Skip to main content
Top
Published in: BMC Gastroenterology 1/2020

Open Access 01-12-2020 | Acute Pancreatitis | Research article

Increased circulating total bile acid levels were associated with organ failure in patients with acute pancreatitis

Authors: Xiaochun Xie, Jie Dong, Guotao Lu, Kun Gao, Xiaoyao Li, Wenjian Mao, Faxi Chen, Zhihui Tong, Baiqiang Li, Weiqin Li

Published in: BMC Gastroenterology | Issue 1/2020

Login to get access

Abstract

Background

Recent studies have shown that bile acids (BAs) are closely related to metabolic and inflammatory diseases. Our study aimed to investigate whether circulating total bile acid (TBA) levels were associated with the severity of acute pancreatitis (AP).

Methods

We retrospectively collected data on patients diagnosed with AP in a tertiary center from 01 January 2014 to 31 December 2016. The highest TBA value during the first 1,2,3,5,7 days after admission was determined as D1, D2, D3, D5, D7 TBAmax. Patients were divided into the high TBA (HTBA) group and the normal TBA (NTBA) group according to whether the TBAmax was ≥10 μmol/L. The prognosis and complications, including death, organ failure (OF) and pancreatic necrosis, were compared between the two groups. Logistic regression analysis and receiving operating characteristic (ROC) curve were used to evaluate the relationship between circulating TBA and organ failure in AP patients.

Results

Through stratified analysis of each time period, we found that the incidence of OF in the HTBA group was significantly higher than that in the NTBA group, and the AP severity classification in the HTBA group was more serious than that in the NTBA group. In addition, according to the D7 TBAmax values, the pancreatic necrosis rate, percutaneous catheter drainage (PCD) rate and mortality in the HTBA group were higher than those in the NTBA group. Multivariate regression analysis showed that HTBA (odds ratio (OR), 4.894; P = 0.002) was an independent risk factor for AP complicated with OF, which was verified in the grouping based on D7 TBAmax. ROC analysis revealed that a circulating D7 TBAmax cutoff point of 6.450 umol/L had optimal predictive value for the development of OF in AP patients with an area under the curve of the ROC curve (AUCROC) of 0.777.

