欧洲肝病协会（European Association for the Study of the Liver，EASL）于2012年6月发布了最新版《酒精性肝病临床实践指南》（EASL Clinical Practical Guidelines：Management of Alcoholic Liver Disease）。本指南涉及脂肪肝炎...欧洲肝病协会（European Association for the Study of the Liver，EASL）于2012年6月发布了最新版《酒精性肝病临床实践指南》（EASL Clinical Practical Guidelines：Management of Alcoholic Liver Disease）。本指南涉及脂肪肝炎、肝纤维化、肝硬化等各类酒精相关肝损害的流行病学、筛查、公共卫生管控、临床表现、诊断与治疗，内容全面丰富，可操作性很强。现将与临床诊疗密切相关的部分解读如下。展开更多
Kupffer cells, the resident liver macrophages have long been considered as mostly scavenger cells responsible for removing particulate material from the portal circulation. However, evidence derived mostly from animal...Kupffer cells, the resident liver macrophages have long been considered as mostly scavenger cells responsible for removing particulate material from the portal circulation. However, evidence derived mostly from animal models, indicates that Kupffer cells may be implicated in the pathogenesis of various liver diseases including viral hepatitis, steatohepatitis, alcoholic liver disease, intrahepatic cholostasis, activation or rejection of the liver during liver transplantation and liver fibrosis. There is accumulating evidence, reviewed in this paper, suggesting that Kupffer cells may act both as effector cells in the destruction of hepatocytes by produdng harmful soluble mediators as well as antigen presenting cells during viral infections of the liver. Moreover they may represent a significant source of chemoattractant molecules for cytotoxic CD8 and regulatory T cells. Their role in fibrosis is well established as they are one of the main sources of TGFβ1 production, which leads to the transformation of stellate cells into myofibroblasts. Whether all these variable functions in the liver are mediated by different Kupffer cell subpopulations remains to be evaluated. In this review we propose a model that demonstrates the role of Kupffer cells in the pathogenesis of liver disease.展开更多
目的为深入研究酒精性肝病的发病机制,提供一个简单可行的动物模型,并利用此模型检测血浆PDGF含量在酒精性肝病发生发展中的变化。方法本研究在平衡饮食的条件下,以400mL·L^(-1)乙醇,8g·kg^(-1)·d^(-1),日3次灌胃至4wk末...目的为深入研究酒精性肝病的发病机制,提供一个简单可行的动物模型,并利用此模型检测血浆PDGF含量在酒精性肝病发生发展中的变化。方法本研究在平衡饮食的条件下,以400mL·L^(-1)乙醇,8g·kg^(-1)·d^(-1),日3次灌胃至4wk末,自5wk,以500 mL·L^(-1)乙醇,9g·kg^(-1)·d^(-1),日3次灌胃至8 wk末,自9 wk,以500mL·L^(-1)乙醇,10g·kg^(-1)·d^(-1)日3次灌胃至12wk末,诱导酒精性肝病大鼠动物模型,分别于4wk末、8wk末、12wk末观察肝脏病理学改变,并用生物活性法测定了对照组及实验组不同病理阶段血浆中血小板源性生长因子(PDGF)的含量。结果光镜显示对照组肝细胞以中央静脉为中心呈放射状排列,酒精摄入4wk末,肝细胞中重度脂肪变性,8wk末肝细胞变性坏死,炎性细胞浸润,Mallory染色可见胶原于中央静脉沉积增加,12wk末变性坏死及炎性细胞浸润明显,Mallory染色可见胶原自中央静脉向窦周隙伸展,呈现轻度肝纤维化改变,PDGF含量结果可见与同时期对照组相比,实验组PDGF含量(kU·L^(-1))均有显著增高,4,8,12wk分别为67±15 vs 31±18(P<0.05),130±30vs33±19(P<0.001),202±20 vs 36±6(P<0.001);实验组不同时期差异明显,随病程进展病变加重,8wk与4wk相比,P<0.01,12wk与8wk相比,P<0.001。结论灌胃为一种简单可行的造模方法;PDGF可能在酒精性肝纤维化的发生发展中起重要作用,但详细机制有待进一步探讨。展开更多
AIM: To evaluate safety and feasibility of autologous bone marrow-enriched CD34+ hematopoietic stem cell Tx through the hepatic artery in patients with decompensated cirrhosis.METHODS: Four patients with decompensated...AIM: To evaluate safety and feasibility of autologous bone marrow-enriched CD34+ hematopoietic stem cell Tx through the hepatic artery in patients with decompensated cirrhosis.METHODS: Four patients with decompensated cirrhosis were included. Approximately 200 mL of the bone marrow of the patients was aspirated, and CD34+ stem cells were selected. Between 3 to 10 million CD34+ cells were isolated. The cells were slowly infused through the hepatic artery of the patients.RESULTS: Patient 1 showed marginal improvement in serum albumin and no significant changes in other test results. In patient 2 prothrombin time was decreased; however, her total bilirubin, serum creatinine, and Model of End-Stage Liver Disease (MELD) score worsened at the end of follow up. In patient 3 there was improvement in serum albumin, porthrombin time (PT), and MELD score. Patient 4 developed radiocontrast nephropathy after the procedure, and progressed to type 1 hepatorenal syndrome and died of liver failure a few days later. Because of the major side effects seen in the last patient, the trial was prematurely stopped.CONCLUSION: Infusion of CD34+ stem cells through the hepatic artery is not safe in decompensated cirrhosis. Radiocontrast nephropathy and hepatorenal syndrome could be major side effects. However, this study doesnot preclude infusion of CD34+ stem cells through other routes.展开更多
