scholarly journals The purine pathway in liver tissue biopsies from donors for transplantation is associated to immediate graft function and survival

2019 ◽  
Author(s):  
Jin Xu ◽  
Mohammad Hassan-Ally ◽  
Ana María Casas-Ferreira ◽  
Tommi Suvitaival ◽  
Yun Ma ◽  
...  
Keyword(s):  
Liver Function ◽  
Clinical Data ◽  
Liver Tissue ◽  
Graft Function ◽  
List Type ◽  
Purine Metabolites ◽  
Data Driven Approach ◽  
Liver Biopsies ◽  
Purine Pathway ◽  
Underlying Mechanisms

AbstractBackground & AimsThe current shortage of livers for transplantation has increased the use of organs sourced from donation after circulatory death (DCD). These organs are prone to higher incidence of graft failure, but the underlying mechanisms are largely unknown. Here we aimed to find biomarkers of liver function before transplantation to better inform clinical evaluation.MethodsMatched pre- and post-transplant liver biopsies from DCD (n=24) and donation after brain death (DBD, n=70) were collected. Liver biopsies were analysed using mass spectroscopy molecular phenotyping. First, a discrimination analysis DCD vs DBD was used to parse metabolites associated to DCD. Then a data-driven approach was used to predict Immediate Graft Function (IGF). The metabolites were tested in models to predict survival.ResultsFive metabolites in the purine pathway were selected and investigated. The ratios of: adenine monophosphate (AMP), adenine, adenosine and hypoxanthine to urate, differed between DBD and DCD biopsies at pre-transplantation stage (q<0.05). The ratios of AMP and adenine to urate also differed in biopsies from recipients undergoing IGF (q<0.05). Using random forest a panel composed by alanine aminotransferase (ALT) and AMP, adenine, hypoxanthine ratio to urate predicted IGF with AUC 0.84 (95% CI [0.71, 0.97]). In comparison AUC 0.71 (95%CI [0.52, 0.90]) was achieved by clinical measures. Survival analysis revealed that the metabolite classifier could stratify 6-year survival outcomes (p = 0.0073) while clinical data and donor class could not.ConclusionsAt liver pre-transplantation stage, a panel composed of purine metabolites and ALT in tissue could improve prediction of IGF and survival.Lay summaryNew liver function biomarkers could help clinicians assess livers before transplantation. Purines are small molecules that are found in healthy livers, and in this work we found that their levels changed critically in livers from cardiac death donors. Measuring them before transplantation improved the prediction of the liver’s immediate graft function.Graphic abstractHighlightsThe ratios of purine metabolites to urate differ between DCD and DBD in liver tissue at pre-transplantation.The ratios of purine metabolites to urate and ALT pre-transplantation can improve prediction of IGF after transplantation.Purine metabolites ratios to urate stratified 6-year survival outcome better than clinical data and donor class.

scholarly journals Deregulation of the Purine Pathway in Pre-Transplant Liver Biopsies Is Associated with Graft Function and Survival after Transplantation

2020 ◽  
Vol 9 (3) ◽  
pp. 711 ◽  
Author(s):  
Jin Xu ◽  
Mohammad Hassan-Ally ◽  
Ana María Casas-Ferreira ◽  
Tommi Suvitaival ◽  
Yun Ma ◽  
...  
Keyword(s):  
Graft Function ◽  
Area Under The Curve ◽  
Adenosine Monophosphate ◽  
Donation After Circulatory Death ◽  
Discrimination Analysis ◽  
Donation After Brain Death ◽  
Early Graft ◽  
Liver Biopsies ◽  
Purine Pathway ◽  
Early Allograft Dysfunction

