Preview

Russian Journal of Gastroenterology, Hepatology, Coloproctology

Advanced search

Diagnostic Effectiveness of Transforming Growth Factor Beta 1 in Assessing the Risk of Developing Graft Dysfunction in Liver Recipient Children

https://doi.org/10.22416/1382-4376-2019-29-3-58-65

Abstract

The problem of non-invasive monitoring of the liver condition is particularly relevant in liver transplantation among young children. Transforming growth factor beta 1 (TGF-β1) is a pleiotropic cytokine with a profibrogenic and immunosuppressive effect that can have a definite effect on the liver transplant functioning.

Aim. To determine the diagnostic efficacy of TGF-β1 in blood when assessing the risk of developing graft dysfunction in liver recipient children.

Materials and methods. 95 children aged 3 to 73 months with liver cirrhosis of various etiologies were surveyed. All the patients underwent liver transplantation (LT) from a living related donor. The TGF-β1 concentration in plasma was determined using ELISA on average 3 ± 2 days prior to liver transplantation and in the early post-transplant period.

Results. The level of TGF-β1 in the blood of children with liver cirrhosis was lower than in healthy children (p = 0.001). LT was accompanied by an increase in the TGF-β1 content in the blood of recipients (p = 0.001). The incidence of graft dysfunction in the early postoperative period correlated with the pre-transplantation level of TGF-β1 (r = 0.40, p = 0.00), which was lower in recipients with developed graft dysfunction than in patients without dysfunction (1.7 ± 1.3 ng/ml versus 6.7 ± 5.3 ng/ml, p = 0.001). The analysis of the test diagnostic efficiency showed that the area under the ROC curve (AUC) was 0.85 ± 0.05, 95 % CI 0.75–0.94, the sensitivity of the method was 83 %, its specificity was 77 %. When the marker value was less than the threshold (2.2 ng/ml), the relative risk of developing graft dysfunction was 11.4 ± 0.7, 95 % CI 2.7-48.7. The accuracy of the method, the positive predictive value and the negative predictive value of the results were 78, 83 and 77 %, respectively.

Conclusion. The level of TGF-β1 in the blood of liver recipient children before transplantation below 2.2 ng/ml increases the risk of developing graft dysfunction in the early postoperative period 11-fold. Measuring the TGF-β1 level in the blood prior to liver transplantation makes it possible to identify recipients with 85 % chance of developing a graft dysfunction. 

About the Authors

R. M. Kurabekova
V.I. Shumakov National Medical Research Center of Transplantology and Artificial Organs
Russian Federation

Dr. Sci. (Med.), Leading Researcher, Department of Regulatory Mechanisms in Transplantology

123182, Moscow, Shchukinskaya str., 1



O. M. Tsiroulnikova
V.I. Shumakov National Medical Research Center of Transplantology and Artificial Organs; I.M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

Dr. Sci. (Med.), Prof., Department  of Transplantology and Artificial Organs; Therapist, Therapeutic Department

123182, Moscow, Shchukinskaya str., 1

 



I. E. Pashkova
V.I. Shumakov National Medical Research Center of Transplantology and Artificial Organs
Russian Federation

Cand. Sci. (Med.), Leading Researcher,  Centre for Personified Translational Technologies of Critical  Condition Treatment; Departmental Head, Paediatric Department

123182, Moscow, Shchukinskaya str., 1



A. G. Olefirenko
V.I. Shumakov National Medical Research Center of Transplantology and Artificial Organs

Dr. Sci. (Med.), Principal Researcher, Department of Regulatory Mechanisms in Transplantology

123182, Moscow, Shchukinskaya str., 1



O. E. Gichkun
V.I. Shumakov National Medical Research Center of Transplantology and Artificial Organs; I.M. Sechenov First Moscow State Medical University (Sechenov University)

Cand. Sci. (Med.), Leading Researcher,  Department  of  Regulatory  Mechanisms  in  Transplantology; Assoc. Prof., Department  of Transplantology and Artificial Organs

123182, Moscow, Shchukinskaya str., 1



L. V. Makarova
V.I. Shumakov National Medical Research Center of Transplantology and Artificial Organs

Cand. Sci. (Biol.), Laboratory Researcher, Department of Regulatory Mechanisms in Transplantology

123182, Moscow, Shchukinskaya str., 1



R. A. Monakhov
V.I. Shumakov National Medical Research Center of Transplantology and Artificial Organs; I.M. Sechenov First Moscow State Medical University (Sechenov University)

 Cand.  Sci.  (Med.),  Departmental  Head, Surgical Department No 2; As sistant, Department of Transplantology and Artificial  Organs

123182, Moscow, Shchukinskaya str., 1



P. O. Shevchenko
V.I. Shumakov National Medical Research Center of Transplantology and Artificial Organs; I.M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation

 Dr. Sci. (Med.), Prof., Departmental  Head, Department of Regulatory Mechanisms in Transplantology; Prof., Department of  Transplantology and Artificial Organs

123182, Moscow, Shchukinskaya str., 1



References

1. Готье СВ. Трансплантология: итоги и перспективы.Том VI. 2014 год. М.- Тверь: Триада; 2015. Gautier SV. Transplantologiya: itogi i perspectivy. Tom VI. 2014 god. M. - Tver: Triada; 2015. 448. [In Russian]

2. Lim W-X, Cheng Y-F, Huang T-L, Chen T-Y, Tsang L-C, Ou H-Y et al: Graft Regeneration in Pediatric Living Donor Liver Transplantation. In: Transplantation proceedings: 2014: Elsevier; 2014: 767-769.

3. Jadlowiec CC, Taner T. Liver transplantation: Current status and challenges. World J Gastroenterol 2016, 22(18):4438-4445.

