FROM ALCOHOL TO LITHIASIS - VARIED RISK FACTORS OF CHRONIC PANCREATITIS
Abstract
Introduction: Chronic pancreatitis is a growing health concern with an incidence of about 10 cases per 100,000 people per year. Alcohol-related CP is more common in men, typically appearing in their 40s or 50s, while idiopathic CP affects both sexes equally. CP is a persistent inflammatory condition of the pancreas, leading to irreversible structural damage, pain, and gradual loss of both exo- and endocrine function. Symptoms include epigastric pain, bloating, digestive issues, glucose intolerance or diabetes, and physical signs like epigastric tenderness, and abdominal mass and jaundice.
Materials and methods: A review of 47 sources from publicly available databases such as PubMed and Google Scholar was conducted. Cited publications were published mainly in English. The main topic of these publications was focused on risk factors of CP.
State of knowledge: In the following article we discuss the risk factors of CP which are described in acronym TIGAR-O. The main etiology factor of CP is alcohol consumption which is responsible for over a half the cases. Negative effect of ethanol is particularly significant in smokers. Tobacco is an inependent risk factor of CP but combined with alcohol use, risk of chronic pancreatitis is increasing. In the development of pancreatitis gene mutations play a significant role. Autoimmune pancreatitis has two subtypes and its patomechanism is complex. Acute pancreatitis and its recurrences may lead to repetitive inflammation of pancreas and its chronicisation. Obstructive chronic pancreatitis develops due to a mechanical blockage that hinders the flow of pancreatic juice.
Conclusions: Expanding access to genetic and immunological testing will help identify groups especially vulnerable to CP, potentially leading to fewer complications, lower treatment costs, and improved treatment outcomes. Understanding how modifiable risk factors affect CP can enhance both primary and secondary prevention efforts.
References
Bai, H. X., Giefer, M., Patel, M., Orabi, A. I., & Husain, S. Z. (2012). The association of primary hyperparathyroidism with pancreatitis. In Journal of Clinical Gastroenterology (Vol. 46, Issue 8, pp. 656–661). https://doi.org/10.1097/MCG.0b013e31825c446c
Bhardwaj, P., & and Yadav, R. K. (2013). Chronic pancreatitis: role of oxidative stress and antioxidants. Free Radical Research, 47(11), 941–949. https://doi.org/10.3109/10715762.2013.804624
Edmiston, T., Kittane, V., & and Chanmugam, A. (2024). Recurrent acute pancreatitis: a harbinger for irreversible chronic pancreatitis. Hospital Practice, 52(1–2), 5–12. https://doi.org/10.1080/21548331.2024.2348990
Etemad, B., & Whitcomb, D. C. (2001). Chronic pancreatitis: Diagnosis, classification, and new genetic developments. Gastroenterology, 120(3), 682–707. https://doi.org/10.1053/gast.2001.22586
Forsmark, C., & Pham, A. (2018). Chronic pancreatitis: Review and update of etiology, risk factors, and management. In F1000Research (Vol. 7). F1000 Research Ltd. https://doi.org/10.12688/f1000research.12852.1
Fortunato, F., Bürgers, H., Bergmann, F., Rieger, P., Büchler, M. W., Kroemer, G., & Werner, J. (2009). Impaired Autolysosome Formation Correlates With Lamp-2 Depletion: Role of Apoptosis, Autophagy, and Necrosis in Pancreatitis. Gastroenterology, 137(1). https://doi.org/10.1053/j.gastro.2009.04.003
Gallo, C., Dispinzieri, G., Zucchini, N., Invernizzi, P., & Massironi, S. (2024). Autoimmune pancreatitis: Cornerstones and future perspectives. In World Journal of Gastroenterology (Vol. 30, Issue 8, pp. 817–832). Baishideng Publishing Group Inc. https://doi.org/10.3748/wjg.v30.i8.817
Gerasimenko, J. V., Gryshchenko, O., Ferdek, P. E., Stapleton, E., Hébert, T. O. G., Bychkova, S., Peng, S., Begg, M., Gerasimenko, O. V., & Petersen, O. H. (2013). Ca2+ release-activated Ca2+ channel blockade as a potential tool in antipancreatitis therapy. Proceedings of the National Academy of Sciences of the United States of America, 110(32), 13186–13191. https://doi.org/10.1073/pnas.1300910110
Glaubitz, J., Asgarbeik, S., Lange, R., Mazloum, H., Elsheikh, H., Weiss, F. U., & Sendler, M. (2023). Immune response mechanisms in acute and chronic pancreatitis: strategies for therapeutic intervention. In Frontiers in Immunology (Vol. 14). Frontiers Media SA. https://doi.org/10.3389/fimmu.2023.1279539
