First Application of a Mixed Porcine-Human Repopulated Bioengineered Liver in a Preclinical Model of Post-Resection Liver Failure.

In this study, a mixed porcine-human bioengineered liver (MPH-BEL) was used in a preclinical setup of extracorporeal liver support devices as a treatment for a model of post-resection liver failure (PRLF). The potential for human clinical application is further illustrated by comparing the functional capacity of MPH-BEL grafts as assessed using this porcine PRLF model with fully human (FH-BEL) grafts which were perfused and assessed in vitro. BEL grafts were produced by reseeding liver scaffolds with HUVEC and primary porcine hepatocytes (MPH-BEL) or primary human hepatocytes (FH-BEL).

Producing Human Livers From Human Stem Cells Via Blastocyst Complementation.

The need for organ transplants exceeds donor organ availability. In the quest to solve this shortage, the most remarkable area of advancement is organ production through the use of chimeric embryos, commonly known as blastocyst complementation. This technique involves the combination of different species to generate chimeras, where the extent of donor cell contribution to the desired tissue or organ can be regulated.

Comprehensive analysis of brain injury parameters in a preclinical porcine model of acute liver failure.

Introduction: Acute liver failure (ALF) is defined as acute loss of liver function leading to hepatic encephalopathy associated with a high risk of patient death. Brain injury markers in serum and tissue can help detect and monitor ALF-associated brain injury. This study compares different brain injury parameters in plasma and tissue along with the progression of ALF.

First-in-class MKK4 inhibitors enhance liver regeneration and prevent liver failure.

Diminished hepatocyte regeneration is a key feature of acute and chronic liver diseases and after extended liver resections, resulting in the inability to maintain or restore a sufficient functional liver mass. Therapies to restore hepatocyte regeneration are lacking, making liver transplantation the only curative option for end-stage liver disease. Here, we report on the structure-based development and characterization (nuclear magnetic resonance [NMR] spectroscopy) of first-in-class small molecule inhibitors of the dual-specificity kinase MKK4 (MKK4i).

Clinical characterization of a hypersensitivity mixed bacterial and fungal dermatitis in a translational model of porcine NASH.

Introduction: The development of animal models of chronic liver disease via diet modification is a promising avenue for translational research but can lead to unexpected side effects that impact model adoption. While these side effects are well characterized in rodent models of nonalcoholic steatohepatitis (NASH), limited knowledge of these effects exists for novel porcine models of NASH. To close this gap, the present study investigates the side effects of diet-based NASH induction in pigs, with a systematic analysis of the pathologic mechanisms underlying dermatitis development and evaluation of treatment approaches.

Biodegradable biliary stents coated with mesenchymal stromal cells in a porcine choledochojejunostomy model.

Background Aims: Roux en y anastomosis is a preferred method of biliary reconstruction in liver transplantation that involves living donors or pediatric patients. However, biliary stricture is a frequent and serious complication, accounting for up to 40% of biliary complications in these patients. Previously, we demonstrated that extraluminal delivery of adipose-derived (AD) mesenchymal stromal cells (MSCs) decreased peri-biliary fibrosis and increased neo-angiogenesis in a porcine model of duct-to-duct biliary anastomosis.

Re-Endothelialization of Decellularized Liver Scaffolds: A Step for Bioengineered Liver Transplantation.

Bioengineered livers (BELs) are an attractive therapeutic alternative to address the donor organ shortage for liver transplantation. The goal of BELs technology aims at replacement or regeneration of the native human liver. A variety of approaches have been proposed for tissue engineering of transplantable livers; the current review will highlight the decellularization-recellularization approach to BELs.

Pathogen detection in patients with perihilar cholangiocarcinoma: Implications for targeted perioperative antibiotic therapy.

Background: Cholestasis should be relieved by biliary drainage prior to major liver resection. This condition is often associated with bacterial colonization of the otherwise sterile biliary system. Cholangitis reduces the regenerative capacity of the remaining liver.

Simultaneous right-sided nephrectomy with orthotopic liver and kidney transplantation-An alternative method for patients with autosomal dominant polycystic liver and kidney disease.

