Blood Biomarkers of Intestinal Epithelium Damage Regenerating Islet-derived Protein 3α and Trefoil Factor 3 Are Persistently Elevated in Patients with Alcoholic Hepatitis.
Blood Biomarkers of Intestinal Epithelium Damage Regenerating Islet-derived Protein 3α and Trefoil Factor 3 Are Persistently Elevated in Patients with Alcoholic Hepatitis.
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DOI：
10.1111/acer.14579
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发表时间：
2021-04
期刊：
影响因子：
--
通讯作者：
Li W
中科院分区：
文献类型：
--
作者：
Yang J;Syed F;Xia Y;Sanyal AJ;Shah VH;Chalasani N;Zheng X;Yu Q;Lou Y;Li W
酒精滥用会破坏肠道上皮细胞的完整性，导致胃肠道通透性增加，进而导致微生物移位。再生胰岛衍生蛋白3α(REG3α)和三叶因子3(TFF3)分别主要由胰岛细胞和杯状细胞分泌到肠腔，在功能上与肠道屏障的完整性有关。循环中的REG3、α和TFF3水平已被确定为几种人类疾病中肠道损伤的生物标志物。我们的目的是确定在伴有和不伴有酒精性肝炎(AH)的酗酒者中，血浆REG3、α和TFF3水平是否失调，并与微生物易位(MT)和促炎介质的传统标记物相关。对79例AH患者、66例无肝病的酗酒者和46例健康对照(HC)在登记时、6个月和12个月随访时进行了横断面和纵向研究，以监测血浆中α和TFF3的水平。用Spearman相关分析研究α和TFF3水平与MT、疾病严重程度、炎症和戒酒效果的关系。在登记时，AH患者的REG3、α和TFF3水平显著高于HDC和HC。REG3α水平升高与30天病死率呈正相关。AH患者血浆REG3、α和TFF3水平与传统的MT标志物(sCD14、sCD163和LBP)以及几种高度上调的炎性细胞因子/趋化因子/生长因子存在差异相关。在随访中，酒精戒断的AH患者的REG3α和TFF3水平有所下降，但并未完全恢复到基线水平。α和TFF3水平在AH患者中显著升高，并且与AH疾病严重程度、MT和炎症显著相关，因此可作为AH患者MT和肠上皮损伤的潜在生物标志物。
Alcohol abuse disrupts gut epithelial integrity, leading to increased permeability of the gastrointestinal tract and subsequent translocation of microbes. Regenerating islet-derived protein 3α (REG3α) and Trefoil factor 3 (TFF3) are mainly secreted to the gut lumen by Paneth and Goblet cells, respectively, and are functionally linked to gut barrier integrity. Circulating levels of REG3α and TFF3 have been identified as biomarkers for gut damage in several human diseases. We aimed to identify whether plasma levels of REG3α and TFF3 were dysregulated and correlated with conventional markers of microbial translocation (MT) and pro-inflammatory mediators in heavy drinkers with and without alcoholic hepatitis (AH). Cross-sectional and longitudinal studies were performed to monitor plasma levels of REG3α and TFF3 in 79 AH patients, 66 heavy drinkers without liver disease (HDC), and 46 healthy controls (HC) at enrollment, 6- and 12-month follow-ups. Spearman correlation was carried out to study the relationships of REG3α and TFF3 levels with MT, disease severity, inflammation, and alcohol abstinent effects. At enrollment, AH patients had significantly higher levels of REG3α and TFF3 than HDC and HC. The elevated REG3α levels positively correlated to the 30-day fatality rate. Plasma levels of REG3α and TFF3 in AH patients differentially correlated with conventional MT markers (sCD14, sCD163, and LBP) and several highly up-regulated inflammatory cytokines/chemokines/growth factors. At follow-ups, REG3α and TFF3 levels were decreased in AH patients with alcohol abstinence, but did not fully return to baseline levels. Circulating levels of REG3α and TFF3 were highly elevated in AH patients and differentially correlated with AH disease severity, MT, and inflammation, thereby serving as potential biomarkers of MT and gut epithelial damage in AH patients.
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发表时间：
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ALCOHOL-CLINICAL AND EXPERIMENTAL RESEARCH
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