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Molecular Biomarkers as Predictors for Biliary Complications Following Liver Transplantation. A Prospective Study

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Bogdan Dorobantu1, Irinel Popescu1, Simona Dima1, Anca Nastase2, Speranta Iacob3

1) Dan Setlacec General Surgery and Liver Transplantation Department; 2) Research Department;
3) Gastroenterology Department, Fundeni Clinical Institute, Bucharest, Romania

DOI: http://dx.doi.org/10.15403/jgld.2014.1121.263.dor

Background: The biliary complications (BC) have been always considered the „Achilles’ heel” of liver transplantation (LT), being one of the leading causes of postoperative morbidity. Aim: To analyse predictors of BC, by monitoring in the peripheral blood the biomarkers involved in the inflammation and hepatic fibrosis, such as the matrix metalloproteinases (MMP 2, 9) and their tissue inhibitors (TIMP1), the interleukins (IL 2, 8), alfa-TNF, the endothelins and their receptors.
Methods: Thirty LT patients were followed-up prospectively for 5 years. The mRNA for the following biomarkers was quantified in the peripheral blood by qRTPCR and protein expression investigated by ELISA: MMP 2, 9, TIMP1, IL 2, IL 8, TNF-alfa, and endothelins and their receptors.
Results: Five patients developed anastomotic stenosis (AS). There was no difference regarding mRNA levels for all studied genes between AS and non-AS patients. Two cytokines were significantly different: pre-LT TNF alpha was higher in the non-AS group and post-LT endothelin-1 at day 7 and month 3 were higher in the AS group. There was a trend for lower levels of serum cytokines for patients without AS compared to patients with AS.
Conclusion: BC play an important role in the patients‘ postoperative morbidity and molecular biomarkers prediction should improve their early recognition and treatment.
Key words: liver transplantation – biliary complications – inflammatory genes – cytokines – enzymes.
Abbreviations: ALT: alanine aminotransferase; AS: anastomotic stenosis; AST: aspartate aminotransferase; BC: Biliary complications ; HBV: hepatitis B virus; HCV: hepatitis C virus; HDV: hepatitis D virus; HSC: hepatic stellate cells; IL: interleukin; IR: ischemia reperfusion; LT: liver transplantation ; MMP: matrix metalloproteinases; TIMP: metalloproteinases tissue inhibitor; TGF: tumor growth factor; TNF: tumor necrosis factor.