Skip to main content
Erschienen in: Digestive Diseases and Sciences 11/2018

09.08.2018 | Original Article

Plasma mtDNA Analysis Aids in Predicting Pancreatic Necrosis in Acute Pancreatitis Patients: A Pilot Study

verfasst von: Lin Wu, Wujian Xu, Fangyu Wang, Tangfeng Lv, Zhiqiang Yin, Yong Song

Erschienen in: Digestive Diseases and Sciences | Ausgabe 11/2018

Einloggen, um Zugang zu erhalten

Abstract

Background

Specific plasma biomarkers in predicting pancreatic necrosis (PNec) are needed in treating acute pancreatitis (AP).

Aims

To investigate the prognostic value of plasma mitochondrial DNA fragments (mtDNA) in patient with AP for PNec.

Methods

AP patients with symptoms onset within 72 h were prospectively enrolled from June 2015 through June 2017 and were assessed for PNec using contrast-enhanced CT scan. Plasma mtDNA concentration (specific mitochondrial gene ND1) was measured using qRT-PCR.

Results

Of the 74 AP patients included, significant higher median level of plasma mtDNA was found in severe AP patients than in mild AP patients and healthy controls, but not in moderately severe AP patients. Patients with PNec had higher level of plasma mtDNA than those without PNec (774.2 [IQR 397.6–2205.0] vs. 169.5 [IQR 73.6–683.4] pg/ml, P < 0.05). The area under the receiver operator characteristic curve (ROC-AUC) of mtDNA for predicting PNec was higher than that of CRP (0.813 [95% CI 0.705–0.895] vs. 0.678 [95% CI 0.558–0.783]). Using a cutoff value of 302.5 pg/ml, the sensitivity and specificity for diagnosing PNec were 90.9 and 68.3%, respectively. Finally, plasma mtDNA levels decreased significantly after continuous renal replacement therapy (717.7 [IQR 307.00–1370.00] vs. 237.5 [IQR 117.20–464.80] pg/ml, P < 0.01).

