MicroRNAs versus traditional biomarkers in predicting reperfusion injury in Hepatitis C Patients after major surgery
Keywords:
miRNA, chronic hepatitis C, Ischemia, reperfusion, propofol, sevoflurane.
Abstract
Background: Exposure to anesthesia in patients with chronic hepatitis C (CHC) may induce hepatic ischemia / reperfusion (I/R) with subsequent biochemical changes, provoked by alteration in molecular processes. This study explored miR-122 and miR-223 expression changes induced by anesthesia in CHC patients and their role in predicting hepatic I/R injury. Methods: This study included two hundered ASA II - III adult patients, scheduled for major surgery under general anesthesia. Patients were divided into 2 main groups; CHC patients group and non-hepatitis patients group. Each group was further divided into 2 equal subgroups (50 patients each) according to type of anesthesia received either Sevoflurane SC /S or Propofol PC/P ). Blood samples were analyzed for liver enzymes, prothrombin time, and serum lactate at several intervals; preoperative, 12 and 48 hours postoperative. Also, plasma miR-122 and miR-223 were estimated by Reverse Transcription PCR preoperative and 12 hours postoperative.Results: CHC groups showed significantly increased preoperative expression of both miR-122 and miR-223 compared to non-hepatitis groups (P<0.05). Moreover, postoperative samples revealed more exaggerated expression miR-122 and miR-223. Receiver operating characteristic curve (ROC) results revealed;values for area under the ROC for miR-122, miR-223, ALT and serum Lactate were 0.991, 0.965, 0.746 and 0.732 respectively. Based on the ROC finding, for prediction IR in CHC patients receiving anesthesia miR-122 had best Accuracy, sensitivity, and specificity.Conclusion: Our results suggested that both miR-122 and miR-223 could be regarded as more sensitive and specific biomarkers for predicting hepatic I/R injury than traditional biomarkers particularly in CHC patients undergoing major surgery. DOI: 10.21276/APALM.1718References
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2. Banga NR, Homer-Vanniasinkam S, Graham A, Al-Mukhtar A, White SA, Prasad KR. Ischaemic preconditioning in transplantation and major resection of the liver. Br J Surg 2005; 92:528–38.
3. Zhai Y, Petrowsky H, Hong JC, Busuttil RW, Kupiec-Weglinski JW. Ischaemia-reperfusion injury in liver transplantation--from bench to bedside. Nat Rev Gastroenterol Hepatol. 2013;10(2):79-89.3.
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5. Bahde R, Spiegel HU. Hepatic ischaemia-reperfusion injury from bench to bedside. Br J Surg. 2010;1461-75.56.
6. Laterza OF, Lim L, Garrett-Engele PW, et al. Plasma microRNA as sensitive and specific biomarkers of tissue injury. Clin Chem 2009; 55:1977–1983.
7. Turchinovich A, Weiz L, Langheinz A and Burwinkel B: Characterization of extracellular circulating microRNA. Nucleic Acids Res 2011; 39: 7223-7233.
8. Wang K, Zhang S, Marzolf B, et al: Circulating microRNAs, potential biomarkers for drug‑induced liver injury. Proc Natl Acad Sci USA 2009;106: 4402-07.
9. Ishak K, Baptista A, bianchi L, et al. Histological grading and staging of chronic hepatitis. J Hepatol 1995; 22: 696-99.
10. Stehling LC, Doherty DC, Faust RJ, Greenburg AG, Harrison CR, Landers DF, Laros RK, Pierce EC, Prust RS, Rosenberg AD, Weiskopf RB, Woolf SH, Zeiger JF. Practice Guidelines for Blood Component Therapy: A Report by the American Society of Anesthesiologists Task Force on Blood Component Therapy. Anesthesiology1996; 84: 732–4.
11. Sakamoto A, Imai J, Nishikawa A, Honma R, Ito E, Yanagisawa Y, Kawamura M, Ogawa R, Watanabe S. Influence of inhala¬tion anesthesia assessed by comprehensive gene expression profiling. Gene2005; 356:39–48.
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13. Ishikawa M, Tanaka S, Arai M, Genda Y, Sakamoto A. Differences in microRNA Changes of Healthy Rat Liver between Sevoflurane and Propofol Anesthesia. Anesthesiology 2012; 117:1245-52.
