Liver Transplant Disorder

Discarded perfusate samples will be collected from donors after circulatory death (DCD) or donors after brain death (DBD) organs during the machine perfusion period prior to transplantation by the study team. FMN will be measured as is standard of care for all machine perfusion liver transplant cases at Cleveland Clinic. Participating centers will be provided with sample collection and shipping instructions to ensure sample preservation in accordance with IATA guidelines. Samples from outside sites will not be stored for future research and will be discarded once analysis is completed. After the collection of the samples from machine perfusion, the transplant procedure will continue according to standard process.

The study will evaluate the results of endoscopic treatment of NON-anastomotic biliary strictures following liver transplantation

There is a significant unmet need for safe and effective therapeutic approaches to prevent immune-mediated graft injury and its complications in liver transplant (LT) recipients with autoimmune liver disease (AILD) including autoimmune hepatitis and primary sclerosing cholangitis. Siplizumab is an anti-cluster of differentiation 2 (CD2) monoclonal antibody that has demonstrated a favorable safety profile of siplizumab in over 779 human subjects and has been shown to target memory T cells-a key driver in the immune processes surrounding rejection and autoimmunity post LT in AILD. The purpose of this pilot, open-label phase 1 study is to determine the safety of siplizumab for induction in patients with AILD undergoing LT. Up to eight (8) subjects will receive siplizumab 0.6 mg/kg/dose on the day of transplant (Day 0) and Day 4 post-transplant, for a total of two doses. All subjects will be followed in the study for 12 months post-LT.

Evaluation Of Liver Resection Using Harmonic Scalpel Versus Cavitron Ultrasonic Surgical Aspirator (CUSA) Introduction The mode of parenchymal transection in hepatic resection has been a topic of great debate for decades. Many resections have now evolved into laparoscopic , and robotic-assisted procedures to limit morbidity. Morbidity and mortality after hepatic resection has progressively improved over the years due to improved equipment, operative technique \[3\], and anesthetic management. Prior to 1980, mortality rates were reported to be in the 10-20% range with many deaths related to perioperative hemorrhage. Now perioperative mortality has dropped significantly to approximately 5%. The clamp-crush technique, first reported in 1974, has been used for decades and remains the standard means of parenchymal division for many surgeons. Control of intraoperative hemorrhage has been one of the principle technical problems in advancing liver surgery. Excess blood loss and intraoperative blood transfusions have been shown to be associated with increased perioperative mortality and morbidity including an increased rate of hepatocellular carcinoma recurrence . Transfusions are also associated with increased infections and with increased cost. Costs of blood transfusions were recently examined in surgical patients. Many devices are now available to surgeons for division of the liver parenchyma in both open and minimally invasive surgery including: the CUSA (Tyco Healthcare, Mansfield, MA), Harmonic Scalpel (Ethicon Endo-Surgery, Cincinnati, OH, USA), Ligasure (Valley Lab, Tyco Healthcare, Boulder, CO, USA), Tissue Link (Salient Surgical Technologies, Portsmouth, NH), water-jet dissection, radiofrequency, microwave assisted resection, vascular staplers, and others In this study, we looked at the TissueLink bipolar sealer device that was used in combination with the CUSA in group 1 termed the CUSA/TissueLink group, and the Harmonic Scalpel in the group 2 termed Harmonic Scalpel/TissueLink. The TissueLink uses radiofrequency energy focused near the end of the device for electrocautery and a low volume saline drip that produces ohmic heat causing precoagulation of hepatic parenchyma. The saline keeps the temperature at or below 100 C to avoid eshcar formation ultimately helping prevent delayed biliary leak and hemorrhage. The hemostatic effects of TissueLink are a result of its disruption of the collagen in blood vessels causing closing of the lumen . The CUSA, a commonly used device in hepatic resection, was used in combination with the TissueLink in this study. We previously described this combination of devices reporting a shorter length of hospital stay, decreased operative time, and decreased intraoperative blood transfusion . CUSA uses ultrasonic energy to fragment and aspirate parenchymal tissue. This exposes biliary as well as vascular structures that may then be closed in a variety of ways at the surgeon's discretion. It allows for a precise transection plane allowing preservation of normal hepatic tissue . The Harmonic Scalpel, used in this study in combination with the TissueLink, utilizes ultrasonic vibration of two blades causing destruction of hydrogen bonds. This disruption of hydrogen bonds causes protein denaturization coagulating small vessels of 3 mm diameter. The parenchyma is also cut when the blades move in a saw-like fashion In this study, we evaluated the safety and efficacy of two different techniques described above for the division of the hepatic parenchyma in order to improve perioperative outcomes.