Conclusions

Elevated plasma mtDNA content in AP patients may be used as a more accurate early predictor of PNec in contrast to traditional CRP.
Literatur
1.
Zurück zum Zitat Vege SS, DiMagno MJ, Forsmark CE, Martel M, Barkun AN. Initial medical treatment of acute pancreatitis: american gastroenterological association institute technical review. Gastroenterology. 2018;154(4):1103–1139.CrossRef Vege SS, DiMagno MJ, Forsmark CE, Martel M, Barkun AN. Initial medical treatment of acute pancreatitis: american gastroenterological association institute technical review. Gastroenterology. 2018;154(4):1103–1139.CrossRef
2.
Zurück zum Zitat Hasibeder WR, Torgersen C, Rieger M, Dünser M. Critical care of the patient with acute pancreatitis. Anaesth Intensive Care. 2009;37:190–206.PubMed Hasibeder WR, Torgersen C, Rieger M, Dünser M. Critical care of the patient with acute pancreatitis. Anaesth Intensive Care. 2009;37:190–206.PubMed
3.
Zurück zum Zitat Bai Y, Liu Y, Jia L, et al. Severe acute pancreatitis in China: etiology and mortality in 1976 patients. Pancreas. 2007;35:232–237.CrossRef Bai Y, Liu Y, Jia L, et al. Severe acute pancreatitis in China: etiology and mortality in 1976 patients. Pancreas. 2007;35:232–237.CrossRef
4.
Zurück zum Zitat Petrov MS, Shanbhag S, Chakraborty M, Phillips AR, Windsor JA. Organ failure and infection of pancreatic necrosis as determinants of mortality in patients with acute pancreatitis. Gastroenterology. 2010;139:813–820.CrossRef Petrov MS, Shanbhag S, Chakraborty M, Phillips AR, Windsor JA. Organ failure and infection of pancreatic necrosis as determinants of mortality in patients with acute pancreatitis. Gastroenterology. 2010;139:813–820.CrossRef
5.
Zurück zum Zitat Beger HG, Rau B, Mayer J, Pralle U. Natural course of acute pancreatitis. World J Surg. 1997;21:130–135.CrossRef Beger HG, Rau B, Mayer J, Pralle U. Natural course of acute pancreatitis. World J Surg. 1997;21:130–135.CrossRef
6.
Zurück zum Zitat Tsuji Y, Takahashi N, Isoda H, et al. Early diagnosis of pancreatic necrosis based on perfusion CT to predict the severity of acute pancreatitis. J Gastroenterol. 2017;52:1130–1139.CrossRef Tsuji Y, Takahashi N, Isoda H, et al. Early diagnosis of pancreatic necrosis based on perfusion CT to predict the severity of acute pancreatitis. J Gastroenterol. 2017;52:1130–1139.CrossRef
7.
Zurück zum Zitat Cardoso FS, Ricardo LB, Oliveira AM, et al. C-reactive protein prognostic accuracy in acute pancreatitis: timing of measurement and cutoff points. Eur J Gastroenterol Hepatol. 2013;25:784–789.CrossRef Cardoso FS, Ricardo LB, Oliveira AM, et al. C-reactive protein prognostic accuracy in acute pancreatitis: timing of measurement and cutoff points. Eur J Gastroenterol Hepatol. 2013;25:784–789.CrossRef
8.
Zurück zum Zitat West AP, Shadel GS. Mitochondrial DNA in innate immune responses and inflammatory pathology. Nat Rev Immunol. 2017;17:363–375.CrossRef West AP, Shadel GS. Mitochondrial DNA in innate immune responses and inflammatory pathology. Nat Rev Immunol. 2017;17:363–375.CrossRef
9.
Zurück zum Zitat Zhang Q, Raoof M, Chen Y, et al. Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature. 2010;464:104–107.CrossRef Zhang Q, Raoof M, Chen Y, et al. Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature. 2010;464:104–107.CrossRef
10.
Zurück zum Zitat Yamanouchi S, Kudo D, Yamada M, Miyagawa N, Furukawa H, Kushimoto S. Plasma mitochondrial DNA levels in patients with trauma and severe sepsis: time course and the association with clinical status. J Crit Care. 2013;28:1027–1031.CrossRef Yamanouchi S, Kudo D, Yamada M, Miyagawa N, Furukawa H, Kushimoto S. Plasma mitochondrial DNA levels in patients with trauma and severe sepsis: time course and the association with clinical status. J Crit Care. 2013;28:1027–1031.CrossRef
11.
Zurück zum Zitat Jansen MPB, Pulskens WP, Butter LM, et. al. Mitochondrial DNA is released in urine of sirs Patients with acute kidney injury and correlates with severity of renal dysfunction. Shock. 2018;49(3):301–310.CrossRef Jansen MPB, Pulskens WP, Butter LM, et. al. Mitochondrial DNA is released in urine of sirs Patients with acute kidney injury and correlates with severity of renal dysfunction. Shock. 2018;49(3):301–310.CrossRef
12.
Zurück zum Zitat Gu X, Yao Y, Wu G, Lv T, Luo L, Song Y. The plasma mitochondrial DNA is an independent predictor for post-traumatic systemic inflammatory response syndrome. PLoS ONE. 2013;8:e72834.CrossRef Gu X, Yao Y, Wu G, Lv T, Luo L, Song Y. The plasma mitochondrial DNA is an independent predictor for post-traumatic systemic inflammatory response syndrome. PLoS ONE. 2013;8:e72834.CrossRef
13.
Zurück zum Zitat Weerts MJA, Hollestelle A, Sieuwerts AM, Foekens JA, Sleijfer S, Martens JWM. Low tumor mitochondrial DNA content is associated with better outcome in breast cancer patients receiving anthracycline-based chemotherapy. Clin Cancer Res. 2017;23:4735–4743.CrossRef Weerts MJA, Hollestelle A, Sieuwerts AM, Foekens JA, Sleijfer S, Martens JWM. Low tumor mitochondrial DNA content is associated with better outcome in breast cancer patients receiving anthracycline-based chemotherapy. Clin Cancer Res. 2017;23:4735–4743.CrossRef
14.
Zurück zum Zitat Banks PA, Bollen TL, Dervenis C, et al. Acute pancreatitis classification working group. Classification of acute pancreatitis—2012: revision of the Atlanta classification and definitions by international consensus. Gut. 2013;62:102–111.CrossRef Banks PA, Bollen TL, Dervenis C, et al. Acute pancreatitis classification working group. Classification of acute pancreatitis—2012: revision of the Atlanta classification and definitions by international consensus. Gut. 2013;62:102–111.CrossRef
15.
Zurück zum Zitat Sarr MG, Banks PA, Bollen TL, et al. The new revised classification of acute pancreatitis 2012. Surg Clin North Am. 2013;93:549–562.CrossRef Sarr MG, Banks PA, Bollen TL, et al. The new revised classification of acute pancreatitis 2012. Surg Clin North Am. 2013;93:549–562.CrossRef
16.
