Circulating Citrate Is Associated with Liver Fibrosis in Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis.
Circulating Citrate Is Associated with Liver Fibrosis in Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis.
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循环柠檬酸盐与非酒精性脂肪肝病和非酒精性脂肪性肝炎中的肝纤维化有关。
DOI：
10.3390/ijms241713332
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发表时间：
2023-08-28
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
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作者：
非酒精性脂肪肝（NAFLD）与线粒体损伤有关。循环线粒体代谢物可能在NAFLD中升高，但其与肝损伤的关系尚不清楚。本研究旨在评估关键线粒体代谢物与NAFLD和非酒精性脂肪性肝炎（NASH）背景下肝纤维化程度的相关性。对活检证实的NAFLD和/或NASH受试者的两个队列进行了横断面分析。使用线性回归分析评估循环线粒体代谢物浓度与肝纤维化的相关性。在NAFLD受试者的单中心队列中（n = 187），平均年龄为54.9 ±13.0岁，40.1%为女性，86.1%为白色。2型糖尿病（51.3%）、高血压（43.9%）和肥胖（72.2%）是高发人群。高柠檬酸盐水平的患者中中度/显著肝纤维化（F ≥ 2期）（68.4 vs. 39.6%，p = 0.001）和晚期纤维化（F ≥ 3期）（31.6 vs. 13.6%，p = 0.01）的比例较高。柠檬酸盐与肝纤维化相关，与年龄、性别、NAFLD活动评分和代谢综合征无关（每增加1个SD：β = 0.19，95% CI：0.03-0.35，p = 0.02）。在NASH受试者队列（n = 176）中也观察到这种相关性（β = 0.21，95% CI：0.07-0.36，p = 0.005）。在雄性动物（p = 0.005）中观察到柠檬酸盐与肝纤维化相关，但在雌性动物（p = 0.41）中未观察到。总之，循环柠檬酸盐升高并与肝纤维化相关，特别是在NAFLD和NASH男性受试者中。线粒体功能可能是减少肝纤维化和NASH进展的一个考虑目标。
Nonalcoholic fatty liver disease (NAFLD) is associated with mitochondrial damage. Circulating mitochondrial metabolites may be elevated in NAFLD but their associations with liver damage is not known. This study aimed to assess the association of key mitochondrial metabolites with the degree of liver fibrosis in the context of NAFLD and nonalcoholic steatohepatitis (NASH). Cross-sectional analyses were performed on two cohorts of biopsy-proven NAFLD and/or NASH subjects. The association of circulating mitochondrial metabolite concentrations with liver fibrosis was assessed using linear regression analysis. In the single-center cohort of NAFLD subjects (n = 187), the mean age was 54.9 ±13.0 years, 40.1% were female and 86.1% were White. Type 2 diabetes (51.3%), hypertension (43.9%) and obesity (72.2%) were prevalent. Those with high citrate had a higher proportion of moderate/significant liver fibrosis (stage F ≥ 2) (68.4 vs. 39.6%, p = 0.001) and advanced fibrosis (stage F ≥ 3) (31.6 vs. 13.6%, p = 0.01). Citrate was associated with liver fibrosis independent of age, sex, NAFLD activity score and metabolic syndrome (per 1 SD increase: β = 0.19, 95% CI: 0.03–0.35, p = 0.02). This association was also observed in a cohort of NASH subjects (n = 176) (β = 0.21, 95% CI: 0.07–0.36, p = 0.005). The association of citrate with liver fibrosis was observed in males (p = 0.005) but not females (p = 0.41). In conclusion, circulating citrate is elevated and associated with liver fibrosis, particularly in male subjects with NAFLD and NASH. Mitochondrial function may be a target to consider for reducing the progression of liver fibrosis and NASH.
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影响因子：
6.7
作者：
Damba, Turtushikh;Bourgonje, Arno R.;Moshage, Han
通讯作者：
Moshage, Han
影响因子：
16.2
作者：
Sacks DB;Arnold M;Bakris GL;Bruns DE;Horvath AR;Kirkman MS;Lernmark A;Metzger BE;Nathan DM;National Academy of Clinical Biochemistry;Evidence-Based Laboratory Medicine Committee of the American Association for Clinical Chemistry
通讯作者：
Evidence-Based Laboratory Medicine Committee of the American Association for Clinical Chemistry
影响因子：
13.5
作者：
Kleiner, DE;Brunt, EM;Sanyal, AJ
通讯作者：
Sanyal, AJ
DOI：
10.1111/liv.13076
发表时间：
2016-08
期刊：
Liver international : official journal of the International Association for the Study of the Liver
影响因子：
--
作者：
Jiang ZG;Tapper EB;Connelly MA;Pimentel CF;Feldbrügge L;Kim M;Krawczyk S;Afdhal N;Robson SC;Herman MA;Otvos JD;Mukamal KJ;Lai M
通讯作者：
Lai M
影响因子：
3.9
作者：
Garcia, Erwin;Shalaurova, Irina;Connelly, Margery A.
通讯作者：
Connelly, Margery A.