Research ArticleClinical Studies
Open Access

Endotoxin Activity Assay as a Novel Predictor of Disease Progression in Patients With Mild Cholangitis

KOICHI MORI, KENTARO MIYAKE, RYUSEI MATSUYAMA, KOKI GOTO, SAYAKA ARISAKA, YUSUKE SUWA, TOSHIAKI KADOKURA, YUKI HOMMA and ITARU ENDO
In Vivo May 2025, 39 (3) 1685-1693; DOI: https://doi.org/10.21873/invivo.13970

Abstract

Background/Aim: Acute cholangitis is a critical biliary infection that can swiftly evolve into sepsis and organ failure. Certain patients with mild acute cholangitis might advance to a more severe status. Identifying predictive factors for such exacerbation is of paramount importance. This study aimed to investigate whether the endotoxin activity assay (EAA) could serve as a predictive biomarker for the progression of mild acute cholangitis.

Patients and Methods: We conducted a retrospective observational study at Yokohama City University Hospital, enrolling 200 patients hospitalized with acute cholangitis between May 2011 and June 2015. Patients with initially mild acute cholangitis were stratified into two groups based on their severity on Day 1: the stable group (remaining mild) and the exacerbation group (progressing to moderate/severe cholangitis). Clinical parameters were analyzed to assess risk factors for exacerbation.

Results: Among 74 patients with mild acute cholangitis at admission, 33 (44.6%) progressed to moderate/severe cholangitis within 24 h. Multivariate logistic regression analysis identified chemotherapy within 28 days [odds ratio (OR)=3.440, 95% confidence interval (CI)=1.170-10.100, p=0.025], serum albumin levels (OR=0.303, 95%CI=0.094-0.975, p=0.045), and EAA ≥0.4 (OR=3.880, 95%CI=1.210-12.500, p=0.023) as independent predictors of disease exacerbation. A predictive equation was developed using the logistic regression model: log (P/1-P)=3.285-1.265×Alb (mg/dl) + 1.291 × (Chemotherapy within 28 days) +1.343 × (EAA ≥0.4) (P: the probability of exacerbation).

Conclusion: EAA was identified as the most significant factor for exacerbating mild acute cholangitis. The combination of EAA, albumin levels, and a history of chemotherapy within the past 28 days suggests the potential to predict the progression of mild acute cholangitis to a more severe form.

Keywords:

Introduction

Acute cholangitis is a potentially life-threatening biliary infection that results from bacterial invasion due to biliary obstruction. The condition can rapidly escalate to sepsis and multi-organ failure if left untreated (1). The Tokyo Guidelines (TG13, TG18) have provided standardized criteria for diagnosis and severity classification, categorizing cases as mild, moderate, or severe based on clinical and laboratory parameters (2, 3). The mortality rate among patients with acute cholangitis ranges from 2.7% to 10.0%; however, in those with severe cholangitis, it can increase to nearly 20.0% (3). While mild cases are often manageable with conservative therapy, some patients experience rapid disease progression, leading to increased morbidity and mortality.

Despite advances in risk stratification, predicting the deterioration of mild acute cholangitis remains challenging. The current severity classification relies on clinical judgment and laboratory markers, but these assessments may not adequately capture early signs of exacerbation (4). Identifying reliable biomarkers that predict progression to moderate or severe cholangitis is crucial for optimizing early therapeutic interventions, such as timely antibiotic administration, biliary drainage, and intensive care support.

Endotoxins, primarily lipopolysaccharides (LPS) from Gram-negative bacteria, play a central role in the pathophysiology of sepsis and severe biliary infections. These endotoxins trigger a systemic inflammatory response, leading to endothelial dysfunction, disseminated intravascular coagulation (DIC), and multiple organ failure (5). The Endotoxin Activity Assay (EAA) is a novel diagnostic tool that quantifies endotoxin-related neutrophil activation, offering a rapid and reliable method to assess bacterial endotoxemia (6). We demonstrated a correlation between high EAA levels and disease severity in acute cholangitis, suggesting that EAA could serve as an early predictor of worsening clinical status (7).

The aim of this study was to investigate potential predictive factors for exacerbation of mild acute cholangitis to moderate/severe cholangitis by evaluating clinical variables and biomarkers including EAA.

