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Background. Liver transplantation is limited by the insufficiency of liver organ donors when treating end-stage liver disease or acute liver failure (ALF). Ectodermal mesenchymal stem cells (EMSCs) derived from nasal mucosa have emerged as an alternative cell-based therapy. However, the role of EMSCs in acute liver failure remains unclear. Methods. EMSCs were obtained from the nasal mucosa tissue of rats. First, EMSCs were seeded on the gelatin-chitosan scaffolds, and the biocompatibility was evaluated. Next, the protective effects of EMSCs were investigated in carbon tetrachloride- (CCl4-) induced ALF rats. Finally, we applied an indirect coculture system to analyze the paracrine effects of EMSCs on damaged hepatocytes. A three-step nontransgenic technique was performed to transform EMSCs into hepatocyte-like cells (HLCs) in vitro. Results. EMSCs exhibited a similar phenotype to other mesenchymal stem cells along with self-renewal and multilineage differentiation capabilities. EMSC-seeded gelatin-chitosan scaffolds can increase survival rates and ameliorate liver function and pathology of ALF rat models. Moreover, transplanted EMSCs can secrete paracrine factors to promote hepatocyte regeneration, targeted migration, and transdifferentiate into HLCs in response to the liver's microenvironment, which will then repair or replace the damaged hepatocytes. Similar to mature hepatocytes, HLCs generated from EMSCs possess functions of expressing specific hepatic markers, storing glycogen, and producing urea. Conclusions. These results confirmed the feasibility of EMSCs in acute hepatic failure treatment. To our knowledge, this is the first time that EMSCs are used in the therapy of liver diseases. EMSCs are expected to be a novel and promising cell source in liver tissue engineering. [ABSTRACT FROM AUTHOR]

Background. The incidence of chronic liver disease is increasing in the Nepalese population. Liver transplantation (LT) is the best option for patients with end-stage liver disease (ESLD). Nepal's first liver transplant was performed in 2016 in an international collaborative effort at Shahid Dharmabhakta National Transplant Centre (SDNTC), Bhaktapur, Nepal. We aim to report details of the first five patients who had undergone liver transplantation in SDNTC before the beginning of the COVID-19 outbreak in the history of transplantation in Nepal. Method. A descriptive analysis of the clinical data of five adult recipients of liver transplantation at SDNTC was done. We described the patient's demographics, length of stay, and survival of all the first five patients who had undergone four living donor liver transplantations and one brain-dead donor liver transplantation in SDNTC before the beginning of the COVID-19 outbreak. Results. Recipients were between 36 and 63 years old. The recipients of the four live donor liver transplants (LDLT) and one brain-dead donor liver transplant (DDLT) had alcoholic liver disease and cryptogenic liver disease, leading to end-stage liver disease. The model for end-stage liver disease (MELD) scores ranged from 23 to 34. Out of five, four recipients and four donors are doing well and relishing the prospect of a normal life, while the recipient of a brain-dead donor liver transplant passed away due to postoperative primary graft failure. Conclusion. Despite the small number of liver transplants that have been done, the success of these has created confidence in a sustainable liver transplantation program in Nepal. [ABSTRACT FROM AUTHOR]

Introduction. Orthotopic liver transplants are characterized by sudden changes in hemodynamics, intraoperative hemorrhage, metabolic and electrolyte derangements, and arrhythmias. Many of these features are also hallmarks of malignant hyperthermia episodes and make differentiation difficult intraoperatively. Additionally, the treatment for malignant hyperthermia, dantrolene, can cause hepatotoxicity in already damaged native livers and newly reperfused organ allografts. Thus, it is imperative to avoid a triggering anesthetic in these patients. Here we report on a successful total intravenous anesthetic in a malignant hyperthermia susceptible individual undergoing an orthotopic liver transplant for acutely decompensated end-stage liver disease. Case Presentation. A 49-year-old male with a past medical history significant for malignant hyperthermia episodes as a child was admitted with decompensated alcoholic cirrhosis. He underwent uneventful total intravenous general anesthesia with propofol and sufentanil continuous infusions for an orthotopic liver transplant. He required minimal vasoactive agents to maintain a mean arterial blood pressure >65 mmHg and was extubated on postoperative day 1. Conclusions. Total intravenous anesthesia is necessary for patients with a personal history of malignant hyperthermia. However, this type of general anesthesia is difficult in the setting of fluctuating hemodynamics, hemorrhage, and changes in drug metabolism and clearance during the anhepatic and reperfusion phases of an orthotopic liver transplant. Propofol and sufentanil continuous infusions provided stable hemodynamics and an excellent plane of anesthesia throughout the case and should be considered in other individuals undergoing this procedure who require a total intravenous anesthetic. [ABSTRACT FROM AUTHOR]

