Kkc Ng

Fat-derived hormone adiponectin combined with FTY720 significantly improves small-for-size fatty liver graft survival.

Owing to the discrepancy between organ donation and the demand for liver transplantation, expanding the liver donor pool is of vital importance. However, marginal liver grafts, such as small‐for‐size and/or fatty grafts, were associated with primary graft nonfunction or poor function. Therefore, novel combination therapies to rescue small‐for‐size fatty liver grafts should be investigated. In this study, we applied a combination therapy using a fat‐derived hormone adiponectin (anti‐steatosis) plus immunomodulator FTY720 (anti‐inflammatory) in a rat liver transplantation model using small‐for‐size fatty liver grafts, and investigated the underlying protective mechanism such as anti‐steatosis, intra‐graft energy metabolism, hepatic microcirculatory changes, cell signaling cascades for survival, apoptosis and inflammation. The current study demonstrated that even a single treatment of adiponectin or FTY720 improved the 7‐day graft survival from 0% to 62.5% (p = 0.001). The combination therapy significantly increased the 7‐day graft survival rate to 100% by remarkable attenuation of graft steatosis and acute phase inflammatory response, significant activation of cell survival Akt pathway and maintenance of intra‐graft adenosine triphosphate metabolism and improvement of hepatic microcirculation. In conclusion, the fat‐derived hormone adiponectin combined with FTY720 might be a novel combination drug therapy for prevention of small‐for‐size fatty liver graft injury.

Distinct Mechanism of Small‐for‐Size Fatty Liver Graft Injury—Wnt4 Signaling Activates Hepatic Stellate Cells

In this study, we aimed to investigate the significance of hepatic stellate cells (HSCs) activation in small‐for‐size fatty liver graft injury and to explore the underlying molecular mechanism in a rat liver transplantation model. A rat orthotopic liver transplantation model using fatty grafts (40% of fatty changes) and cirrhotic recipients was applied. Intragraft gene expression profiles, ultrastructure features and HSCs activation were compared among the rats received different types of grafts (whole vs. small‐for‐size, normal vs. fatty). The distinct molecular signature of small‐for‐size fatty graft injury was identified by cDNA microarray screening and confirmed by RT‐PCR detection. In vitro functional studies were further conducted to investigate the direct effect of specific molecular signature on HSCs activation. HSCs activation was predominantly present in small‐for‐size fatty grafts during the first 2 weeks after transplantation, and was strongly correlated with progressive hepatic sinusoidal damage and significant upregulation of intragraft Wnt4 signaling pathway. In vitro suppression of Wnt4 expression could inhibit HSC activation directly. In conclusion, upregulation of Wnt4 signaling led to direct HSC activation and subsequently induced small‐for‐size fatty liver grafts injury. Discovery of this distinct mechanism may lay the foundation for prophylactic treatment for marginal graft injury in living donor liver transplantation.

Rapamycin attenuates liver graft injury in cirrhotic recipient--the significance of down-regulation of Rho-ROCK-VEGF pathway.

To investigate whether rapamycin could attenuate hepatic I/R injury in a cirrhotic rat liver transplantation model, we applied a rat orthotopic liver transplantation model using 100% or 50% of liver grafts and cirrhotic recipients. Rapamycin was given (0.2 mg/kg, i.v.) at 30 min before graft harvesting in the donor and 24 h before operation, 30 min before total hepatectomy and immediately after reperfusion in the recipient. Rapamycin significantly improved small‐for‐size graft survival from 8.3% (1/12) to 66.7% (8/12) (p = 0.027). It also increased 7‐day survival rates of whole grafts (58.3%[7/12] vs. 83.3%[10/12], p = 0.371). Activation of hepatic stellate cells was mainly found in small‐for‐size grafts during the first 7 days after liver transplantation. Rapamycin suppressed expression of smooth muscle actin, which is a marker of hepatic stellate cell activation, especially in small‐for‐size grafts. Intragraft protein expression and mRNA levels of vascular endothelial growth factor (VEGF) were down‐regulated by rapamycin at 48 h both in whole and small‐for‐size grafts. Consistently, mRNA levels and protein expression of Rho and ROCK I were decreased by rapamycin during the 48 h after liver transplantation. In conclusion, rapamycin attenuated graft injury in a cirrhotic rat liver transplantation model by suppression of hepatic stellate cell activation, related to down‐regulation of Rho‐ROCK‐VEGF pathway.