Patients and Methods

We conducted a retrospective observational study in the Department of Gastroenterological Surgery at Yokohama City University Hospital (Yokohama, Japan). This study protocol was approved by the Ethical Review Board of Yokohama City University Hospital (Yokohama, Japan) (approval number: 110512019), and informed consent was obtained from all patients. We enrolled 200 patients who were hospitalized for acute cholangitis at our department between May 2011 and June 2015 to this study. All patients underwent blood sampling, blood culture, and computed tomography (CT) examination upon admission, and the severity of cholangitis was assessed based on TG18 (3). Additionally, EAA, which indicates neutrophil activity, was measured using the remaining admission blood sample as we described before (7). DIC was diagnosed using the Japanese Association for Acute Medicine criteria (JAAM criteria), and organ dysfunction was evaluated using the sequential organ failure assessment score (SOFA score) (8-10). The initial treatment consisted of antimicrobial therapy, with piperacillin/tazobactam (PIPC/TAZ) as the first-line agent. In cases where resistant strains had been previously identified, carbapenems or other alternative antibiotics were administered. Stent replacement was considered if the initial treatment was ineffective regardless of whether a stent was present. If two months had passed since the previous stent placement, stent replacement was performed during hospitalization.

Patients with mild acute cholangitis on admission (Day 0) were stratified according to their severity of cholangitis on Day 1 into the following two groups: the Stable group (the severity on Day 1 was mild) and the Exacerbation group (the severity on Day 1 was moderate or severe). Clinical findings were retrospectively analyzed to evaluate the risk of progression to severe cholangitis in patients with mild cholangitis.

EAA. EAA was measured using residual blood from the admission blood test, following the manufacturer’s instructions (Spectral Diagnostics, Toronto, ON, Canada). The method for EAA measurement was previously described (8).

Statistical analysis. All statistical analyses were conducted using EZR (Saitama Medical Center, Jichi Medical University, Saitama, Japan), a graphical user interface for R (The R Foundation for Statistical Computing, Vienna, Austria) (11). All values are expressed as median and interquartile range or a number and percentage (%). The Mann-Whitney U-test was used to analyze the continuous variables, while the χ2 test was used to analyze the categorical variables.

Univariate logistic regression analysis was conducted to assess the association between each independent variable and exacerbation. Variables with p<0.1 in the univariate analysis were considered potential predictors and included in the multivariable analysis. Multivariable logistic regression analysis with a stepwise selection method was applied to identify the most relevant predictors. Variables that remained significant (p<0.1) were included in the final model.

A predictive model for exacerbation was constructed using statistically significant factors identified in the multivariable logistic regression analysis. The performance of the final model was assessed using a receiver operating characteristic (ROC) curve analysis. The optimal cutoff value for predicting exacerbation was determined using Youden’s Index.

Results

Patient characteristics. The patient demographic and clinical characteristics are presented in Table I. The cohort comprised 149 men and 51 women, with a median age of 73 years. A total of 136 patients (68.0%) had underlying malignancies, of whom 85 (42.5%) had undergone chemotherapy within the preceding 28 days. Biliary drainage stents were present in 120 patients (60.0%), whereas 100 patients (50.0%) had previously undergone choledochojejunostomy. Additionally, 15 patients (7.5%) had liver abscesses, and 89 patients (44.5%) underwent biliary drainage within 24 h of admission. Based on the Tokyo Guidelines 2018 (TG18), acute cholangitis severity was classified as mild in 74 patients (37.0%), moderate in 51 patients (25.5%), and severe in 75 patients (37.5%).

View this table:
Table I.

Characteristics of patients.

The characteristics of the patients with mild acute cholangitis are shown in Table II. There were 50 men and 24 women, with a median age of 70 years. Forty-eight patients (64.9%) were cancer-bearing, 29 of whom (39.2%) had received chemotherapy with 28 days. Forty-six patients (62.2%) had a bile duct drainage stent, 40 patients (54.1%) were post-choledochojejunostomy, and five patients (2.5%) had liver abscess. Thirty-two patients (43.2%) underwent bile duct drainage within 24 h.

View this table:
Table II.

Characteristics of patients with mild cholangitis on admission.

The patients with mild acute cholangitis on admission (Day0) were divided into two groups (the Stable group and the Exacerbation group) according to the severity of cholangitis on the day after admission (Day1) (Figure 1).

Figure 1.
Figure 1.

Flowchart depicting patients with mild cholangitis at admission. They were categorized into two groups: the Stable group and the Exacerbation group, based on the severity of cholangitis on the day after admission (Day 1). The severity was classified according to the Tokyo Guidelines 2018 (TG18).

