Sex difference in non‐alcoholic fatty liver disease and non‐alcoholic steatohepatitis
Sex difference in non‐alcoholic fatty liver disease and non‐alcoholic steatohepatitis
复制标题
DOI：
10.1111/j.1872-034x.2009.00611.x
复制
发表时间：
2010-01
影响因子：
4.2
通讯作者：
T. Tomiya
中科院分区：
文献类型：
--
作者：
T. Tomiya
非酒精性脂肪性肝病（NAFLD）是西方和亚洲国家常见的肝病之一。患者数量正在迅速增加，在日本和美国，超过五分之一的人口被认为患有NAFLD。其组织学谱从简单的脂肪变性扩展到脂肪性肝炎、肝硬化和最终肝细胞癌（HCC）。在该谱中，脂肪性肝炎和进一步的晚期形式被认为是非酒精性脂肪性肝炎（NASH）。NAFLD通常与肥胖、内脏肥胖、胰岛素抵抗和2型糖尿病相关。许多研究者认为NAFLD是代谢综合征的肝脏表现。各种肥胖和/或胰岛素抵抗的动物模型，由基因突变引起的，并通过药理学或饮食操作，已被用于研究。细胞因子、促炎介质和氧化应激是单纯脂肪变性向NASH转变的候选因素。然而，NAFLD的病因及其进展是复杂的，并且基本的细胞事件尚未完全理解。来自日本的报告表明，存在无肥胖的NAFLD病例，并且当非肥胖被定义为体重指数（BMI）小于25 kg/m2时，最近NAFLD的增加不能仅归因于肥胖的增加。最近的研究表明，NAFLD的易感性存在种族差异，这不能简单地用先前饮酒，饮食和社会经济差异的背景偏差来解释。认为西班牙裔受试者的患病率高于白色受试者。在亚洲NAFLD患者中，BMI低于美国人群中的白色、西班牙裔和黑人受试者。遗传因素可能导致NAFLD。然而，迄今为止，在一般NAFLD中没有发现特定的遗传改变。NAFLD患病率的性别差异已被广泛报道。早期的一系列报告显示，NAFLD在女性中比男性更常见。然而，最近的研究表明，NAFLD在男性和女性中同样常见。据报道，日本男性NAFLD或脂肪肝的患病率约为女性的两倍。亚裔美国公民的男性发病率是女性的3.5倍。与此同时，患病率随着年龄的增长而增加，尤其是在女性中，老年男性和女性之间的患病率似乎相似。这一观察结果意味着处于绝经后状态可能会影响女性NAFLD的发展。研究设计的差异，如受试者的种族和年龄，可能是研究之间缺乏一致性的原因。NASH患病率的性别差异也存在争议。1979年，Adler和Schaffner发现，大约80%的脂肪性肝炎、纤维化和肝硬化患者是女性。Ludwig等人在1980年也报道了65%的NASH患者为女性。这些先驱性研究给人留下了强烈的印象，即NASH是一种女性占主导地位的疾病。然而，最近的研究表明，NASH在男性中与女性相比相似或更普遍。如果两种性别的肝脂肪变性以相似的方式进展为NASH，则NASH的患病率将反映单纯性脂肪肝或NAFLD的患病率。Yatsuji等人2年前发表在该杂志上，报告了一项横断面研究，显示肝病学研究2010; 40：108-110 doi：10.1111/j.1872-034X.2009.00611.x
Non-alcoholic fatty liver disease (NAFLD) emerges as one of the common liver diseases in Western as well as Asian countries. The number of patients is rapidly increasing, and more than one-fifth of the population is thought to suffer from NAFLD in Japan and the USA. Its histological spectrum extends from simple steatosis to steatohepatitis, cirrhosis and eventually hepatocellular carcinoma (HCC). In this spectrum, steatohepatitis and further advanced forms are recognized as nonalcoholic steatohepatitis (NASH). NAFLD is generally associated with obesity, visceral adiposity, insulin resistance and type 2 diabetes. Many investigators consider NAFLD a hepatic manifestation of the metabolic syndrome. Various kinds of obese and/or insulin-resistant animal models, caused by genetic mutation and produced by pharmacological or dietary manipulation, have been utilized for the studies. Cytokines, proinflammatory mediators and oxidative stress are candidate factors in transition of simple steatosis to NASH. However, the etiology of NAFLD and its progression is complicated and the fundamental cellular events are not yet fully understood. Reports from Japan indicate that there are NAFLD cases without obesity, and recent increase of NAFLD could not be attributable only to the increase of obesity, when non-obesity is defined as a body mass index (BMI) of less than 25 kg/m. Recent studies revealed that ethnic differences exist in susceptibility to NAFLD, which cannot be explained simply by the bias of a background of prior alcohol intake, diet and socioeconomic differences. The prevalence is thought to be higher in Hispanic subjects relative to white. In Asian NAFLD patients, BMI is lower compared to those of white, Hispanic and black subjects in a US population. Genetic factors may predispose to NAFLD. However, to date, no specific genetic alternations have been found in general NAFLD. The sex difference in the prevalence of NAFLD has been variably reported. An earlier series of reports showed that NAFLD was more common in women than in men. However, recent studies identified that NAFLD was as frequent in men as women. Approximately twofold higher incidence of the prevalence of NAFLD or fatty liver disease has been reported in men than in women in Japan. Asian US-based citizens showed 3.5fold higher incidence of the disease in men than in women. Meanwhile, the prevalence was shown to increase by age, especially in women, and seemed to be similar between old-aged men and women. This observation implies the possibility that being in a postmenopausal condition might affect the development of NAFLD in women. Differences of study design such as ethnicity and age of participants may account for the lack of the consistency across studies. Controversy also exists for the sex difference in the prevalence of NASH. In 1979, Adler and Schaffner showed that approximately 80% of patients with fatty hepatitis, fibrosis and cirrhosis were women. Ludwig et al. also reported in 1980 that 65% of NASH patients were women. These pioneer studies made a strong impression that NASH was a female-predominant disease. However, recent studies imply that NASH is similarly or more prevalent in men compared to women. If hepatic steatosis in both sexes progresses to NASH in a similar manner, the prevalence of NASH would reflect that of simple fatty liver or NAFLD. Published in the Journal 2 years ago, Yatsuji et al. reported cross-sectional study showing that Hepatology Research 2010; 40: 108–110 doi: 10.1111/j.1872-034X.2009.00611.x