For Personal Use. Only Reproduce with Permission from the Lancet Primary Biliary Cirrhosis
For Personal Use. Only Reproduce with Permission from the Lancet Primary Biliary Cirrhosis
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通讯作者：
J. Talwalkar;K. Lindor;J. Talwalkar
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作者：
J. Talwalkar;K. Lindor;J. Talwalkar
原发性胆汁性肝硬化是一种原因不明的慢性胆汁淤积性肝病。由门静脉和门静脉周围炎症引起的进行性胆管损伤可导致进行性纤维化和最终肝硬化。迄今为止的证据表明，免疫和遗传因素可能导致这种疾病。受影响的个体通常是中年妇女，血清肝脏生化指标无症状升高。最初出现的疲劳、瘙痒或不明原因的高脂血症也可能提示原发性胆汁性肝硬化的诊断。血清抗线粒体抗体阳性是本病的基本诊断指标。疾病识别很重要，因为熊去氧胆酸的有效治疗可以阻止疾病进展并延长无肝移植的生存期。准确描述原发性胆汁性肝硬化自然病史的数学模型也有助于确定肝移植的最佳时机。原发性胆汁性肝硬化影响所有种族，但似乎集中在特定的地理区域。1女性主要受影响，男女比例为9/1。疾病发病的中位年龄为50岁，但在20至90岁之间变化。年发病率2、3和患病率3、4的估计值分别为每百万人2至24例和每百万人19至240例。来自美国明尼苏达州奥姆斯特德县（Olmsted County, Minnesota， USA）的数据显示，在过去25年中发病率稳定，但患病率高于加拿大。5方法和病例定义的差异阻碍了系列之间的比较。世界范围内疾病患病率的差异表明，环境因素是原发性胆汁性肝硬化表型表达的必要因素。从英格兰北部的一项基于人群的研究和美国的一项大型病例对照调查来看，与对照组相比，吸烟和肝外自身免疫性疾病的存在与该疾病有关。原发性胆汁性肝硬化患者的一级亲属患自身免疫性疾病的风险至少增加两倍。吸烟者患这种疾病的尿路感染率很高，这增加了感染原因的可能性。妊娠与原发性胆汁性肝硬化之间的关联数据是相互矛盾的。原发性胆汁性肝硬化自身免疫的遗传易感性与MHC基因座的等位基因有关。然而，2类MHC位点，包括DR8、DQA1*0102和DQ/ / 1*0402，只在特定的患者中被报道。与日本患者的DR2和DR8单倍型相比，DR3、DR8和DR4单倍型在白人人群中更为常见。…
53 Primary biliary cirrhosis is a chronic cholestatic liver disease of unknown cause. Progressive bile-duct injury from portal and periportal inflammation could result in progressive fibrosis and eventual cirrhosis. Evidence to date suggests that immunological and genetic factors might cause the disease. Affected individuals are typically middle-aged women with asymptomatic rises of serum hepatic biochemical variables. Fatigue, pruritus, or unexplained hyperlipidaemia at initial presentation might also suggest a diagnosis of primary biliary cirrhosis. Serum antimitochondrial antibody positivity is nearly diagnostic of the disease. Disease identification is important because effective medical treatment with ursodeoxycholic acid can halt disease progression and extend survival free of liver transplantation. Mathematical models that accurately characterise the natural history of primary biliary cirrhosis may also assist in determining the optimum timing for liver transplantation when indicated. Epidemiology Primary biliary cirrhosis affects all races, yet seems to cluster within specific geographical areas. 1 Women are mainly affected, with a female/male ratio of 9/1. The median age of disease onset is 50 years, but varies between 20 and 90 years. Estimates of annual incidence 2,3 and prevalence 3,4 range from 2 to 24 cases per million and 19 to 240 cases per million population, respectively. Data from Olmsted County, Minnesota, USA, 4 suggest a stable incidence rate over the past 25 years but a higher prevalence than described in Canada. 5 Differences in methodology and case definitions have impeded comparisons between series. The worldwide variation in disease prevalence suggests that environmental factors are needed for phenotypic expression of primary biliary cirrhosis. From a population-based study in northern England 6 and a large case-control US investigation, 7 presence of tobacco use and extrahepatic autoimmune disorders have been associated with the disease when compared with controls. First-degree relatives of people with primary biliary cirrhosis are also known to have at least a twofold increased risk of autoimmune diseases. A high rate of urinary-tract infections in smokers with the disease has raised the possibility of an infectious cause. 8 Data of the association between gravidity and primary biliary cirrhosis are conflicting. Genetics Genetic predisposition to autoimmunity in primary biliary cirrhosis has been associated with alleles from MHC loci. However, class 2 MHC loci, including DR8, DQA1*0102, and DQ/1*0402, have only been reported in selected patients with the disorder. 11–13 The haplotypes DR3, DR8, and DR4 are more frequent in white populations by contrast with DR2 and DR8 haplotypes in Japanese patients. …