Pancreatic steatosis: a giant step forward or recognition of ignorance
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Keywords

pancreatic steatosis, terminology, epidemiology, pathogenesis, clinical picture, diagnosis, treatment

How to Cite

Gubergrits, N. B., Byelyayeva, N. V., Mozhyna, T. L., Monogarova, N. E., Borodiy, K. N., & Yuryeva, A. V. (2020). Pancreatic steatosis: a giant step forward or recognition of ignorance. Herald of Pancreatic Club, 49(4), 21-41. https://doi.org/10.33149/vkp.2020.04.02

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Abstract

This review analyzes the terminology of pancreatic steatosis, the data about the prevalence of non-alcoholic fatty pancreas disease (NAFPD) were given.

The etiological factors of NAFPD are usually subdivided into hereditary, metabolic, and toxic ones. The main etiopathogenetic factor of pancreatic fatty infiltration is obesity: it causes pancreatic infiltration by adipocytes, leading to the development of NAFPD. The pathogenesis of the disease is associated with adipocytic tissue dysfunction, which induces local and systemic inflammatory response with corresponding clinical consequences. Insulin resistance and oxidative stress play major role in the pathogenesis of NAFPD. From a histological point of view, NAFPD is a heterogeneous process, characterized by excessive intracellular accumulation of lipids and fatty infiltration followed by fatty replacement of the pancreas.

NAFPD clinical picture is asymptomatic and nonspecific. Diagnosis of NAFPD is based primarily on the results of imaging methods (ultrasound, CT, MRI). A consequence of NAFPD is exocrine pancreatic insufficiency requiring enzyme replacement therapy. One of the NAFPD complications is the development of pancreatic adenocarcinoma.

Currently, standards for the diagnosis, treatment and management of patients with NAFPD have not been developed yet, but on used the guidelines for the treatment of non-alcoholic fatty liver disease (rational diet, exercises, weight loss). The “gold standard” of enzyme replacement therapy, such as Creon®, is used for correction of exocrine pancreatic insufficiency. The detailed analysis of the clinical case of total pancreatic steatosis with severe exocrine pancreatic insufficiency was done in this article.

https://doi.org/10.33149/vkp.2020.04.02
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References