Conclusions

The increase of circulating TBA in early stage of AP is independently related to organ failure, which indicates the adverse prognosis of AP patients.
Appendix
Available only for authorised users
Literature
2.
go back to reference Peery AF, Dellon ES, Lund J, Crockett SD, McGowan CE, Bulsiewicz WJ, et al. Burden of gastrointestinal disease in the United States: 2012 update. Gastroenterology. 2012;143(5):1179–87.e3.PubMedPubMedCentralCrossRef Peery AF, Dellon ES, Lund J, Crockett SD, McGowan CE, Bulsiewicz WJ, et al. Burden of gastrointestinal disease in the United States: 2012 update. Gastroenterology. 2012;143(5):1179–87.e3.PubMedPubMedCentralCrossRef
3.
go back to reference Tenner S, Baillie J, DeWitt J, Vege SS. American College of Gastroenterology guideline: management of acute pancreatitis. Am J Gastroenterol. 2013;108(9):1400–15 16.PubMedCrossRef Tenner S, Baillie J, DeWitt J, Vege SS. American College of Gastroenterology guideline: management of acute pancreatitis. Am J Gastroenterol. 2013;108(9):1400–15 16.PubMedCrossRef
4.
go back to reference Banks PA, Freeman ML. Practice guidelines in acute pancreatitis. Am J Gastroenterol. 2006;101(10):2379–400.PubMedCrossRef Banks PA, Freeman ML. Practice guidelines in acute pancreatitis. Am J Gastroenterol. 2006;101(10):2379–400.PubMedCrossRef
5.
go back to reference Babu RY, Gupta R, Kang M, Bhasin DK, Rana SS, Singh R. Predictors of surgery in patients with severe acute pancreatitis managed by the step-up approach. Ann Surg. 2013;257(4):737–50.PubMedCrossRef Babu RY, Gupta R, Kang M, Bhasin DK, Rana SS, Singh R. Predictors of surgery in patients with severe acute pancreatitis managed by the step-up approach. Ann Surg. 2013;257(4):737–50.PubMedCrossRef
6.
go back to reference Banks PA, Bollen TL, Dervenis C, Gooszen HG, Johnson CD, Sarr MG, et al. Classification of acute pancreatitis--2012: revision of the Atlanta classification and definitions by international consensus. Gut. 2013;62(1):102–11.PubMedCrossRef Banks PA, Bollen TL, Dervenis C, Gooszen HG, Johnson CD, Sarr MG, et al. Classification of acute pancreatitis--2012: revision of the Atlanta classification and definitions by international consensus. Gut. 2013;62(1):102–11.PubMedCrossRef
8.
go back to reference Fuchs C, Claudel T, Trauner M. Bile acid-mediated control of liver triglycerides. Semin Liver Dis. 2013;33(4):330–42.PubMedCrossRef Fuchs C, Claudel T, Trauner M. Bile acid-mediated control of liver triglycerides. Semin Liver Dis. 2013;33(4):330–42.PubMedCrossRef
10.
go back to reference McGlone ER, Bloom SR. ANNALS EXPRESS: Bile acids and the metabolic syndrome. Ann Clin Biochem. 2019;56(3):326–37. McGlone ER, Bloom SR. ANNALS EXPRESS: Bile acids and the metabolic syndrome. Ann Clin Biochem. 2019;56(3):326–37.
11.
go back to reference Han CY. Update on FXR Biology: Promising Therapeutic Target? Int J Mol Sci. 2018;19(7):2069. Han CY. Update on FXR Biology: Promising Therapeutic Target? Int J Mol Sci. 2018;19(7):2069.
12.
go back to reference Xie Y, He Y, Cai Z, Cai J, Xi M, Zhang Y, et al. Tauroursodeoxycholic acid inhibits endoplasmic reticulum stress, blocks mitochondrial permeability transition pore opening, and suppresses reperfusion injury through GSK-3ss in cardiac H9c2 cells. Am J Transl Res. 2016;8(11):4586–97.PubMedPubMedCentral Xie Y, He Y, Cai Z, Cai J, Xi M, Zhang Y, et al. Tauroursodeoxycholic acid inhibits endoplasmic reticulum stress, blocks mitochondrial permeability transition pore opening, and suppresses reperfusion injury through GSK-3ss in cardiac H9c2 cells. Am J Transl Res. 2016;8(11):4586–97.PubMedPubMedCentral
