肝内胆管缺失是指肝内胆管数量的减少或消失,是胆管树基本病理改变之一。免疫紊乱、肿瘤、感染、药物、缺血、遗传等因素都有可能引起胆管缺失。临床上,通过肝活组织检查,在10个及以上门管区的标本里,发现50%以上的小叶间胆管缺失,即可...肝内胆管缺失是指肝内胆管数量的减少或消失,是胆管树基本病理改变之一。免疫紊乱、肿瘤、感染、药物、缺血、遗传等因素都有可能引起胆管缺失。临床上,通过肝活组织检查,在10个及以上门管区的标本里,发现50%以上的小叶间胆管缺失,即可确诊[1]。胆管缺失的预后取决于病因和损伤程度。晚期出现不可逆的广泛胆管缺失甚至胆管消失时,该病理综合征称为胆管消失综合征(vanishing bile duct syndrome,VBDS),仅发生在0.5%小胆管病[2]。随后,可进展至广泛的胆管纤维化或肝硬化。有趣的是,也有部分患者表现为胆管上皮细胞再生,在数月或数年后得到恢复。本文总结了胆管缺失发病的分子机制,并重点强调近年来免疫介导的胆管病和胆管缺失的研究进展。展开更多
AIM:Primary biliary cirrhosis (PBC) is a chronic, cholestatic disease of autoimmune etiology,the histology of which shows a destruction of the intrahepatic bile duct and portal inflammation. Ursodeoxycholic acid (UDCA...AIM:Primary biliary cirrhosis (PBC) is a chronic, cholestatic disease of autoimmune etiology,the histology of which shows a destruction of the intrahepatic bile duct and portal inflammation. Ursodeoxycholic acid (UDCA) is now used as a first-line drug for asymptomatic PBC (aPBC) because it is reported that UDCA decreases mortality and prolongs the time of liver transplantation.However, only 20-30% of patients respond fully to UDCA.Recently,lipoprotein-lowering agents have been found to be effective for PBC.The aim of this study was to examine the safety and efficacy of fenofibrate, a member of the fibrate class of hypolipidemic and anti-inflammatory agent via peroxysome proliferatory-activated receptor α,in patients with aPBC.METHODS:Fenofibrate was administered for twelve weeks in nine patients with aPBC who failed to respond to UDCA.UDCA was used along with fenofibrate during the study.The data from aPBC patients were analyzed to assess the biochemical effect of fenofibrate during the study.RESULTS: The serum levels of alkaline phosphatase (ALP)(285±114.8IU/L) and immunoglobulin M (IgM) (255.8±85.9mg/dl) significantly decreased to 186.9±76.2IU/L and 192.9±67.5mg/dL respectively, after fenofibrate treatment in patients with aPBC (P<0.05). Moreover,the titer of antimitochondrial antibody (AMA) also decreased in 4 of 9 patients with aPBC. No adverse reactions were observed in any patients.CONCLUSION:Fenofibrate appears to be significantly effective in treating patients with aPBC who respond incompletely to UDCA alone.Although the mechanism of fenofibrate on aPBC has not yet been fully clarified,combination therapy using fenofibrate and UDCA might be related to the anti-immunological effects, such as the suppression of AMA production as well as its antiinflammatory effect.展开更多
文摘肝内胆管缺失是指肝内胆管数量的减少或消失,是胆管树基本病理改变之一。免疫紊乱、肿瘤、感染、药物、缺血、遗传等因素都有可能引起胆管缺失。临床上,通过肝活组织检查,在10个及以上门管区的标本里,发现50%以上的小叶间胆管缺失,即可确诊[1]。胆管缺失的预后取决于病因和损伤程度。晚期出现不可逆的广泛胆管缺失甚至胆管消失时,该病理综合征称为胆管消失综合征(vanishing bile duct syndrome,VBDS),仅发生在0.5%小胆管病[2]。随后,可进展至广泛的胆管纤维化或肝硬化。有趣的是,也有部分患者表现为胆管上皮细胞再生,在数月或数年后得到恢复。本文总结了胆管缺失发病的分子机制,并重点强调近年来免疫介导的胆管病和胆管缺失的研究进展。
文摘AIM:Primary biliary cirrhosis (PBC) is a chronic, cholestatic disease of autoimmune etiology,the histology of which shows a destruction of the intrahepatic bile duct and portal inflammation. Ursodeoxycholic acid (UDCA) is now used as a first-line drug for asymptomatic PBC (aPBC) because it is reported that UDCA decreases mortality and prolongs the time of liver transplantation.However, only 20-30% of patients respond fully to UDCA.Recently,lipoprotein-lowering agents have been found to be effective for PBC.The aim of this study was to examine the safety and efficacy of fenofibrate, a member of the fibrate class of hypolipidemic and anti-inflammatory agent via peroxysome proliferatory-activated receptor α,in patients with aPBC.METHODS:Fenofibrate was administered for twelve weeks in nine patients with aPBC who failed to respond to UDCA.UDCA was used along with fenofibrate during the study.The data from aPBC patients were analyzed to assess the biochemical effect of fenofibrate during the study.RESULTS: The serum levels of alkaline phosphatase (ALP)(285±114.8IU/L) and immunoglobulin M (IgM) (255.8±85.9mg/dl) significantly decreased to 186.9±76.2IU/L and 192.9±67.5mg/dL respectively, after fenofibrate treatment in patients with aPBC (P<0.05). Moreover,the titer of antimitochondrial antibody (AMA) also decreased in 4 of 9 patients with aPBC. No adverse reactions were observed in any patients.CONCLUSION:Fenofibrate appears to be significantly effective in treating patients with aPBC who respond incompletely to UDCA alone.Although the mechanism of fenofibrate on aPBC has not yet been fully clarified,combination therapy using fenofibrate and UDCA might be related to the anti-immunological effects, such as the suppression of AMA production as well as its antiinflammatory effect.
