scholarly journals Canine Liver Transplantation Model and the Intermediate Filaments of the Cytoskeleton of the Hepatocytes

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Consolato Sergi ◽  
Reem Abdualmjid ◽  
Yasser Abuetabh

Liver transplantation has been a successful therapy for liver failure. However, a significant number of recipients suffer from graft dysfunction. Considerably, ischemia and reperfusion (I/R) injury is the most important factor leading to organ dysfunction, although the pathogenesis has not been fully described. I/R injury have several established features that are accompanied by and/or linked to bile duct loss or ductopenia, cholestasis, and biliary ductular proliferations in the posttransplant liver biopsy. However, biliary marker levels increase usually only 5–7 days after transplantation. Intermediate filaments are one of the three cytoskeletal proteins that have a major role in liver protection and maintaining both cellular structure and integrity of eukaryotic cells. We reviewed the canine liver transplantation model as I/R injury model to delineate the intermediate filaments of the cytoskeleton that are probably the determinants in changing the phenotype of hepatocytes to cholangiocytes. Remarkably, this interesting feature seems to occur earlier than frank cholestasis. We speculate that I/R liver injury through a phenotypical switch of the hepatocytes may contribute to the poor outcome of the liver graft.

2021 ◽  
Vol 14 (5) ◽  
pp. 1491-1495
Author(s):  
Peilin Li ◽  
Masaaki Hidaka ◽  
Yu Huang ◽  
Takanobu Hara ◽  
Kantoku Nagakawa ◽  
...  

AbstractGraft calcification after liver transplantation (LT) has seldom been reported, but almost of all previously reported cases have been attributed to graft dysfunction. We herein report two cases of graft calcification without liver dysfunction after living donor liver transplantation (LDLT). Two patients who underwent LDLT were found to have graft calcification in the early postoperative period (< 1 month). Calcification in the first case was found at the cut edge of the liver at post-operative day (POD) 10, showing a time-dependent increase in calcification severity. The second patient underwent hepatic artery re-anastomosis due to hepatic artery thrombosis on POD4 and received balloon-occluded retrograde transvenous obliteration of the splenic kidney shunt due to decreased portal vein blood flow on POD6. She was found to have diffuse hepatic calcification in the distant hepatic artery area at 1-month post-operation followed by gradual graft calcification at the resection margin at 6-month post-operation. Neither case showed post-operative graft dysfunction. Calcification of the liver graft after LDLT is likely rare, and graft calcification does not seem to affect the short-term liver function in LDLT cases. We recommend strictly controlling the warm/cold ischemia time and reducing the physical damage to the donor specimen as well as monitoring for early calcification by computed tomography.


2000 ◽  
Vol 32 (7) ◽  
pp. 2103 ◽  
Author(s):  
A.R.N Rao ◽  
A.K.K Chui ◽  
L.W Shi ◽  
L Tsai ◽  
C.D Leon ◽  
...  

2020 ◽  
Vol 4 (2) ◽  
pp. 177-183
Author(s):  
S. V. Korotkov ◽  
◽  
V. N. Smolnikova ◽  
V. Y. Hrynevich ◽  
O. A. Lebed ◽  
...  

Background. Immune-mediated graft dysfunction with the prevalence of 40% is one of the main problems of modern transplantology. Although percutaneous liver graft biopsy is associated with the development of different complications occurring in 2,2% of cases and can also lead to fatal outcome. Objective – to develop a noninvasive method of graft dysfunction diagnostics in the late post-transplant period using terminally differentiated effector CD8+ T-lymphocytes. Material and methods. There was carried out a single center observational retrospective case-control pilot study, including 45 recipients after orthotopic liver transplantation. According to the postoperative clinical course the patients were stratifed into 2 groups depending on the presence of graft rejection episodes. All patients got immunosuppressive therapy after liver transplantation. Immunophenotypes of the recipients were determined by flow cytometry method. Percutaneous liver graft biopsy was performed in all patients, the results of histological examination were evaluated according to the international Banff schema for grading liver allograft rejection. Results. The results of liver biopsies showed that 14 (31%) out of 45 patients had morphological signs of rejection. The patients with rejection had a reliably higher level of CD8+ Temra cells absolute number (0,23 (0,14;0,38) x 109/l) in comparison to those without rejection (0,09) (0,034;0,16) x 109/l (p=0,034)). The results of ROC-analysis have shown that the most optimal cut-off threshold of CD8+ T-lymphocytes level in immune-mediated graft dysfunction diagnostics in the late post-transplant period is 0,1882x109/l; sensitivity and specifcity in this case being 73,33 (95%; 44,9-92,0) and 96,55 (95%; 82,2-99,4) respectively. Conclusions. The increase of terminally differentiated effector CD8+ T-lymphocytes absolute number has diagnostic importance in patients with immune-mediated graft dysfunction in the late post-transplant period. High sensitivity and specifcity of cut-off threshold of CD8+ Temra lymphocytes absolute number in patients after liver transplantation as well as reliable difference between cell number in patients with normal postoperative period and in patients with immune-mediated graft dysfunction allow considering T-lymphocyte subpopulation as a rejection predictor in the late post-transplant period. The correlation between CD8+ T-lymphocyte absolute number and the results of histological examination makes the former an alternative and, what is more, safe noninvasive method in early diagnostics of liver graft rejection.


Author(s):  
S. E. Voskanyan ◽  
V. E. Syutkin ◽  
M. V. Shabalin ◽  
A. I. Artemyev ◽  
I. Yu. Kolyshev ◽  
...  