13.
go back to reference Cummings BP, Bettaieb A, Graham JL, Kim J, Ma F, Shibata N, et al. Bile-acid-mediated decrease in endoplasmic reticulum stress: a potential contributor to the metabolic benefits of ileal interposition surgery in UCD-T2DM rats. Dis Model Mech. 2013;6(2):443–56.PubMedCrossRef Cummings BP, Bettaieb A, Graham JL, Kim J, Ma F, Shibata N, et al. Bile-acid-mediated decrease in endoplasmic reticulum stress: a potential contributor to the metabolic benefits of ileal interposition surgery in UCD-T2DM rats. Dis Model Mech. 2013;6(2):443–56.PubMedCrossRef
14.
go back to reference Trauner M, Claudel T, Fickert P, Moustafa T, Wagner M. Bile acids as regulators of hepatic lipid and glucose metabolism. Dig Dis. 2010;28(1):220–4.PubMedCrossRef Trauner M, Claudel T, Fickert P, Moustafa T, Wagner M. Bile acids as regulators of hepatic lipid and glucose metabolism. Dig Dis. 2010;28(1):220–4.PubMedCrossRef
15.
go back to reference Maleszka A, Dumnicka P, Matuszyk A, Pedziwiatr M, Mazur-Laskowska M, Sporek M, et al. The Diagnostic Usefulness of Serum Total Bile Acid Concentrations in the Early Phase of Acute Pancreatitis of Varied Etiologies. Int J Mol Sci. 2017;18(1):106. Maleszka A, Dumnicka P, Matuszyk A, Pedziwiatr M, Mazur-Laskowska M, Sporek M, et al. The Diagnostic Usefulness of Serum Total Bile Acid Concentrations in the Early Phase of Acute Pancreatitis of Varied Etiologies. Int J Mol Sci. 2017;18(1):106.
17.
go back to reference Haeusler RA, Camastra S, Nannipieri M, Astiarraga B, Castro-Perez J, Xie D, et al. Increased bile acid synthesis and impaired bile acid transport in human obesity. J Clin Endocrinol Metab. 2016;101(5):1935–44.PubMedCrossRef Haeusler RA, Camastra S, Nannipieri M, Astiarraga B, Castro-Perez J, Xie D, et al. Increased bile acid synthesis and impaired bile acid transport in human obesity. J Clin Endocrinol Metab. 2016;101(5):1935–44.PubMedCrossRef
18.
go back to reference Sonne DP, van Nierop FS, Kulik W, Soeters MR, Vilsboll T, Knop FK. Postprandial plasma concentrations of individual bile acids and FGF-19 in patients with type 2 diabetes. J Clin Endocrinol Metab. 2016;101(8):3002–9.PubMedCrossRef Sonne DP, van Nierop FS, Kulik W, Soeters MR, Vilsboll T, Knop FK. Postprandial plasma concentrations of individual bile acids and FGF-19 in patients with type 2 diabetes. J Clin Endocrinol Metab. 2016;101(8):3002–9.PubMedCrossRef
19.
go back to reference Wewalka M, Patti ME, Barbato C, Houten SM, Goldfine AB. Fasting serum taurine-conjugated bile acids are elevated in type 2 diabetes and do not change with intensification of insulin. J Clin Endocrinol Metab. 2014;99(4):1442–51.PubMedPubMedCentralCrossRef Wewalka M, Patti ME, Barbato C, Houten SM, Goldfine AB. Fasting serum taurine-conjugated bile acids are elevated in type 2 diabetes and do not change with intensification of insulin. J Clin Endocrinol Metab. 2014;99(4):1442–51.PubMedPubMedCentralCrossRef
20.
go back to reference Sun W, Zhang D, Wang Z, Sun J, Xu B, Chen Y, et al. Insulin resistance is associated with Total bile acid level in type 2 diabetic and nondiabetic population: a cross-sectional study. Medicine. 2016;95(10):e2778.PubMedPubMedCentralCrossRef Sun W, Zhang D, Wang Z, Sun J, Xu B, Chen Y, et al. Insulin resistance is associated with Total bile acid level in type 2 diabetic and nondiabetic population: a cross-sectional study. Medicine. 2016;95(10):e2778.PubMedPubMedCentralCrossRef