1. Бельмер С. В. Болезни поджелудочной железы у детей. М.: Медпрактика-М, 2015. 452 с.
2. Бельмер С. В. Болезни поджелудочной железы у детей. М.: Медпрактика-М, 2019. 528 с.
3. Бєляєва Н.В. Оптимізація діагностики і лікування хронічного біліарного панкреатиту у хворих з ожирінням [Текст] : автореф. дис. ... канд. мед. наук : 14.01.02 / Бєляєва Н. В.; ДЗ «Луган. держ. мед. ун-т». Луганськ, 2011. 24 с.
4. Бондаренко О. О. Патогенез, клініка, діагностика та лікування хронічного панкреатиту у хворих на ожиріння з інсулінорезистентністю [Текст] : автореф. дис. ... д-ра мед. наук : 14.01.02 / Бондаренко О. О.; Львівський національний медичний університет ім. Данила Галицького. Тернопіль, 2015. 42 с.
5. Губергриц Н. Б., Беляева Н. В., Лукашевич Г. М., Фоменко П. Г., Бережная Э. В., Рахметова В. С. Доказательная панкреатология: что мы знаем о хроническом панкреатите к 2020 году? Вестник Клуба Панкреатологов. 2020. № 2. С. 18–31.
6. Губергриц Н. Б., Казюлин А. Н. Метаболическая панкреатология. Донецк: Лебедь, 2011. 464 с.
7. Губергриц Н. Б., Бондаренко О. А. Неалкогольная жировая болезнь поджелудочной железы: терминология, этиология, патогенез, клиника, диагностика, лечение : уч.-метод. пособие. К.: РПХ «ФЕРЗЬ», 2012. 54 с.
8. Губергриц Н. Б., Христич Т. Н., Бондаренко О. А. Неалкогольная жировая болезнь поджелудочной железы. Донецк: Лебедь, 2013. 236 с.
9. Ивашкин В. Т., Шифрин О. С., Соколина И. А. Хронический панкреатит, стеатоз поджелудочной железы и стеатопанкреатит. М.: Литтерра, 2014. 240 с.
10. Стародубова А. В., Косюра С. Д., Ливанцова Е. Н., Вараева Ю. Р., Красилова А. А. Диагностика стеатоза поджелудочной железы у лиц с ожирением. Вестник Клуба Панкреатологов. 2019. № 4. С. 30–33.
11. Степанов Ю. М., Завгородня Н. Ю., Лук’яненко О. Ю. Стеатоз підшлункової залози в дітей. Частина 1. Етіологія, епідеміологія та патогенез. Гастроентерологія. 2017. Вип. 51, № 1. С. 46–55.
12. Степанов Ю. М., Завгородня Н. Ю., Лук’яненко О. Ю. Стеатоз підшлункової залози в дітей. Частина 2. Фактори ризику, можливості діагностики та лікування. Гастроентерологія. 2017. Вип. 51, № 2. С. 144–151.
13. Фадеенко Г. Д., Просоленко К. А., Дубров К. Ю. Стеатоз поджелудочной железы в рамках метаболического синдрома: уравнение со многими неизвестными. Вестник Клуба Панкреатологов. 2010. № 1. С. 21–25.
14. Христич Т. Н., Пишак В. П., Кендзерская Т. Б. Хронический панкреатит: нерешенные проблемы. Черновцы: Медуниверситет, 2006. 280 с.
15. Acharya C., Navina S., Singh V. P. Role of pancreatic fat in the outcomes of pancreatitis. Pancreatology. 2014. Vol. 14, No 5. P. 403–408.
16. Alempijevic T., Dragasevic S., Zec S., Popovic D., Milosavljevic T. Non-alcoholic fatty pancreas disease. Postgrad. Med. J. 2017. Vol. 93, No 1098. P. 226–230.
17. Boga S., Koksal A. R., Sen I., Yeniay M. K., Yilmaz Ozguven M. B., Serin E., Erturk S. M., Alkim H., Alkim C. Liver and pancreas: “Castor and Pollux” regarding the relationship between hepatic steatosis and pancreas exocrine insufficiency. Pancreatology. 2020. Ahead of print. doi: https://doi.org/10.1016/j.pan.2020.04.020
18. Beger H. G., Buchler M., Kozarek R. (eds). The pancreas: An integrated textbook of basic science, medicine and surgery. Oxford: Willey Blackwell, 2018. 1173 p.
19. Bi Y., Wang J. L., Li M. L., Zhou J., Sun X. L. The association between pancreas steatosis and metabolic syndrome: a systematic review and meta-analysis. Diabetes Metab. Res. Rev. 2019. Vol. 35, No 5. P e3142.
20. Capurso G., Traini M., Piciucchi M., Signoretti M., Arcidiacono P. G. Exocrine pancreatic insufficiency: prevalence, diagnosis, and management. Clin. Exp. Gastroenterol. 2019. Vol. 12. P. 129–139.