We present an uncommon case of liver graft dysfunction caused by seronegative hepatitis C-related fibrosing cholestatic hepatitis after cadaver liver transplantation for unresectable liver metastases of neuroendocrine small intestine cancer followed by living relation donor liver fragment retransplantation for primary graft nonfunction. Early postoperative period was complicated by hepatic artery thrombosis, cerebral hemorrhage, acute cellular rejection, bilateral polysegmental pneumonia, bleeding into neck soft tissues, severe surgical site infection, and sepsis. Anticoagulant therapy, as well as the absence of Hepatitis C Virus antibodies made difficult early diagnostics of fibrosing cholestatic hepatitis. A present-day antiviral therapy produced a complete clinical and virological response. At control examination performed at 240 days after surgery, there were neither signs of cancer progression no graft dysfunction. Liver transplantation in that case was an example of radical and effective treatment method for unresectable liver metastases of neuroendocrine small intestine cancer. Timely diagnosis and proper treatment of fibrosing cholestatic hepatitis made it possible to save the liver graft and patient's life.


2014 ◽  
Vol 306 (7) ◽  
pp. G575-G581 ◽  
Author(s):  
Lihong Chen ◽  
Lin Zheng ◽  
Wubing He ◽  
Minglian Qiu ◽  
Lingyun Gao ◽  
...  

Dendritic cells transfected with interleukin (IL)-10 and transforming growth factor-β1 (TGF-β1) enhance T cell immunity and tolerance. However, no quantitative studies have investigated the suppressive functions of immature dendritic cells (imDC) cotransfected with IL-10 and TGF-β1. The effects of imDC cotransfected with IL-10 and TGF-β1 (IL-10-TGF-β1-imDC) on immune tolerance induction in a rat transplantation model were investigated. In addition, effects of IL-10-TGF-β1-imDC relative to IL-10-transfected imDC (IL-10-imDC) and TGF-β1-transfected imDC (TGF-β1-imDC) were compared. The infusion of IL-10-TGF-β1-imDC into recipients prolonged liver graft survival, which was sustained for >90 days. IL-12 serum levels decreased, whereas alanine transaminase and total bilirubin slightly increased in rats infused with IL-10-TGF-β1-imDC compared with the IL-10-imDC and TGF-β1-imDC groups. Furthermore, a higher percentage of terminal transferase-mediated UTP nick end-labeling-positive cells was observed, and histological analysis of the allografts indicated a rejection activity index of mild acute rejection. Our results suggest infusion of IL-10 and TGF-β1 cotransfected imDC induces alloantigen-specific T cell hyporesponsiveness, inhibits antigen-specific immunological responses to liver allografts, prolongs liver allograft survival, and enhances the immune tolerance. This approach may provide a promising alternative for enhancing donor-specific tolerance during liver transplantation.


Author(s):  
A. Yu. Maksimova ◽  
E. N. Bessonova ◽  
V. V. Bazarnyy

Introduction. One of the urgent tasks in modern transplantology is the search of biomarkers for predicting and early diagnosis of graft dysfunction.Objective. The study objective was to determine the biomarkers of liver graft dysfunction.Material and methods. We have examined 19 recipients who underwent liver transplantation and 36 healthy blood donors. Levels of 7 serum cytokines were measured by multiparametric fluorescence analysis with magnetic microspheres (xMAP technology, Luminex 200, USA). Statistical analysis was carried out by methods of nonparametric statistics. To determine the predictive value of the test, a ROC-analysis was performed.Results and discussion. We found that the interleukin-8 level was 3.6 times higher in recipients with liver graft dysfunction compared to those who had an uneventful postoperative course. The diagnostic sensitivity of the test was 75%, the specificity was 91%, and negative predictive value was 84.6.Conclusion. Serum interleukin-8 measurement provides a biomarker for early predicting a post-transplant liver graft dysfunction development


2018 ◽  
Vol 19 (4) ◽  
pp. 991 ◽  
Author(s):  
Victoria Mücke ◽  
Janis Gerharz ◽  
Katja Jakobi ◽  
Dominique Thomas ◽  
Nerea Ferreirós Bouzas ◽  
...  

2021 ◽  
Vol 8 ◽  
Author(s):  
Margot Fodor ◽  
Adriana Woerdehoff ◽  
Wolfgang Peter ◽  
Hannah Esser ◽  
Rupert Oberhuber ◽  
...  

Introduction: Early graft dysfunction (EAD) complicates liver transplantation (LT). The aim of this analysis was to discriminate between the weight of each variable as for its predictive value toward patient and graft survival.Methods: We reviewed all LT performed at the Medical University of Innsbruck between 2007 and 2018. EAD was recorded when one of the following criteria was present: (i) aspartate aminotransferase (AST) levels &gt;2,000 IU/L within the first 7 days, (ii) bilirubin levels ≥10mg/dL or (iii) international normalized ratio (INR) ≥1.6 on postoperative day 7.Results: Of 616 LT, 30.7% developed EAD. Patient survival did not differ significantly (P = 0.092; log rank-test = 2.87), graft survival was significantly higher in non-EAD patients (P = 0.008; log rank-test = 7.13). Bilirubin and INR on postoperative day 7 were identified as strong mortality predictors (Bilirubin HR = 1.71 [1.34, 2.16]; INR HR = 2.69 [0.51, 14.31]), in contrast to AST (HR = 0.91 [0.75, 1.10]). Similar results were achieved for graft loss estimation. A comparison with the Model for Early Allograft Function (MEAF) and the Liver Graft Assessment Following Transplantation (L-GrAFT) score identified a superior discrimination potential but lower specificity.Conclusion: Contrarily to AST, bilirubin and INR have strong predictive capacity for patient and graft survival. This fits well with the understanding, that bile duct injury and deprivation of synthetic function rather than hepatocyte injury are key factors in LT.


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