Comparison between the Stable Group and the Exacerbation Group. Table III shows the comparison between the Stable Group (n=41) and the Exacerbation Group (n=33). Among patients aged 75 years or older, six cases (14.6%) were in the Stable group, whereas 11 cases (33.3%) were in the Exacerbation group, indicating a higher prevalence in the Exacerbation group (p=0.057). Chemotherapy within 28 days prior to admission was statistically more common in the Exacerbation Group, with 18 patients (54.6%) having undergone chemotherapy, compared to 11 patients (26.8%) in the Stable Group (p=0.015). C-reactive protein (CRP) levels were significantly higher in the Exacerbation group than in the Stable group (1.55 vs. 4.6, p=0.006). Conversely, serum albumin (Alb) levels were significantly lower in the Exacerbation group compared to the Stable group (3.7 vs. 3.4, p=0.007). EAA levels were also significantly elevated in the Exacerbation group (0.24 vs. 0.35, p=0.001). Moreover, the number of patients with an EAA value of ≥0.4 was significantly higher in the Exacerbation group [7 cases (17.1%) in the Stable group vs. 14 cases (42.4%) in the Exacerbation group]. There were no significant differences between the two groups in terms of drainage timing or the choice of antimicrobial agents. Although the difference was not statistically significant, the number of intensive care unit (ICU) admissions was higher in the Exacerbation group (2.4% vs. 12.1%, p=0.099), and all 28-day mortality cases were observed exclusively in the Exacerbation group (0% vs. 6.06%, p=0.110).

View this table:
Table III.

Characteristics of patients in two groups depending on severity of cholangitis on Day1.

Univariate and multivariate logistic regression analysis. Table IV presents the results of the logistic regression analysis identifying risk factors associated with the exacerbation of acute cholangitis. In the univariate analysis, several factors showed potential associations with disease progression. Advanced age (≥75 years) exhibited a trend towards significance [odds ratio (OR)=2.917, 95% confidence interval (CI)=0.943-9.020, p=0.063]. Serum albumin levels were significantly associated with a lower risk of cholangitis exacerbation (OR=0.303, 95%CI=0.106-0.865, p=0.026), while CRP levels correlated positively with worsening disease (OR=1.147, 95%CI=1.020-1.290, p=0.018). Additionally, recent chemotherapy within 28 days (OR=3.273, 95%CI=1.240-8.660, p=0.017), SOFA score (OR=1.533, 95%CI=1.000-2.340, p=0.048) and EAA ≥0.4 (OR=3.579, 95%CI=1.231-10.402, p=0.019) demonstrated associations with cholangitis progression.

View this table:
Table IV.

Independent variables in multivariate logistic regression analyses associated with predictive factors for exacerbation of mild acute cholangitis.

In the multivariate analysis, serum albumin levels (OR=0.303, 95%CI=0.094-0.975, p=0.045), chemotherapy within 28 days (OR=3.440, 95%CI=1.170-10.100, p=0.025), and EAA ≥0.4 (OR=4.632, 95%CI=1.589-13.515, p=0.005) were identified as independent risk factors for the worsening of acute cholangitis.

Prediction model based on statistically significant factors. A predictive model for exacerbation was constructed using statistically significant factors identified in the multivariable logistic regression analysis. The final model included serum Alb, chemotherapy history within last 28 days, and EAA ≥0.4 at admission as independent predictors. A predictive equation was developed using the logistic regression model: log (P/1-P)=3.285-1.265×Alb (mg/dl) + 1.291 × (Chemotherapy within 28 days) +1.343 × (EAA ≥0.4) (P: the probability of exacerbation). Figure 2 illustrates the performance of the final model using the ROC curve, with the area under the curve (AUC) measured at 0.75. The optimal cutoff value for predicting exacerbation was determined using Youden’s Index, establishing a threshold of 0.455, which resulted in a sensitivity of 69.7% and specificity of 68.3%.

Figure 2.
Figure 2.

The performance of the prognostic model was assessed by the ROC curve, with the area under the curve (AUC) measured at 0.75. The optimal cutoff value for predicting exacerbation was determined using Youden’s Index, establishing a threshold of 0.455, which resulted in a sensitivity of 69.7% and specificity of 68.3%.