The current shortage of livers for transplantation has increased the use of marginal organs sourced from donation after circulatory death (DCD). However, these organs have a higher incidence of graft failure, and pre-transplant biomarkers which predict graft function and survival remain limited. Here, we aimed to find biomarkers of liver function before transplantation to allow better clinical evaluation. Matched pre- and post-transplant liver biopsies from DCD (n = 24) and donation after brain death (DBD, n = 70) were collected. Liver biopsies were analysed using mass spectroscopy molecular phenotyping. Discrimination analysis was used to parse metabolites differentiated between the two groups. Five metabolites in the purine pathway were investigated. Of these, the ratios of the levels of four metabolites to those of urate differed between DBD and DCD biopsies at the pre-transplantation stage (q < 0.05). The ratios of Adenosine monophosphate (AMP) and adenine levels to those of urate also differed in biopsies from recipients experiencing early graft function (EGF) (q < 0.05) compared to those of recipients experiencing early allograft dysfunction (EAD). Using random forest, a panel consisting of alanine aminotransferase (ALT) and the ratios of AMP, adenine, and hypoxanthine levels to urate levels predicted EGF with area under the curve (AUC) of 0.84 (95% CI (0.71, 0.97)). Survival analysis revealed that the metabolite classifier could stratify six-year survival outcomes (p = 0.0073). At the pre-transplantation stage, a panel composed of purine metabolites and ALT could improve the prediction of EGF and survival.

Mitochondrial Changes in Cholestasis

1972 ◽  
Vol 30 ◽  
pp. 258-259
Author(s):  
F. G. Zaki
Keyword(s):  
Biliary Obstruction ◽  
Alcoholic Cirrhosis ◽  
Ultrastructural Changes ◽  
List Type ◽  
Common Occurrence ◽  
Extrahepatic Cholestasis ◽  
Mitochondrial Alteration ◽  
Extrahepatic Biliary Obstruction ◽  
Liver Biopsies ◽  
Mitochondrial Anomalies

Alterations of liver cell mitochondria represent pathologic phenomenon of a fundamental nature. Mitochondrial anomalies have been often described in association with cholestasis. In attempt to determine whether a given pattern of mitochondrial alteration has any correlation with the cause of cholestasis, liver biopsies were examined from 38 patients showing :a. extrahepatic cholestasis due to complete or partial extrahepatic biliary obstruction (8 cases proven at operation)b. intrahepatic cholestasis due to drugs (9 cases), viral hepatitis (6 cases) and alcoholic cirrhosis (15 cases).Mitochondria exhibiting ultrastructural changes due to aging or to the ‘wear and teart’ processes were not considered. In this study, the only profound and most prominent mitochondrial deformation was reported on basis of their common occurrence in randomly examined sections.

scholarly journals Application of micro-computer tomography and inverse finite element analysis for characterizing the visco-hyperelastic response of bulk liver tissue using indentation

2021 ◽  
Vol 3 (5) ◽  
Author(s):  
Rajeswara R. Resapu ◽  
Roger D. Bradshaw
Keyword(s):  
Finite Element ◽  
Liver Tissue ◽  
Loading Rate ◽  
Time Dependent ◽  
Nonlinear Material ◽  
Computational Time ◽  
List Type ◽  
Prony Series ◽  
Time Dependent Behaviour ◽  
Dependent Behaviour

Abstract In-vitro mechanical indentation experimentation is performed on bulk liver tissue of lamb to characterize its nonlinear material behaviour. The material response is characterized by a visco-hyperelastic material model by the use of 2-dimensional inverse finite element (FE) analysis. The time-dependent behaviour is characterized by the viscoelastic model represented by a 4-parameter Prony series, whereas the large deformations are modelled using the hyperelastic Neo-Hookean model. The shear response described by the initial and final shear moduli and the corresponding Prony series parameters are optimized using ANSYS with the Root Mean Square (RMS) error being the objective function. Optimized material properties are validated using experimental results obtained under different loading histories. To study the efficacy of a 2D model, a three dimensional (3D) model of the specimen is developed using Micro-CT of the specimen. The initial elastic modulus of the lamb liver obtained was found to 13.5 kPa for 5% indentation depth at a loading rate of 1 mm/sec for 1-cycle. These properties are able to predict the response at 8.33% depth and a loading rate of 5 mm/sec at multiple cycles with reasonable accuracy. Article highlights The visco-hyperelastic model accurately models the large displacement as well as the time-dependent behaviour of the bulk liver tissue. Mapped meshing of the 3D FE model saves computational time and captures localized displacement in an accurate manner. The 2D axisymmetric model while predicting the force response of the bulk tissue, cannot predict the localized deformations.