21.
go back to reference Dellinger EP, Forsmark CE, Layer P, Levy P, Maravi-Poma E, Petrov MS, et al. Determinant-based classification of acute pancreatitis severity: an international multidisciplinary consultation. Ann Surg. 2012;256(6):875–80.PubMedCrossRef Dellinger EP, Forsmark CE, Layer P, Levy P, Maravi-Poma E, Petrov MS, et al. Determinant-based classification of acute pancreatitis severity: an international multidisciplinary consultation. Ann Surg. 2012;256(6):875–80.PubMedCrossRef
22.
go back to reference Petrov MS, Windsor JA. Conceptual framework for classifying the severity of acute pancreatitis. Clin Res Hepatol Gastroenterol. 2012;36(4):341–4.PubMedCrossRef Petrov MS, Windsor JA. Conceptual framework for classifying the severity of acute pancreatitis. Clin Res Hepatol Gastroenterol. 2012;36(4):341–4.PubMedCrossRef
23.
go back to reference Hennekens CH, DeMets D. Statistical association and causation: contributions of different types of evidence. Jama. 2011;305(11):1134–5.PubMedCrossRef Hennekens CH, DeMets D. Statistical association and causation: contributions of different types of evidence. Jama. 2011;305(11):1134–5.PubMedCrossRef
24.
go back to reference Working Group IAP/APA Acute Pancreatitis Guidelines. IAP/APA evidence-based guidelines for the management of acute pancreatitis. Pancreatology. 2013;13(4 Suppl 2):e1–15. Working Group IAP/APA Acute Pancreatitis Guidelines. IAP/APA evidence-based guidelines for the management of acute pancreatitis. Pancreatology. 2013;13(4 Suppl 2):e1–15.
25.
go back to reference Mofidi R, Duff MD, Wigmore SJ, Madhavan KK, Garden OJ, Parks RW. Association between early systemic inflammatory response, severity of multiorgan dysfunction and death in acute pancreatitis. Br J Surg. 2006;93(6):738–44.PubMedCrossRef Mofidi R, Duff MD, Wigmore SJ, Madhavan KK, Garden OJ, Parks RW. Association between early systemic inflammatory response, severity of multiorgan dysfunction and death in acute pancreatitis. Br J Surg. 2006;93(6):738–44.PubMedCrossRef
26.
go back to reference Singh VK, Wu BU, Bollen TL, Repas K, Maurer R, Mortele KJ, et al. Early systemic inflammatory response syndrome is associated with severe acute pancreatitis. Clin Gastroenterol Hepatol. 2009;7(11):1247–51.PubMedCrossRef Singh VK, Wu BU, Bollen TL, Repas K, Maurer R, Mortele KJ, et al. Early systemic inflammatory response syndrome is associated with severe acute pancreatitis. Clin Gastroenterol Hepatol. 2009;7(11):1247–51.PubMedCrossRef
27.
go back to reference Garg PK, Singh VP. Organ Failure due to Systemic Injury in Acute Pancreatitis. Gastroenterol. 2019;156(7):2008–23.CrossRef Garg PK, Singh VP. Organ Failure due to Systemic Injury in Acute Pancreatitis. Gastroenterol. 2019;156(7):2008–23.CrossRef
28.
go back to reference Parniczky A, Kui B, Szentesi A, Balazs A, Szucs A, Mosztbacher D, et al. Prospective, multicentre, Nationwide clinical data from 600 cases of acute pancreatitis. PLoS One. 2016;11(10):e0165309.PubMedPubMedCentralCrossRef Parniczky A, Kui B, Szentesi A, Balazs A, Szucs A, Mosztbacher D, et al. Prospective, multicentre, Nationwide clinical data from 600 cases of acute pancreatitis. PLoS One. 2016;11(10):e0165309.PubMedPubMedCentralCrossRef
29.
