Introduction
Acute pancreatitis (AP) is one of the most common and widely increasing gastrointestinal diseases leading to hospitalization without specifically available therapy [1]. It is mainly caused by gallstones, possibly by increasing the pressure in pancreatic duct with refluxing of bile acids (BAs) or changing of serum BA concentration due to bile duct obstruction [2]. So far, few existing reports only mentioned total BA measurements without considering their hydrophilic potential. Our data from experimental work showed that systemic BAs can modulate severity of AP depending on their hydrophobicity and the involvement of cholecystokinin [3]. As a further translational step, we aimed to investigate the role of systemic BAs profiles and analysed their association with the etiology and severity of AP in human.
Aims & Methods
Serum from AP patients and a healthy control group was collected and stored at -800C. A profile of 20 different BAs was quantified by liquid chromatography tandem mass spectrometry-based assay using the AbsoluteIDQBAs kit according to the manufacturer’s instruction. The workflow was managed by MetIDQ and the data was analyzed by Oracle database XE software. Acute Physiology and Chronic Health Evaluation (APACHE) II scores were calculated for each patient at the first and third day of hospitalization and were compared by subtraction of the values (Δ APACHE II). Diagnosis criteria and severity of pancreatitis were assessed according to the Revised Atlanta classification and the APACHE II score.
Results
There were 214 AP patients with mean age of 60±16 (range 26-87) years and 50.4 % were female. Biliary origin was diagnosed in 133 (62.1%) patients and non-biliary pancreatitis (mainly alcoholic AP) in 81 (37.9 %) cases. In non-biliary AP, profiles of both hydrophobic and hydrophilic BAs did not differ from controls. In biliary AP, significantly elevated levels were detected for hydrophobic BAs but not hydrophilic one. The total concentrations of hydrophobic BAs were 33.86±4.51 μM in biliary AP and 8.068±1.98 μM in non-biliary AP (p < 0.0001). Cut-off values were 0.30 μM and 3.78 μM for hydrophilic and hydrophobic BAs, respectively. The total amount of hydrophilic BAs was not different between the groups of deteriorated (Δ APACHE II >0) and ameliorated or stable AP (Δ APACHE II ≤ 0). Conversely, total hydrophobic BAs concentrations were significantly higher in the worsened AP (55.8±12.3 μM) group than in those who recovered or at least did not deteriorate (5.9±0.6 μM). However, ursodeoxycholic acid (UDCA), a hydrophilic BA, was significantly decreased in severe disease and showed a reduced trend in moderately severe AP.
Hydrophobic BAs had more predictive potential with an area under the curve (AUC) of 0.762, a sensitivity of 83.75% and a specificity of 60% at the cut-off value 11.84 μM, whereas hydrophilic BAs were only of limited use for the prediction of AP deterioration, as AUC was 0.57 with a sensitivity of 65% and a specificity of 44% at the cut-off 0.7 μM. Additionally, UDCA concentrations of less than 19 nM can be used to distinguish biliary AP from non-biliary AP with an AUC of 0.723, sensitivity 75%, and specificity 65%. For detection of deterioration, UDCA alone with cut-off concentration 18 nM showed a value with an AUC of 0.68, sensitivity 76%, and specificity 61%.
Conclusion
In patients, the sum of hydrophobic but not total hydrophilic BAs associated with the etiology and severity of AP. Serum levels of UDCA, a particular type of hydrophilic BAs, inversely associated with the severity of AP, which suggests a protective role.
References
[1]. Iannuzzi, J.P.; King, J.A.; Leong, J.H.; Quan, J.; Windsor, J.W.; Tanyingoh, D.; Coward, S.; Forbes, N.; Heitman, S.J.; Shaheen, A.A.; et al. Global Incidence of Acute Pancreatitis Is Increasing Over Time: A Systematic Review and Meta-Analysis. Gastroenterology 2022, 162, 122-134, doi:10.1053/j.gastro.2021.09.043
[2]. Lerch, M.M.; Aghdassi, A.A. The role of bile acids in gallstone-induced pancreatitis. Gastroenterology 2010, 138, 429-433, doi:10.1053/j.gastro.2009.12.012
[3]. Tran, Q.T.; Sendler, M.; Wiese, M.L.; Doller, J.; Zierke, L.; Gischke, M.; Glaubitz, J.; Tran, V.H.; Lalk, M.; Bornscheuer, U.T.; Weiss F.U; Lerch, M.M and Aghdassi A.A. Systemic Bile Acids Affect the Severity of Acute Pancreatitis in Mice Depending on Their Hydrophobicity and the Disease Pathogenesis. International journal of molecular sciences 2022, 23, 13592. doi: 10.3390/ijms232113592
Disclosure
The authors declared no Conflict of Interest.