Głuszek, S., & Kozieł, D. (2018). Genetic determination of pancreatitis. Medical Studies, 34(1), 70–77. https://doi.org/10.5114/ms.2018.74823
Gu, H., Fortunato, F., Bergmann, F., Büchler, M. W., Whitcomb, D. C., & Werner, J. (2013). Alcohol Exacerbates LPS-Induced Fibrosis in Subclinical Acute Pancreatitis. The American Journal of Pathology, 183(5), 1508–1517. https://doi.org/10.1016/j.ajpath.2013.07.023
Hansen, S. E. J., Nordestgaard, B. G., & Langsted, A. (2023). Smoking as the most important risk factor for chronic pancreatitis in the general population. European Journal of Epidemiology, 38(1), 95–107. https://doi.org/10.1007/s10654-022-00945-7
Hoste, P., F., L., & and Rottiers, R. (1978). Chronic Relapsing Pancreatitis in Twin-Brothers with Type V Hyperlipoproteinemia. Acta Clinica Belgica, 33(5), 313–322. https://doi.org/10.1080/22953337.1978.11718649
Huang, H., Liu, Y., Daniluk, J., Gaiser, S., Chu, J., Wang, H., Li, Z. S., Logsdon, C. D., & Ji, B. (2013). Activation of Nuclear Factor-κB in Acinar Cells Increases the Severity of Pancreatitis in Mice. Gastroenterology, 144(1), 202–210. https://doi.org/10.1053/J.GASTRO.2012.09.059
Icholas, N., Harer, S., Artin, M., Chwarz, S., Eraldine, G., Alone, M., Ndrea, A., Owarth, H., Ohn, J., Ainter, P., Aurice, M., Uper, S., Oan, J., & Raganza, B. (1998). The New England Journal of Medicine MUTATIONS OF THE CYSTIC FIBROSIS GENE IN PATIENTS WITH CHRONIC PANCREATITIS A BSTRACT Background The pancreatic lesions of cystic fi (Vol. 339).
JACKSON, C. E. (1958). HEREDITARY HYPERPARATHYROIDISM ASSOCIATED WITH RECURRENT PANCREATITIS. Annals of Internal Medicine, 49(4), 829–836. https://doi.org/10.7326/0003-4819-49-4-829
Jacob, J. J., John, M., Thomas, N., Chacko, A., Cherian, R., Selvan, B., Nair, A., & Seshadri, M. S. (2006). DOES HYPERPARATHYROIDISM CAUSE PANCREATITIS? A SOUTH INDIAN EXPERIENCE AND A REVIEW OF PUBLISHED WORK. ANZ Journal of Surgery, 76(8), 740–744. https://doi.org/https://doi.org/10.1111/j.1445-2197.2006.03845.x
Kaufman, M. B. (2013). Drug-induced pancreatitis a potentially serious and underreported problem Pharmacovigilance Forum (Vol. 38, Issue 6). www.accessdata.fda.gov/
Krauss, R. M., & Levy, A. G. (1977). Subclinical chronic pancreatitis in type I hyperlipoproteinemia. The American Journal of Medicine, 62(1), 144–149. https://doi.org/10.1016/0002-9343(77)90361-8
Lin, Y., Tamakoshi, A., Hayakawa, T., Ogawa, M., Ohno, Y., & Diseases, R. C. on I. P. (2000a). Cigarette Smoking as a Risk Factor for Chronic Pancreatitis: A Case-Control Study in Japan. Pancreas, 21(2). https://journals.lww.com/pancreasjournal/fulltext/2000/08000/cigarette_smoking_as_a_risk_factor_for_chronic.1.aspx
Lin, Y., Tamakoshi, A., Hayakawa, T., Ogawa, M., Ohno, Y., & Diseases, R. C. on I. P. (2000b). Cigarette Smoking as a Risk Factor for Chronic Pancreatitis: A Case-Control Study in Japan. Pancreas, 21(2). https://journals.lww.com/pancreasjournal/fulltext/2000/08000/cigarette_smoking_as_a_risk_factor_for_chronic.1.aspx
Löhr, J.-M., Vujasinovic, M., Rosendahl, J., Stone, J. H., & Beuers, U. (2022). IgG4-related diseases of the digestive tract. Nature Reviews Gastroenterology & Hepatology, 19(3), 185–197. https://doi.org/10.1038/s41575-021-00529-y
Lv, J., Ji, L., Wang, G., Sun, B., & Tong, J. (2022). Alcohol Aggravates Acute Pancreatitis by Impairing Autophagic Flux Through Activation of AMPK Signaling Pathway. Digestive Diseases and Sciences, 67(2), 524–535. https://doi.org/10.1007/s10620-021-06870-1
Mallory, A., & Kern, F. (1980). Drug-induced pancreatitis: A critical review. In Gastroenterology (Vol. 78, Issue 4, pp. 813–820). https://doi.org/10.1016/0016-5085(80)90689-7
Masamune, A., Watanabe, T., Kikuta, K., Satoh, K., & Shimosegawa, T. (2008). NADPH oxidase plays a crucial role in the activation of pancreatic stellate cells. Am J Physiol Gastrointest Liver Phy-Siol, 294, 99–108. https://doi.org/10.1152/ajpgi.00272.2007.-Activated
Mithofer, K., Castillo, C. F.-D., Frick, T. W., Lewandrowski, K. B., Rattner, D. W., & Warshaw, A. L. (1995). Acute Hypercalcemia Causes Acute Pancreatitis and Ectopic Trypsinogen Activation in the Rat. In GASTROENTEROLOGY (Vol. 109).