Discussion

This study investigated potential predictors of disease progression in patients with mild acute cholangitis, with a particular focus on the EAA. Among 74 patients initially diagnosed with mild acute cholangitis, 44.6% progressed to moderate or severe cholangitis within 24 h. Multivariate logistic regression analysis identified three independent risk factors for exacerbation: recent chemotherapy within the past 28 days, lower serum albumin levels, and EAA ≥0.4. Notably, EAA was the most significant predictor of worsening disease status, emphasizing its potential utility as an early biomarker.

To our knowledge, this study is the first to comprehensively evaluate EAA as a predictive biomarker for acute cholangitis progression. The key strengths of this study include its systematic assessment of a novel biomarker (EAA), its analysis of independent risk factors, and its potential implications for early risk stratification. The identification of EAA ≥0.4 as a strong predictor provides a new approach for clinical decision-making, allowing for timely intervention before severe complications arise. Additionally, the study reinforces the importance of considering albumin levels and recent chemotherapy history in predicting disease progression.

Previous studies have explored various clinical and laboratory markers for assessing cholangitis severity, including the Tokyo Guidelines (TG18) criteria and inflammatory biomarkers such as CRP and procalcitonin (3, 12-15). However, these conventional markers may not fully capture the early pathophysiological changes leading to disease progression. Endotoxins, primarily derived from Gram-negative bacterial infections, have been implicated in the development of sepsis and multi-organ failure (16-18). However, endotoxin levels are not included in the TG18 severity assessment criteria, as no correlation has been observed between endotoxin levels and the severity of acute cholangitis (3).

The utility of EAA as a biomarker has been demonstrated in other critical conditions, including sepsis and systemic inflammatory response syndrome (7, 19-21). We previously reported that EAA levels at admission were significantly correlated with the severity of cholangitis and were also associated with the positive rate of blood cultures (7). By increasing the number of cases to more than twice the original, similar results were obtained in the present analysis (Data not shown). Our study extends these findings by demonstrating that EAA can serve as an early predictor of worsening acute cholangitis, supplementing traditional severity assessments.

The association between elevated EAA levels and cholangitis progression highlights the critical role of endotoxemia in disease exacerbation. A higher EAA value reflects increased neutrophil activation in response to endotoxins, which may indicate a heightened inflammatory state preceding overt clinical deterioration. The predictive value of serum albumin levels suggests that nutritional status and systemic inflammation play a role in disease severity (22). Albumin is a well-established marker of systemic illness and has been linked to worse outcomes in infectious diseases (23). Similarly, the impact of recent chemotherapy suggests that immunosuppression and gut translocation of endotoxins may contribute to a higher risk of disease progression. These findings collectively underscore the need for closer monitoring and early therapeutic intervention in patients with mild acute cholangitis who present these risk factors.

Despite its strengths, this study has several limitations. First, the study was conducted retrospectively at a single institution, which may limit generalizability to other clinical settings. Second, although EAA was identified as a significant predictor, its widespread implementation in routine clinical practice requires further validation through prospective multicenter studies. Additionally, we did not evaluate dynamic changes in EAA over time, which could provide further insights into its role in disease monitoring.

Conclusion

This study demonstrates that EAA is a valuable predictor of disease progression in patients with mild acute cholangitis. Patients with EAA ≥ 0.4, lower serum albumin levels, and a history of recent chemotherapy are at higher risk of worsening cholangitis. These findings suggest that incorporating EAA into routine risk assessment may enhance early identification of high-risk patients, facilitating timely interventions such as intensified antibiotic therapy, early biliary drainage, and close clinical monitoring. Future prospective studies are warranted to further validate these findings and refine risk stratification strategies in acute cholangitis management.

Acknowledgements

The Authors have no acknowledgements to declare.

Footnotes

  • Authors’ Contributions

    IE, RM, and KM conceptualized the study. KM, KG, SA, YS, and TK collected the clinical data. KM, KM, and YH designed the statistical analysis plan and performed the statistical analyses. KM, KM, and YH contributed to the interpretation of the results. KM and KM prepared the initial manuscript draft. IE and RM supervised the study. All Authors reviewed the manuscript draft, provided critical revisions for intellectual content, and approved the final version for publication.

  • Funding

    This study was not supported by any specific grant from public, commercial, or non-profit funding agencies.

  • Conflicts of Interest

    The Authors declare that they have no conflicts of interest in relation to this study.

