Pathogenesis, Diagnosis and Treatment of Gallstone Disease
A Brief Review
DOI:
https://doi.org/10.48112/bcs.v1i2.99Abstract
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Gallstone disease is a gastrointestinal disease that results from the dysfunction of cholesterol, bile, and bilirubin metabolism. Gallstones in the gallbladder are common and form through cholelithiasis. They can also grow in biliary ducts through choledocholithiasis. In industrial countries, gallstone disease has increased in prevalence and affects up to 20% of the adult population. Its major risk factors are female gender, age, obesity, type 2 diabetes, rapid weight loss, physical inactivity, and genetic traits. Various systems for gallstone classification are available. Gallstones are classified as cholesterol, pigmented, and mixed gallstones in accordance with their chemical composition. Gallstone disease is either asymptomatic or has symptoms that manifest as pain in the right upper part of the abdomen, fever, and jaundice. The pathogenesis of this disease is related to the interaction between genetic and environmental factors, which include hepatic cholesterol hypersecretion, bile supersaturation, mucin, inflammatory changes, intestinal hypomotility, intestinal cholesterol hyperabsorption, and gut microbe alterations. The major genetic factors of this disease are the mutations in the hepatic cholesterol transporter ABCC8 and the cholecystokinin a receptor gene. Metabolic syndrome, insulin resistance, and type 2 diabetes increase the risk of developing gallstone disease. The standard diagnostic method for gallstone disease is ultrasound imaging. Medical treatment involves the administration of bile acid drugs and/or cholecystectomy.
Keywords:
Bilirubin, Cholecystitis, Cholesterol, Gallbladder, Inflammation
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Abdullah, U. Y., Jassim, H. M., Baig, A. A., Khorsheed, R. M., Al-Khayat, A. M., Sulong, A. F., ... & Yassin, W. A. (2015). Gallstones in patients with inherited hemolytic diseases. International Journal of Pharmacy and Pharmaceutical Sciences, 7(7), 9-15.
Afdhal, N. H. (2007). Diseases of the Gallbladder and Bile Ducts/Ed. by L. Goldman, D. Ausiello. Cecil Textbook of Medicine.—23rd ed.—Philadelphia: Saunders Elsevier.
Amaral, J., Xiao, Z. L., Chen, Q., Yu, P., Biancani, P., & Behar, J. (2001). Gallbladder muscle dysfunction in patients with chronic acalculous disease. Gastroenterology, 120(2), 506-511. https://doi.org/10.1053/gast.2001.21190
Aslam, H. M., Saleem, S., Edhi, M. M., Shaikh, H. A., Hafiz, M., & Saleem, M. (2013). Assessment of gallstone predictor: comparative analysis of ultrasonographic and biochemical parameters. International archives of medicine, 6(1), 1-7. https://doi.org/10.1186/1755-7682-6-17
Bagepally, B. S., Haridoss, M., Sasidharan, A., Jagadeesh, K. V., & Oswal, N. K. (2021). Systematic review and meta-analysis of gallstone disease treatment outcomes in early cholecystectomy versus conservative management/delayed cholecystectomy. BMJ open gastroenterology, 8(1), e000675. http://dx.doi.org/10.1136/bmjgast-2021-000675
Berger, M. Y., & Bohnen, A. M. (2003). Abdominal symptoms: do they disappear after cholecystectomy?. Surgical Endoscopy And Other Interventional Techniques, 17(11), 1723-1728. https://doi.org/10.1007/s00464-002-9154-6
Buch, S., Schafmayer, C., Völzke, H., Becker, C., Franke, A., von Eller-Eberstein, H., ... & Hampe, J. (2007). A genome-wide association scan identifies the hepatic cholesterol transporter ABCG8 as a susceptibility factor for human gallstone disease. Nature genetics, 39(8), 995-999. https://doi.org/10.1038/ng2101
Carey, M. C. (1993). Pathogenesis of gallstones. The American journal of surgery, 165(4), 410-419. https://doi.org/10.1016/S0002-9610(05)80932-8
Chong, V. H. (2005). Iatrogenic biliary stone. Surgical technology international, 14, 147-155.