go back to reference Sathyanarayan G, Garg PK, Prasad H, Tandon RK. Elevated level of interleukin-6 predicts organ failure and severe disease in patients with acute pancreatitis. J Gastroenterol Hepatol. 2007;22(4):550–4.PubMedCrossRef Sathyanarayan G, Garg PK, Prasad H, Tandon RK. Elevated level of interleukin-6 predicts organ failure and severe disease in patients with acute pancreatitis. J Gastroenterol Hepatol. 2007;22(4):550–4.PubMedCrossRef
30.
go back to reference Whitcomb DC, Muddana V, Langmead CJ, Houghton FD Jr, Guenther A, Eagon PK, et al. Angiopoietin-2, a regulator of vascular permeability in inflammation, is associated with persistent organ failure in patients with acute pancreatitis from the United States and Germany. Am J Gastroenterol. 2010;105(10):2287–92.PubMedCrossRef Whitcomb DC, Muddana V, Langmead CJ, Houghton FD Jr, Guenther A, Eagon PK, et al. Angiopoietin-2, a regulator of vascular permeability in inflammation, is associated with persistent organ failure in patients with acute pancreatitis from the United States and Germany. Am J Gastroenterol. 2010;105(10):2287–92.PubMedCrossRef
31.
go back to reference Kolber W, Kusnierz-Cabala B, Dumnicka P, Maraj M, Mazur-Laskowska M, Pedziwiatr M, et al. Serum Urokinase-Type Plasminogen Activator Receptor Does Not Outperform C-Reactive Protein and Procalcitonin as an Early Marker of Severity of Acute Pancreatitis. J Clin Med. 2018;7(10):305. Kolber W, Kusnierz-Cabala B, Dumnicka P, Maraj M, Mazur-Laskowska M, Pedziwiatr M, et al. Serum Urokinase-Type Plasminogen Activator Receptor Does Not Outperform C-Reactive Protein and Procalcitonin as an Early Marker of Severity of Acute Pancreatitis. J Clin Med. 2018;7(10):305.
32.
go back to reference Chiang JY. Bile acid regulation of gene expression: roles of nuclear hormone receptors. Endocr Rev. 2002;23(4):443–63.PubMedCrossRef Chiang JY. Bile acid regulation of gene expression: roles of nuclear hormone receptors. Endocr Rev. 2002;23(4):443–63.PubMedCrossRef
34.
go back to reference Luo L, Aubrecht J, Li D, Warner RL, Johnson KJ, Kenny J, et al. Assessment of serum bile acid profiles as biomarkers of liver injury and liver disease in humans. PLoS One. 2018;13(3):e0193824.PubMedPubMedCentralCrossRef Luo L, Aubrecht J, Li D, Warner RL, Johnson KJ, Kenny J, et al. Assessment of serum bile acid profiles as biomarkers of liver injury and liver disease in humans. PLoS One. 2018;13(3):e0193824.PubMedPubMedCentralCrossRef
35.
go back to reference Bayerdorffer E, Mannes GA, Ochsenkuhn T, Dirschedl P, Wiebecke B, Paumgartner G. Unconjugated secondary bile acids in the serum of patients with colorectal adenomas. Gut. 1995;36(2):268–73.PubMedPubMedCentralCrossRef Bayerdorffer E, Mannes GA, Ochsenkuhn T, Dirschedl P, Wiebecke B, Paumgartner G. Unconjugated secondary bile acids in the serum of patients with colorectal adenomas. Gut. 1995;36(2):268–73.PubMedPubMedCentralCrossRef
36.
go back to reference Costarelli V, Key TJ, Appleby PN, Allen DS, Fentiman IS, Sanders TA. A prospective study of serum bile acid concentrations and colorectal cancer risk in post-menopausal women on the island of Guernsey. Br J Cancer. 2002;86(11):1741–4.PubMedPubMedCentralCrossRef Costarelli V, Key TJ, Appleby PN, Allen DS, Fentiman IS, Sanders TA. A prospective study of serum bile acid concentrations and colorectal cancer risk in post-menopausal women on the island of Guernsey. Br J Cancer. 2002;86(11):1741–4.PubMedPubMedCentralCrossRef
37.
go back to reference Feng HY, Chen YC. Role of bile acids in carcinogenesis of pancreatic cancer: an old topic with new perspective. World J Gastroenterol. 2016;22(33):7463–77.PubMedPubMedCentralCrossRef Feng HY, Chen YC. Role of bile acids in carcinogenesis of pancreatic cancer: an old topic with new perspective. World J Gastroenterol. 2016;22(33):7463–77.PubMedPubMedCentralCrossRef