14. Jaeschke H: Molecular mechanisms of hepatic ischemia-reperfusion injury and preconditioning. Am J Physiol Gastrointest Liver Physiol 2003;284: G15-26.
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18. Subhi M, Islam M, Bassam AL, Mohamed M, Fayez S, Hamdi AA. Effects of sevoflurane on postoperative liver functions in morbidly obese as compared to the non-obese patients. M E J ANESTH 2009;20(2):207-11.
19. Choi Y, Dienes HP, Krawczynski K. Kinetics of miR-122 expression in the liver during acute HCV infection. PLoS ONE. 2013;8: e76501.
20. Pirola CJ, Fernandez Gianotti T, Castano GO, Mallardi P, San Martino J, Mora Gonzalez Lopez Ledesma M, et al. Circulating microRNA signature in non-alcoholic fatty liver disease: from serum non-coding RNAs to liver histology and disease pathogenesis. Gut 2015; 64:800–12.
21. Bala S, Petrasek J, Mundkur S, et al. Circulating microRNAs in exosomes indicate hepatocyte injury and inflammation in alcoholic, drug-induced and inflammatory liver diseases. Hepatology 2012; 56:1946–57.
22. Zhang Y, Jia Y, Zheng R, Guo Y, Wang Y. Plasma microRNA-122 as a biomarker for viral-, alcohol-, and chemical-related hepatic diseases. Clin Chem 2010; 56:1830–8.
23. Patrik A, Olof G, Oscar Ö B, Matthias G, Jesper V, Erlinge O. Plasma Levels of Liver-Specific miR-122 Is Massively Increased in a Porcine Cardiogenic Shock Model and Attenuated by Hypothermia. Shock 2012;37(2):234-38.
24. Ko J, Gwak M, Choi S, Yang M, Kim M, Lee J, Kim G, Kwon C and Joh J. The effects of desflurane and sevoflurane on hepatic and renal functions after right hepatectomy in living donors. European Society for Organ Transplantation 2010; 23: 736–744.
25. Koeppel TA, Thies JC, Schemmer P, Trauner M, Gebhard MM, Otto G, Post S. Inhibition of nitric oxide synthesis in ischemia/reperfusion of the rat liver is followed by impairment of hepatic microvascular blood flow. J Hepatol 1997; 27:163-69.
26. Yu C, Xu C, Li Y. Association of MicroRNA-223 Expression with Hepatic Ischemia/Reperfusion Injury in Mice. Dig Dis Sci 2009; 54:2362–2366.
27. Zhuang G, Meng C, Guo X, Cheruku PS, Shi L, Xu H, Li H, Wang G, Evans AR, Safe S, Wu C, Zhou B. A novel regulator of macrophage activation: miR-223 in obesity-associated adipose tissue inflammation. Circulation 2012; 125: 2892-903.
28. Takahashi K, Oda Y, Toyoda Y, Fukami T, Yokoi T, Nakajima M. Regulation of Cytochrome b5 Expression by miR-223 in Human Liver: Effects on Cytochrome P450 Activities. Pharm Res 2014; 31:780–94.
29. Nagai T, Egashira T and Yamanak Y. Effect of Bifemelane Hydrochloride on an Injury of the Liver Caused by Ischemia-Reperfusion in Rats. Japan J of Pharmacol 1990; 52:383-385.
30. Qian YB, Liu ZG, Geng XP. Lack of protection of ischemic preconditioning in the rat model of major hepatectomy with ischemia reperfusion injury. Asian J Surg 2008; 31: 140-47.
31. Teoh NC, Farrell GC. Hepatic ischemia reperfusion injury: pathogenic mechanisms and basis for hepatoprotection. J Gastroenterol Hepatol 2003; 18: 891–902.
32. Lee J, Shin J, Lee E, Baek S, Ku S, and Kim J. Comparison of the effects of propofol and pentobarbital on hydrogen peroxide-stimulated hepatic SNU761 cells. Korean J of Anesthesiol 2010; 58(3):277–282.
33. Vaja R, McNicol L, Sisley I. Anaesthesia for patients with liver disease. (CEACCP). 2009;10(1):15–9.
34. Xu Z , Yu J, Wu J, Qi F, Wang H, Wang Z, Wang Z. The Effects of Two Anesthetics, Propofol and Sevoflurane, on Liver Ischemia/Reperfusion Injury. Cell Physiol Biochem. 2016;38(4):1631-42.
