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Progress in liver transplantation

Monica Serra, Michela Marongiu, Antonella Contini, Toshio Miki, Erika Cadoni, Ezio Laconi, Fabio Marongiu
Amniotic epithelial cells (AECs) represent a useful and noncontroversial source for liver-based regenerative medicine, as they can differentiate into hepatocytes upon transplantation into the liver. However, the possibility that AECs can differentiate into other liver cell types, such as hepatic sinusoidal endothelial cells (HSECs), has never been assessed. In order to test this hypothesis, rat- and human-derived AECs (rAECs and hAECs, respectively) were subjected to endothelial cell tube formation assay in vitro...
January 2018: Cell Transplantation
Hanna Svitina, Inessa Skrypkina, Pavlo Areshkov, Vitaliy Kyryk, Tetiana Bukreieva, Pavlo Klymenko, Liudmyla Garmanchuk, Galyna Lobintseva, Volodymyr Shablii
Transplantation of placenta-derived multipotent cells (PDMCs) is a promising treatment method for many diseases. However, the impact of PDMCs on colon cancer has not yet been studied. PDMCs were obtained from rat placentas by culturing tissue explants. Colon cancer was experimentally induced in male albino Wistar rats by administering 20 mg/kg dimethylhydrazine (DMH) once a week for 20 consecutive weeks. The administration of the PDMCs was performed at the 20th week after the first DMH injection. The number and size of each tumour lesion were calculated in the 5th week after transplantation...
April 2018: Oncology Letters
Antonietta Romano, Paolo Angeli, Sara Piovesan, Franco Noventa, Georgios Anastassopoulos, Liliana Chemello, Luisa Cavalletto, Martina Gambato, Francesco Paolo Russo, Patrizia Burra, Valter Vincenzi, Pier Giorgio Scotton, Sandro Panese, Diego Tempesta, Tosca Bertin, Maurizio Carrara, Antonio Carlotto, Franco Capra, Giada Carolo, Giovanna Scroccaro, Alfredo Alberti
BACKGROUND & AIMS: Direct-acting antiviral agents (DAAs) are safe and effective in patients with hepatitis C. Conflicting data were reported on the risk of Hepatocellular carcinoma (HCC) during/after therapy with DAAs. Aim of this study was to evaluate incidence of newly diagnosed hepatocellular carcinoma and associated risk factors in patients with advanced hepatitis C treated with DAAs. METHODS: The study is based on the NAVIGATORE platform, a prospectively recording database of all patients with hepatitis C receiving DAAs in Veneto region (Italy)...
March 15, 2018: Journal of Hepatology
Keri E Lunsford, Milind Javle, Kirk Heyne, Rachna T Shroff, Reham Abdel-Wahab, Nakul Gupta, Constance M Mobley, Ashish Saharia, David W Victor, Duc T Nguyen, Edward A Graviss, Ahmed O Kaseb, Robert S McFadden, Thomas A Aloia, Claudius Conrad, Xian C Li, Howard P Monsour, A Osama Gaber, Jean-Nicolas Vauthey, R Mark Ghobrial
BACKGROUND: At present, intrahepatic cholangiocarcinoma is a contraindication for liver transplantation. However, previous studies in this field did not preselect patients on the basis of chemosensitivity or disease trajectory after neoadjuvant therapy. Experience with hilar cholangiocarcinoma has indicated that neoadjuvant therapy followed by liver transplantation in patients without disease progression results in a long-term survival benefit. We aimed to establish the potential efficacy of liver transplantation in patients with biologically responsive intrahepatic cholangiocarcinoma who have had sustained tumour stability or regression with neoadjuvant therapy...
March 13, 2018: Lancet. Gastroenterology & Hepatology
Salvatore Sutti, Frank Tacke
Drug-induced liver injury (DILI) remains a clinical challenge due to the poorly predictable outcomes. Accordingly, considerable efforts have been devoted to unravel the risk factors responsible for DILI worsening toward acute liver failure (ALF), liver transplantation (LT), and/or death. From a pathogenic point of view, exhaustion of drug metabolizing pathways, cell death mechanisms, activation of local immune cells, such as Kupffer cells, and recruitment of inflammatory leukocytes including monocytes and lymphocytes are key drivers of DILI progression...
March 15, 2018: Clinical Science (1979-)
Bangari Haldipur, Prudhvi Lal Bhukya, Vidya Arankalle, Kavita Lole
Molecular mechanisms of liver pathology and clinical disease in HEV infection remain unclear. MicroRNAs are known to modulate viral pathogenesis either by directly altering viral gene expression or by enhancing cellular antiviral responses. Given the importance of microRNA-122 (miR-122) in liver pathobiology, we investigated possible role of miR-122 in HEV infection. In silico predictions using genotype 1, 2, 3 and 4 HEV sequences showed that majority of genomes (203/222) harbor at least one miR-122/miR-122* target site...