Chuang, S. C., Hsi, E., & Lee, K. T. (2012). Mucin genes in gallstone disease. Clinica Chimica Acta, 413(19-20), 1466-1471. https://doi.org/10.1016/j.cca.2012.06.015
Chuang, S. C., Hsi, E., Wang, S. N., Yu, M. L., Lee, K. T., & Juo, S. H. H. (2011). Polymorphism at the mucin-like protocadherin gene influences susceptibility to gallstone disease. Clinica Chimica Acta, 412(23-24), 2089-2093. https://doi.org/10.1016/j.cca.2011.07.015
Cohen, D. E., Kaler, E. W., & Carey, M. C. (1993). Cholesterol carriers in human bile: are “lamellae” involved?. Hepatology, 18(6), 1522-1531. https://doi.org/10.1002/hep.1840180635
Cox, M. R., Eslick, G. D., & Padbury, R. (Eds.). (2018). The management of gallstone disease: a practical and evidence-based approach. Springer.
Dai, X. Z., Li, G. Q., Zhang, F., Wang, X. H., & Zhang, C. Y. (2013). Gallstone ileus: case report and literature review. World Journal of Gastroenterology: WJG, 19(33), 5586. https://dx.doi.org/10.3748%2Fwjg.v19.i33.5586
De Bari, O., Wang, T. Y., Liu, M., Portincasa, P., & Wang, D. Q. (2015). Estrogen induces two distinct cholesterol crystallization pathways by activating ERα and GPR30 in female mice. Journal of Lipid Research, 56(9), 1691-1700. https://doi.org/10.1194/jlr.M059121
Di Ciaula, A., & Portincasa, P. (2014). Fat, epigenome and pancreatic diseases. Interplay and common pathways from a toxic and obesogenic environment. European Journal of Internal Medicine, 25(10), 865-873. https://doi.org/10.1016/j.ejim.2014.10.012
Di Ciaula, A., Wang, D. Q. H., & Portincasa, P. (2018). An update on the pathogenesis of cholesterol gallstone disease. Current opinion in gastroenterology, 34(2), 71. https://dx.doi.org/10.1097%2FMOG.0000000000000423
Di Ciaula, A., Wang, D. Q. H., Bonfrate, L., & Portincasa, P. (2013). Current views on genetics and epigenetics of cholesterol gallstone disease. Cholesterol, 2013.
Everhart, J. E., Khare, M., Hill, M., & Maurer, K. R. (1999). Prevalence and ethnic differences in gallbladder disease in the United States. Gastroenterology, 117(3), 632-639. https://doi.org/10.1016/S0016-5085(99)70456-7
Febyan, F. (2020). Cholelithiasis: A Brief Review on Diagnostic Approach and Management in Clinical Practice. International Journal of Medical Reviews, 7(3), 98-101. https://doi.org/10.19080/argh.2020.15.555913
Ghai, C. L. (2012). A textbook of practical physiology. JP Medical Ltd.
Giljaca, V., Gurusamy, K. S., Takwoingi, Y., Higgie, D., Poropat, G., Štimac, D., & Davidson, B. R. (2015). Endoscopic ultrasound versus magnetic resonance cholangiopancreatography for common bile duct stones. Cochrane Database of Systematic Reviews, (2). https://doi.org/10.1002/14651858.CD011549
Grigorieva, I. N. (2007). Major risk factors of cholelithiasis. Rossiyskiy Zhurnal Gastroenterologii, Gepatologii i Koloproktologii, 6, 17-19.
