Recently,there have been reports from liver biopsies that showed the progression of liver fibrosis in liver transplant patients after the cessation of immunosuppression.Herein,we focused on activated hepatic stellate ...Recently,there have been reports from liver biopsies that showed the progression of liver fibrosis in liver transplant patients after the cessation of immunosuppression.Herein,we focused on activated hepatic stellate cells expressing alpha smooth muscle actin(α-SMA)to understand the correlation between immunosuppressant medication and liver fibrosis.The study enrolled two pediatric patients who underwent living donor liver transplantation and ceased immunosuppressant therapy.The number ofα-SMA-positive cells in the specimens obtained by liver biopsy from these two patients showed a three-fold increase compared with the number from four transplanted pediatric patients who were continuing immunosuppressant therapy.In addition,theα-SMA-positive area evaluated using the WinRooF image processing software program continued toincrease over time in three adult transplanted patients with liver fibrosis,and theα-SMA-positive area was increasing even during the pre-fibrotic stage in these adult cases,according to a retrospective review.Therefore,α-SMA could be a useful marker for the detection of early stage fibrosis.展开更多
AIM:To investigate time-dependent changes caused by temporal portal vein obstruction and subsequent reperfusion in the lobe with or without an occluded portal vein.METHODS:The portal vein(PV)of the anterior lobe of th...AIM:To investigate time-dependent changes caused by temporal portal vein obstruction and subsequent reperfusion in the lobe with or without an occluded portal vein.METHODS:The portal vein(PV)of the anterior lobe of the liver of a male Wistar rat(8 wk-old)was obstructed(70%)for 12,24,36 and 48 h,respectively,and models were sacrificed at 48 h after reperfusion(each group:n=10).The histological changes and the status of liver regeneration were compared between a liver biopsy performed on each lobe after temporary obstruction of the portal vein in the same rat liver,and the liver extracted at the time of sacrifice(48 h after reperfusion).RESULTS:With regard to the obstructed lobe,the liver weight/body weight ratio significantly decreased according to obstruction time.On the other hand,in thenon-obstructed lobe,there were no significant differences within each group.The duration of PV occlusion did not seem to be strong enough to introduce liver weight increase.Stimulation of liver regeneration was brought about in the non-occluded lobe by 12-h occlusion,and was sustained even at 48 h after reperfusion.The obstructed lobe atrophied with the passage of time in the obstructed state.However,the proliferating-cell nuclear antigen labeling index also increased at 48 h after reperfusion,and a repair mechanism was observed.CONCLUSION:Temporary blood flow obstruction of the portal vein may become a significant trigger for liver regeneration,even with an obstruction of 12 h.展开更多
AIM: To elucidate the metabolism and the effect of the cyclosporin A (CyA) as a representative immuno-suppressive drug used in transplantation in a partially hepatectomized rat model. METHODS: CyA was administered to ...AIM: To elucidate the metabolism and the effect of the cyclosporin A (CyA) as a representative immuno-suppressive drug used in transplantation in a partially hepatectomized rat model. METHODS: CyA was administered to rats that under- went a 70% hepatectomy. These rats were randomly assigned into three groups according to the dose of CyA administration as follows; (group 1) water, (group 2) 5 mg/kg CyA, (group 3) 10 mg/kg CyA. On post- operative days-1, 3, 7 and 14, the rats were killed to analyze the serum concentration of CyA, the liver re- generation ratio, biochemical or histological markers, and mRNA expression using reverse transcriptase-poly- merase chain reaction method to determine albumin and cytochrome p450 expression. RESULTS: The serum concentration of CyA in group 3 was significantly higher than group 2 during liver regeneration. CyA enhanced the liver regeneration in a dose dependent manner. The mRNA expression associ- ated with CyA metabolism was signifi cantly decreased on day 14, while preserving the albumin producing activity. CONCLUSION: These data indicate that the p-450 ac-tivity required to metabolize the CyA may be reduced during regeneration of the remnant liver after a hepa- tectomy, which may, therefore, be linked to diffi culty in controlling the optimal dose of CyA during early period of LDLT.展开更多
Background:Thrombocytopenia commonly occurs early after liver transplantation.Heparin,usually administered as anticoagulant ther-apy for thrombosis,a common complication after liver transplantation,may cause heparin-i...Background:Thrombocytopenia commonly occurs early after liver transplantation.Heparin,usually administered as anticoagulant ther-apy for thrombosis,a common complication after liver transplantation,may cause heparin-induced thrombocytopenia.Heparin-induced thrombocytopenia is a rare but life-threatening complication,and its diagnosis after liver transplantation is challenging.Case presentation:We report a case of heparin-induced thrombocytopenia after living donor liver transplantation with a good out-come because of early diagnosis and discontinuation of heparin.After liver transplantation,the platelet count usually reaches a nadir on postoperative days 3–5 and gradually recovers.In contrast,heparin-induced thrombocytopenia typically occurs 5–10 days after heparin administration;therefore,if heparin is started intraoperatively,then thrombocytopenia will occur on postoperative days 5–10.Conclusion:Monitoring the trend and timing of thrombocytopenia and detailed examination for thrombosis may help confirm the diag-nosis of heparin-induced thrombocytopenia in the early stage after liver transplantation.展开更多