21. Catanzaro R., Cuffari B., Italia A., Marotta F. Exploring the metabolic syndrome: nonalcoholic fatty pancreas disease. World J. Gastroenterol. 2016. Vol. 22, No 34. P. 7660–7675.
22. Dite P., Blaho M., Bojkova M., Jabandziev P., Kunovsky L. Nonalcoholic fatty pancreas disease: clinical consequences. Dig. Dis. 2020. Vol. 38, No 2. P. 143–149.
23. Dominguez-Munoz J. E., Drewes A. M., Lindkvist B. et al. Recommendations from the United European Gastroenterology evidence-based guidelines for the diagnosis and therapy of chronic pancreatitis [published correction appears in Pancreatology. 2020. Vol. 20, No 1. P. 148. Okhlobystin A. V. [corrected to Okhlobystin A. V.]]. Pancreatology. 2018. Vol. 18, No 8. P. 847–854.
24. Ferrara D., Montecucco F., Dallegri F., Carbone F. Impact of different ectopic fat depots on cardiovascular and metabolic diseases. J. Cell Physiol. 2019. Vol. 234, No 12. P. 21630–21641.
25. Fujii M., Ohno Y., Yamada M., Kamada Y., Miyoshi E. Impact of fatty pancreas and lifestyle on the development of subclinical chronic pancreatitis in healthy people undergoing a medical checkup. Environ. Health Prev. Med. 2019. Vol. 24, No 1. P. 10.
26. Gaborit B., Abdesselam I., Kober F. et al. Ectopic fat storage in the pancreas using 1H-MRS: importance of diabetic status and modulation with bariatric surgery-induced weight loss. Int. J. Obes. (Lond.). 2015. Vol. 39, No 3. P. 480–487.
27. Garcia T. S., Rech T. H., Leitao C. B. Pancreatic size and fat content in diabetes: a systematic review and meta-analysis of imaging studies. PLoS One. 2017. Vol. 12, No 7.
28. Gardner T. B., Adler D. G., Forsmark C. E., Sauer B. G., Taylor J. R., Whitcomb D. C. ACG clinical guideline: chronic pancreatitis. Am. J. Gastroenterol. 2020. Vol. 115, No 3. P. 322–339.
29. Gerst F., Wagner R., Oquendo M. B., Siegel-Axel D., Fritsche A., Heni M., Staiger H., Haring H. U., Ullrich S. What role do fat cells play in pancreatic tissue? Mol. Metab. 2019. Vol. 25. P. 1–10.
30. Heiskanen M. A., Motiani K. K., Mari A. et al. Exercise training decreases pancreatic fat content and improves beta cell function regardless of baseline glucose tolerance: a randomised controlled trial. Diabetologia. 2018. Vol. 61, No 8. P. 1817–1828.
31. Honka H., Koffert J., Hannukainen J. C. et al. The effects of bariatric surgery on pancreatic lipid metabolism and blood flow. J. Clin. Endocrinol. Metab. 2015. Vol. 100, No 5. P. 2015–2023.
32. Huang C., Lin C. K., Lee T. H., Liang Y. J. Pancreatic fibrosis and chronic pancreatitis: mini-review of non-histologic diagnosis for clinical applications. Diagnostics (Basel). 2020. Vol. 10, No 2. P. E87.
33. Ketwaroo G. A., Graham D. Y. Rational use of pancreatic enzymes for pancreatic insufficiency and pancreatic pain. Adv. Exp. Med. Biol. 2019. Vol. 1148. P. 323–343.
34. Lesmana C. R., Pakasi L. S., Inggriani S., Aidawati M. L., Lesmana L. A. Prevalence of non-alcoholic fatty pancreas disease (NAFPD) and its risk factors among adult medical check-up patients in a private hospital: a large cross sectional study. BMC Gastroenterol. 2015. Vol. 15. P. 174.
35. Lesmana C. R. A., Gani R. A., Lesmana L. A. Non-alcoholic fatty pancreas disease as a risk factor for pancreatic cancer based on endoscopic ultrasound examination among pancreatic cancer patients: a single-center experience. JGH Open. 2017. Vol. 2, No 1. P. 4–7.
36. Majumder S., Philip N. A., Takahashi N., Levy M. J., Singh V. P., Chari S. T. Fatty pancreas: should we be concerned? Pancreas. 2017. Vol. 46, No 10. P. 1251–1258.
37. Mandai K., Uno K., Nakase K., Kawamura T., Yasuda K. Association between hyperechogenic pancreas and pancreatic ductal adenocarcinoma concomitant with intraductal papillary mucinous neoplasms. J. Med. Ultrason. 2019. Vol. 46, No 4. P. 435–439.