Zurück zum Zitat Balthazar EJ, Robinson DL, Megibow AJ, Ranson JH. Acute pancreatitis: value of CT in establishing prognosis. Radiology. 1990;174:331–336.CrossRef Balthazar EJ, Robinson DL, Megibow AJ, Ranson JH. Acute pancreatitis: value of CT in establishing prognosis. Radiology. 1990;174:331–336.CrossRef
17.
Zurück zum Zitat Chiu RW, Chan LY, Lam NY, et al. Quantitative analysis of circulating mitochondrial DNA in plasma. Clin Chem. 2003;49:719–726.CrossRef Chiu RW, Chan LY, Lam NY, et al. Quantitative analysis of circulating mitochondrial DNA in plasma. Clin Chem. 2003;49:719–726.CrossRef
18.
Zurück zum Zitat Frezza C, Cipolat S, Scorrano L. Organelle isolation: functional mitochondria from mouse liver, muscle and cultured fibroblasts. Nat Protoc. 2007;2:287–295.CrossRef Frezza C, Cipolat S, Scorrano L. Organelle isolation: functional mitochondria from mouse liver, muscle and cultured fibroblasts. Nat Protoc. 2007;2:287–295.CrossRef
19.
Zurück zum Zitat Kung CT, Hsiao SY, Tsai TC, et al. Plasma nuclear and mitochondrial DNA levels as predictors of outcome in severe sepsis patients in the emergency room. J Transl Med. 2012;10:130.CrossRef Kung CT, Hsiao SY, Tsai TC, et al. Plasma nuclear and mitochondrial DNA levels as predictors of outcome in severe sepsis patients in the emergency room. J Transl Med. 2012;10:130.CrossRef
20.
Zurück zum Zitat Boyapati RK, Tamborska A, Dorward DA, Ho GT. Advances in the understanding of mitochondrial DNA as a pathogenic factor in inflammatory diseases. F1000Research. 2017;6:169.CrossRef Boyapati RK, Tamborska A, Dorward DA, Ho GT. Advances in the understanding of mitochondrial DNA as a pathogenic factor in inflammatory diseases. F1000Research. 2017;6:169.CrossRef
21.
Zurück zum Zitat Qin C, Gu J, Liu R, et al. Release of mitochondrial DNA correlates with peak inflammatory cytokines in patients with acute myocardial infarction. Anatol J Cardiol. 2017;17:224–228.PubMed Qin C, Gu J, Liu R, et al. Release of mitochondrial DNA correlates with peak inflammatory cytokines in patients with acute myocardial infarction. Anatol J Cardiol. 2017;17:224–228.PubMed
22.
Zurück zum Zitat Gu X, Wu G, Yao Y, et al. Intratracheal administration of mitochondrial DNA directly provokes lung inflammation through the TLR9-p38 MAPK pathway. Free Radic Biol Med. 2015;83:149–158.CrossRef Gu X, Wu G, Yao Y, et al. Intratracheal administration of mitochondrial DNA directly provokes lung inflammation through the TLR9-p38 MAPK pathway. Free Radic Biol Med. 2015;83:149–158.CrossRef
23.
Zurück zum Zitat Knez J, Marrachelli VG, Cauwenberghs N, et al. Peripheral blood mitochondrial DNA content in relation to circulating metabolites and inflammatory markers: a population study. PLoS ONE. 2017;12:e0181036.CrossRef Knez J, Marrachelli VG, Cauwenberghs N, et al. Peripheral blood mitochondrial DNA content in relation to circulating metabolites and inflammatory markers: a population study. PLoS ONE. 2017;12:e0181036.CrossRef
24.
Zurück zum Zitat Muddana V, Whitcomb DC, Papachristou GI. Current management and novel insights in acute pancreatitis. Expert Rev Gastroenterol Hepatol. 2009;3:435–444.CrossRef Muddana V, Whitcomb DC, Papachristou GI. Current management and novel insights in acute pancreatitis. Expert Rev Gastroenterol Hepatol. 2009;3:435–444.CrossRef
25.
Zurück zum Zitat Khanna AK, Meher S, Prakash S, et al. Comparison of Ranson, Glasgow, MOSS, SIRS, BISAP, APACHE-II, CTSI Scores, IL-6, CRP, and Procalcitonin in predicting severity, organ failure, pancreatic necrosis, and mortality in acute pancreatitis. HPB Surg. 2013;2013:367581.CrossRef Khanna AK, Meher S, Prakash S, et al. Comparison of Ranson, Glasgow, MOSS, SIRS, BISAP, APACHE-II, CTSI Scores, IL-6, CRP, and Procalcitonin in predicting severity, organ failure, pancreatic necrosis, and mortality in acute pancreatitis. HPB Surg. 2013;2013:367581.CrossRef
26.
Zurück zum Zitat Türkoğlu A, Böyük A, Tanrıverdi MH, et al. The potential role of BMI, plasma leptin, nesfatin-1 and ghrelin levels in the early detection of pancreatic necrosis and severe acute pancreatitis: a prospective cohort study. Int J Surg. 2014;12:1310–1313.CrossRef Türkoğlu A, Böyük A, Tanrıverdi MH, et al. The potential role of BMI, plasma leptin, nesfatin-1 and ghrelin levels in the early detection of pancreatic necrosis and severe acute pancreatitis: a prospective cohort study. Int J Surg. 2014;12:1310–1313.CrossRef
27.
Zurück zum Zitat Sharaiha RZ, Tyberg A, Khashab MA, et al. Endoscopic therapy with lumen-apposing metal stents is safe and effective for patients with pancreatic walled-off necrosis. Clin Gastroenterol Hepatol. 2016;14:1797–1803.CrossRef Sharaiha RZ, Tyberg A, Khashab MA, et al. Endoscopic therapy with lumen-apposing metal stents is safe and effective for patients with pancreatic walled-off necrosis. Clin Gastroenterol Hepatol. 2016;14:1797–1803.CrossRef
28.
Zurück zum Zitat Tenner S, Baillie J, DeWitt J, Vege SS. American College of Gastroenterology guideline: management of acute pancreatitis. Am J Gastroenterol. 2013;108:1400–1415.CrossRef Tenner S, Baillie J, DeWitt J, Vege SS. American College of Gastroenterology guideline: management of acute pancreatitis. Am J Gastroenterol. 2013;108:1400–1415.CrossRef
29.
Zurück zum Zitat Garcia-Martinez I, Santoro N, Chen Y, et al. Hepatocyte mitochondrial DNA drives nonalcoholic steatohepatitis by activation of TLR9. J Clin Invest. 2016;126:859–864.CrossRef Garcia-Martinez I, Santoro N, Chen Y, et al. Hepatocyte mitochondrial DNA drives nonalcoholic steatohepatitis by activation of TLR9. J Clin Invest. 2016;126:859–864.CrossRef
Metadaten
Titel
Plasma mtDNA Analysis Aids in Predicting Pancreatic Necrosis in Acute Pancreatitis Patients: A Pilot Study
verfasst von
Lin Wu
Wujian Xu
Fangyu Wang
Tangfeng Lv
Zhiqiang Yin
Yong Song
Publikationsdatum
09.08.2018
Verlag
Springer US
Erschienen in
Digestive Diseases and Sciences / Ausgabe 11/2018
Print ISSN: 0163-2116
Elektronische ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-018-5227-9

