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THE COMBINATION OF YKL-40 AND INTERLEUKIN 6 PREDICTS MORE ACCURATELY THE SEVERITY OF ACUTE PANCREATITIS THAN EITHER BIOMARKER ALONE: A CROATIAN SINGLE-CENTER PROSPECTIVE OBSERVATIONAL STUDY.

Nina Blazevic 1, Stipe Pelajic 1, Dunja Rogic 2, Vladimir Trkulja 3, Marijana Miler 1, Marko Nikolic 1, Mario Zivkovic 1, Neven Barsic 1, Davor Hrabar 1, Tajana Pavic 1

Affiliations

1 Sestre milosrdnice University Hospital Center, Zagreb, Croatia, Zagreb, Croatia

2 University Hospital Center Zagreb, Zagreb, Croatia, Zagreb, Croatia

3 University of Zagreb School of Medicine, Zagreb, Croatia, Zagreb, Croatia

Summary

AI Generated

Combined YKL-40 and IL-6 concentrations predict moderate or severe acute pancreatitis more strongly than either biomarker alone, independently of C-reactive protein levels.

In 150 consecutive adults with acute pancreatitis, patients with both YKL-40 above 190 ng/mL and IL-6 above 42 pg/mL had higher odds of more severe disease than patients with either biomarker elevated alone, measured both on admission and at 48 hours.
The predictive association remained after adjusting for age, body mass index, time from symptom onset to admission, and CRP concentrations, though the strength of association was lower after adjustment.
At CRP concentrations of 90 mg/L and 180 mg/L, the combination of elevated YKL-40 and IL-6 was particularly associated with higher odds of severe disease, while at CRP 45 mg/L no association was observed.
Non-AP control adults showed YKL-40 concentrations below 50 ng/mL and IL-6 below 20 pg/mL, lower than levels observed in AP patients.
This prospective study from a single center used revised Atlanta classification for disease severity and enzyme-linked immunosorbent assays for biomarker quantification.

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This summary was generated by an AI large language model based on the content transcript. It is for informational purposes only and should not be considered a substitute for clinical judgment. Always rely on your professional expertise and the full clinical context when making clinical decisions.

Abstract

Introduction

Acute pancreatitis (AP) often has unpredictable and complicated clinical course. Numerous biochemical predictors may aid in the risk stratification of AP (including interleukin 6 (IL-6)), but none of them are accurate. YKL-40 is glycoprotein playing mayor role in inflammation and angiogenesis, with reported average serum concentrations of ≥ 190 ng/mL in inflammatory diseases. It has been shown that IL-6 stimulates the production of YKL-40 and, in reverse, YKL-40 (at least in some tissues) induces the production of IL-6.

Aims & Methods

The aim of our study is to assess whether combined concentrations of both YKL-40 and IL-6 could be more informative in risk stratification of developing more severe form of AP than concentrations of either biomarker alone.
We included 150 consecutive consenting adults with AP admitted to Sestre milosrdnice UHC, Zagreb (June 2020-June 2023). Patients with any acute/chronic diseases known to be associated with dysregulated expression of YKL-40 were excluded. Alongside routine laboratory studies (including C-reactive protein (CRP)), 7 mLs of blood were withdrawn for determining YKL-40 and IL-6 concentrations on admission and 48h after. Severity of disease was defined using revised Atlanta classification. Blood samples for YKL-40 and IL-6 quantification in 30 consenting non-AP adults consistent with previously mentioned exclusion criteria were withdrawn. They were matched 1:1 by age and sex to randomly selected 10 patients from each of AP severity categories. Analysis were performed using enzyme-linked immunosorbent assays. AP patients were classified into 2 categories for each biomarker (based on YKL-40 and IL-6 concentrations on admission and 48h after): 1. for YKL-40: low (<190 ng/mL) and high (≥190 ng/mL); 2. for IL-6: low (<42 pg/mL) and high (≥42 pg/mL). Cumulative multimodal logit models were fitted to ordinal outcome “AP severity” – using raw data, and data after entropy balancing undertaken to balance the two categories of YKL-40 and IL-6 concentrations on age, sex, time between symptom onset and admission, and CRP concentrations.

Results

The results showed lower YKL-40 (<50 ng/mL) and IL-6 (<20 pg/mL) concentrations in 30 non-AP adults compared to AP patients. At both time points (on admission and 48h after), odds of more severe AP were clearly higher with YKL-40 and IL-6 concentrations above vs. below the cut-off values (190 ng/mL and 42 pg/mL, respectively), and were particulary higher in patients with both cytokines above the cut-off vs. patients with both cytokines below the cut-off. The same relationship was maintained with adjustments for age, body mass index, days elapsed since symptom onset and admission, and for CRP concentrations – however, the strength of association was lower. This is in line with the fact that high CRP concentration predicts more strongly severe AP forms when taken 48h after compared to admission. This phenomenon was apparent also when the interaction term was included in the model: at CRP concentrations 45 mg/L, neither YKL-40, or IL-6 or their combination above the cut-off values were associated with the outcome; at CRP concentrations 90 mg/L, odds were higher, and were particularly high for a combination of high YKL-40 and high IL-6. The same was observed at CRP concentrations 180 mg/L.

Conclusion

Overall, data suggest that combined YKL-40 and IL-6 concentrations in acute AP, taken either on admission or 48h after, predict more strongly moderate and/or severe (vs. mild) AP than either cytokine alone, and do so 'on-top' of the CRP concentrations.

References

1. 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):102–111.
2. van den Berg FF, de Bruijn AC, van Santvoort HC, Issa Y, Boermeester MA. Early laboratory biomarkers for severity in acute pancreatitis; A systematic review and meta-analysis. Pancreatology. 2020;20(7):1302-1311.
3. Tizaoui K, Yang JW, Lee KH, Kim JH, Kim M, Yoon S et al. The role of YKL-40 in the pathogenesis of autoimmune diseases: a comprehensive review. Int J Biol Sci. 2022;18(9):3731-3746. doi: 10.7150/ijbs.67587.
4. Blazevic N, Rogic D, Pelajic S, Miler M, Glavcic G, Ratkajec V et al. YKL-40 as a biomarker in various inflammatory diseases: A review. Biochem Med. 2023;34(1):010502.

Conference

UEG Week Vienna 2024

Topics

Pancreas

Submission format

Abstract

Session

Outcomes and implications of pancreatic disease (Posters)

Citation

United European Gastroenterology Journal 2024; 12 (Supplement 8)

Published

2024

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