Guarino, M. P. L., Cocca, S., Altomare, A., Emerenziani, S., & Cicala, M. (2013). Ursodeoxycholic acid therapy in gallbladder disease, a story not yet completed. World Journal of Gastroenterology: WJG, 19(31), 5029. https://dx.doi.org/10.3748%2Fwjg.v19.i31.5029
Gutt, C., Schläfer, S., & Lammert, F. (2020). The treatment of gallstone disease. Deutsches Ärzteblatt International, 117(9), 148. https://dx.doi.org/10.3238%2Farztebl.2020.0148
Gylling, H., Hallikainen, M., Pihlajamäki, J., Simonen, P., Kuusisto, J., Laakso, M., & Miettinen, T. A. (2010). Insulin sensitivity regulates cholesterol metabolism to a greater extent than obesity: lessons from the METSIM Study 1. Journal of lipid research, 51(8), 2422-2427. https://doi.org/10.1194/jlr.P006619
Heuman, D.M., Mihas, A.A., Allen, J. (2019). Gallstones (Cholelithiasis). Emedicine.medscape.com. Retrieved 29 March 2022, from https://emedicine.medscape.com/article/175667-overview.
Hirobe-Jahn, S., Harsch, S., Renner, O., Richter, D., Müller, O., & Stange, E. F. (2015). Association of FXR gene variants with cholelithiasis. Clinics and research in hepatology and gastroenterology, 39(1), 68-79. https://doi.org/10.1016/j.clinre.2014.07.002
Hofmann, A. F. (2007). Biliary secretion and excretion in health and disease: current concepts. Annals of hepatology, 6(1), 15-27.
Hsing, A. W., Bai, Y., Andreotti, G., Rashid, A., Deng, J., Chen, J., ... & Gao, Y. T. (2007). Family history of gallstones and the risk of biliary tract cancer and gallstones: a population‐based study in Shanghai, China. International journal of cancer, 121(4), 832-838. https://doi.org/10.1002/ijc.22756
Ilychenko, A. A. (2004). Gallstone disease. Lechashchiy Vrach, 4, 27-33.
Iqbal, M. N., Iqbal, M. A., Javaid, R., & Abbas, M. W. (2019). Gall stones: A fundamental clinical review.
Jüngst, C., Sreejayan, N., Eder, M. I., Von Stillfried, N., Zündt, B., Spelsberg, F. W., ... & Von Ritter, C. (2007). Lipid peroxidation and mucin secretagogue activity in bile of gallstone patients. European journal of clinical investigation, 37(9), 731-736. https://doi.org/10.1111/j.1365-2362.2007.01853.x
Kaechele, V., Wabitsch, M., Thiere, D., Kessler, A. L., Haenle, M. M., Mayer, H., & Kratzer, W. (2006). Prevalence of gallbladder stone disease in obese children and adolescents: influence of the degree of obesity, sex, and pubertal development. Journal of pediatric gastroenterology and nutrition, 42(1), 66-70.
Katsika, D., Grjibovski, A., Einarsson, C., Lammert, F., Lichtenstein, P., & Marschall, H. U. (2005). Genetic and environmental influences on symptomatic gallstone disease: a Swedish study of 43,141 twin pairs. Hepatology, 41(5), 1138-1143. https://doi.org/10.1002/hep.20654
Keren, N., Konikoff, F. M., Paitan, Y., Gabay, G., Reshef, L., Naftali, T., & Gophna, U. (2015). Interactions between the intestinal microbiota and bile acids in gallstones patients. Environmental microbiology reports, 7(6), 874-880. https://doi.org/10.1111/1758-2229.12319
Kern, F. (1994). Effects of dietary cholesterol on cholesterol and bile acid homeostasis in patients with cholesterol gallstones. The Journal of clinical investigation, 93(3), 1186-1194. https://doi.org/10.1172/JCI117072