scholarly journals Postprandial Glycogen Content Is Increased in the Hepatocytes of Human and Rat Cirrhotic Liver

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 976
Author(s):  
Natalia N. Bezborodkina ◽  
Sergey V. Okovityi ◽  
Boris N. Kudryavtsev
Keyword(s):  
Rat Liver ◽  
Liver Tissue ◽  
Glycogen Content ◽  
Glycogen Synthase ◽  
Fibrous Tissue ◽  
Glycogen Metabolism ◽  
Liver Parenchyma ◽  
Dry Mass ◽  
Cirrhotic Liver ◽  
Liver Biopsies

Chronic hepatitises of various etiologies are widespread liver diseases in humans. Their final stage, liver cirrhosis (LC), is considered to be one of the main causes of hepatocellular carcinoma (HCC). About 80–90% of all HCC cases develop in LC patients, which suggests that cirrhotic conditions play a crucial role in the process of hepatocarcinogenesis. Carbohydrate metabolism in LC undergoes profound disturbances characterized by altered glycogen metabolism. Unfortunately, data on the glycogen content in LC are few and contradictory. In this study, the material was obtained from liver biopsies of patients with LC of viral and alcohol etiology and from the liver tissue of rats with CCl4-induced LC. The activity of glycogen phosphorylase (GP), glycogen synthase (GS), and glucose-6-phosphatase (G6Pase) was investigated in human and rat liver tissue by biochemical methods. Total glycogen and its labile and stable fractions were measured in isolated individual hepatocytes, using the cytofluorometry technique of PAS reaction in situ. The development of LC in human and rat liver was accompanied by an increase in fibrous tissue (20- and 8.8-fold), an increase in the dry mass of hepatocytes (by 25.6% and 23.7%), and a decrease in the number of hepatocytes (by 50% and 28%), respectively. The rearrangement of the liver parenchyma was combined with changes in glycogen metabolism. The present study showed a significant increase in the glycogen content in the hepatocytes of the human and the rat cirrhotic liver, by 255% and 210%, respectively. An increased glycogen content in cells of the cirrhotic liver can be explained by a decrease in glycogenolysis due to a decreased activity of G6Pase and GP.

Persistently raised aspartate aminotransferase (AST) due to macro-AST in a rheumatology clinic

Diagnosis ◽  
2015 ◽  
Vol 2 (2) ◽  
pp. 137-140 ◽  
Author(s):  
Wycliffe Mbagaya ◽  
Joanne Foo ◽  
Ahai Luvai ◽  
Claire King ◽  
Sarah Mapplebeck ◽  
...  
Keyword(s):  
Liver Function ◽  
Aspartate Aminotransferase ◽  
Normal Liver ◽  
Abdominal Ultrasound ◽  
Liver Function Tests ◽  
Analytical Investigation ◽  
Normal Liver Function ◽  
Rheumatology Clinic ◽  
History Of ◽  
Liver Biopsies

AbstractMacrocomplexes between immunoglobins and aspartate aminotransferase (macro-AST) may result in persistently increased AST concentration. The presence of macro-AST in patients has been implicated in unnecessary investigations of abnormal liver function tests. We report the case of a 44-year-old female who presented to the rheumatology clinic with a 12-months’ history of constant widespread pain affecting her limbs and was found to have an elevated AST concentration. Further information from her GP revealed a 14-years’ history of elevated AST with otherwise normal liver function. Previous abdominal ultrasound and two liver biopsies carried out 2 years apart were normal. This prompted further analytical investigation by the biochemistry department which identified macro-AST as the cause. This case illustrates that persistently raised isolated AST concentration with no other abnormal indices may warrant macroenzyme analysis potentially avoiding unnecessary invasive investigations.

scholarly journals Implication of Mitochondrial Cytoprotection in Human Islet Isolation and Transplantation