Nemoda, Z., & Sahin-Tóth, M. (n.d.). CHYMOTRYPSIN C (CALDECRIN) STIMULATES AUTOACTIVATION OF HUMAN CATONIC TRYPSINOGEN. www.uni-leipzig.de/pancreasmutation
Pelletier, A.-L., Bienvenu, T., Rebours, V., O’Toole, D., Hentic, O., Maire, F., Hammel, P., Ruszniewski, P., & Lévy, P. (2010). CFTR Gene Mutation in Patients with Apparently Idiopathic Pancreatitis: Lack of Phenotype-Genotype Correlation. Pancreatology, 10(2), 158–164. https://doi.org/https://doi.org/10.1159/000231976
Perkins, P. S., Rutherford, R. E., & Pandol, S. J. (1995). Effect of chronic ethanol feeding on digestive enzyme synthesis and mRNA content in rat pancreas. Pancreas, 10(1), 14–21. https://doi.org/10.1097/00006676-199501000-00002
Podręcznik Interna - Medycyna Praktyczna: Ostre zapalenie trzustki. (n.d.). Retrieved April 25, 2025, from https://www.mp.pl/interna/chapter/B16.II.5.1
Ren, Z., Wang, X., Xu, M., Yang, F., Frank, J. A., Ke, Z.-J., & Luo, J. (n.d.). Binge ethanol exposure causes endoplasmic reticulum stress, oxidative stress and tissue injury in the pancreas (Vol. 7, Issue 34). www.impactjournals.com/oncotarget
Roberts-Thomson, I. C. (2021). Progression from acute to chronic pancreatitis. In JGH Open (Vol. 5, Issue 12, pp. 1321–1322). John Wiley and Sons Inc. https://doi.org/10.1002/jgh3.12698
Rola włóknienia w przewlekłym zapaleniu trzustki i raku trzustki** • Postępy Nauk Medycznych 2a/2018 • Czytelnia Medyczna BORGIS. (n.d.). Retrieved April 25, 2025, from https://www.czytelniamedyczna.pl/6506,rola-wlknienia-w-przewlekym-zapaleniu-trzustki-i-raku-trzustki.html#kod
Rosendahl, J., Witt, H., Szmola, R., Bhatia, E., Ózsvári, B., Landt, O., Schulz, H. U., Gress, T. M., Pfützer, R., Löhr, M., Kovacs, P., Blüher, M., Stumvoll, M., Choudhuri, G., Hegyi, P., Te Morsche, R. H. M., Drenth, J. P. H., Truninger, K., Macek, M., … Sahin-Tóth, M. (2008). Chymotrypsin C (CTRC) variants that diminish activity or secretion are associated with chronic pancreatitis. Nature Genetics, 40(1), 78–82. https://doi.org/10.1038/ng.2007.44
Sah, R. P., Chari, S. T., Pannala, R., Sugumar, A., Clain, J. E., Levy, M. J., Pearson, R. K., Smyrk, T. C., Petersen, B. T., Topazian, M. D., Takahashi, N., Farnell, M. B., & Vege, S. S. (2010). Differences in Clinical Profile and Relapse Rate of Type 1 Versus Type 2 Autoimmune Pancreatitis. Gastroenterology, 139(1), 140–148. https://doi.org/10.1053/j.gastro.2010.03.054
Scherer, J., Singh, V. P., Pitchumoni, C. S., & Yadav, D. (2014). Issues in hypertriglyceridemic pancreatitis: An update. In Journal of Clinical Gastroenterology (Vol. 48, Issue 3, pp. 195–203). https://doi.org/10.1097/01.mcg.0000436438.60145.5a
Schnúr, A., Beer, S., Witt, H., Hegyi, P., & Sahin-Tóth, M. (2014). Functional effects of 13 Rare PRSS1 variants presumed to cause chronic pancreatitis. Gut, 63(2), 337–343. https://doi.org/10.1136/gutjnl-2012-304331
Shalbueva, N., Mareninova, O. A., Gerloff, A., Yuan, J., Waldron, R. T., Pandol, S. J., & Gukovskaya, A. S. (2013). Effects of oxidative alcohol metabolism on the mitochondrial permeability transition pore and necrosis in a mouse model of alcoholic pancreatitis. Gastroenterology, 144(2). https://doi.org/10.1053/j.gastro.2012.10.037