  • Received February 16, 2025.
  • Revision received March 4, 2025.
  • Accepted March 5, 2025.

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (https://creativecommons.org/licenses/by-nc-nd/4.0).

References

  1. ↵
    1. Lipsett PA,
    2. Pitt HA
    : Acute cholangitis. Surg Clin North Am 70(6): 1297-1312, 1990. DOI: 10.1016/s0039-6109(16)45285-0
    OpenUrlCrossRefPubMed
  2. ↵
    1. Kimura Y,
    2. Takada T,
    3. Kawarada Y,
    4. Nimura Y,
    5. Hirata K,
    6. Sekimoto M,
    7. Yoshida M,
    8. Mayumi T,
    9. Wada K,
    10. Miura F,
    11. Yasuda H,
    12. Yamashita Y,
    13. Nagino M,
    14. Hirota M,
    15. Tanaka A,
    16. Tsuyuguchi T,
    17. Strasberg SM,
    18. Gadacz TR
    : Definitions, pathophysiology, and epidemiology of acute cholangitis and cholecystitis: Tokyo Guidelines. J Hepatobiliary Pancreat Surg 14(1): 15-26, 2007. DOI: 10.1007/s00534-006-1152-y
    OpenUrlCrossRefPubMed
  3. ↵
    1. Kiriyama S,
    2. Kozaka K,
    3. Takada T,
    4. Strasberg SM,
    5. Pitt HA,
    6. Gabata T,
    7. Hata J,
    8. Liau KH,
    9. Miura F,
    10. Horiguchi A,
    11. Liu KH,
    12. Su CH,
    13. Wada K,
    14. Jagannath P,
    15. Itoi T,
    16. Gouma DJ,
    17. Mori Y,
    18. Mukai S,
    19. Giménez ME,
    20. Huang WS,
    21. Kim MH,
    22. Okamoto K,
    23. Belli G,
    24. Dervenis C,
    25. Chan ACW,
    26. Lau WY,
    27. Endo I,
    28. Gomi H,
    29. Yoshida M,
    30. Mayumi T,
    31. Baron TH,
    32. de Santibañes E,
    33. Teoh AYB,
    34. Hwang TL,
    35. Ker CG,
    36. Chen MF,
    37. Han HS,
    38. Yoon YS,
    39. Choi IS,
    40. Yoon DS,
    41. Higuchi R,
    42. Kitano S,
    43. Inomata M,
    44. Deziel DJ,
    45. Jonas E,
    46. Hirata K,
    47. Sumiyama Y,
    48. Inui K,
    49. Yamamoto M
    : Tokyo Guidelines 2018: diagnostic criteria and severity grading of acute cholangitis (with videos). J Hepatobiliary Pancreat Sci 25(1): 17-30, 2018. DOI: 10.1002/jhbp.512
    OpenUrlCrossRefPubMed
  4. ↵
    1. Sperna Weiland CJ,
    2. Busch CBE,
    3. Bhalla A,
    4. Bruno MJ,
    5. Fockens P,
    6. van Hooft JE,
    7. Poen AC,
    8. Timmerhuis HC,
    9. Umans DS,
    10. Venneman NG,
    11. Verdonk RC,
    12. Drenth JPH,
    13. de Wijkerslooth TR,
    14. van Geenen EJM, Dutch Pancreatitis Study Group
    : Performance of diagnostic tools for acute cholangitis in patients with suspected biliary obstruction. J Hepatobiliary Pancreat Sci 29(4): 479-486, 2022. DOI: 10.1002/jhbp.1096
    OpenUrlCrossRefPubMed
  5. ↵
    1. Marshall JC,
    2. Foster D,
    3. Vincent JL,
    4. Cook DJ,
    5. Cohen J,
    6. Dellinger RP,
    7. Opal S,
    8. Abraham E,
    9. Brett SJ,
    10. Smith T,
    11. Mehta S,
    12. Derzko A,
    13. Romaschin A
    : Diagnostic and prognostic implications of endotoxemia in critical illness: results of the MEDIC study. J Infect Dis 190(3): 527-534, 2004. DOI: 10.1086/422254
    OpenUrlCrossRefPubMed
  6. ↵
    1. Romaschin AD,
    2. Harris DM,
    3. Ribeiro MB,
    4. Paice J,
    5. Foster DM,
    6. Walker PM,
    7. Marshall JC
    : A rapid assay of endotoxin in whole blood using autologous neutrophil dependent chemiluminescence. J Immunol Methods 212(2): 169-185, 1998. DOI: 10.1016/s0022-1759(98)00003-9