Background:The end-stage liver disease causes a metabolic dysfunction whose most prominent clinical feature is the loss of skeletal muscle mass(SMM).In living-donor liver transplantation(LDLT),liver graft regeneration...Background:The end-stage liver disease causes a metabolic dysfunction whose most prominent clinical feature is the loss of skeletal muscle mass(SMM).In living-donor liver transplantation(LDLT),liver graft regeneration(GR)represents a crucial process to normalize the portal hypertension and to meet the metabolic demand of the recipient.Limited data are available on the correlation between pre-LDLT low SMM and GR.Methods:Retrospective study on a cohort of 106 LDLT patients receiving an extended left liver lobe graft.The skeletal muscle index(SMI)at L3 level was used for muscle mass measurement,and the recommended cut-off values of the Japanese Society of Hepatology guidelines were used as criteria for defining low muscularity.GR was evaluated as rate of volume increase at 1 month post-LT[graft regeneration rate(GRR)].Results:The median GRR at 1 month post-LT was 91%(IQR,65-128%)and a significant correlation with graft volume-to-recipient standard liver volume ratio(GV/SLV)(rho-0.467,P<0.001),graft-to-recipient weight ratio(GRWR)(rho-0.414,P<0.001),donor age(rho-0.306,P=0.001),1 month post-LT cholinesterase serum levels(rho 0.397,P=0.002)and pre-LT low muscularity[absent vs.present GRR 97.5%(73.1-130%)vs.83.5%(45.2-110.9%),P=0.041]was noted.Moreover in male recipients,but not in women,it was shown a direct correlation with pre-LT SMI(rho 0.352,P=0.020)and inverse correlation with 1 month post-LT SMI variation(rho-0.301,P=0.049).A low GRR was identified as an independent prognostic factor for recipient overall survival(HR 6.045,P<0.001).Conclusions:Additionally to the hemodynamic factors of portal circulation and the quality of the graft,the metabolic status of the recipients has a significant role in the GR process.A pre-LT low SMM is associated with impaired GRR and this negative impact is more evident in male recipients.展开更多
文摘Recently,there have been reports from liver biopsies that showed the progression of liver fibrosis in liver transplant patients after the cessation of immunosuppression.Herein,we focused on activated hepatic stellate cells expressing alpha smooth muscle actin(α-SMA)to understand the correlation between immunosuppressant medication and liver fibrosis.The study enrolled two pediatric patients who underwent living donor liver transplantation and ceased immunosuppressant therapy.The number ofα-SMA-positive cells in the specimens obtained by liver biopsy from these two patients showed a three-fold increase compared with the number from four transplanted pediatric patients who were continuing immunosuppressant therapy.In addition,theα-SMA-positive area evaluated using the WinRooF image processing software program continued toincrease over time in three adult transplanted patients with liver fibrosis,and theα-SMA-positive area was increasing even during the pre-fibrotic stage in these adult cases,according to a retrospective review.Therefore,α-SMA could be a useful marker for the detection of early stage fibrosis.
文摘AIM:To investigate time-dependent changes caused by temporal portal vein obstruction and subsequent reperfusion in the lobe with or without an occluded portal vein.METHODS:The portal vein(PV)of the anterior lobe of the liver of a male Wistar rat(8 wk-old)was obstructed(70%)for 12,24,36 and 48 h,respectively,and models were sacrificed at 48 h after reperfusion(each group:n=10).The histological changes and the status of liver regeneration were compared between a liver biopsy performed on each lobe after temporary obstruction of the portal vein in the same rat liver,and the liver extracted at the time of sacrifice(48 h after reperfusion).RESULTS:With regard to the obstructed lobe,the liver weight/body weight ratio significantly decreased according to obstruction time.On the other hand,in thenon-obstructed lobe,there were no significant differences within each group.The duration of PV occlusion did not seem to be strong enough to introduce liver weight increase.Stimulation of liver regeneration was brought about in the non-occluded lobe by 12-h occlusion,and was sustained even at 48 h after reperfusion.The obstructed lobe atrophied with the passage of time in the obstructed state.However,the proliferating-cell nuclear antigen labeling index also increased at 48 h after reperfusion,and a repair mechanism was observed.CONCLUSION:Temporary blood flow obstruction of the portal vein may become a significant trigger for liver regeneration,even with an obstruction of 12 h.