35. Faga E, De Cento M, Giordanino C, Barletti C, Bruno M, Carucci P, et al. Safety of propofol in cirrhotic patients undergoing colonoscopy and endoscopic retrograde cholangiography: results of a prospective controlled study. Eur J Gastroenterol Hepatol. 2012;24(1):70–6.
36. Shimono H, Goromaru T, Kadota Y, Tsurumaru T, Kanmura Y. Propofol Displays No Protective Effect against Hypoxia/Reoxygenation Injury in Rat Liver Slices Anesth Analg 2003;97:(2) 442-8.
37. Bozdogan N, Madenoglu H, Dogru K, et al. Effects of isoflurane, sevoflurane and desflurane on platelet function: a prospective, randomized, single blind, in vivo study Curr Therap Res 2005;66:375-84.
38. Yokubol B, Hirakata H, Nakamura K, et al. Anesthesia with sevoflurane, but not with isoflurane, prolongs bleeding time in humans. J Anesth 1999; 13:193-6.
39. Linden MD, Whittaker P, Frelinger AL, Barnard MR, Michelson AD, Przyklenk K. Preconditioning ischemia attenuates molecular indices of platelet activation-aggregation. J Thromb Haemost 2006; 4:2670–7.
40. Huang GS, Li CY, Hsu PC, Tsai CS, Lin TC, Wong CS. Sevoflurane anesthesia attenuates adenosine diphosphate-induced P-selectin expression and platelet-leukocyte conjugate formation. Anesth Analg 2004; 99:1121–6.
41. Pak S, Kondo T, Nakano Y,et al. Platelet adhesion in the sinusoid caused hepatic injury by neutrophils after hepatic ischemia reperfusion. Platelets 2010;21(4): 282–8.
42. Kurokawa T, Zheng Y, Ohkohchi N. Novel functions of platelets in the liver. J of Gastroenterol and Hepatol 2016;31: 745-751.
43. Montalvo-Jave EE, Escalante-Tattersfield T, Ortega-Salgado JA, Piña E, Geller DA. Factors in the pathophysiology of the liver ischemia-reperfusion injury.J. Surg. Res.2008;147(1): 153–9.
44. Suttner W, Schmidt C, Boldt J et al. Low flow desflurane and Sevoflurane anesthesia minimally affect hepatic integrity and function in elderly patients. Anesthesia Analg2000; 91(1):206-10.
2. Banga NR, Homer-Vanniasinkam S, Graham A, Al-Mukhtar A, White SA, Prasad KR. Ischaemic preconditioning in transplantation and major resection of the liver. Br J Surg 2005; 92:528–38.
3. Zhai Y, Petrowsky H, Hong JC, Busuttil RW, Kupiec-Weglinski JW. Ischaemia-reperfusion injury in liver transplantation--from bench to bedside. Nat Rev Gastroenterol Hepatol. 2013;10(2):79-89.3.
4. Videla LA. Oxidative stress signaling underlying liver disease and hepatoprotective mechanisms. World J Hepatol. 2009;1(1):72-8.5.
5. Bahde R, Spiegel HU. Hepatic ischaemia-reperfusion injury from bench to bedside. Br J Surg. 2010;1461-75.56.
6. Laterza OF, Lim L, Garrett-Engele PW, et al. Plasma microRNA as sensitive and specific biomarkers of tissue injury. Clin Chem 2009; 55:1977–1983.
7. Turchinovich A, Weiz L, Langheinz A and Burwinkel B: Characterization of extracellular circulating microRNA. Nucleic Acids Res 2011; 39: 7223-7233.
8. Wang K, Zhang S, Marzolf B, et al: Circulating microRNAs, potential biomarkers for drug‑induced liver injury. Proc Natl Acad Sci USA 2009;106: 4402-07.
9. Ishak K, Baptista A, bianchi L, et al. Histological grading and staging of chronic hepatitis. J Hepatol 1995; 22: 696-99.
10. Stehling LC, Doherty DC, Faust RJ, Greenburg AG, Harrison CR, Landers DF, Laros RK, Pierce EC, Prust RS, Rosenberg AD, Weiskopf RB, Woolf SH, Zeiger JF. Practice Guidelines for Blood Component Therapy: A Report by the American Society of Anesthesiologists Task Force on Blood Component Therapy. Anesthesiology1996; 84: 732–4.