Keus, F., de Jong, J., Gooszen, H. G., & Laarhoven, C. J. (2006). Laparoscopic versus open cholecystectomy for patients with symptomatic cholecystolithiasis. Cochrane database of systematic reviews, (4). https://doi.org/10.1002/14651858.CD006231
Krawczyk, M., Lütjohann, D., Schirin‐Sokhan, R., Villarroel, L., Nervi, F., Pimentel, F., ... & Miquel, J. F. (2012). Phytosterol and cholesterol precursor levels indicate increased cholesterol excretion and biosynthesis in gallstone disease. Hepatology, 55(5), 1507-1517. https://doi.org/10.1002/hep.25563
Lammert, F., Gurusamy, K., Ko, C. W., Miquel, J. F., Méndez-Sánchez, N., Portincasa, P., ... & Wang, D. Q. H. (2016). Gallstones. Nature reviews Disease primers, 2(1), 1-17. https://doi.org/10.1038/nrdp.2016.24
Lin, J., Shao, W. Q., Chen, Q. Z., Zhu, W. W., Lu, L., Jia, H. L., & Chen, J. H. (2017). Osteopontin deficiency protects mice from cholesterol gallstone formation by reducing expression of intestinal NPC1L1. Molecular medicine reports, 16(2), 1785-1792. https://doi.org/10.3892/mmr.2017.6774
Liu, Q., Shao, W., Zhang, C., Xu, C., Wang, Q., Liu, H., ... & Gu, A. (2017). Organochloride pesticides modulated gut microbiota and influenced bile acid metabolism in mice. Environmental pollution, 226, 268-276. https://doi.org/10.1016/j.envpol.2017.03.068
Loginov, A. S., Chebanov, S. M., Petrakov, A. V., Saparin, G. V., Obyden, S. K., & Ivannikov, P. V. (1998). Investigation of cholesterol, bilirubin, and protein distribution in human gallstones by color cathodoluminescence scanning electron microscopy and transmission electron microscopy. Scanning: The Journal of Scanning Microscopies, 20(1), 17-22. https://doi.org/10.1002/sca.1998.4950200103
Loginov, A. S., Chebanov, S. M., Saparin, G. V., & Obyden, S. K. (1998). The morphology and composition of cholesterol, protein, and bilirubin deposits in dried human bile: cathodoluminescence and backscattered electron imaging. Scanning: The Journal of Scanning Microscopies, 20(6), 442-446. https://doi.org/10.1002/sca.1998.4950200604
Martinez-Lopez, E., Curiel-Lopez, F., Hernandez-Nazara, A., Moreno-Luna, L. E., Ramos-Marquez, M. E., Roman, S., & Panduro, A. (2015). Influence of ApoE and FABP2 polymorphisms and environmental factors in the susceptibility to gallstone disease. Annals of hepatology, 14(4), 515-523.
Moore, K. J., Rayner, K. J., Suárez, Y., & Fernández-Hernando, C. (2010). microRNAs and cholesterol metabolism. Trends in Endocrinology & Metabolism, 21(12), 699-706. https://doi.org/10.1016/j.tem.2010.08.008
Nakeeb, A., Comuzzie, A. G., Martin, L., Sonnenberg, G. E., Swartz-Basile, D., Kissebah, A. H., & Pitt, H. A. (2002). Gallstones: genetics versus environment. Annals of surgery, 235(6), 842. https://dx.doi.org/10.1097%2F00000658-200206000-00012
Olokoba, A. B., Bojuwoye, B. J., Olokoba, L. B., Wahab, K. W., Salami, A. K., Braimoh, K. T., & Inikori, A. K. (2008). The relationship between gallstone disease and gall bladder volume. Nigerian journal of clinical practice, 11(2), 89-93.