38.
go back to reference Hao H, Cao L, Jiang C, Che Y, Zhang S, Takahashi S, et al. Farnesoid X Receptor Regulation of the NLRP3 Inflammasome Underlies Cholestasis-Associated Sepsis. Cell Metab. 2017;25(4):856–67.e5.PubMedPubMedCentralCrossRef Hao H, Cao L, Jiang C, Che Y, Zhang S, Takahashi S, et al. Farnesoid X Receptor Regulation of the NLRP3 Inflammasome Underlies Cholestasis-Associated Sepsis. Cell Metab. 2017;25(4):856–67.e5.PubMedPubMedCentralCrossRef
39.
go back to reference Garcia-Irigoyen O, Moschetta A. A novel protective role for FXR against Inflammasome activation and Endotoxemia. Cell Metab. 2017;25(4):763–4.PubMedCrossRef Garcia-Irigoyen O, Moschetta A. A novel protective role for FXR against Inflammasome activation and Endotoxemia. Cell Metab. 2017;25(4):763–4.PubMedCrossRef
40.
go back to reference Iracheta-Vellve A, Calenda CD, Petrasek J, Ambade A, Kodys K, Adorini L, et al. FXR and TGR5 agonists ameliorate liver injury, Steatosis, and inflammation after binge or prolonged alcohol feeding in mice. Hepatol Commun. 2018;2(11):1379–91.PubMedPubMedCentralCrossRef Iracheta-Vellve A, Calenda CD, Petrasek J, Ambade A, Kodys K, Adorini L, et al. FXR and TGR5 agonists ameliorate liver injury, Steatosis, and inflammation after binge or prolonged alcohol feeding in mice. Hepatol Commun. 2018;2(11):1379–91.PubMedPubMedCentralCrossRef
41.
go back to reference Cipriani S, Mencarelli A, Chini MG, Distrutti E, Renga B, Bifulco G, et al. The bile acid receptor GPBAR-1 (TGR5) modulates integrity of intestinal barrier and immune response to experimental colitis. PLoS One. 2011;6(10):e25637.PubMedPubMedCentralCrossRef Cipriani S, Mencarelli A, Chini MG, Distrutti E, Renga B, Bifulco G, et al. The bile acid receptor GPBAR-1 (TGR5) modulates integrity of intestinal barrier and immune response to experimental colitis. PLoS One. 2011;6(10):e25637.PubMedPubMedCentralCrossRef
42.
go back to reference Zhou X, Xie L, Bergmann F, Endris V, Strobel O, Buchler MW, et al. The bile acid receptor FXR attenuates acinar cell autophagy in chronic pancreatitis. Cell Death Dis. 2017;3:17027.CrossRef Zhou X, Xie L, Bergmann F, Endris V, Strobel O, Buchler MW, et al. The bile acid receptor FXR attenuates acinar cell autophagy in chronic pancreatitis. Cell Death Dis. 2017;3:17027.CrossRef
43.
go back to reference Li B, Yang N, Li C, Li C, Gao K, Xie X, et al. INT-777, a bile acid receptor agonist, extenuates pancreatic acinar cells necrosis in a mouse model of acute pancreatitis. Biochem Biophys Res Commun. 2018;503(1):38–44.PubMedCrossRef Li B, Yang N, Li C, Li C, Gao K, Xie X, et al. INT-777, a bile acid receptor agonist, extenuates pancreatic acinar cells necrosis in a mouse model of acute pancreatitis. Biochem Biophys Res Commun. 2018;503(1):38–44.PubMedCrossRef
Metadata
Title
Increased circulating total bile acid levels were associated with organ failure in patients with acute pancreatitis
Authors
Xiaochun Xie
Jie Dong
Guotao Lu
Kun Gao
Xiaoyao Li
Wenjian Mao
Faxi Chen
Zhihui Tong
Baiqiang Li
Weiqin Li
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Gastroenterology / Issue 1/2020
Electronic ISSN: 1471-230X
DOI
https://doi.org/10.1186/s12876-020-01243-w

Other articles of this Issue 1/2020

BMC Gastroenterology 1/2020 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine