Bile acids profile, histopathological indices and genetic variants for non-alcoholic fatty liver disease progression.
Bile acids profile, histopathological indices and genetic variants for non-alcoholic fatty liver disease progression.
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胆汁酸的特征，组织病理学指数和非酒精性脂肪肝脏疾病进展的遗传变异。
DOI：
10.1016/j.metabol.2020.154457
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Hazen SL
中科院分区：
文献类型：
--
作者：
Nimer N;Choucair I;Wang Z;Nemet I;Li L;Gukasyan J;Weeks TL;Alkhouri N;Zein N;Tang WHW;Fischbach MA;Brown JM;Allayee H;Dasarathy S;Gogonea V;Hazen SL
代谢组学研究表明，与健康对照相比，非酒精性脂肪性肝病（NAFLD）受试者的胆汁酸（BA）血浆水平升高。然而，目前尚不清楚特异性BA是否与从非酒精性脂肪肝（即单纯性脂肪变性）到非酒精性脂肪性肝炎（NASH）的临床相关转变，或肝纤维化的加速进展，或NAFLD/NASH的遗传决定因素相关。在接受诊断性肝活检的连续受试者（n=102）中，我们检查了一组广泛的BA与NAFLD的不同组织病理学特征、NASH的存在及其与NAFLD和NASH相关的遗传变异的相关性。在整个NAFLD谱中观察到血浆BA改变，其中几种甘氨酸缀合形式的BA显示与更高级别的炎症和纤维化显著相关。血浆7-Keto-DCA水平显示与晚期肝纤维化最强的相关性[比值比（95%置信区间）]，4.2（1.2-16.4），NASH 24.5（4.1-473）和气球样变18.7（4.8-91.9）。血浆7-酮-LCA水平与NASH 9.4（1.5-185）和气球样变5.9（1.4-28.8）相关。几个NAFLD/NASH基因座的遗传变异与7-酮和甘氨酸结合形式的BA水平增加名义上相关，TRIB 1基因座的NAFLD风险等位基因显示出GCA（p=0.02）和GUDCA（p=0.009）血浆水平增加的强烈趋势。循环胆汁酸水平与单纯性脂肪肝向NASH转变的组织病理学和遗传决定因素相关。需要进一步研究探索胆汁酸代谢在NASH不同组织病理学特征的发生和/或进展中的潜在参与。
Metabolomic studies suggest plasma levels of bile acids (BAs) are elevated amongst subjects with non-alcoholic fatty liver disease (NAFLD) compared to healthy controls. However, it remains unclear whether or not specific BAs are associated with the clinically relevant transition from nonalcoholic fatty liver (i.e. simple steatosis) to non-alcoholic steatohepatitis (NASH), or enhanced progression of hepatic fibrosis, or genetic determinants of NAFLD/NASH. Among sequential subjects (n=102) undergoing diagnostic liver biopsy, we examined the associations of a broad panel of BAs with distinct histopathological features of NAFLD, the presence of NASH, and their associations with genetic variants linked to NAFLD and NASH. Plasma BA alterations were observed through the entire spectrum of NAFLD, with several glycine conjugated forms of the BAs demonstrating significant associations with higher grades of inflammation and fibrosis. Plasma 7-Keto-DCA levels showed the strongest associations with advanced stages of hepatic fibrosis [odds ratio(95% confidence interval)], 4.2(1.2–16.4), NASH 24.5(4.1–473), and ballooning 18.7(4.8–91.9). Plasma 7-Keto-LCA levels were associated with NASH 9.4(1.5–185) and ballooning 5.9(1.4–28.8). Genetic variants at several NAFLD/NASH loci were nominally associated with increased levels of 7-Keto- and glycine-conjugated forms of BAs, and the NAFLD risk allele at the TRIB1 locus showed strong tendency toward increased plasma levels of GCA (p=0.02) and GUDCA (p=0.009). Circulating bile acid levels are associated with histopathological and genetic determinants of the transition from simple hepatic steatosis into NASH. Further studies exploring the potential involvement of bile acid metabolism in the development and/or progression of distinct histopathological features of NASH are warranted.
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DOI：
10.1097/meg.0b013e328345c8c7
发表时间：
2011-05
影响因子：
2.1
作者：
Dasarathy S;Yang Y;McCullough AJ;Marczewski S;Bennett C;Kalhan SC
通讯作者：
Kalhan SC
影响因子：
5.1
作者：
Brouwers, Martijn C. G. J.;Simons, Nynke;Isaacs, Aaron
通讯作者：
Isaacs, Aaron
影响因子：
9.8
作者：
Buzzetti, Elena;Pinzani, Massimo;Tsochatzis, Emmanuel A.
通讯作者：
Tsochatzis, Emmanuel A.
影响因子：
13.5
作者：
Bechmann, Lars P.;Kocabayoglu, Peri;Canbay, Ali
通讯作者：
Canbay, Ali
胆汁酸、肥胖和代谢综合征。
影响因子：
3.2
作者：
Ma, Huijuan;Patti, Mary Elizabeth
通讯作者：
Patti, Mary Elizabeth