March 14, 2018: Journal of Virology
Liaoran Wang, David K C Cooper, Lars Burdorf, Yi Wang, Hayato Iwase
There has recently been considerable progress in the results of pig organ transplantation in nonhuman primates (NHPs), largely associated with the availability of (i) pigs genetically-engineered to overcome coagulation dysregulation, and (ii) novel immunosuppressive agents. The barriers of thrombotic microangiopathy and/or consumptive coagulation were believed to be associated with (i) activation of the graft vascular endothelial cells (VECs) by a low level of anti-pig antibody binding and/or complement deposition and/or innate immune cell activity, and (ii) molecular incompatibilities between the NHP and pig coagulation-anticoagulation systems...
March 10, 2018: Transplantation
Tiong Y Lim, Enoka Gonsalkorala, Mary D Cannon, Stella Gabeta, Leonie Penna, Nigel D Heaton, Michael A Heneghan
BACKGROUND: Liver transplantation (LT) is a successful treatment for both acute liver failure and end-stage liver disease. The number of women of reproductive age undergoing LT is increasing. Pregnancy outcomes are favourable but there is still a lack of prognostic markers. We aimed to identify factors predictive of adverse pregnancy outcomes in LT recipients. METHODS: An analysis of all pregnancies occurring in LT recipients from 1989-2016 at King's College Hospital was performed...
March 14, 2018: Liver Transplantation
Chun Han Nigel Tan, Yue Yu, Yan Rui Nicholas Tan, Boon Leng Kieron Lim, Shridhar Ganpathi Iyer, Krishnakumar Madhavan, Alfred Wei Chieh Kow
Backgrounds/Aims: Liver Transplantation (LT) is a recognized treatment for Hepatocellular Carcinoma (HCC). The role of Bridging Therapies (BT) remains controversial. Methods: From January 2001 to October 2012, 192 patients were referred to the National University Hospital, Singapore for consideration of LT for HCC. Sixty-five patients (33.8%) were found suitable for transplant and were placed on the waitlist. Analysis was performed in these patients. Results: The most common etiology of HCC was Hepatitis B (n=28, 43...
February 2018: Annals of Hepato-Biliary-Pancreatic Surgery
Yoshihide Ueda, Toshimi Kaido, Hideaki Okajima, Koichiro Hata, Takayuki Anazawa, Atsushi Yoshizawa, Shintaro Yagi, Kojiro Taura, Toshihiko Masui, Noriyo Yamashiki, Hironori Haga, Miki Nagao, Hiroyuki Marusawa, Hiroshi Seno, Shinji Uemoto
Background: Primary sclerosing cholangitis (PSC) is a progressive cholestatic liver disease, with liver transplantation being the sole life-saving treatment for end-stage PSC-related liver disease. However, recurrence of PSC after liver transplantation is a common complication, with the risk factors for recurrence being controversial. Methods: We conducted a retrospective chart review of 45 patients who had undergone liver transplantation for PSC at our institute...
December 2017: Transplantation Direct
David Noiva Perdigoto, Pedro Amaro, Manuela Ferreira, Luis Tomé
A patient is admitted with complaints of recent onset nausea, discomfort, jaundice and blood tests that reveal severe hepatitis. At the time, she had been taking medication with Hypericum perforatum (St John's wort) for 6 months, and 6 weeks before this event, she took flupirtine maleate. A few days after being admitted, she developed encephalopathy progressing to acute liver failure (ALF) requiring unsuccessful liver transplantation. The patient was ultimately diagnosed with drug-induced liver injury (DILI)...
March 9, 2018: BMJ Case Reports
Mohamad A Mouchli, Siddharth Singh, Lisa Boardman, David H Bruining, Amy L Lightner, Charles B Rosen, Julie K Heimbach, Bashar Hasan, John J Poterucha, Kymberly D Watt, Sunanda V Kane, Laura E Raffals, Edward V Loftus
Background: The course of inflammatory bowel disease (IBD) after liver transplantation (LT) for primary sclerosing cholangitis (PSC) is poorly understood. We describe the natural history of established IBD after LT (including risk of disease progression, colectomy, and neoplasia) and de novo IBD. Methods: In a retrospective cohort, we identified all patients with PSC who underwent LT for advanced PSC at Mayo Clinic, Rochester, Minnesota. Risk factors were identified using multivariate Cox proportional hazard analysis...
March 7, 2018: Inflammatory Bowel Diseases
Chetan Mandelia, Mohammad Nasser Kabbany, Praveen Kumar Conjeevaram Selvakumar, Naim Alkhouri
Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the obesity epidemic. Recent studies have clearly shown that the stage of fibrosis in adults with NAFLD is the most important histological feature in long-term outcomes and the development of liver-related complications. Despite the paucity of data regarding the natural history of pediatric NAFLD, its progression to cirrhosis and end-stage liver disease requiring liver transplantation is well documented. Given the high prevalence of NAFLD in children and adults, there is an urgent need to find safe and cost-effective alternatives to biopsy to determine the stage of liver fibrosis...