文摘欧洲肝病协会（European Association for the Study of the Liver，EASL）于2012年6月发布了最新版《酒精性肝病临床实践指南》（EASL Clinical Practical Guidelines：Management of Alcoholic Liver Disease）。本指南涉及脂肪肝炎、肝纤维化、肝硬化等各类酒精相关肝损害的流行病学、筛查、公共卫生管控、临床表现、诊断与治疗，内容全面丰富，可操作性很强。现将与临床诊疗密切相关的部分解读如下。
文摘Kupffer cells, the resident liver macrophages have long been considered as mostly scavenger cells responsible for removing particulate material from the portal circulation. However, evidence derived mostly from animal models, indicates that Kupffer cells may be implicated in the pathogenesis of various liver diseases including viral hepatitis, steatohepatitis, alcoholic liver disease, intrahepatic cholostasis, activation or rejection of the liver during liver transplantation and liver fibrosis. There is accumulating evidence, reviewed in this paper, suggesting that Kupffer cells may act both as effector cells in the destruction of hepatocytes by produdng harmful soluble mediators as well as antigen presenting cells during viral infections of the liver. Moreover they may represent a significant source of chemoattractant molecules for cytotoxic CD8 and regulatory T cells. Their role in fibrosis is well established as they are one of the main sources of TGFβ1 production, which leads to the transformation of stellate cells into myofibroblasts. Whether all these variable functions in the liver are mediated by different Kupffer cell subpopulations remains to be evaluated. In this review we propose a model that demonstrates the role of Kupffer cells in the pathogenesis of liver disease.
文摘目的为深入研究酒精性肝病的发病机制,提供一个简单可行的动物模型,并利用此模型检测血浆PDGF含量在酒精性肝病发生发展中的变化。方法本研究在平衡饮食的条件下,以400mL·L^(-1)乙醇,8g·kg^(-1)·d^(-1),日3次灌胃至4wk末,自5wk,以500 mL·L^(-1)乙醇,9g·kg^(-1)·d^(-1),日3次灌胃至8 wk末,自9 wk,以500mL·L^(-1)乙醇,10g·kg^(-1)·d^(-1)日3次灌胃至12wk末,诱导酒精性肝病大鼠动物模型,分别于4wk末、8wk末、12wk末观察肝脏病理学改变,并用生物活性法测定了对照组及实验组不同病理阶段血浆中血小板源性生长因子(PDGF)的含量。结果光镜显示对照组肝细胞以中央静脉为中心呈放射状排列,酒精摄入4wk末,肝细胞中重度脂肪变性,8wk末肝细胞变性坏死,炎性细胞浸润,Mallory染色可见胶原于中央静脉沉积增加,12wk末变性坏死及炎性细胞浸润明显,Mallory染色可见胶原自中央静脉向窦周隙伸展,呈现轻度肝纤维化改变,PDGF含量结果可见与同时期对照组相比,实验组PDGF含量(kU·L^(-1))均有显著增高,4,8,12wk分别为67±15 vs 31±18(P<0.05),130±30vs33±19(P<0.001),202±20 vs 36±6(P<0.001);实验组不同时期差异明显,随病程进展病变加重,8wk与4wk相比,P<0.01,12wk与8wk相比,P<0.001。结论灌胃为一种简单可行的造模方法;PDGF可能在酒精性肝纤维化的发生发展中起重要作用,但详细机制有待进一步探讨。
文摘AIM: To evaluate safety and feasibility of autologous bone marrow-enriched CD34+ hematopoietic stem cell Tx through the hepatic artery in patients with decompensated cirrhosis.METHODS: Four patients with decompensated cirrhosis were included. Approximately 200 mL of the bone marrow of the patients was aspirated, and CD34+ stem cells were selected. Between 3 to 10 million CD34+ cells were isolated. The cells were slowly infused through the hepatic artery of the patients.RESULTS: Patient 1 showed marginal improvement in serum albumin and no significant changes in other test results. In patient 2 prothrombin time was decreased; however, her total bilirubin, serum creatinine, and Model of End-Stage Liver Disease (MELD) score worsened at the end of follow up. In patient 3 there was improvement in serum albumin, porthrombin time (PT), and MELD score. Patient 4 developed radiocontrast nephropathy after the procedure, and progressed to type 1 hepatorenal syndrome and died of liver failure a few days later. Because of the major side effects seen in the last patient, the trial was prematurely stopped.CONCLUSION: Infusion of CD34+ stem cells through the hepatic artery is not safe in decompensated cirrhosis. Radiocontrast nephropathy and hepatorenal syndrome could be major side effects. However, this study doesnot preclude infusion of CD34+ stem cells through other routes.