The overall goal is to describe the oxidation state of albumin before, during and after liver transplantation. This is a pilot observational study in which the oxidative state in 10 patients undergoing liver transplantation will be described. Samples for analysing the oxidation state of albumin, general oxidative damage and anti-oxidant state, the activation of the complement system and factors involved in coagulation will be obtained before transplantation, before and after reperfusion of the portal vein and on postop days 1, 2 and about 30.

The goal of this observational study is to develop a nomogram model to predict biliary complications within 90 days in adult patients after liver transplantation. The main questions it aims to answer are: Can the nomogram predict biliary complications within 90 days in adult patients after liver transplantation? What about the performance of the nomogram? Researchers will compare patients' preoperative variables, intraoperative factors, and postoperative outcomes to see what factors are associated with biliary complications.Subsequently, multivariable logistic regression analysis was conducted to evaluate the factors associated with biliary complications occurring within 90 days post-liver transplantation. Finally, a nomogram was developed.

The prevalence of chronic liver disease and primary liver cancer is still increasing on a global scale, and so are their associated deaths. Compared to other diseases, death from liver disease often means premature death, because two-thirds of the lives lost are working years. Liver transplantation (LT) is an important and life-saving treatment option for the treatment of congenital metabolic disorders, acute liver failure, end-stage chronic liver disease (ESLD) and primary liver cancers. Modern liver transplantation is characterized by significant improvements in post-transplant patient survival, graft survival, and quality of life. Impaired physical fitness of patients with end-stage liver disease often persists after liver transplantation and compromises post-transplant recovery. Prior to liver transplantation, excess ammonia taken up by skeletal muscle is a major metabolic driver of muscle wasting in end-stage liver disease and mainly inhibits the mTOR signaling pathway that supports muscle protein synthesis. Because excess ammonia is no longer present after transplantation, recovery of muscle mass and function can be expected in patients. However, immunosuppression with calcineurin inhibitors that inhibit the mTOR signaling pathway may improve lethal length. It is also thought that post-transplant treatment regimens contribute to delayed recovery of decreased bone mineral density and increased fracture risk. Greater muscle mass, as measured by creatinine clearance at 1 year after transplantation, was associated with longer recipient and allograft survival. The results of previous studies indicate low cardiovascular fitness in patients after liver transplantation. Since after liver transplantation, cardiovascular diseases cause 19 to 42% of deaths not related to the liver, performing aerobic exercises to obtain and maintain cardiovascular fitness after liver transplantation can reduce the mortality rate. After transplanting, reduced significantly. Considering the important role of the immune system in transplant rejection, the safety of sports training is very important in terms of not over-activating the immune system and endangering the life of the transplanted tissue. In previous studies related to exercise and immune system activity and inflammatory cytokines after transplantation, it has been shown that moderate exercise including aerobic and resistance exercises can inhibit inflammatory cytokines and have beneficial effects on the immune system. High levels of tumor necrosis factor-alpha (TNF-α) in the period after transplant surgery are associated with an increased risk of transplant rejection. Aerobic exercise reduces levels of inflammatory cytokine TNF-α and markers of liver function in patients with chronic liver diseases. According to this evidence, it seems that doing sports exercises is effective in reducing the risk of transplant rejection and modulating the patient's immune system. Acute graft rejection occurs days to weeks after transplantation. The immune system can see the transplanted organ as foreign and attack it, destroy it and lead to transplant rejection. Considering the mentioned benefits of exercise therapy after liver transplantation, it is possible that the early start of exercise therapy in the hospitalization phase leads to a reduction in the risk of transplant rejection and improvement of allograft residues in patients after liver transplantation. Considering that the current evidence shows that there is no use of a specific rehabilitation protocol in the hospitalization phase of patients after liver transplantation, we intend to evaluate its effects with changes in the common physiotherapy program in these departments according to the specific conditions of these patients. In other words, despite the acceptable therapeutic effects, the use of a combined protocol of aerobic and resistance exercises in the hospitalization phase of these patients has not been reported so far.

Colon cancer and primary liver cancer are common malignant tumors with low survival rate worldwide, and unresectable primary liver cancer and colon cancer liver metastases have worse prognosis. End-stage liver disease is equated with advanced liver disease, liver failure and decompensated cirrhosis because they are generally irreversible. Liver transplantation is a treatment option for the above-mentioned patients and is expected to improve the prognosis of the patients, but the biggest problem faced by such patients is the shortage of donor livers. Recently, a new surgical modality, resection and partial liver segment 2-3 transplantation with delayed total hepatectomy (RAPID), can greatly alleviate these problems.Based on clinical surgical experience, our center proposes and designs a clinical study of adjuvant liver transplantation combined with two-stage hepatectomy in the treatment of patients with unresectable primary liver cancer, colorectal cancer liver metastases, or end-stage liver disease. By improvement of RAPID operation, the safety and efficacy of this treatment method in patients with those disease were evaluated.