11. Sakamoto A, Imai J, Nishikawa A, Honma R, Ito E, Yanagisawa Y, Kawamura M, Ogawa R, Watanabe S. Influence of inhala¬tion anesthesia assessed by comprehensive gene expression profiling. Gene2005; 356:39–48.
12. Nakazato K, Yoshida Y, Takemori K, Kobayashi K, Sakamoto A. Expressions of genes encoding drug-metabolizing enzymes are altered after sevoflurane, isoflurane, propofol or dexmedetomidine anesthesia. Biomed Res 2009; 30:17–24.
13. Ishikawa M, Tanaka S, Arai M, Genda Y, Sakamoto A. Differences in microRNA Changes of Healthy Rat Liver between Sevoflurane and Propofol Anesthesia. Anesthesiology 2012; 117:1245-52.
14. Jaeschke H: Molecular mechanisms of hepatic ischemia-reperfusion injury and preconditioning. Am J Physiol Gastrointest Liver Physiol 2003;284: G15-26.
15. Bihrer V, Friedrich-Rust M, Kronenberger B, Forestier N, Haupenthal J, Shi Y, Peveling-Oberhag J, Radeke H, Sarrazin C, et al.Serum miR-122 as a biomarker of necroinflammation in patients with chronic hepatitis C virus infection. Am J Gastroenterol 2011; 106: 1663–69.
16. Van der Meer AJ, Farid WR, Sonneveld MJ, et al. Sensitive detection of hepatocellular injury in chronic hepatitis C patients with circulating hepatocyte-derived microRNA-122. J Viral Hepat. 2013; 20: 158–66.
17. Wang J, Jiang D, Rao HY, Zhao JM, Wang Y, Wei L. Absolute quantification of serum microRNA-122 and its correlation with liver inflammation grade and serum alanine aminotransferase in chronic hepatitis C patients. Int J Infect Dis 2015; 30: 52–56.
18. Subhi M, Islam M, Bassam AL, Mohamed M, Fayez S, Hamdi AA. Effects of sevoflurane on postoperative liver functions in morbidly obese as compared to the non-obese patients. M E J ANESTH 2009;20(2):207-11.
19. Choi Y, Dienes HP, Krawczynski K. Kinetics of miR-122 expression in the liver during acute HCV infection. PLoS ONE. 2013;8: e76501.
20. Pirola CJ, Fernandez Gianotti T, Castano GO, Mallardi P, San Martino J, Mora Gonzalez Lopez Ledesma M, et al. Circulating microRNA signature in non-alcoholic fatty liver disease: from serum non-coding RNAs to liver histology and disease pathogenesis. Gut 2015; 64:800–12.
21. Bala S, Petrasek J, Mundkur S, et al. Circulating microRNAs in exosomes indicate hepatocyte injury and inflammation in alcoholic, drug-induced and inflammatory liver diseases. Hepatology 2012; 56:1946–57.
22. Zhang Y, Jia Y, Zheng R, Guo Y, Wang Y. Plasma microRNA-122 as a biomarker for viral-, alcohol-, and chemical-related hepatic diseases. Clin Chem 2010; 56:1830–8.
23. Patrik A, Olof G, Oscar Ö B, Matthias G, Jesper V, Erlinge O. Plasma Levels of Liver-Specific miR-122 Is Massively Increased in a Porcine Cardiogenic Shock Model and Attenuated by Hypothermia. Shock 2012;37(2):234-38.
24. Ko J, Gwak M, Choi S, Yang M, Kim M, Lee J, Kim G, Kwon C and Joh J. The effects of desflurane and sevoflurane on hepatic and renal functions after right hepatectomy in living donors. European Society for Organ Transplantation 2010; 23: 736–744.
25. Koeppel TA, Thies JC, Schemmer P, Trauner M, Gebhard MM, Otto G, Post S. Inhibition of nitric oxide synthesis in ischemia/reperfusion of the rat liver is followed by impairment of hepatic microvascular blood flow. J Hepatol 1997; 27:163-69.
26. Yu C, Xu C, Li Y. Association of MicroRNA-223 Expression with Hepatic Ischemia/Reperfusion Injury in Mice. Dig Dis Sci 2009; 54:2362–2366.