Advantage of anterior resection in major resection for colorectal liver metastases

Objective: We described histologic findings bile canalicular–ductule networks in the future liver remnant (FLR) during associating liver partition with portal vein ligation for staged hepatectomy (ALPPS). Background: Little is known about regeneration of bile canalicular–ductule networks during short interval of ALPPS. Methods: Bile canalicular–ductule networks were examined using specimens obtained from 8 patients treated with ALPPS and 6 patients with hepatectomy following portal vein embolization (PVE). The expression of multidrug resistance 1 (MDR1), a membrane transporter of the bile canaliculi (BC), was analyzed immunohistochemically. The morphological changes of the BC and tight junction (TJ) surrounding BC were also assessed electron microscopically. Results: Extrapolated kinetic growth of FLR was greater during ALPPS (17.2 ± 6.8 mL/day) than that after PVE (6.3 ± 3.4 mL/day, P=0.005). The continuity of MDR1–positive bile canalicular networks was less evident in ALPPS than in PVE (P<0.001). Electron microscopically, no significant difference was evident in number of BC, size of BC s̓ lumen between the 2 groups. However, in the ALPPS group, development of microvilli in the BC was poorer than the PVE group (P<0.001). Length of the TJ and desmosome complex were shorter in the ALPPS group (0.69±0.52μm) than in the PVE group (1.09±0.50μm; P<0.001). Leaky TJ was more evident in the ALPPS group (64.9% vs. 23.6%; P=0.001). Conclusions: Regeneration of bile canalicular–ductule networks in FLR was less evident in ALPPS than PVE. This phenomenon may be associated with prolonged cholestasis following final hepatectomy in ALPPS. J Hepatobiliary Pancreat Sci (2017) 24.S1 Oral A150

Long-term survival analysis of living donor liver transplantation for hepatocellular carcinoma across Milan criteria

This journal suppl. entitled: Supplement: The International Liver Transplantation Society: 15th Annual International Congress

Primary versus salvage liver transplantation for hepatocellular carcinoma within Milan criteria: a single center experience

This journal suppl. entitled: Supplement: The International Liver Transplantation Society: 15th Annual International Congress

Salvage Transplantation for Recurrent Hepatocellular Carcinoma within Milan Criteria: Is It Worthwhile?

P-203 DISSEMINATED NOCARDIOSIS: A RARE INFECTIOUS COMPLICATION FOLLOWING NON-HEART-BEATING DONOR LIVER TRANSPLANTATION. Santos JiménezGalanes, Juan Carlos Meneu Diaz, Baltasar Perez-Saborido, Almudena Moreno Elola-Olaso, Yiliam Fundora Suarez, Manuel Abradelo Usera, Alberto Gimeno Calvo, Enrique Moreno González. Surgery and Abdominal Organs Transplantation Department, 12 de Octubre University Hospital, Madrid, Spain INTRODUCTION Nocardiosis is an infrequent disease that use to affect patients who present a cellular immunodeficiency, such as transplant recipients on immunosuppression treatment, and although uncommon associate high rates of morbidity and mortality. Disseminated Nocardiasis affecting central nervous system (CNS), abdomen, skin and lungs has been described in bone marrow, lung and kidney transplanted patients. However, to our knowledge, no cases involving these three structures have been reported in liver transplant recipients. CASE REPORT Herein, we report a case of CNS, pulmonary and cutaneous nocardiosis in a liver transplant recipient from a non-heart-beating donor due to hepatitis C virus related cirrhosis and hepatocellular carcinoma. At 7 postransplant month, patient was admitted at emergency department presenting bad general health status, fever, edema and subcutaneous nodules in legs. A computed tomography scan was performed revealing multiple nodules disseminated thorough both lungs, abdomen, brain a subcutaneous tissue. By these clinical and radiogical fi ndings needle biopsy was performed over one of the subcutaneous nodules. Cultures of the material tested positive for Nocardia farcinica. Thus, we started treatment with intravenous sulfamethoxazoletrimethoprim (SMZ-TMP) shifted after one month to oral. Radiological examination performed after two weeks of treatment showed a 70% reduction on subcutaneous, pulmonary and cerebral lesions. After six months of SMZTMP treatment, patient remained free of the symptoms, with involution of the subcutaneous nodules and signifi cant radiological improvement. CONCLUSION Among opportunistic infections appearing in liver transplant recipients, Nocardia spp. should have special consideration according to the success in early treated patients and bad prognosis in cases of delayed diagnose.This journal supplement labeled: The International Liver Transplantation Society: 16th Annual International Congress