4. Austin MT, Feurer ID, Chari RS, Gorden DL, Wright JK, Pinson CW. Survival after pediatric liver transplantation: why does living donation offer an advantage? Archives of Surgery 2005, 140(5):465-471.

5. Becker NS, Barshes NR, Aloia TA, Nguyen T, Rojo J, Rodriguez JA et al. Analysis of recent pediatric orthotopic liver transplantation outcomes indicates that allograft type is no longer a predictor of survivals. Liver Transplantation 2008, 14(8):1125-1132.

6. Girometti R, Como G, Bazzocchi M, Zuiani C. Post-operative imaging in liver transplantation: State-of-the-art and future perspectives. World J Gastroenterol 2014, 20(20):6180-6200.

7. Schlickeiser S, Boes D, Streitz M, Sawitzki B. The use of novel diagnostics to individualize immunosuppression following transplantation. Transpl Int 2015, 28(8):911-920.

8. Aimaiti Y, Jin X, Shao Y, Wang W, Li D. Hepatic stellate cells regulate hepatic progenitor cells differentiation via the TGF-beta1/Jagged1 signaling axis. J Cell Physiol 2018, 14(10):27609.

9. Qiu M, Chen Y, Chen L, Zeng J, Liu J. Transforming growth factor beta1 and Fas ligand synergistically enhance immune tolerance in dendritic cells in liver transplantation. J Surg Res 2017, 218:180-193.

10. Poniatowski LA, Wojdasiewicz P, Gasik R, Szukiewicz D. Transforming growth factor beta family: insight into the role of growth factors in regulation of fracture healing biology and potential clinical applications. Mediators Inflamm 2015, 137823(10):29.

11. Kang LI, Mars WM, Michalopoulos GK. Signals and cells involved in regulating liver regeneration. Cells 2012, 1(4):1261-1292.

12. Kotlarz D, Marquardt B, Baroy T, Lee WS, Konnikova L, Hollizeck S et al. Human TGF-beta1 deficiency causes severe inflammatory bowel disease and encephalopathy. Nat Genet 2018, 50(3):344-348.

13. Lin M, Chang Y, Xie F, Shi Y, Pang L, Chen D. ASPP2 Inhibits the Profibrotic Effects of Transforming Growth Factor-beta1 in Hepatic Stellate Cells by Reducing Autophagy. Dig Dis Sci 2018, 63(1):146-154.

14. Шевченко ОП, Цирульникова ОМ, Курабекова РМ, Цирульникова ИЕ, Олефиренко ГА, Готье СВ. Уровень трансформирующего фактора роста β1 в плазме крови детей-реципиентов печени и его связь с функцией трансплантата. Иммунология 2015, 36(6):343-347. Shevchenko OP, Tsirulnikova OM, Kurabekova RM, Tsirulnikova IE, Olefirenko GA, Gautier SV. Blood plasma level of transforming growth factor β1 in pediatric liver transplant recipients and its relationship with graft function. Immunologiya 2015, 36(6):343-347. [In Russian]

15. Курабекова РМ, Шевченко ОП, Цирульникова ОМ, Можейко НП, Цирульникова ИЕ, Монахов А. и др. Уровень трансформирующего фактора роста бета 1 связан с тяжестью врожденных заболеваний печени у детей раннего возраста. Вестник трансплантологии и искусственных органов 2016, XVIII(3):16-21. Kurabekova RM, Shevchenko OP, Tsirulnikova OM, Tsirulnikova IE, Monakhov A.R. et al. Level of transforming growth factor β1 relats with severity of congenital liver disease in children of early age. Vestnik transplantologii i iskusstvennykh organov 2016, XVIII(3):16-21. [In Russian]

16. Pencina MJ, D'Agostino RB, Sr., D'Agostino RB, Jr., Vasan RS. Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med 2008, 27(2):157-172.

17. Долгов ВВ, Шевченко ОП, Шевченко АО. Биомаркеры в лабораторной диагностике. М.: Триада; 2014. 288 с. Dolgov VV, Shevchenko OP, Shevchenko AO. Biomarkers in laboratory diagnostics. Moscow: Triada; 2014. 288 [In Russian]

18. Briem-Richter A, Leuschner A, Krieger T, Grabhorn E, Fischer L, Nashan B et al. Peripheral blood biomarkers for the characterization of alloimmune reactivity after pediatric liver transplantation. Pediatr Transplant 2013, 17(8):757-764.

19. Gautier SV, Shevchenko OP, Tsirulnikova OM, Kurabekova RM, Lugovskaya SA, Naumova EV et al. The hematopoietic stem cell number in the peripheral blood of pediatric recipients correlates with the outcome after living donor liver transplantation. Pediatr Transplant 2015, 19(5):531-537.

20. Zweig MH, Campbell G. Receiver-operating characteristic (ROC) plots: a fundamental evaluation tool in clinical medicine. Clinical chemistry 1993, 39(4):561-577.

21. Sood S, Haifer C, Yu L, Pavlovic J, Churilov L, Gow PJ et al. A novel immune function biomarker identifies patients at risk of clinical events early following liver transplantation. Liver Transpl 2017, 23(4):487-497.


Review

For citations:


Kurabekova R.M., Tsiroulnikova O.M., Pashkova I.E., Olefirenko A.G., Gichkun O.E., Makarova L.V., Monakhov R.A., Shevchenko P.O. Diagnostic Effectiveness of Transforming Growth Factor Beta 1 in Assessing the Risk of Developing Graft Dysfunction in Liver Recipient Children. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2019;29(3):58-65. (In Russ.) https://doi.org/10.22416/1382-4376-2019-29-3-58-65

Views: 1170


ISSN 1382-4376 (Print)
ISSN 2658-6673 (Online)