Incidence and risk factors for non-alcoholic steatohepatitis: prospective study of 5408 women enrolled in Italian tamoxifen chemoprevention trial
Incidence and risk factors for non-alcoholic steatohepatitis: prospective study of 5408 women enrolled in Italian tamoxifen chemoprevention trial
复制标题
DOI：
10.1136/bmj.38391.663287.e0
复制
发表时间：
2005-04-23
影响因子：
105.7
通讯作者：
Veronesi, U
中科院分区：
文献类型：
--
作者：
Bruno, S;Maisonneuve, P;Veronesi, U
目的评估三苯氧胺对女性非酒精性脂肪性肝病（包括非酒精性脂肪性肝炎）的发病率、辅助因素和过度风险。安慰剂对照试验。设置和参与者5408名健康妇女谁了直肠切除术招募到意大利他莫昔芬化学预防试验从58个中心在意大利。干预妇女被随机分配接受他莫昔芬主要观察指标：所有基线肝功能正常、丙氨酸氨基转移酶至少有两次升高的女性患者发生非酒精性脂肪肝的情况结果在随访期间，64名妇女符合预定义的标准：12例丙型肝炎病毒检测呈阳性，其余52例疑似患有非酒精性脂肪肝（34例他莫昔芬，18例安慰剂）-风险比= 2.0（95%置信区间1.1至3.5; P = 0.04）。在所有52名妇女超声检查证实存在脂肪肝。与非酒精性脂肪肝发生相关的其他因素包括超重（2.4，1.2至4.8）、肥胖（3.6，1.7至7.6）、高胆固醇血症（3.4，1.4至7.8）和动脉高血压（2.0，1.0至3.8）。20名女性进行了肝活检：15名被诊断为轻度至中度脂肪性肝炎（12名他莫昔芬，3名安慰剂），5名仅患有脂肪肝（1名他莫昔芬，4名安慰剂）。没有临床，生化，超声，或组织学迹象表明肝硬化的进展后，观察到的中位数随访8.7 years.Conclusions他莫昔芬与非酒精性脂肪性肝炎的发展风险较高，仅在超重和肥胖的妇女代谢综合征的功能，但疾病，在他莫昔芬和安慰剂组，10年的随访后似乎是惰性的。
Objective To assess the incidence, cofactors, and excess risk of development of non-alcoholic fatty liver disease, including non-alcoholic steatohepatitis, attributable to tamoxifen in women.Design Prospective, randomised, double blind, placebo controlled trial.Setting and participants 5408 healthy women who had had hysterectomies recruited into the Italian tamoxifen chemoprevention trial from 58 centres in Italy.Intervention Women were randomly assigned to receive tamoxifen (20 mg daily) or placebo for five years.Main outcome measure Development of non-alcoholic fatty liver disease in all women with normal baseline liver function who showed at least two elevations of alanine amino transferase ( >= 1.5 times upper limit of normal) over a six month period.Results During follow up, 64 women met the predefined criteria: 12 tested positive for hepatitis C virus, and the remaining 52 were suspected of having developed non-alcoholic fatty liver disease (34 tamoxifen, 18 placebo)-hazard ratio = 2.0 (95% confidence interval 1.1 to 3.5; P = 0.04). In all 52 women ultrasonography confirmed the presence of fatty liver. Other factors associated with the development of non-alcoholic fatty liver disease included overweight (2.4, 1.2 to 4.8), obesity (3.6, 1.7 to 7.6), hypercholesterolaemia (3.4, 1.4 to 7.8), and arterial hypertension (2.0, 1.0 to 3.8). Twenty women had liver biopsies: 15 were diagnosed as having mild to moderate steatohepatitis (12 tamoxifen, 3 placebo), and five had fatty liver alone (I tamoxifen, 4 placebo). No clinical, biochemical, ultrasonic, or histological signs suggestive of progression to cirrhosis were observed after a median follow up of 8.7 years.Conclusions Tamoxifen was associated with higher risk of development of non-alcoholic steatohepatitis only in overweight and obese women with features of metabolic syndrome, but the disease, in both the tamoxifen and the placebo group, after 10 years of follow-up seems to be indolent.