2012 ◽  
Vol 2012 ◽  
pp. 1-16 ◽  
Author(s):  
Yong Wang ◽  
Joshua E. Mendoza-Elias ◽  
Meirigeng Qi ◽  
Tricia A. Harvat ◽  
Sang Joon Ahn ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Islet Transplantation ◽  
Mitochondrial Function ◽  
Graft Function ◽  
Complex Nature ◽  
Islet Isolation ◽  
Success Rates ◽  
Mitochondrial Integrity ◽  
Multistep Process ◽  
Underlying Mechanisms

Islet transplantation is a promising therapy for type 1 diabetes mellitus; however, success rates in achieving both short- and long-term insulin independence are not consistent, due in part to inconsistent islet quality and quantity caused by the complex nature and multistep process of islet isolation and transplantation. Since the introduction of the Edmonton Protocol in 2000, more attention has been placed on preserving mitochondrial function as increasing evidences suggest that impaired mitochondrial integrity can adversely affect clinical outcomes. Some recent studies have demonstrated that it is possible to achieve islet cytoprotection by maintaining mitochondrial function and subsequently to improve islet transplantation outcomes. However, the benefits of mitoprotection in many cases are controversial and the underlying mechanisms are unclear. This article summarizes the recent progress associated with mitochondrial cytoprotection in each step of the islet isolation and transplantation process, as well as islet potency and viability assays based on the measurement of mitochondrial integrity. In addition, we briefly discuss immunosuppression side effects on islet graft function and how transplant site selection affects islet engraftment and clinical outcomes.

Liver function in toxicosis of pregnancy

1927 ◽  
Vol 23 (6-7) ◽  
pp. 745-745
Keyword(s):  
Differential Diagnosis ◽  
Liver Function ◽  
Clinical Data ◽  
Color Test

King studied liver function in toxicosis of pregnancy by means of a color test with bromsulfalein, which proved to be suitable for the differential diagnosis of nephritic and preeclampsic conditions. There is complete correspondence between the results of the test and the clinical data.

scholarly journals The Yale Department of Medicine COVID-19 Data Explorer and Repository (DOM-CovX): An Innovative Approach to Promoting Collaborative Scholarship During a Pandemic

2021 ◽  
Author(s):  
Tanima Arora ◽  
Michael Simonov ◽  
Jameel Alausa ◽  
Labeebah Subair ◽  
Brett Gerber ◽  
...  
Keyword(s):  
Clinical Data ◽  
Large Scale ◽  
Innovative Approach ◽  
Academic Productivity ◽  
List Type ◽  
Digital Revolution ◽  
Institutional Climate ◽  
Novel Approach ◽  
Dissemination Of Research ◽  
Academic Faculty

ABSTRACTBackgroundThe COVID-19 pandemic has led to an explosion of research publications spanning epidemiology, basic and clinical science. While a digital revolution has allowed for open access to large datasets enabling real-time tracking of the epidemic, detailed, locally-specific clinical data has been less readily accessible to a broad range of academic faculty and their trainees. This perpetuates the separation of the primary missions of clinically-focused and primary research faculty resulting in lost opportunities for improved understanding of the local epidemic; expansion of the scope of scholarship; limitation of the diversity of the research pool; lack of creation of initiatives for growth and dissemination of research skills needed for the training of the next generation of clinicians and faculty.ObjectivesCreate a common, easily accessible and up-to-date database that would promote access to local COVID-19 clinical data, thereby increasing efficiency, streamlining and democratizing the research enterprise. By providing a robust dataset, a broad range of researchers (faculty, trainees) and clinicians are encouraged to explore and collaborate on novel clinically relevant research questions.MethodsWe constructed a research platform called the Yale Department of Medicine COVID-19 Explorer and Repository (DOM-CovX), to house cleaned, highly granular, de-identified, continually-updated data from over 7,000 patients hospitalized with COVID-19 (1/2020-present) across the Yale New Haven Health System. This included a front-end user interface for simple data visualization of aggregate data and more detailed clinical datasets for researchers after a review board process. The goal is to promote access to local COVID-19 clinical data, thereby increasing efficiency, streamlining and democratizing the research enterprise.Expected OutcomesAccelerate generation of new knowledge and increase scholarly productivity with particular local relevanceImprove the institutional academic climate by:Broadening research scopeExpanding research capability to more diverse group of stakeholders including clinical and research-based faculty and traineesEnhancing interdepartmental collaborationsConclusionsThe DOM-CovX Data Explorer and Repository have great potential to increase academic productivity. By providing an accessible tool for simple data analysis and access to a consistently updated, standardized and large-scale dataset, it overcomes barriers for a wide variety of researchers. Beyond academic productivity, this innovative approach represents an opportunity to improve the institutional climate by fostering collaboration, diversity of scholarly pursuits and expanding medical education. It provides a novel approach that can be expanded to other diseases beyond COVID 19.