Origa, R., Galanello, R., Perseu, L., Tavazzi, D., Domenica Cappellini, M., Terenzani, L., ... & Piga, A. (2009). Cholelithiasis in thalassemia major. European journal of haematology, 82(1), 22-25. https://doi.org/10.1111/j.1600-0609.2008.01162.x
Pamuk, G. E., Ümit, H., Harmandar, F., & Yeşil, N. (2009). Patients with iron deficiency anemia have an increased prevalence of gallstones. Annals of hematology, 88(1), 17-20. https://doi.org/10.1007/s00277-008-0557-x
Paramsothy, P., Knopp, R. H., Kahn, S. E., Retzlaff, B. M., Fish, B., Ma, L., & Ostlund Jr, R. E. (2011). Plasma sterol evidence for decreased absorption and increased synthesis of cholesterol in insulin resistance and obesity. The American journal of clinical nutrition, 94(5), 1182-1188. https://doi.org/10.3945/ajcn.110.006668
Poupon, R., Rosmorduc, O., Boëlle, P. Y., Chrétien, Y., Corpechot, C., Chazouillères, O., ... & Barbu, V. (2013). Genotype‐phenotype relationships in the low‐phospholipid‐associated cholelithiasis syndrome: a study of 156 consecutive patients. Hepatology, 58(3), 1105-1110. https://doi.org/10.1002/hep.26424
Ramaswamy, K., Killilea, D. W., Kapahi, P., Kahn, A. J., Chi, T., & Stoller, M. L. (2015). The elementome of calcium-based urinary stones and its role in urolithiasis. Nature Reviews Urology, 12(10), 543-557. https://doi.org/10.1038/nrurol.2015.208
Renner, O., Lütjohann, D., Richter, D., Strohmeyer, A., Schimmel, S., Müller, O., ... & Harsch, S. (2013). Role of the ABCG8 19H risk allele in cholesterol absorption and gallstone disease. BMC gastroenterology, 13(1), 1-11. https://doi.org/10.1186/1471-230X-13-30
Reshetnyak, T. M., Saparin, G. V., Ivannikov, P. V., & Reshetnyak, V. I. (2009). Corticosteroids and cholelithiasis in systemic lupus erythematosus. Scholarly Research Exchange, 2009.
Reshetnyak, V. I. (2012). Concept of the pathogenesis and treatment of cholelithiasis. World journal of hepatology, 4(2), 18. https://dx.doi.org/10.4254%2Fwjh.v4.i2.18
Rudkowska, I., & Jones, P. J. (2008). Polymorphisms in ABCG5/G8 transporters linked to hypercholesterolemia and gallstone disease. Nutrition reviews, 66(6), 343-348. https://doi.org/10.1111/j.1753-4887.2008.00042.x
Ruhl, C. E., & Everhart, J. E. (2011). Gallstone disease is associated with increased mortality in the United States. Gastroenterology, 140(2), 508-516. https://doi.org/10.1053/j.gastro.2010.10.060
Sayers, C., Wyatt, J., Soloway, R. D., Taylor, D. R., & Stringer, M. D. (2007). Gallbladder mucin production and calcium carbonate gallstones in children. Pediatric surgery international, 23(3), 219-223. https://doi.org/10.1007/s00383-006-1867-5
Shabanzadeh, D. M. (2018). New determinants for gallstone disease. Dan Med J, 65(2), B5438.
Singh, V. K., Singh, V., Rai, A. K., Thakur, S. N., Rai, P. K., & Singh, J. P. (2008). Quantitative analysis of gallstones using laser-induced breakdown spectroscopy. Applied Optics, 47(31), G38-G47. https://doi.org/10.1364/AO.47.000G38
Stewart, L., Grifiss, J. M., Jarvis, G. A., & Way, L. W. (2006). Biliary bacterial factors determine the path of gallstone formation. The American journal of surgery, 192(5), 598-603. https://doi.org/10.1016/j.amjsurg.2006.08.001
Sun, H., Tang, H., Jiang, S., Zeng, L., Chen, E. Q., Zhou, T. Y., & Wang, Y. J. (2009). Gender and metabolic differences of gallstone diseases. World journal of gastroenterology: WJG, 15(15), 1886. https://dx.doi.org/10.3748%2Fwjg.15.1886
Takemoto, M., Tada, K., Nakatsuka, K., Moriyama, Y., Kazui, H., Yokote, K., ... & Mori, S. (1999). Effects of aging and hyperlipidemia on plasma osteopontin level. Nihon Ronen Igakkai zasshi. Japanese journal of geriatrics, 36(11), 799-802. https://doi.org/10.3143/geriatrics.36.799
Tayeb, M., Raza, S. A., Khan, M. R., & Azami, R. (2005). Conversion from laparoscopic to open cholecystectomy: multivariate analysis of preoperative risk factors. Journal of postgraduate medicine, 51(1), 17.
