Recent Advances in Decellularization and Recellularization for Tissue-Engineered Liver Grafts

2017 ◽  
Vol 204 (3-4) ◽  
pp. 125-136 ◽  
Author(s):  
Yujia Wang ◽  
Clara T. Nicolas ◽  
Harvey S. Chen ◽  
Jeffery J. Ross ◽  
Silvana B. De Lorenzo ◽  
...  

Liver transplantation from deceased or living human donors remains the only proven option for patients with end-stage liver disease. However, the shortage of donor organs is a significant clinical concern that has led to the pursuit of tissue-engineered liver grafts generated from decellularized liver extracellular matrix and functional cells. Investigative efforts on optimizing both liver decellularization and recellularization protocols have been made in recent decades. In the current review, we briefly summarize these advances, including the generation of high-quality liver extracellular matrix scaffolds, evaluation criteria for quality control, modification of matrix for enhanced properties, and reseeding strategies. These efforts to optimize the methods of decellularization and recellularization lay the groundwork towards generating a transplantable, human-sized liver graft for the treatment of patients with severe liver disease.

2016 ◽  
Vol 203 (4) ◽  
pp. 203-214 ◽  
Author(s):  
Yujia Wang ◽  
Clara T. Nicolas ◽  
Harvey S. Chen ◽  
Jeffery J. Ross ◽  
Silvana B. De Lorenzo ◽  
...  

Liver transplantation from deceased or living human donors remains the only proven option for patients with end-stage liver disease. However, the shortage of donor organs is a significant clinical concern that has led to the pursuit of tissue-engineered liver grafts generated from decellularized liver extracellular matrix and functional cells. Investigative efforts on optimizing both liver decellularization and recellularization protocols have been made in recent decades. In the current review, we briefly summarize these advances, including the generation of high-quality liver extracellular matrix scaffolds, evaluation criteria for quality control, modification of matrix for enhanced properties, and reseeding strategies. These efforts to optimize the methods of decellularization and recellularization lay the groundwork towards generating a transplantable, human-sized liver graft for the treatment of patients with severe liver disease.


2015 ◽  
Author(s):  
Andreea M. Catana ◽  
Michael P. Curry

The first liver transplantation (LT) was performed in 1963, and currently more than 65,000 people in the United States are living with a transplanted liver. In 2012, the number of adults who registered on the LT waiting list decreased for the first time since 2002; 10,143 candidates were added compared with 10,359 in 2011. LT offers long-term survival for complications of end-stage liver disease and prolongs life in properly selected patients, but problems such as donor deficit, geographic disparities, and long waiting lists remain. This overview of LT for the gastroenterologist details the indications for LT and patient selection, evaluation, liver organ allocation, prioritization for transplantation, transplantation benefit by the Model for End-Stage Liver Disease (MELD), MELD limitations, sources of liver graft, strategies employed to decrease the donor deficit, complications, and outcomes. Figures include indications for LT in Europe and the United States, Organ Procurement and Transplantation Network regions in the United States, the number of transplants and size of active waiting lists, mortality by MELD, regional disparity, patient survival rates with and without hepatitis C virus, and unadjusted patient and graft survival. Tables list LT milestones, indications for LT, contraindications for LT, minimal listing criteria for LT, criteria for LT in acute liver failure, LT evaluation process, adult recipient listing status 1A, and early posttransplantation complications. This review contains 7 highly rendered figures, 8 tables, and 46 references. 


2021 ◽  
pp. 1-4
Author(s):  
Marlon F. Levy ◽  
Daisuke Imai ◽  
Vinay Kumaran ◽  
David A. Bruno ◽  
Chandra S. Bhati ◽  
...  