Purpose: In patients suffering from autosomal dominant polycystic liver and kidney disease (ADPLKD), combined organ transplantation often poses a technical challenge due to the large volume of both organs. To simplify the transplantation procedure by improving the exposure of anatomical structures, we introduce a novel surgical technique of orthotopic liver and kidney transplantation.

Methods: The modified simultaneous liver and kidney transplantation technique via a right-sided L-incision included three steps: (1) right-sided nephrectomy in the recipient followed by (2) orthotopic liver transplantation in cava replacement technique and (3) the orthotopic kidney transplantation with arterial reconstruction to the right common iliac artery.

Ligation of the middle hepatic vein to increase hypertrophy induction during the ALPPS procedure.

Purpose: Here, we analyse the technical modification of the ALPPS procedure, ligating the middle hepatic vein during the first step of the operation to enhance remnant liver hypertrophy.

Methods: In 20 of 37 ALPPS procedures, the middle hepatic vein was ligated during the first step. Hypertrophy of the functional remnant liver volume was assessed in addition to postoperative courses.

Identification of tissue sections from decellularized liver scaffolds for repopulation experiments.

Background: Biological organ engineering is a novel experimental approach to generate functional liver grafts by decellularization and repopulation. Currently, healthy organs of small or large animals and human organs with preexisting liver diseases are used to optimize decellularization and repopulation.However, the effects of morphological changes on allo- and xenogeneic cell-scaffold interactions during repopulation procedure, e.

Milan criteria in the MELD era-is it justifiable to extend the limits for orthotopic liver transplantation?

Background: The Milan criteria (MC) are widely used for the indication of liver transplantation (LTx) in hepatocellular carcinoma (HCC). Good long-term results have also been reported following LTx for patients exceeding the MC. In this article, we compare the overall and recurrence-free survival of our patients fulfilling and exceeding the MC according to the post-transplant histopathological results.

Liver Transplant Due to Flupirtine-Induced Acute Liver Failure.

Objectives: Acute drug-induced liver failure is a rare indication for liver transplant. There is only one case of flupirtine-induced liver failure requiring transplant in the literature. In February 2018, the European Medicines Agency issued a withdrawal of approval for flupirtine medication in European countries as a result of the risk of acute liver failure.

[Video-based Analysis of Practical Skills - a Suitable Tool to Develop Surgical Training?].

Background: Video-based analysis concepts are being is increasingly applied in medical education. These tools are mainly used to obtain information about the individual performance of a candidate and to provide feedback. The present study explores whether video-based analysis of practical skills can also be used for the development of surgical training.

Tissue-based miRNA mapping in alcoholic liver cirrhosis: different profiles in cirrhosis with or without hepatocellular carcinoma.

Alcoholic liver cirrhosis is a significant risk factor for the development of hepatocellular carcinoma (HCC). The importance of tumour-associated cirrhosis in the development or progression of HCC is not understood. MiRNAs are important regulators for HCC development, but their role in HCC due to alcoholic liver cirrhosis is unclear.

The impact of immunosuppression on postoperative graft function after graft-unrelated surgery: a retrospective controlled cohort study.

Background: Physicians are faced with a growing number of patients after renal transplantation undergoing graft-unrelated surgery. So far, little is known about the postoperative restitution of graft function and the risk factors for a poor outcome.

Methods: One hundred one kidney transplant recipients undergoing graft-unrelated surgery between 2005 and 2015 were reviewed retrospectively.

Liver Transplant for Perihilar Cholangiocarcinoma (Klatskin Tumor): The Essential Role of Patient Selection.

Objectives: Perihilar cholangiocarcinoma (Klatskin tumor) is a rare tumor entity, which is diagnosed late due to uncharacteristic symptoms. The therapeutic strategy for cure is still liver resection. Liver transplant in cases of locally irresectable tumors represents an alternative potential curative therapy for a select group of patients.

The value of microparticles in detecting acute rejection episodes after liver transplantation.

Context: Non-invasive markers for diagnosis of acute rejection (AR) following liver transplantation have not been developed, yet.

Objective: We analyzed the correlation of plasma microparticle levels (MP) with AR.

Materials And Methods: MP (CD4, CD8, CD25, CD31, MHC) of 11 AR patients and 11 controls were analyzed within the first week after transplantation.