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The Amount of Liver Fat Predicts Mortality and Development of Type 2 Diabetes in Non-alcoholic Fatty Liver Disease.

肝脏脂肪量预测非酒精性脂肪性肝病的死亡率和 2 型糖尿病的发展。

  • 影响因子:3.87
  • DOI:10.1111/liv.14414
  • 作者列表:"Nasr P","Fredrikson M","Ekstedt M","Kechagias S
  • 发表时间:2020-02-22
Abstract

BACKGROUND & AIMS:Non-alcoholic fatty liver disease (NAFLD) is a risk factor for development of type 2 diabetes mellitus (T2DM). We aimed to evaluate whether conventional histological grading of steatosis and accurate quantification of fat content in liver biopsies using stereological point counting (SPC) can predict mortality and future development of T2DM in NAFLD patients. METHODS:129 patients with biopsy proven NAFLD, enrolled between 1988 and 1992, were re-evaluated on two occasions, after 13.7 (±1.5) and 23.2 (±6.8) years. In patients accepting to undergo the procedure, repeat liver biopsies were performed on each follow-up and were evaluated with conventional histopathological methodology and SPC. RESULTS:Of the 106 patients without T2DM at baseline, 66 (62%) developed T2DM during a mean follow-up of 23.2 (± 6.8) years. Steatosis grade and liver fat measured with SPC independently (adjusted for age, BMI, fibrosis stage) predicted development of T2DM with an aHR of 1.60 per grade and 1.03 for each SPC percentage increase, respectively. Overall mortality and development of T2DM was more common in patients with grade 3 steatosis compared to lower grades of steatosis. Liver fat measured with SPC was significant for overall mortality (aHR 1.04). In patients that underwent repeat biopsy, reduction of liver fat measured with SPC was associated with decreased risk of developing T2DM (aHR 0.91 for each SPC percentage decrease). CONCLUSION:Steatosis grade and liver fat measured with SPC predict mortality and the risk of developing T2DM in NAFLD. Reduction of liver fat decreases the risk of developing T2DM.

摘要

背景与目的: 非酒精性脂肪性肝病 (NAFLD) 是 2 型糖尿病 (T2DM) 的危险因素。我们的目的是评估使用体视学点计数 (SPC) 对脂肪变性的常规组织学分级和肝活检中脂肪含量的准确定量是否可以预测 NAFLD 患者的死亡率和未来 T2DM 的发展。 方法: 129 和 1988年入组的 1992 例活检证实为 NAFLD 的患者,在 13.7 (± 1.5) 年和 23.2 (± 6.8) 年后进行了两次重新评估。在接受手术的患者中,每次随访均进行重复肝活检,并用常规组织病理学方法和 SPC 进行评价。 结果: 在 106 例基线无 T2DM 的患者中,66 例 (62%) 在平均 23.2 (± 6.8) 年的随访期间发生 T2DM。用 SPC 独立测量的脂肪变性分级和肝脏脂肪 (校正年龄、 BMI 、纤维化分期) 预测 T2DM 的发展,每级 aHR 分别为 1.60,每级 SPC 百分比增加 1.03。与较低等级的脂肪变性相比,3 级脂肪变性患者的总体死亡率和发展为 T2DM 更常见。SPC 测量的肝脏脂肪对总死亡率 (aHR 1.04) 有显著影响。在接受重复活检的患者中,SPC 测量的肝脏脂肪减少与发生 T2DM 的风险降低相关 (SPC 百分比每降低 0.91 的 aHR)。 结论: SPC 测量的脂肪变性分级和肝脏脂肪可预测 NAFLD 的死亡率和发展为 T2DM 的风险。减少肝脏脂肪可降低发生 T2DM 的风险。

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翻译标题与摘要 下载文献
影响因子:3.87
发表时间:2020-02-01
DOI:10.1111/liv.14321
作者列表:["Chen VL","Chen Y","Du X","Handelman SK","Speliotes EK"]

METHODS:BACKGROUND AND AIMS:Cirrhosis is characterized by extensive fibrosis of the liver and is a major cause of liver-related mortality. Cirrhosis is partially heritable but genetic contributions to cirrhosis have not been systemically explored. Here, we carry out association analyses with cirrhosis in two large biobanks and determine the effects of cirrhosis associated variants on multiple human disease/traits. METHODS:We carried out a genome-wide association analysis of cirrhosis as a diagnosis in UK BioBank (UKBB; 1088 cases vs. 407 873 controls) and then tested top-associating loci for replication with cirrhosis in a hospital-based cohort from the Michigan Genomics Initiative (MGI; 875 cases of cirrhosis vs. 30 346 controls). For replicating variants or variants previously associated with cirrhosis that also affected cirrhosis in UKBB or MGI, we determined single nucleotide polymorphism effects on all other diagnoses in UKBB (PheWAS), common metabolic traits/diseases and serum/plasma metabolites. RESULTS:Unbiased genome-wide association study identified variants in/near PNPLA3 and HFE, and candidate variant analysis identified variants in/near TM6SF2, MBOAT7, SERPINA1, HSD17B13, STAT4 and IFNL4 that reproducibly affected cirrhosis. Most affected liver enzyme concentrations and/or aspartate transaminase-to-platelet ratio index. PheWAS, metabolic trait and serum/plasma metabolite association analyses revealed effects of these variants on lipid, inflammatory and other processes including new effects on many human diseases and traits. CONCLUSIONS:We identified eight loci that reproducibly associate with population-based cirrhosis and define their diverse effects on human diseases and traits.

翻译标题与摘要 下载文献
影响因子:2.57
发表时间:2020-02-01
DOI:10.1111/eci.13198
作者列表:["Li H","Wieser A","Zhang J","Liss I","Markwardt D","Hornung R","Neumann-Cip AC","Mayerle J","Gerbes A","Steib CJ"]

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