38. Milovanovic T., Dragasevic S., Stojkovic Lalosevic M. et al. Ultrasonographic evaluation of fatty pancreas in serbian patients with non alcoholic fatty liver disease — a cross sectional study. Medicina (Kaunas). 2019. Vol. 55, No 10. P. 697.
39. Nghiem D. D., Olson P. R., Ormond D. The “fatty pancreas allograft”: anatomo-pathologic findings and clinical experience. Transplant. Proc. 2004. Vol. 36, No 4. P. 1045–1047.
40. Ogilvie R. F. The islands of Langerhans in 19 cases of obesity. J. Pathol. Bacteriol. 1933. Vol. 37, No 3. P. 473–481.
41. Pinnick K. E., Collins S. C., Londos C., Gauguier D., Clark A., Fielding B. A. Pancreatic ectopic fat is characterized by adipocyte infiltration and altered lipid composition. Obesity. 2008. Vol. 16, No 3. P. 522–530.
42. Pinte L., Balaban D. V., Baicus C., Jinga M. Non-alcoholic fatty pancreas disease — practices for clinicians. Rom. J. Intern. Med. 2019. Vol. 57, No 3. P. 209–219.
43. Prachayakul V., Aswakul. P. Pancreatic steatosis: what should gastroenterologists know? JOP. 2015. URL: http://pancreas.imedpub.com/pancreatic-steatosis-what-should-gastroenterologists-know.php?aid=4927 (Last accessed: 10.08.2020)
44. Ramkissoon R., Gardner T. B. Pancreatic steatosis: an emerging clinical entity. Am. J. Gastroenterol. 2019. Vol. 114, No 11. P. 1726–1734.
45. Romana B. S., Chela H., Dailey F. E., Nassir F., Tahan V. Non-alcoholic fatty pancreas disease (NAFPD): a silent spectator or the fifth component of metabolic syndrome? A literature review. Endocr. Metab. Immune Disord. Drug Targets. 2018. Vol. 18, No 6. P. 547–554.
46. Sabag A., Way K. L., Keating S. E. et al. Exercise and ectopic fat in type 2 diabetes: a systematic review and meta-analysis. Diabetes Metab. 2017. Vol. 43, No 3. P. 195–210.
47. Sakai N. S., Taylor S. A., Chouhan M. D. Obesity, metabolic disease and the pancreas-quantitative imaging of pancreatic fat. Br. J. Radiol. 2018. Vol. 91, No 1089. ID. 20180267.
48. Shah N., Rocha J. P., Bhutiani N., Endashaw O. Nonalcoholic fatty pancreas disease. Nutr. Clin. Pract. 2019. Vol. 34, Suppl. 1. P. S49–S56.
49. Shobassy M., Husainat N., Tabash A., Patel K., El-Serag H. B., Othman M. O. Endoscopic ultrasound findings in patients diagnosed with exocrine pancreatic insufficiency by low fecal elastase-1. Gastroenterol. Res. Pract. 2019. Vol. 2019. ID. 5290642.
50. Singh R. G., Yoon H. D., Poppitt S. D., Plank L. D., Petrov M. S. Ectopic fat accumulation in the pancreas and its biomarkers: a systematic review and meta-analysis. Diabetes Metab. Res. Rev. 2017. Vol. 33, No 8. P. 10.
51. Singh R. G., Yoon H. D., Wu L. M., Lu J., Plank L. D., Petrov M. S. Ectopic fat accumulation in the pancreas and its clinical relevance: a systematic review, meta-analysis, and meta-regression. Metabolism. 2017. Vol. 69. P. 1–13.
52. Skurk T., Alberti-Huber C., Herder C., Hauner H. Relationship between adipocyte size and adipokine expression and secretion. J. Clin. Endocrinol. Metab. 2007. Vol. 92, No 3. P. 1023–1033.
53. Smereczynski A., Kolaczyk K. Is a fatty pancreas a banal lesion? J. Ultrason. 2016. Vol. 16, No 66. P. 273–280.
54. Smits M. M., van Geenen E. J. M. The clinical significance of pancreatic steatosis. Nat. Rev. Gastroenterol. Hepatol. 2011. Vol. 8. P. 169–177.
55. Souza-Mello V., Gregorio B. M., Cardoso-de-Lemos F. S., de Carvalho L., Aguila M. B., Mandarim-de-Lacerda C. A. Comparative effects of telmisartan, sitagliptin and metformin alone or in combination on obesity, insulin resistance, and liver and pancreas remodelling in C57BL/6 mice fed on a very high-fat diet. Clin. Sci. 2010. Vol. 119, No 6. P. 239–250.