March 8, 2018: Biomarkers in Medicine
Chao Du, Mingde Jiang, Xiaolong Wei, Jianpin Qin, Hui Xu, Yunxia Wang, Yong Zhang, Dejiang Zhou, Hongli Xue, Shumei Zheng, Weizheng Zeng
It has been reported that bone marrow-derived mesenchymal stem cells (BMSCs) alleviated liver fibrosis. We investigated whether BMSCs transfected with human matrix metalloproteinase 1 (BMSCs/MMP1) would improve their therapeutic effect in liver fibrosis induced by carbon tetrachloride (CCl4) in rats. BMSCs were transfected with an adenovirus carrying enhanced green fluorescence protein (GFP) and human MMP1 gene. BMSCs or BMSCs/MMP1 were directly injected into fibrotic rats via the tail vein. GFP-labeled cells appeared in the fibrotic liver after BMSC transplantation...
February 27, 2018: International Journal of Molecular Medicine
Christian Rupp, Alexander Rössler, Taotao Zhou, Conrad Rauber, Kilian Friedrich, Andreas Wannhoff, Karl-Heinz Weiss, Peter Sauer, Peter Schirmacher, Caner Süsal, Wolfgang Stremmel, Daniel N Gotthardt
Background: The median age of diagnosis of primary sclerosing cholangitis (PSC) is ∼30-40 years. Objective: We aimed to analyse disease progression and liver-dependent survival in patients diagnosed with PSC after 50 years of age. Methods: Patients with PSC were analysed with regard to their age at diagnosis. Patients with a first diagnosis of PSC after the age of 50 years were considered as the late-onset group. Results: A total of 32/215 (14...
March 2018: United European Gastroenterology Journal
Francesca Maione, Nicholas Gilbo, Silvia Lazzaro, Peter Friend, Giovanni Camussi, Renato Romagnoli, Jacques Pirenne, Ina Jochmans, Diethard Monbaliu
BACKGROUND: Understanding ischemia reperfusion injury (IRI) is essential to further improve outcomes after liver transplantation (LT). Porcine isolated liver perfusion (ILP) is increasingly used to reproduce LT-associated IRI in a strictly controlled environment. However, whether ILP is a reliable substitute of LT was never validated. METHODS: We systematically reviewed the current experimental set-ups for ILP and parameters of interest reflecting IRI. RESULTS: ILP was never compared to transplantation in animals...
March 5, 2018: Transplantation
Urs Christen, Edith Hintermann
Autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC) are serious autoimmune liver diseases that are characterized by a progressive destruction of the liver parenchyma and/or the hepatic bile ducts and the development of chronic fibrosis. Left untreated autoimmune liver diseases are often life-threatening, and patients require a liver transplantation to survive. Thus, an early and reliable diagnosis is paramount for the initiation of a proper therapy with immunosuppressive and/or anticholelithic drugs...
2018: Frontiers in Immunology
Stephanie E Cordts, Lukas Schneble, Paul Schnitzler, Jürgen J Wenzel, Tobias Vinke, Susanne Rieger, Alexander Fichtner, Burkhard Tönshoff, Britta Höcker
BACKGROUND: Hepatitis E virus (HEV) infection in immunocompromised patients such as solid organ transplant recipients may bear a high risk of becoming a chronic infection with progression to liver cirrhosis. So far, data on HEV infection in pediatric renal transplant recipients are limited. METHODS: This single-center cohort study investigated period prevalence, morbidity, and treatment of HEV infection in 90 pediatric renal allograft recipients aged 9.9 ± 5...
March 2, 2018: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
Jessica R Salas, Bao Ying Chen, Alicia Wong, Sergio Duarte, Stephanie A K Angarita, Gerald S Lipshutz, Owen N Witte, Peter M Clark
Drug-induced liver failure is a significant indication for a liver transplant, and unexpected liver toxicity is a major reason that otherwise effective therapies are removed from the market. Various methods exist for monitoring liver injury but are often inadequate to predict liver failure. New diagnostic tools are needed. Methods: We evaluate in a preclinical model whether18 F-2-deoxy-2-fluoroarabinose (18 F-DFA), a PET radiotracer that measures the ribose salvage pathway, can be used to monitor acetaminophen-induced liver injury and failure...
March 1, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Rui Miguel Martins, João Soeiro Teodoro, Emanuel Furtado, Anabela Pinto Rolo, Carlos Marques Palmeira, José Guilherme Tralhão
Ischemia/reperfusion (I/R) injury in liver transplantation can disrupt the normal activity of mitochondria in the hepatic parenchyma. This potential dysfunction of mitochondria after I/R injury could be responsible for the initial poor graft function or primary nonfunction observed after liver transplantation. Thus, determining the mechanisms that lead to human hepatic mitochondrial dysfunction might contribute to improving the outcome of liver transplantation. Furthermore, early identification of novel prognostic factors involved in I/R injury could serve as a key endpoint to predict the outcome of liver grafts and also to promote the early adoption of novel strategies that protect against I/R injury...
2018: International Journal of Medical Sciences
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