Background: Trauma victims with liver lacerations in the hilum are typically excluded from liver donation. We report a case of a successful liver transplant from a deceased donor with a grade 4 hilar liver laceration. Case Presentation: We used a liver with a high-grade laceration from a 28-year-old brain-dead traffic accident victim. The liver had grade IV lacerations in the right and caudate lobes. In situ split liver technique was applied to control the lacerations after an intraoperative cholangiogram revealed favourable anatomy. The left hemi-liver graft was procured, retaining the entire vena cava and the full length of the main hepatic vasculature. The recipient was a 62-year-old female patient with end-stage liver disease, with a Model for End-Stage Liver Disease-Sodium score of 19. The left lobe graft was transplanted using the standard piggy-back technique. The patient was discharged on postoperative day 7 after an uneventful recovery. At two-month follow-up, she continues to do well, with normal hepatic function and unremarkable imaging studies. Conclusion: This is the first reported case of a successful liver transplant of a severely lacerated liver made possible by the application of split liver techniques. In situ splitting of a severely traumatized liver could permit the utilization of a reduced graft for small recipients.


Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 619
Author(s):  
Safak Gül-Klein ◽  
Deana Haxhiraj ◽  
Julian Seelig ◽  
Anika Kästner ◽  
Julian Hackler ◽  
...  

The trace element selenium (Se) is taken up from the diet and is metabolized mainly by hepatocytes. Selenoprotein P (SELENOP) constitutes the liver-derived Se transporter. Biosynthesis of extracellular glutathione peroxidase (GPx3) in kidney depends on SELENOP-mediated Se supply. We hypothesized that peri-operative Se status may serve as a useful prognostic marker for the outcome in patients undergoing liver transplantation due to hepatocellular carcinoma. Serum samples from liver cancer patients were routinely collected before and after transplantation. Concentrations of serum SELENOP and total Se as well as GPx3 activity were determined by standardized tests and related to survival, etiology of cirrhosis/carcinoma, preoperative neutrophiles, lymphocytes, thyrotropin (TSH) and Child–Pugh and Model for End-Stage Liver Disease (MELD) scores. A total of 221 serum samples from 79 transplanted patients were available for analysis. The Se and SELENOP concentrations were on average below the reference ranges of healthy subjects. Patients with ethanol toxicity-dependent etiology showed particularly low SELENOP and Se concentrations and GPx3 activity. Longitudinal analysis indicated declining Se concentrations in non-survivors. We conclude that severe liver disease necessitating organ replacement is characterized by a pronounced Se deficit before, during and after transplantation. A recovering Se status after surgery is associated with positive prognosis, and an adjuvant Se supplementation may, thus, support convalescence.


2008 ◽  
Vol 137 (4) ◽  
pp. 513-518 ◽  
Author(s):  
A. G. MANN ◽  
M. E. RAMSAY ◽  
L. J. BRANT ◽  
M. A. BALOGUN ◽  
A. COSTELLA ◽  
...  

SUMMARYMatching individuals reported to a sentinel surveillance scheme for hepatitis C between 2000 and 2005 to individuals with a hospital episode for hepatitis C-related liver disease in the same hospitals, we estimated that the number of cases of hepatitis C-related end-stage liver disease in these English hospitals was 42% (597/419) higher than Hospital Episode Statistics (HES) would indicate. Further, matching records of hepatitis C-related deaths in HES to death certificates, we estimated that, between 2000 and 2005, the true number of deaths from hepatitis C-related end-stage liver disease was between 185% (353/124) and 257% (378/106) higher than the number recorded in routine mortality statistics. We provide estimates of under-recording that can be used to modify existing models of disease burden due to hepatitis C and provide a simple approach to improve the monitoring of trends in severe hepatitis C-related morbidity over time.


2006 ◽  
Vol 21 (suppl 1) ◽  
pp. 12-14 ◽  
Author(s):  
Andreza Correa Teixeira ◽  
Fernanda Fernandes Souza ◽  
Gustavo de Assis Mota ◽  
Ana de Lourdes Candolo Martinelli ◽  
Ajith Kumar Sankarankutty ◽  
...  