Weitere Artikel der Ausgabe 11/2018

Digestive Diseases and Sciences 11/2018 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Schadet Ärger den Gefäßen?

14.05.2024 Arteriosklerose Nachrichten

In einer Studie aus New York wirkte sich Ärger kurzfristig deutlich negativ auf die Endothelfunktion gesunder Probanden aus. Möglicherweise hat dies Einfluss auf die kardiovaskuläre Gesundheit.

Intervallfasten zur Regeneration des Herzmuskels?

14.05.2024 Herzinfarkt Nachrichten

Die Nahrungsaufnahme auf wenige Stunden am Tag zu beschränken, hat möglicherweise einen günstigen Einfluss auf die Prognose nach akutem ST-Hebungsinfarkt. Darauf deutet eine Studie an der Uniklinik in Halle an der Saale hin.

Klimaschutz beginnt bei der Wahl des Inhalators

14.05.2024 Klimawandel Podcast

Auch kleine Entscheidungen im Alltag einer Praxis können einen großen Beitrag zum Klimaschutz leisten. Die neue Leitlinie zur "klimabewussten Verordnung von Inhalativa" geht mit gutem Beispiel voran, denn der Wechsel vom klimaschädlichen Dosieraerosol zum Pulverinhalator spart viele Tonnen CO2. Leitlinienautor PD Dr. Guido Schmiemann erklärt, warum nicht nur die Umwelt, sondern auch Patientinnen und Patienten davon profitieren.

Zeitschrift für Allgemeinmedizin, DEGAM

Typ-2-Diabetes und Depression folgen oft aufeinander

14.05.2024 Typ-2-Diabetes Nachrichten

Menschen mit Typ-2-Diabetes sind überdurchschnittlich gefährdet, in den nächsten Jahren auch noch eine Depression zu entwickeln – und umgekehrt. Besonders ausgeprägt ist die Wechselbeziehung laut GKV-Daten bei jüngeren Erwachsenen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.