Prediction of hospital mortality after liver transplantation for acute liver failure

P-203 DISSEMINATED NOCARDIOSIS: A RARE INFECTIOUS COMPLICATION FOLLOWING NON-HEART-BEATING DONOR LIVER TRANSPLANTATION. Santos JiménezGalanes, Juan Carlos Meneu Diaz, Baltasar Perez-Saborido, Almudena Moreno Elola-Olaso, Yiliam Fundora Suarez, Manuel Abradelo Usera, Alberto Gimeno Calvo, Enrique Moreno González. Surgery and Abdominal Organs Transplantation Department, 12 de Octubre University Hospital, Madrid, Spain INTRODUCTION Nocardiosis is an infrequent disease that use to affect patients who present a cellular immunodeficiency, such as transplant recipients on immunosuppression treatment, and although uncommon associate high rates of morbidity and mortality. Disseminated Nocardiasis affecting central nervous system (CNS), abdomen, skin and lungs has been described in bone marrow, lung and kidney transplanted patients. However, to our knowledge, no cases involving these three structures have been reported in liver transplant recipients. CASE REPORT Herein, we report a case of CNS, pulmonary and cutaneous nocardiosis in a liver transplant recipient from a non-heart-beating donor due to hepatitis C virus related cirrhosis and hepatocellular carcinoma. At 7 postransplant month, patient was admitted at emergency department presenting bad general health status, fever, edema and subcutaneous nodules in legs. A computed tomography scan was performed revealing multiple nodules disseminated thorough both lungs, abdomen, brain a subcutaneous tissue. By these clinical and radiogical fi ndings needle biopsy was performed over one of the subcutaneous nodules. Cultures of the material tested positive for Nocardia farcinica. Thus, we started treatment with intravenous sulfamethoxazoletrimethoprim (SMZ-TMP) shifted after one month to oral. Radiological examination performed after two weeks of treatment showed a 70% reduction on subcutaneous, pulmonary and cerebral lesions. After six months of SMZTMP treatment, patient remained free of the symptoms, with involution of the subcutaneous nodules and signifi cant radiological improvement. CONCLUSION Among opportunistic infections appearing in liver transplant recipients, Nocardia spp. should have special consideration according to the success in early treated patients and bad prognosis in cases of delayed diagnose.This journal supplement labeled: The International Liver Transplantation Society: 16th Annual International Congress

Recurrent hepatitis B infection after liver transplantation for hepatitis B related diseases in Asian population: long term results of a single centre