Tazuma, S., Unno, M., Igarashi, Y., Inui, K., Uchiyama, K., Kai, M., ... & Shimosegawa, T. (2017). Evidence-based clinical practice guidelines for cholelithiasis 2016. Journal of gastroenterology, 52(3), 276-300. https://doi.org/10.1007/s00535-016-1289-7
Thomas, L. A., Veysey, M. J., Murphy, G. M., Russell-Jones, D., French, G. L., Wass, J. A. H., & Dowling, R. H. (2005). Octreotide induced prolongation of colonic transit increases faecal anaerobic bacteria, bile acid metabolising enzymes, and serum deoxycholic acid in patients with acromegaly. Gut, 54(5), 630-635. http://dx.doi.org/10.1136/gut.2003.028431
Tsukanov, V. V., Nozdrachev, K. G., IuL, T., Bronnikova, E. P., & EIu, K. (2007). The mechanism of reverse cholesterol transport and cholelithiasis in northern ethnic groups. Klinicheskaia meditsina, 85(2), 33-35.
Uchiyama, K., Kawai, M., Tani, M., Terasawa, H., Tanimura, H., & Yamaue, H. (2007). Pathogenesis of hepatolithiasis based on the analysis of components of intrahepatic stones. Hepato-gastroenterology, 54(78), 1798-1804.
Villanacci, V., Del Sordo, R., Salemme, M., Cadei, M., Sidoni, A., & Bassotti, G. (2016). The enteric nervous system in patients with calculous and acalculous gallbladder. Digestive and Liver Disease, 48(7), 792-795. https://doi.org/10.1016/j.dld.2016.03.014
Von Kampen, O., Buch, S., Nothnagel, M., Azocar, L., Molina, H., Brosch, M., ... & Hampe, J. (2013). Genetic and functional identification of the likely causative variant for cholesterol gallstone disease at the ABCG5/8 lithogenic locus. Hepatology, 57(6), 2407-2417. https://doi.org/10.1002/hep.26009
von Schönfels, W., Buch, S., Wölk, M., Aselmann, H., Egberts, J. H., Schreiber, S., ... & Schafmayer, C. (2013). Recurrence of gallstones after cholecystectomy is associated with ABCG5/8 genotype. Journal of gastroenterology, 48(3), 391-396. https://doi.org/10.1007/s00535-012-0639-3
Wang, D. Q. H. (2007). Regulation of intestinal cholesterol absorption. Annu. Rev. Physiol., 69, 221-248. https://doi.org/10.1146/annurev.physiol.69.031905.160725
Wang, D. Q. H., & Lee, S. P. (2008). Physical chemistry of intestinal absorption of biliary cholesterol in mice. Hepatology, 48(1), 177-185. https://doi.org/10.1002/hep.22286
Wang, D. Q. H., Neuschwander-Tetri, B. A., & Portincasa, P. (2012). The Biliary System, Colloquium Series on Integrated Systems Physiology: From Molecule to Function. Morgan & Claypool, 109-145.
Wang, H. H., Li, T., Portincasa, P., Ford, D. A., Neuschwander-Tetri, B. A., Tso, P., & Wang, D. Q. H. (2017). New insights into the role of Lith genes in the formation of cholesterol-supersaturated bile. Liver Research, 1(1), 42-53. https://doi.org/10.1016/j.livres.2017.05.005
Wang, H. H., Portincasa, P., & Wang, D. Q. (2008). Molecular pathophysiology and physical chemistry of cholesterol gallstones. Front Biosci, 13(4), 401-423.
Wang, L. J., Wang, J., Li, N., Ge, L., Li, B. L., & Song, B. L. (2011). Molecular characterization of the NPC1L1 variants identified from cholesterol low absorbers. Journal of Biological Chemistry, 286(9), 7397-7408. https://doi.org/10.1074/jbc.M110.178368
Wang, R., Hong, J., Cao, Y., Shi, J., Gu, W., Ning, G., & Wang, W. (2015). Elevated circulating microRNA-122 is associated with obesity and insulin resistance in young adults. Eur J Endocrinol, 172(3), 291-300. https://doi.org/10.1530/eje-14-0867
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