Application of autologous multipotent mesenchymal stromal cells for correction of liver function in patients suffering from alcoholic liver cirrhosis

2020 ◽  
Vol 22 (4) ◽  
pp. 33-36
Author(s):  
I. E. Kotkas ◽  
V. I. Masurov ◽  
I. G. Bakulin ◽  
N. I. Enukashvili ◽  
Sh. M. Asadulayev
Keyword(s):  
Liver Cirrhosis ◽  
Liver Function ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Liver Tissue ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Cirrhosis Of The Liver ◽  
Alternative Methods ◽  
Tissue Sampling ◽  
Satisfactory Condition

Clinical experience of application of autologous multipotent mesenchymal stromal cells in treatment of patient suffering from liver cirrhosis of alcoholic etiology is presented. A special feature is that the hepatocyte precursors were isolated directly from the patients liver tissue. The patient underwent laparoscopic surgery to obtain the largest volume of material and to be able to visually control the tissue sampling with minimal fibrotic changes. After liver tissue sampling, the patient was discharged for outpatient treatment in a satisfactory condition. Subsequently, the patient was re-admitted to the hospital. During repeated hospitalization, multipotent mesenchymal stromal cells in the amount of 20 million were injected into the arterial bed of the liver using x-ray endovascular technique. In the control study, 6 months after treatment, according to the 13C-metacetin test, normalization of liver function, regression of portal hypertension, and an increase in platelet levels were noted. There were no complications during this treatment. Treatment of patients suffering from cirrhosis of the liver is quite a serious and complex task. As a rule, the patient learns about his diagnosis already in the presence of complications, when the liver function is already significantly impaired. The propensity of the population to alcoholism leads to the formation of fibrosis, and subsequently cirrhosis of the liver. The absence of anti-fibrotic drugs contributes to the implementation of research to find alternative methods of treatment for this category of patients. In General, the use of autologous multipotent mesenchymal stromal cells is an effective and promising method, and research in this direction should be continued.

scholarly journals Assessment of liver function: pre- and peritransplant evaluation

1997 ◽  
Vol 43 (8) ◽  
pp. 1539-1545 ◽  
Author(s):  
Abraham Shaked ◽  
Fredrick A Nunes ◽  
Kim M Olthoff ◽  
Michael R Lucey
Keyword(s):  
Liver Function ◽  
Graft Function ◽  
Terminal Condition ◽  
High Rate ◽  
Liver Graft ◽  
Therapeutic Modality ◽  
Donor Liver ◽  
Laboratory Assessment ◽  
Residual Liver Function ◽  
End Stage

Abstract Liver transplantation has been demonstrated to be a successful therapeutic modality for patients with end-stage liver disease. The high rate of survival for an otherwise terminal condition has resulted in significant expansion of the indications and diseases treated by this procedure, and is hampered only by the limited numbers of organs available for transplantation. Efforts in clinical and laboratory medicine should be directed to identify candidates who would benefit most from this procedure, to provide better means for accurate assessment of liver reserve and the appropriate timing for transplantation, to identify quality liver grafts that would have the potential to tolerate cold preservation and reperfusion injury, and to assist in accurate monitoring of graft function immediately after transplantation. The aim of this manuscript is to describe the existing pathways for clinical and laboratory assessment of pretransplant residual liver function, the donor liver graft, and immediate posttransplantation function.

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