P-203 DISSEMINATED NOCARDIOSIS: A RARE INFECTIOUS COMPLICATION FOLLOWING NON-HEART-BEATING DONOR LIVER TRANSPLANTATION. Santos JiménezGalanes, Juan Carlos Meneu Diaz, Baltasar Perez-Saborido, Almudena Moreno Elola-Olaso, Yiliam Fundora Suarez, Manuel Abradelo Usera, Alberto Gimeno Calvo, Enrique Moreno González. Surgery and Abdominal Organs Transplantation Department, 12 de Octubre University Hospital, Madrid, Spain INTRODUCTION Nocardiosis is an infrequent disease that use to affect patients who present a cellular immunodeficiency, such as transplant recipients on immunosuppression treatment, and although uncommon associate high rates of morbidity and mortality. Disseminated Nocardiasis affecting central nervous system (CNS), abdomen, skin and lungs has been described in bone marrow, lung and kidney transplanted patients. However, to our knowledge, no cases involving these three structures have been reported in liver transplant recipients. CASE REPORT Herein, we report a case of CNS, pulmonary and cutaneous nocardiosis in a liver transplant recipient from a non-heart-beating donor due to hepatitis C virus related cirrhosis and hepatocellular carcinoma. At 7 postransplant month, patient was admitted at emergency department presenting bad general health status, fever, edema and subcutaneous nodules in legs. A computed tomography scan was performed revealing multiple nodules disseminated thorough both lungs, abdomen, brain a subcutaneous tissue. By these clinical and radiogical fi ndings needle biopsy was performed over one of the subcutaneous nodules. Cultures of the material tested positive for Nocardia farcinica. Thus, we started treatment with intravenous sulfamethoxazoletrimethoprim (SMZ-TMP) shifted after one month to oral. Radiological examination performed after two weeks of treatment showed a 70% reduction on subcutaneous, pulmonary and cerebral lesions. After six months of SMZTMP treatment, patient remained free of the symptoms, with involution of the subcutaneous nodules and signifi cant radiological improvement. CONCLUSION Among opportunistic infections appearing in liver transplant recipients, Nocardia spp. should have special consideration according to the success in early treated patients and bad prognosis in cases of delayed diagnose.This journal supplement labeled: The International Liver Transplantation Society: 16th Annual International Congress

Bile duct anastomotic stricture after right lobe adult-to-adult living donor liver transplantation

P-203 DISSEMINATED NOCARDIOSIS: A RARE INFECTIOUS COMPLICATION FOLLOWING NON-HEART-BEATING DONOR LIVER TRANSPLANTATION. Santos JiménezGalanes, Juan Carlos Meneu Diaz, Baltasar Perez-Saborido, Almudena Moreno Elola-Olaso, Yiliam Fundora Suarez, Manuel Abradelo Usera, Alberto Gimeno Calvo, Enrique Moreno González. Surgery and Abdominal Organs Transplantation Department, 12 de Octubre University Hospital, Madrid, Spain INTRODUCTION Nocardiosis is an infrequent disease that use to affect patients who present a cellular immunodeficiency, such as transplant recipients on immunosuppression treatment, and although uncommon associate high rates of morbidity and mortality. Disseminated Nocardiasis affecting central nervous system (CNS), abdomen, skin and lungs has been described in bone marrow, lung and kidney transplanted patients. However, to our knowledge, no cases involving these three structures have been reported in liver transplant recipients. CASE REPORT Herein, we report a case of CNS, pulmonary and cutaneous nocardiosis in a liver transplant recipient from a non-heart-beating donor due to hepatitis C virus related cirrhosis and hepatocellular carcinoma. At 7 postransplant month, patient was admitted at emergency department presenting bad general health status, fever, edema and subcutaneous nodules in legs. A computed tomography scan was performed revealing multiple nodules disseminated thorough both lungs, abdomen, brain a subcutaneous tissue. By these clinical and radiogical fi ndings needle biopsy was performed over one of the subcutaneous nodules. Cultures of the material tested positive for Nocardia farcinica. Thus, we started treatment with intravenous sulfamethoxazoletrimethoprim (SMZ-TMP) shifted after one month to oral. Radiological examination performed after two weeks of treatment showed a 70% reduction on subcutaneous, pulmonary and cerebral lesions. After six months of SMZTMP treatment, patient remained free of the symptoms, with involution of the subcutaneous nodules and signifi cant radiological improvement. CONCLUSION Among opportunistic infections appearing in liver transplant recipients, Nocardia spp. should have special consideration according to the success in early treated patients and bad prognosis in cases of delayed diagnose.This journal supplement labeled: The International Liver Transplantation Society: 16th Annual International Congress