Shimosegawa, T., Chari, S. T., Frulloni, L., Kamisawa, T., Kawa, S., Mino-Kenudson, M., Kim, M.-H., Klöppel, G., Lerch, M. M., Löhr, M., Notohara, K., Okazaki, K., Schneider, A., & Zhang, L. (2011). International Consensus Diagnostic Criteria for Autoimmune Pancreatitis Guidelines of the International Association of Pancreatology. www.pancreasjournal.com
Talamini, G., Bassi, C., Falconi, M., Sartori, N., Salvia, R., Rigo, L., Castagnini, A., Francesco, V. Di, Frulloni, L., Bovo, P., Vaona, B., Angelini, G., Vantini, I., Cavallini, G., & Pederzoli, P. (1999). Alcohol and Smoking as Risk Factors in Chronic Pancreatitis and Pancreatic Cancer. Digestive Diseases and Sciences, 44(7), 1303–1311. https://doi.org/10.1023/A:1026670911955
Thareja, S., Manrai, M., Shukla, R., Kumar Sood, A., Jha, A., Tyagi, A. K., Upreti, V., Gahlot, G. P. S., & Maggo, S. (2019). Pancreatitis and hyperparathyroidism: Still a rare association! Medical Journal Armed Forces India, 75(4), 444–449. https://doi.org/10.1016/j.mjafi.2018.11.004
Tringali, A., Costa, D., Rota, M., Adler, D. G., & Costamagna, G. (2022). Covered self-expandable metal stents for pancreatic duct stricture: a systematic review and meta-analysis. Endoscopy International Open, 10(09), E1311–E1321. https://doi.org/10.1055/a-1880-7430
Weidenbach, H., Lerch, M. M., Gress, T. M., Pfaff, D., Turi, S., & Adler, G. (1995). Vasoactive mediators and the progression from oedematous to necrotising experimental acute pancreatitis. In Gut (Vol. 37).
Weiss, F. U., Laemmerhirt, F., & Lerch, M. M. (2019). Etiology and risk factors of acute and chronic pancreatitis. In Visceral Medicine (Vol. 35, Issue 2, pp. 73–81). S. Karger AG. https://doi.org/10.1159/000499138
Whitcomb, D. C. (2013). Genetic Risk Factors for Pancreatic Disorders. Gastroenterology, 144(6), 1292–1302. https://doi.org/10.1053/j.gastro.2013.01.069
Whitcomb, D. C., Gorry, M. C., Preston, R. A., Furey, W., Sossenheimer, M. J., Ulrich, C. D., Martin, S. P., Gates, L. K., Amann, S. T., Toskes, P. P., Liddle, R., McGrath, K., Uomo, G., Post, J. C., & Ehrlich, G. D. (1996). Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene. Nature Genetics, 14(2), 141–145. https://doi.org/10.1038/ng1096-141
Xia, C. C., Chen, H. T., Deng, H., Huang, Y. T., & Xu, G. Q. (2024). Reactive oxygen species and oxidative stress in acute pancreatitis: Pathogenesis and new therapeutic interventions. In World Journal of Gastroenterology (Vol. 30, Issue 45, pp. 4771–4780). Baishideng Publishing Group Inc. https://doi.org/10.3748/wjg.v30.i45.4771
Views:
13
Downloads:
5
Copyright (c) 2025 Aleksandra Świerczewska, Sylwia Lach, Ilona Bednarek, Kinga Kałuża, Lena Merchel, Karol Seweryn Błąd, Katarzyna Zemsta, Katarzyna Czechowska, Aleksandra Sędek, Olaf Jadanowski

This work is licensed under a Creative Commons Attribution 4.0 International License.
All articles are published in open-access and licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). Hence, authors retain copyright to the content of the articles.
CC BY 4.0 License allows content to be copied, adapted, displayed, distributed, re-published or otherwise re-used for any purpose including for adaptation and commercial use provided the content is attributed.