56. Sreedhar U. L., DeSouza S. V., Park B., Petrov M. S. A systematic review of intra-pancreatic fat deposition and pancreatic carcinogenesis. J. Gastrointest. Surg. 2019. Online ahead of print. doi: https://doi.org/10.1007/s11605-019-04417-4
57. Stepanov Y., Zavhorodnia N., Lukianenko O., Konenko I., Yahmur V. Assessment of the hepatic and pancreatic structure with shear wave elastography and steatometry in obese children. Georgian Med. News. 2019. Vol. 295. P. 51–56.
58. Sujishi T., Fukunishi S., Ii M. et al. Sitagliptin can inhibit the development of hepatic steatosis in high-fructose diet-fed ob/ob mice. J. Clin. Biochem. Nutr. 2015. Vol. 57, No 3. P. 244–253.
59. Tahtaci M., Algin O., Karakan T. et al. Can pancreatic steatosis affect exocrine functions of pancreas? Turk. J. Gastroenterol. 2018. Vol. 29, No 5. P. 588–594.
60. Tirkes T., Jeon C.Y., Li L. et al. Association of pancreatic steatosis with chronic pancreatitis, obesity, and type 2 diabetes mellitus. Pancreas. 2019. Vol. 48, No 3. P. 420–426.
61. Tomita Y., Azuma K., Nonaka Y., Kamada Y., Tomoeda M., Kishida M., Tanemura M., Miyoshi E. Pancreatic fatty degeneration and fibrosis as predisposing factors for the development of pancreatic ductal adenocarcinoma. Pancreas. 2014. Vol. 43, No 7. P. 1032–1041.
62. Tsatsoulis A., Mantzaris M. D., Bellou S., Andrikoula M. Insulin resistance: an adaptive mechanism becomes maladaptive in the current environment — an evolutionary perspective. Metabolism. 2013. Vol. 62, No 5. P. 622–633.
63. Uygun A., Kadayifci A., Demirci H. et al. The effect of fatty pancreas on serum glucose parameters in patients with nonalcoholic steatohepatitis. Eur. J. Intern. Med. 2015. Vol. 26, No 1. P. 37–41.
64. van Geenen E. J., Smits M. M., Schreuder T. C., van der Peet D. L., Bloemena E., Mulder C. J. Nonalcoholic fatty liver disease is related to nonalcoholic fatty pancreas disease. Pancreas. 2010. Vol. 39, No 8. P. 1185–1190.
65. van Raalte D. H., van der Zijl N. J., Diamant M. Pancreatic steatosis in humans: cause or marker of lipotoxicity? Curr. Opin. Clin. Nutr. Metab. Care. 2010. Vol. 13, No 4. P. 478–485.
66. Vege S. S., Gardner T. B., Chari S. T. et al. Low mortality and high morbidity in severe acute pancreatitis without organ failure: a case for revising the Atlanta classification to include “moderately severe acute pancreatitis”. Am. J. Gastroenterol. 2009. Vol. 104. P. 710–715.
67. Virtue S., Vidal-Puig A. It’s not how fat you are, it’s what you do with it that counts. PLoS Biol. 2008. Vol. 6, No 9. P. e237.
68. Weng S., Zhou J., Chen X., Sun Y., Mao Z., Chai K. Prevalence and factors associated with nonalcoholic fatty pancreas disease and its severity in China. Medicine (Baltimore). 2018. Vol. 97, No 26. P. e11293.
69. Whitcomb D.C. Clinical practice. Acute pancreatitis. N. Engl. J. Med. 2006. Vol. 354. P. 2142–2150.
70. Yu T., Wang C. Impact of non-alcoholic fatty pancreas disease on glucose metabolism. J. Diabetes Investig. 2017. Vol. 8. P. 735–747.
71. Zhou J., Li M. L., Zhang D. D. et al. The correlation between pancreatic steatosis and metabolic syndrome in a Chinese population. Pancreatology. 2016. Vol. 16, No 4. P. 578–583.
72. Zsori G., Illes D., Ivany E. et al. In new-onset diabetes mellitus, metformin reduces fat accumulation in the liver, but not in the pancreas or pericardium. Metab. Syndr. Relat. Disord. 2019. Vol. 17, No 5. P. 289–295.
73. Zyromski N. J., White P. B. Pancreatic cancer in obesity: epidemiology, clinical observations, and basic mechanisms. Anticancer Agents Med. Chem. 2011. Vol. 11, No 5. P. 470–478.