Patients with primary biliary cirrhosis have increased serum total antioxidant capacity measured with the crocin bleaching assay

AIM: The balance between oxidants and antioxidants can play an important role in the initiation and development of liver diseases. Recently, we have described a new automated method for the determination of total antioxidant capacity (TAC) in human serum and plasma.METHODS: We measured TAC and corrected TAC (CTAC -abstraction of interactions due to endogenous uric acid,bilirubin and albumin) in 52 patients with chronic liver diseases (41 patients with primary biliary cirrhosis (PBC),10 patients with chronic hepatitis C and 13 patients with viral HCV cirrhosis) as well as in 10 healthy controls. In 23 PBC patients measurement were also done 6 mo after treatment with ursodeoxycholic acid (UDCA). The TAC assay was based on a modification of the crocin bleaching assay. The results were correlated with routine laboratory measurements and the histological stage of PBC.RESULTS: There were no significant differences in TAC between the various groups. However, CTAC was considerably increased in the PBC group compared to controls and cirrhotics. Analysis of these patients according to disease stages showed that this increase was an early phenomenon observed only in stages Ⅰ and Ⅱ compared to controls, cirrhotics and patients with chronic hepatitis C).After 6 mo of treatment with UDCA, levels of CTAC decreased to those similar to that of controls.CONCLUSION: Patients in the early stages of PBC present with high levels of corrected total antioxidant capacity and this maybe related to the pathophysiology of the disease. UDCA treatment restores the levels of CTAC to control levels.

Pathogenesis of primary biliary cirrhosis: A unifying model

主要胆汁性肝硬变(PBC ) 是导致小肝内胆汁管并且最后的进步破坏到肝肝硬化和失败的未知病原学的疾病。它被女优势和浆液自身抗体描述到指向 2-oxoacid 脱氢酶建筑群的 E2 部件的 mitochondrial 抗原。尽管他们与疾病致病被联系，没有具体证据到目前为止被介绍了。流行病学的数据显示盒子和可能的环境因素的一个地理聚类在致病被含有。很多个基因因素在决定疾病危险性或前进起一个作用，尽管没有权威的结论到目前为止被得出了。到有免疫力的致病的一个关键因素被认为是有免疫力的忍耐的故障，通过分子的模仿或通过所谓的决定因素，密度当模特儿。在这评论，关于主要胆汁性肝硬变的致病的可得到的数据被描述并且讨论。一个新统一假设基于在主要胆汁性肝硬变(PBC ) 的早 endothelin 生产过剩被介绍并且讨论。

Increased ΤGF-β3 in primary biliary cirrhosis: An abnormality related to pathogenesis?

AIM: To investigate the transforming growth factor-β (TGF-β) isoforms in the peripheral and hepatic venous blood of primary biliary cirrhosis (PBC) patients. METHODS: We examined TGF-β1, TGF-β2 and TGF-β3 (enzyme-linked immunosorbent assay), in 27 stage Ⅳ PBC patients (27 peripheral and 15 hepatic vein sera), 35 early (Ⅰ-Ⅱ) PBC and 60 healthy controls. As disease controls 28 hepatitis C virus (HCV) cirrhosis (28 peripheral and 17 hepatic vein serum), 44 chronic HCV hepatitis and 38 HCV-related hepatocellular carcinomas were included. We also tested liver tissue by immunohistochemistry to identify localization of TGF isoforms. RESULTS: TGF-β1 was significantly decreased in all cirrhotics (PBC Ⅲ-Ⅳ: median 13.4 ng/mL; range, 7.4-26.2, HCV cirrhosis: 11.6 ng/mL; range, 5.0-33.8), compared to controls (30.9 ng/mL; range, 20.9-37.8). TGF-β2 was increased in viral cirrhosis but not in PBC and chronic hepatitis. TGF-β3 (47.2 pg/mL; range, 27.0-79.7 in healthy controls) was increased in early and late PBC (Ⅰ-Ⅱ: 94.3 pg/mL; range, 41.5-358.6; Ⅲ-Ⅳ: 152.8 pg/mL; range, 60.4-361.2; P < 0.001) and decreased in viral cirrhosis (37.4 pg/mL; range, 13.3-84.0; P < 0.05). Hepatic vein TGF-β levels were analogous to those in peripheral blood. Immunohistochemistry identified all isoforms in portal tract lymphocytes, sinusoidal cells and cholangiocytes. TGF-β3 was additionally overexpressed in hepatocytes in PBC patients. CONCLUSION: The serum profile of TGF-β isoforms is different in cirrhotics. Increased TGF-β3 is characteristic of PBC. These findings may be related to the immunological abnormalities of PBC.

Primary biliary cirrhosis: From bench to bedside

Primary biliary cirrhosis(PBC) is a chronic non-suppurative destructive intrahepatic cholangitis leading to cirrhosis after a protractive non cirrhotic stage. The etiology and pathogenesis are largely unknown and autoimmne mechanisms have been implicated to explain the pathological lesions. Many epitopes and autoantigens have been reported as crucial in the pathophysiology of the disease and T and B cells abnormalities have been described, the exact pathways leading to the destruction of small intrahepatic ductules are mostly speculative. In this review we examined the various epidemiologal and geoepidemiological data as well as the complex pathogenetic aspects of this disease, focusing on recent in vivo and in vitro studies in this field. Initiation and progression of PBC is believed to be a multifactorial process with strong infuences from the patient's genetic background and by various environmental factors. The role of innate and adaptive immunity, including cytokines, chemokines, macrophages and the involvement of apoptosis and reactive oxygen species are outlined in detailed. The current pathogenetic aspects are presented and a novel pathogenetic theory unifying the accumulated clinical information with in vitro and in vivo data is formulated. A review of clinical manifestations and immunological and pathological diagnosis was presented. Treatment modalities, including the multiple mechanisms of action of ursodeoxycholate were finally discussed.