Liver transplantation represents the most effective therapy for patients suffering from chronic end-stage liver disease. Until very recently, in Brazil, liver allocation was based on the Child-Turcotte-Pugh score and the waiting list followed a chronological criterion. In February 2002 the Model for End-stage Liver Disease (MELD) score was adopted for the allocation of donor livers in the US. After that change, an increased number of patients with more severe liver disease was observed, although there was no difference in 1-year patient and graft survival. A reduction in waiting-list mortality was also observed. In Brazil, the MELD score was adopted on May 31st, 2006. Good results are expected regarding the new criterion for allocation.


Author(s):  
Safak Gül-Klein ◽  
Deana Haxhiraj ◽  
Julian Seelig ◽  
Annika Kaestner ◽  
Julian Hackler ◽  
...  

The trace element selenium (Se) is taken up from the diet and becomes metabolized mainly by hepatocytes. Selenoprotein P (SELENOP) constitutes the liver-derived Se transporter. Biosynthesis of extracellular glutathione peroxidase (GPx3) in kidney depends on SELENOP-mediated Se supply. We hypothesized that Se status may serve as a useful prognostic marker for outcome in patients undergoing liver transplantation. Serum samples from patients were routinely collected before and after transplantation. Concentration of serum SELENOP and total Se as well as GPx3 activity were determined by standardized tests and related to survival, aetiology and pre-operative Child-Pugh and Model for End-Stage Liver Disease Scores. A total of 314 serum samples from 78 transplanted patients were available for analysis. The Se and SELENOP concentrations were on average below the reference ranges of healthy subjects. Patients with ethanol toxicity-dependent aetiology showed particularly low SELENOP and Se concentrations and GPx3 activity. Longitudinal analysis indicated declining Se concentrations in non-survivors. We conclude that severe liver disease necessitating organ replacement is characterized by a pronounced Se deficit before, during and after transplantation. A recovering Se status after surgery is associated with positive prognosis, and an adjuvant Se supplementation may thus support convalescence.


2017 ◽  
Vol 26 (2) ◽  
pp. 171-181 ◽  
Author(s):  
Liana Gheorghe ◽  
Ioan Sporea ◽  
Speranţa Iacob ◽  
Roxana Şirli ◽  
Anca Trifan ◽  
...  

Background & Aims: Hepatitis C Virus (HCV) infection is a common condition with endemic prevalence in some areas of the world. In Romania, the mean prevalence is about 3%. New treatments became available on the market in recent years and new drugs are in the pipeline. A re-evaluation of HCV therapy was considered mandatory. The Romanian Society of Gastroenterology and Hepatology undertook this task for the practitioners of this country.Methodology: A group of recognized experts was created who screened the available literature and the major available guidelines. A list of items requiring attention has been created. These items were discussed and rated. Decisions were taken by consensus.Recommendations: We present here the first of the two parts of our Society’s recommendations for chronic HCV infection treatment. An agreement was reached regarding the diagnostic tools, the assessment of severity and the up-dated therapy schedules.Conclusions: This Position Paper represents a guide for the assessment and the therapy of HCV infection. The recommendations are in concordance with other guidelines but are applied to the real-life conditions in this country.Abbreviations: DAAs: Direct-acting antivirals; DDIs: Drug-drug interactions; ESLD: End-stage liver disease; ESRD: End-stage renal disease; eGFR: Estimated glomerular filtration rate; EASL: European Association for the Study of the Liver; EMA: European Medicines Agency; FDA: US Food and Drug Administration; FDC: Fixed-dose combination; GT: Genotype; GRADE: Grading of Recommendations Assessment, Development and Evaluation; HCV: Hepatitis C virus; HCC: Hepatocellular carcinoma; LT: Liver transplantation; LLD: Lower limit of detection; MELD score: Mayo-Clinic End-Stage Liver Disease score; ANMDM: National Agency of Medicines and Medical Devices; PPIs: Proton pump inhibitors; PWID: People who inject drugs; RCT: Randomized controlled trial; RDT: Rapid diagnostic test; RAS: Resistance-associated substitution; SRGH: Romanian Society of Gastroenterology and Hepatology; SAE: serious adverse events; SPC: Summary of Product Characteristics; SVR: Sustained virologic response.


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