27. Zhuang G, Meng C, Guo X, Cheruku PS, Shi L, Xu H, Li H, Wang G, Evans AR, Safe S, Wu C, Zhou B. A novel regulator of macrophage activation: miR-223 in obesity-associated adipose tissue inflammation. Circulation 2012; 125: 2892-903.
28. Takahashi K, Oda Y, Toyoda Y, Fukami T, Yokoi T, Nakajima M. Regulation of Cytochrome b5 Expression by miR-223 in Human Liver: Effects on Cytochrome P450 Activities. Pharm Res 2014; 31:780–94.
29. Nagai T, Egashira T and Yamanak Y. Effect of Bifemelane Hydrochloride on an Injury of the Liver Caused by Ischemia-Reperfusion in Rats. Japan J of Pharmacol 1990; 52:383-385.
30. Qian YB, Liu ZG, Geng XP. Lack of protection of ischemic preconditioning in the rat model of major hepatectomy with ischemia reperfusion injury. Asian J Surg 2008; 31: 140-47.
31. Teoh NC, Farrell GC. Hepatic ischemia reperfusion injury: pathogenic mechanisms and basis for hepatoprotection. J Gastroenterol Hepatol 2003; 18: 891–902.
32. Lee J, Shin J, Lee E, Baek S, Ku S, and Kim J. Comparison of the effects of propofol and pentobarbital on hydrogen peroxide-stimulated hepatic SNU761 cells. Korean J of Anesthesiol 2010; 58(3):277–282.
33. Vaja R, McNicol L, Sisley I. Anaesthesia for patients with liver disease. (CEACCP). 2009;10(1):15–9.
34. Xu Z , Yu J, Wu J, Qi F, Wang H, Wang Z, Wang Z. The Effects of Two Anesthetics, Propofol and Sevoflurane, on Liver Ischemia/Reperfusion Injury. Cell Physiol Biochem. 2016;38(4):1631-42.
35. Faga E, De Cento M, Giordanino C, Barletti C, Bruno M, Carucci P, et al. Safety of propofol in cirrhotic patients undergoing colonoscopy and endoscopic retrograde cholangiography: results of a prospective controlled study. Eur J Gastroenterol Hepatol. 2012;24(1):70–6.
36. Shimono H, Goromaru T, Kadota Y, Tsurumaru T, Kanmura Y. Propofol Displays No Protective Effect against Hypoxia/Reoxygenation Injury in Rat Liver Slices Anesth Analg 2003;97:(2) 442-8.
37. Bozdogan N, Madenoglu H, Dogru K, et al. Effects of isoflurane, sevoflurane and desflurane on platelet function: a prospective, randomized, single blind, in vivo study Curr Therap Res 2005;66:375-84.
38. Yokubol B, Hirakata H, Nakamura K, et al. Anesthesia with sevoflurane, but not with isoflurane, prolongs bleeding time in humans. J Anesth 1999; 13:193-6.
39. Linden MD, Whittaker P, Frelinger AL, Barnard MR, Michelson AD, Przyklenk K. Preconditioning ischemia attenuates molecular indices of platelet activation-aggregation. J Thromb Haemost 2006; 4:2670–7.
40. Huang GS, Li CY, Hsu PC, Tsai CS, Lin TC, Wong CS. Sevoflurane anesthesia attenuates adenosine diphosphate-induced P-selectin expression and platelet-leukocyte conjugate formation. Anesth Analg 2004; 99:1121–6.
41. Pak S, Kondo T, Nakano Y,et al. Platelet adhesion in the sinusoid caused hepatic injury by neutrophils after hepatic ischemia reperfusion. Platelets 2010;21(4): 282–8.
42. Kurokawa T, Zheng Y, Ohkohchi N. Novel functions of platelets in the liver. J of Gastroenterol and Hepatol 2016;31: 745-751.
43. Montalvo-Jave EE, Escalante-Tattersfield T, Ortega-Salgado JA, Piña E, Geller DA. Factors in the pathophysiology of the liver ischemia-reperfusion injury.J. Surg. Res.2008;147(1): 153–9.
44. Suttner W, Schmidt C, Boldt J et al. Low flow desflurane and Sevoflurane anesthesia minimally affect hepatic integrity and function in elderly patients. Anesthesia Analg2000; 91(1):206-10.
Published
2018-01-28
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