Background: The efficacy and necessity of middle hepatic vein(MHV) reconstruction in adult-to-adult right lobe living donor liver transplantation(LDLT) remain controversial. The present study aimed to evaluate the sur...Background: The efficacy and necessity of middle hepatic vein(MHV) reconstruction in adult-to-adult right lobe living donor liver transplantation(LDLT) remain controversial. The present study aimed to evaluate the survival beneficiary of MHV reconstructions in LDLT. Methods: We compared the clinical outcomes of liver recipients with MHV reconstruction( n = 101) and without MHV reconstruction( n = 43) who underwent LDLT using right lobe grafts at our institution from January 2006 to May 2017. Results: The overall survival(OS) rate of recipients with MHV reconstruction was significantly higher than that of those without MHV reconstruction in liver transplantation( P = 0.022; 5-yr OS: 76.2% vs 58.1%). The survival of two segments(segments 5 and 8) hepatic vein reconstruction was better than that of the only one segment(segment 5 or segment 8) hepatic vein reconstruction( P = 0.034; 5-yr OS: 83.6% vs 67.4%). The survival of using two straight vascular reconstructions was better than that using Y-shaped vascular reconstruction in liver transplantation with two segments hepatic vein reconstruction( P = 0.020; 5-yr OS: 100% vs 75.0%). The multivariate analysis demonstrated that MHV tributary reconstructions were an independent beneficiary prognostic factor for OS(hazard ratio = 0.519, 95% CI: 0.282–0.954, P = 0.035). Biliary complications were significantly increased in recipients with MHV reconstruction(28.7% vs 11.6%, P = 0.027). Conclusions: MHV reconstruction ensured excellent outflow drainage and favored recipient outcome. The MHV tributaries(segments 5 and 8) should be reconstructed as much as possible to enlarge the hepatic vein anastomosis and reduce congestion.展开更多
Infections by coronaviruses such as severe acute respiratory syndrome （SARS） coronavirus （SCoV） and mouse hepatitis virus A59 （MHV-A59） result in very little type I interferon （IFN） production by host cells, w...Infections by coronaviruses such as severe acute respiratory syndrome （SARS） coronavirus （SCoV） and mouse hepatitis virus A59 （MHV-A59） result in very little type I interferon （IFN） production by host cells, which is potentially responsible for the rapid viral growth and severe immunopathology associated with SARS. However, the molecular mechanisms for the low IFN production in cells infected with coronaviruses remain unclear. Here, we provide evidence that Papain-like protease domain 2 （PLP2）, a catalytic domain of the nonstructural protein 3 （nsp3） of MHV-A59, can bind to IRF3, cause its deubiquitination and prevent its nuclear translocation. As a consequence, co-expression of PLP2 strongly inhibits CARDIF-, TBK1- and IRF3-mediated IFNp reporter activities. In addition, we show that wild-type PLP2 but not the mutant PLP2 lacking the deubiquitinase （DUB） activity can reduce IFN induction and promote viral growth in cells infected with VSV. Thus, our study uncovered a viral DUB which coronaviruses may use to escape from the host innate antiviral responses.展开更多
基金supported by a grant from the National Science and Technology Major Project of China(2017ZX100203205)
文摘Background: The efficacy and necessity of middle hepatic vein(MHV) reconstruction in adult-to-adult right lobe living donor liver transplantation(LDLT) remain controversial. The present study aimed to evaluate the survival beneficiary of MHV reconstructions in LDLT. Methods: We compared the clinical outcomes of liver recipients with MHV reconstruction( n = 101) and without MHV reconstruction( n = 43) who underwent LDLT using right lobe grafts at our institution from January 2006 to May 2017. Results: The overall survival(OS) rate of recipients with MHV reconstruction was significantly higher than that of those without MHV reconstruction in liver transplantation( P = 0.022; 5-yr OS: 76.2% vs 58.1%). The survival of two segments(segments 5 and 8) hepatic vein reconstruction was better than that of the only one segment(segment 5 or segment 8) hepatic vein reconstruction( P = 0.034; 5-yr OS: 83.6% vs 67.4%). The survival of using two straight vascular reconstructions was better than that using Y-shaped vascular reconstruction in liver transplantation with two segments hepatic vein reconstruction( P = 0.020; 5-yr OS: 100% vs 75.0%). The multivariate analysis demonstrated that MHV tributary reconstructions were an independent beneficiary prognostic factor for OS(hazard ratio = 0.519, 95% CI: 0.282–0.954, P = 0.035). Biliary complications were significantly increased in recipients with MHV reconstruction(28.7% vs 11.6%, P = 0.027). Conclusions: MHV reconstruction ensured excellent outflow drainage and favored recipient outcome. The MHV tributaries(segments 5 and 8) should be reconstructed as much as possible to enlarge the hepatic vein anastomosis and reduce congestion.
基金These authors contributed equally to this work. We thank Drs S Vaidya and E Chow （University of California Los Angeles, USA） for their help in setting up critical experimental systems. We greatly thank Dr K Holmes （University of Colorado Health Sciences Center, USA） for sharing with us 17C1-1 cell line and helping to optimize the protocol to produce high titered MHV-A59 virus stock. We also thank Drs R Baric and L Su （University of North Carolina, USA） for the gift of MHV-A59 and guidance of virus infection. We thank Dr K Lim （National Neuroscience Institute, Singapore） for the gift of Ubi plasmids. We thank Dr M Wathelet （University of Cincinnati College of Medicine, USA） for sharing the nsp3 construct. Also we thank Dr G Gao （Institute of Biophysics, CAS） for providing us with VSV. This research was partly supported by grants from the National Natural Science Foundation of China （30728006） to Genhong Cheng and the National Basic Research Program of MOST （2004BA519A61, 2006CB504300, 2007DFC30190） to Hong Tang.
文摘Infections by coronaviruses such as severe acute respiratory syndrome （SARS） coronavirus （SCoV） and mouse hepatitis virus A59 （MHV-A59） result in very little type I interferon （IFN） production by host cells, which is potentially responsible for the rapid viral growth and severe immunopathology associated with SARS. However, the molecular mechanisms for the low IFN production in cells infected with coronaviruses remain unclear. Here, we provide evidence that Papain-like protease domain 2 （PLP2）, a catalytic domain of the nonstructural protein 3 （nsp3） of MHV-A59, can bind to IRF3, cause its deubiquitination and prevent its nuclear translocation. As a consequence, co-expression of PLP2 strongly inhibits CARDIF-, TBK1- and IRF3-mediated IFNp reporter activities. In addition, we show that wild-type PLP2 but not the mutant PLP2 lacking the deubiquitinase （DUB） activity can reduce IFN induction and promote viral growth in cells infected with VSV. Thus, our study uncovered a viral DUB which coronaviruses may use to escape from the host innate antiviral responses.