Objective. To analyze the diagnosis and treatment of patients with concomitant malignant tumors after organ transplantation by compiling data from organ transplantation patients. Methods. By searching CNKI and PubMed databases, we made a systematic analysis of the studies of postorgan transplantation complicating malignant tumors in the last decade. Results. There were 10 articles on malignant tumors after renal transplantation, 8 articles on liver transplantation, 2 articles on heart transplantation, and 1 article on lung transplantation. The incidence of malignant tumors complicating renal transplantation is 10.4% in Europe, with skin cancer and Kaposi's sarcoma being common; the incidence in the United States is 3.4%, with PTLD having the highest incidence; the incidence of malignant tumors is relatively lowest in Asia, with gastrointestinal malignancies being the main ones. The mean time to complication of malignancy after renal transplantation is 3.83 years. The incidence of concurrent malignancies after liver transplantation is 8.8% in Europe, where skin cancer and Kaposi's sarcoma are common; 5.6% in Asia, where gastrointestinal tract tumors are prevalent; and 4.5% in the United States, where gastrointestinal tract tumors, PTLD, and hematologic diseases are predominant. The mean time to complication of malignancy after liver transplantation is 4.79 years. The incidence of malignancy after heart transplantation is 6.8-10.7%. The incidence of malignancy after lung transplantation is about 10.1%. Minimization of immunosuppression or modification of immunosuppression regimens may be a key component of cancer prevention. mTOR inhibitors and phenolate (MMF) reduce the incidence of de novo malignancies in patients after solid organ transplantation. Surgical treatment improves survival in patients with early malignancies. The use of external beam radiation therapy in the treatment of hepatocellular carcinoma is limited due to the risk of radiation liver disease. Conclusions. The risk of concomitant malignancy needs to be guarded for 5 years of immunosuppressive therapy after organ transplantation surgery. Adjusting the immunosuppressive treatment regimen is an effective way to reduce concurrent malignancies. Systemic chemotherapy or radiotherapy requires vigilance against the toxic effects of drug metabolism kinetics on the transplanted organ. [ABSTRACT FROM AUTHOR]

Acute graft-versus-host disease (aGvHD) is a rare complication of liver transplantation associated with high morbidity and mortality. Death typically occurs due to complications related to severe infection, shock, and multiorgan failure. The clinical presentation involves dysfunction of multiple organ systems with overlapping symptoms that often results in a diagnostic delay. As there are a limited number of cases reported in the literature, there are no clear guidelines for treatment. Many different therapeutic measures have been utilized that target various immune system pathways, but steroids remain the first line of therapy. We report on two patients who developed aGvHD after liver transplantation who were treated with ruxolitinib, a novel Janus kinase 1/2 (JAK) inhibitor that has been shown to improve outcomes in steroid refractory cases of aGvHD after allogenic hematopoietic stem cell transplantation. We reviewed the literature to discuss various therapeutic options currently available for aGvHD after liver transplantation. [ABSTRACT FROM AUTHOR]

Liver fibrosis resulting from chronic liver injury is a key factor to develop liver cirrhosis and risk of hepatocellular carcinoma (HCC) which are major health burden worldwide. Therefore, it is necessary for antifibrotic therapies to prevent chronic liver disease progression and HCC development. There has been tremendous progress in understanding the mechanisms of liver fibrosis in the last decade, which has created new opportunities for the treatment of this condition. In this review, we aim to make an overview on information of different potential therapies (drug treatment, cell therapy, and liver transplantation) for the liver fibrosis and hope to provide the therapeutic options available for the treatment of liver fibrosis and discuss novel approaches. [ABSTRACT FROM AUTHOR]

Liver fibrosis resulting from chronic liver injury is a key factor to develop liver cirrhosis and risk of hepatocellular carcinoma (HCC) which are major health burden worldwide. Therefore, it is necessary for antifibrotic therapies to prevent chronic liver disease progression and HCC development. There has been tremendous progress in understanding the mechanisms of liver fibrosis in the last decade, which has created new opportunities for the treatment of this condition. In this review, we aim to make an overview on information of different potential therapies (drug treatment, cell therapy, and liver transplantation) for the liver fibrosis and hope to provide the therapeutic options available for the treatment of liver fibrosis and discuss novel approaches. [ABSTRACT FROM AUTHOR]