, Li Z, Mo Z. Serum uric acid and non-alcoholic fatty liver disease in non-diabetic Chinese men. Plos One. 2013;8:e67152. doi: 10.1371/journal.pone.0067152.
    1. Targher G, Byrne CD. Clinical review: nonalcoholic fatty liver disease: a novel cardiometabolic risk factor for type 2 diabetes and its complications. J Clin Endocrinol Metab. 2013;98:483–495. doi: 10.1210/jc.2012-3093.
    1. Cirillo DJ, Wallace RB, Rodabough RJ, Greenland P, LaCroix AZ, Limacher MC, Larson JC. Effect of estrogen therapy on gallbladder disease. JAMA. 2005;293:330–339. doi: 10.1001/jama.293.3.330.
    1. Henriksson P, Einarsson K, Eriksson A, Kelter U, Angelin B. Estrogen-induced gallstone formation in males. Relation to changes in serum and biliary lipids during hormonal treatment of prostatic carcinoma. J Clin Invest. 1989;84:811–816. doi: 10.1172/JCI114240.
    1. Wang HH, Liu M, Clegg DJ, Portincasa P, Wang DQ. New insights into the molecular mechanisms underlying effects of estrogen on cholesterol gallstone formation. Biochim Biophys Acta. 2009;1791:1037–1047. doi: 10.1016/j.bbalip.2009.06.006.
    1. Puri P, Baillie RA, Wiest MM, Mirshahi F, Choudhury J, Cheung O, Sargeant C, Contos MJ, Sanyal AJ. A lipidomic analysis of nonalcoholic fatty liver disease. Hepatology. 2007;46:1081–1090. doi: 10.1002/hep.21763.

Source: PubMed

3
Abonnere