Interaction Of Diabetes Mellitus And Liver Transplantation And The Intrinsic Mechanisms

Background:The improved longevity is accompanied by complications of metabolic syndrome, such as diabetes mellitus (DM), which is becoming to be one of the important factors impacts on long-term survival and quality of postsurgical life of LT patients.Aims:To illuminate high risk factors influence post liver transplantation survival of grafts and recipients; To investigate the principal of allocating liver graft from DM donor to appropriate recipient to expand donor pool and then maximize social and individual benefits of this frontier technology.Methods:Meta-analysis of the largest population of patients who have received DM liver grafts with the longest follow-up times available based on the SRTR database. Liver transplantation were operated with normal Brown Norway BN rats or type Ⅱ DM modeling rats as recipients or donor respectively,5 sampling point had been set to collect rogan tissue and serum to perform pathological analysis, metabolic profile assessment and intestinal microecology investigation.Results:It had been indicated with meta-analysis that in patients without HCV infection, using DM donors was not independently associated with worse post-transplantation graft survival. Matching these DM donors to recipients without HCV may be safe.BN rats, modeled to be type II DM or blank control had been chosen to be donors or recipients respectively to perform orthotopic LT. The micostructrural alternatives had been investigated on HE stained paraffin sections with tissues sampling at 2,24,72,120 and 168 hours after LT operation. It had been illustrated that there were significant changes to indicate worse prognosis of the grafts in the group of DM donors but normal recipients; Those changes happened on at least 4 sites inside the graft:intrahepatic portal area, Glisson’s Capsule, necrosis of parenchymal hepatic cells and intrahepatic inflammatory infiltration.Compared with normal BN rats, there are several cytokines shown elevated level of concentration with varying degree at individually different point of observing time in DM rat recipients, including IL-1β, IL-2, IL-6, IL-10, IL-12/P70, IL-13, IP-10, TNF-a, MlP-la, MIP2, EOTAXIN and RANTES. There is no obvious concentration change of GM-CSF, IL-la, IL-4, IL-5, IL-17A, G-CSF and IFN-γ had been found. And there is no significant difference of MCP-1, MCP-3 and GRO-a in all four groups. During 1 week of surgery, there is larger amplitude of fluctuations of serum cytokines concentration to DM recipients, as well as the expression of IL-10 on proximal convoluted tubules. Special concern should also be given to typical protein cast of collecting tubules observed in DM rats. It indicates kidney should under stricter management than liver if it donated from DM donor.There is no obvious structural change had been observed of small intestine in samples collected from all experimental animal groups and within individual sampling time. It had been sorted out and identified to be bile acids, amino acids, phospholipids and sphingolipids that were principal components can discriminate DM and normal rats by assay Rats Serum with PCA and OPLS-DA Model concerning enterohepatic circulation. Furthermore, there are changes of intestinal microflora in the structure had been found by quantitative analysis, the counts of bacteria and element content in the intestinal excrement of rats, such as Lactobacillus, Bifidobacterium, Enterobacteriaceae, Bacteroides group, C.coccoides group, Escherichia coli, Faecalibacterium prausnitzii species, and Prevotella. There will be feasible scheme to regulate immunologic status of liver recipients relative to Diabetes Mellitus by modulate intestinal microbiota.Conclusions:It had been indicated by our clinical retrospective evaluations and animal experiments that should be safer to allocate to Diabetes Mellitus recipient a liver graft donated from a donor suffer same underlying disease. It will be easier to control structural changes concerning poorer prognosis of liver transplantation, including small bile duct proliferation of intrahepatic portal area, and the incrassation of Glisson’s Capsule thickness, increasing number of necrosis of parenchymal hepatic cells and intrahepatic neutrophils and eosinophils infiltration. The adverse impact of these changes to long-term survival of grafts and recipient had not been certainly observed. There should be precisely and scrupulously investigation on scientific and ethical problems of DM donor’s liver grafts allocation.