文摘AIM: To elucidate the metabolism and the effect of the cyclosporin A (CyA) as a representative immuno-suppressive drug used in transplantation in a partially hepatectomized rat model. METHODS: CyA was administered to rats that under- went a 70% hepatectomy. These rats were randomly assigned into three groups according to the dose of CyA administration as follows; (group 1) water, (group 2) 5 mg/kg CyA, (group 3) 10 mg/kg CyA. On post- operative days-1, 3, 7 and 14, the rats were killed to analyze the serum concentration of CyA, the liver re- generation ratio, biochemical or histological markers, and mRNA expression using reverse transcriptase-poly- merase chain reaction method to determine albumin and cytochrome p450 expression. RESULTS: The serum concentration of CyA in group 3 was significantly higher than group 2 during liver regeneration. CyA enhanced the liver regeneration in a dose dependent manner. The mRNA expression associ- ated with CyA metabolism was signifi cantly decreased on day 14, while preserving the albumin producing activity. CONCLUSION: These data indicate that the p-450 ac-tivity required to metabolize the CyA may be reduced during regeneration of the remnant liver after a hepa- tectomy, which may, therefore, be linked to diffi culty in controlling the optimal dose of CyA during early period of LDLT.
文摘Background:Thrombocytopenia commonly occurs early after liver transplantation.Heparin,usually administered as anticoagulant ther-apy for thrombosis,a common complication after liver transplantation,may cause heparin-induced thrombocytopenia.Heparin-induced thrombocytopenia is a rare but life-threatening complication,and its diagnosis after liver transplantation is challenging.Case presentation:We report a case of heparin-induced thrombocytopenia after living donor liver transplantation with a good out-come because of early diagnosis and discontinuation of heparin.After liver transplantation,the platelet count usually reaches a nadir on postoperative days 3–5 and gradually recovers.In contrast,heparin-induced thrombocytopenia typically occurs 5–10 days after heparin administration;therefore,if heparin is started intraoperatively,then thrombocytopenia will occur on postoperative days 5–10.Conclusion:Monitoring the trend and timing of thrombocytopenia and detailed examination for thrombosis may help confirm the diag-nosis of heparin-induced thrombocytopenia in the early stage after liver transplantation.
文摘Background:The end-stage liver disease causes a metabolic dysfunction whose most prominent clinical feature is the loss of skeletal muscle mass(SMM).In living-donor liver transplantation(LDLT),liver graft regeneration(GR)represents a crucial process to normalize the portal hypertension and to meet the metabolic demand of the recipient.Limited data are available on the correlation between pre-LDLT low SMM and GR.Methods:Retrospective study on a cohort of 106 LDLT patients receiving an extended left liver lobe graft.The skeletal muscle index(SMI)at L3 level was used for muscle mass measurement,and the recommended cut-off values of the Japanese Society of Hepatology guidelines were used as criteria for defining low muscularity.GR was evaluated as rate of volume increase at 1 month post-LT[graft regeneration rate(GRR)].Results:The median GRR at 1 month post-LT was 91%(IQR,65-128%)and a significant correlation with graft volume-to-recipient standard liver volume ratio(GV/SLV)(rho-0.467,P<0.001),graft-to-recipient weight ratio(GRWR)(rho-0.414,P<0.001),donor age(rho-0.306,P=0.001),1 month post-LT cholinesterase serum levels(rho 0.397,P=0.002)and pre-LT low muscularity[absent vs.present GRR 97.5%(73.1-130%)vs.83.5%(45.2-110.9%),P=0.041]was noted.Moreover in male recipients,but not in women,it was shown a direct correlation with pre-LT SMI(rho 0.352,P=0.020)and inverse correlation with 1 month post-LT SMI variation(rho-0.301,P=0.049).A low GRR was identified as an independent prognostic factor for recipient overall survival(HR 6.045,P<0.001).Conclusions:Additionally to the hemodynamic factors of portal circulation and the quality of the graft,the metabolic status of the recipients has a significant role in the GR process.A pre-LT low SMM is associated with impaired GRR and this negative impact is more evident in male recipients.