    OpenUrlCrossRefPubMed
  7. ↵
    1. Sato M,
    2. Matsuyama R,
    3. Kadokura T,
    4. Mori R,
    5. Kumamoto T,
    6. Nojiri K,
    7. Taniguchi K,
    8. Takeda K,
    9. Kubota K,
    10. Tanaka K,
    11. Endo I
    : Severity and prognostic assessment of the endotoxin activity assay in biliary tract infection. J Hepatobiliary Pancreat Sci 21(2): 120-127, 2014. DOI: 10.1002/jhbp.10
    OpenUrlCrossRefPubMed
  8. ↵
    1. Seymour CW,
    2. Liu VX,
    3. Iwashyna TJ,
    4. Brunkhorst FM,
    5. Rea TD,
    6. Scherag A,
    7. Rubenfeld G,
    8. Kahn JM,
    9. Shankar-Hari M,
    10. Singer M,
    11. Deutschman CS,
    12. Escobar GJ,
    13. Angus DC
    : Assessment of clinical criteria for sepsis: for the third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 315(8): 762-774, 2016. DOI: 10.1001/jama.2016.0288
    OpenUrlCrossRefPubMed
    1. Asakura H,
    2. Takahashi H,
    3. Uchiyama T,
    4. Eguchi Y,
    5. Okamoto K,
    6. Kawasugi K,
    7. Madoiwa S,
    8. Wada H, DIC subcommittee of the Japanese Society on Thrombosis and Hemostasis
    : Proposal for new diagnostic criteria for DIC from the Japanese Society on Thrombosis and Hemostasis. Thromb J 14: 42, 2016. DOI: 10.1186/s12959-016-0117-x
    OpenUrlCrossRefPubMed
  10. ↵
    1. Raith EP,
    2. Udy AA,
    3. Bailey M,
    4. McGloughlin S,
    5. MacIsaac C,
    6. Bellomo R,
    7. Pilcher DV; Australian and New Zealand Intensive Care Society (ANZICS) Centre for Outcomes and Resource Evaluation (CORE)
    : Prognostic accuracy of the SOFA score, SIRS criteria, and qSOFA score for in-hospital mortality among adults with suspected infection admitted to the intensive care unit. Jama 317(3): 290, 2017. DOI: 10.1001/jama.2016.20328
    OpenUrlCrossRefPubMed
  11. ↵
    1. Kanda Y
    : Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant 48(3): 452-458, 2013. DOI: 10.1038/bmt.2012.244
    OpenUrlCrossRefPubMed
  12. ↵
    1. Wada K,
    2. Takada T,
    3. Kawarada Y,
    4. Nimura Y,
    5. Miura F,
    6. Yoshida M,
    7. Mayumi T,
    8. Strasberg S,
    9. Pitt HA,
    10. Gadacz TR,
    11. Büchler MW,
    12. Belghiti J,
    13. de Santibanes E,
    14. Gouma DJ,
    15. Neuhaus H,
    16. Dervenis C,
    17. Fan ST,
    18. Chen MF,
    19. Ker CG,
    20. Bornman PC,
    21. Hilvano SC,
    22. Kim SW,
    23. Liau KH,
    24. Kim MH
    : Diagnostic criteria and severity assessment of acute cholangitis: Tokyo Guidelines. J Hepatobiliary Pancreat Surg 14(1): 52-58, 2007. DOI: 10.1007/s00534-006-1156-7
    OpenUrlCrossRefPubMed
    1. Ye S,
    2. Lyu Y,
    3. Wang B
    : The predictive value of different laboratory indicators based on the 2018 Tokyo guidelines for the severity of acute cholangitis. J Emerg Med 65(4): e280-e289, 2023. DOI: 10.1016/j.jemermed.2023.05.013
    OpenUrlCrossRefPubMed
    1. Silangcruz K,
    2. Nishimura Y,
    3. Czech T,
    4. Kimura N,
    5. Yess J
    : Procalcitonin to predict severity of acute cholangitis and need for urgent biliary decompression: systematic scoping review. J Clin Med 11(5): 1155, 2022. DOI: 10.3390/jcm11051155
    OpenUrlCrossRefPubMed
  15. ↵
    1. Zhang HY,
    2. Lu ZQ,
    3. Wang GX,
    4. Xie MR,
    5. Li CS
    : Presepsin as a biomarker for risk stratification for acute cholangitis in emergency department: A single-center study. World J Clin Cases 9(32): 9857-9868, 2021. DOI: 10.12998/wjcc.v9.i32.9857
    OpenUrlCrossRefPubMed
  16. ↵
    1. Yang X,
    2. Cheng X,
    3. Tang Y,
    4. Qiu X,
    5. Wang Y,
    6. Kang H,
    7. Wu J,
    8. Wang Z,
    9. Liu Y,
    10. Chen F,
    11. Xiao X,
    12. Mackman N,
    13. Billiar TR,
    14. Han J,
    15. Lu B
    : Bacterial endotoxin activates the coagulation cascade through gasdermin D-dependent phosphatidylserine exposure. Immunity 51(6): 983-996.e6, 2019. DOI: 10.1016/j.immuni.2019.11.005
    OpenUrlCrossRefPubMed
    1. Heumann D,
    2. Roger T
    : Initial responses to endotoxins and Gram-negative bacteria. Clin Chim Acta 323(1-2): 59-72, 2002. DOI: 10.1016/s0009-8981(02)00180-8
    OpenUrlCrossRefPubMed
  18. ↵
    1. Kellum JA,
    2. Ronco C
    : The role of endotoxin in septic shock. Crit Care 27(1): 400, 2023. DOI: 10.1186/s13054-023-04690-5
    OpenUrlCrossRefPubMed
  19. ↵
    1. Valenza F,
    2. Fagnani L,
    3. Coppola S,
    4. Froio S,
    5. Sacconi F,
    6. Tedesco C,
    7. Maffioletti M,
    8. Pizzocri M,
    9. Salice V,
    10. Ranzi ML,
    11. Marenghi C,
    12. Gattinoni L
    : Prevalence of endotoxemia after surgery and its association with ICU length of stay. Crit Care 13(3): R102, 2009. DOI: 10.1186/cc7934
    OpenUrlCrossRefPubMed
    1. Pathan N,
    2. Burmester M,
    3. Adamovic T,
    4. Berk M,
    5. Ng KW,
    6. Betts H,
    7. Macrae D,
    8. Waddell S,
    9. Paul-clark M,
    10. Nuamah R,
    11. Mein C,
    12. Levin M,
    13. Montana G,
    14. Mitchell JA
    : Intestinal injury and endotoxemia in children undergoing surgery for congenital heart disease. Am J Respir Crit Care Med 184(11): 1261-1269, 2011. DOI: 10.1164/rccm.201104-0715OC
    OpenUrlCrossRefPubMed
  21. ↵
    1. Yaroustovsky M,
    2. Rogalskaya E,
    3. Plyushch M,
    4. Klimovich L,
    5. Samsonova N,
    6. Abramyan M
    : The level of oxidative neutrophil response when determining endotoxin activity assay: a new biomarker for defining the indications and effectiveness of intensive care in patients with sepsis. Int J Inflam 2017: 3495293, 2017. DOI: 10.1155/2017/3495293
    OpenUrlCrossRefPubMed
  22. ↵
    1. Don BR,
    2. Kaysen G
    : Serum albumin: Relationship to inflammation and nutrition. Semin Dial 17(6): 432-437, 2004. DOI: 10.1111/j.0894-0959.2004.17603.x
    OpenUrlCrossRefPubMed
  23. ↵
    1. Paliogiannis P,
    2. Mangoni AA,
    3. Cangemi M,
    4. Fois AG,
    5. Carru C,
    6. Zinellu A
    : Serum albumin concentrations are associated with disease severity and outcomes in coronavirus 19 disease (COVID-19): a systematic review and meta-analysis. Clin Exp Med 21(3): 343-354, 2021. DOI: 10.1007/s10238-021-00686-z
    OpenUrlCrossRefPubMed
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Endotoxin Activity Assay as a Novel Predictor of Disease Progression in Patients With Mild Cholangitis
KOICHI MORI, KENTARO MIYAKE, RYUSEI MATSUYAMA, KOKI GOTO, SAYAKA ARISAKA, YUSUKE SUWA, TOSHIAKI KADOKURA, YUKI HOMMA, ITARU ENDO
In Vivo May 2025, 39 (3) 1685-1693; DOI: 10.21873/invivo.13970
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