Theragnostic Efficacy of K18 Response in Alcohol Use Disorder with Clinically Significant Fibrosis Using Gut-Liver Axis.
Theragnostic Efficacy of K18 Response in Alcohol Use Disorder with Clinically Significant Fibrosis Using Gut-Liver Axis.
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DOI：
10.3390/ijms23105852
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发表时间：
2022-05-23
影响因子：
5.6
通讯作者：
Vatsalya, Vatsalya
中科院分区：
文献类型：
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作者：
Sagaram, Manasa;Parthasarathy, Ranganathan;Condon, Sally L.;Closson, Charles F.;Kong, Maiying;Schwandt, Melanie L.;Jophlin, Loretta L.;Feng, Wenke;Barve, Ashutosh J.;Vatsalya, Vatsalya
(1) 背景：早期酒精相关性肝病 (ALD) 中的纤维化在常规临床实践中通常诊断不足。这项研究描述了患有 ALD 的酒精使用障碍 (AUD) 患者的肝损伤和细胞死亡反应，这些患者也表现出纤维化，并评估了标准护理 (SOC) 治疗在改善肝损伤方面的功效。 (2)方法：48例年龄21-65岁的重度饮酒AUD患者。无肝损伤临床表现的患者按纤维化-4（FIB-4）评分分为阴性（Gr.1 < 1.45，n = 21）或阳性（Gr.2 ≥ 1.45，n = 27）。患者接受为期 2 周 (2 w) 的住院 SOC。在基线 (BL) 和 2 周 SOC 后分析人口统计、饮酒模式、肝损伤、免疫标记物和肝细胞死亡 (K18s) 标记物的数据。 (3) 结果：Gr.2 的终生饮酒（LTDH，年）和急性重度饮酒（过去 90 天的大量饮酒天数 [HDD90]）标记明显高于 Gr.1。 BL ALT、AST、AST:ALT 和 K18M65 在第 2 组中显着较高。 Gr.2 中肠道功能失调和免疫活性升高很明显，其特征是 TNF-α、IL-8 和 LPS 水平。 SOC后，Gr.2显示AST、ALT、AST/ALT比值有所改善；以及 K18M65、K18M30 和 K18M65/M30 比率与 Gr.1 的比较。与 2 周 SOC 后未改善的患者相比，BL IL-8 反应预测 Gr.2 患者 K18M65 改善至正常水平的真实阳性率非常高 (AUROC = 0.830，p = 0.042)。 (4)结论：早期ALD AUD患者肠道功能障碍、细胞因子反应升高和坏死性肝细胞死亡升高。 K18有望作为一种预测治疗诊断因素，通过基线IL-8水平区分患有早期ALD和基线纤维化的AUD患者，这些患者的肝损伤有改善，而肝损伤没有改善。
(1) Background: Fibrosis in early-stage alcohol-associated liver disease (ALD) is commonly under-diagnosed in routine clinical practice. This study characterized the liver-injury and cell death response in alcohol use disorder (AUD) patients with ALD who also exhibited fibrosis and assessed the efficacy of standard of care (SOC) treatment in the improvement in liver injury. (2) Methods: Forty-eight heavy-drinking AUD patients aged 21–65 yrs. without clinical manifestations of liver injury were grouped by Fibrosis-4 (FIB-4) score, as negative (Gr.1 < 1.45, n = 21) or positive (Gr.2 ≥ 1.45, n = 27). Patients received 2-weeks (2 w) inpatient SOC. Data on demographics, drinking patterns, liver-injury, immune markers, and liver cell death (K18s) markers were analyzed at baseline (BL) and after 2 w SOC. (3) Results: Lifetime drinking (LTDH, yrs.) and acute heavy drinking (Heavy Drinking Days Past 90 Days [HDD90]) markers were significantly higher in Gr.2 vs. Gr.1. BL ALT, AST, AST:ALT and K18M65 were considerably higher in Gr.2. Dysregulated gut dysfunction and elevated immune activity were evident in Gr.2 characterized by TNF-α, IL-8 and LPS levels. After SOC, Gr.2 showed improvement in AST, ALT, AST/ALT ratio; and in the K18M65, K18M30 and K18M65/M30 ratio vs. Gr.1. The true positivity of BL IL-8 response to predict the improvement in K18M65 to normal levels among Gr.2 patients against those who did not have improvement after 2 w SOC was very high (AUROC = 0.830, p = 0.042). (4) Conclusions: Gut dysfunction, elevated cytokine response and necrotic liver cell death were elevated in AUD patients with early-stage ALD. K18 showed promise as a predictive theragnostic factor to differentiate among the AUD patients with early-stage ALD and baseline fibrosis who had improvement in liver injury against those who did not, by the levels of baseline IL-8.
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影响因子：
4.6
作者：
Kawaratani H;Tsujimoto T;Douhara A;Takaya H;Moriya K;Namisaki T;Noguchi R;Yoshiji H;Fujimoto M;Fukui H
通讯作者：
Fukui H
影响因子：
24.5
作者：
Bellentani, S;Saccoccio, G;Sassatelli, R
通讯作者：
Sassatelli, R
影响因子：
3.7
作者：
Lasiglie, Denise;Traggiai, Elisabetta;Gattorno, Marco
通讯作者：
Gattorno, Marco
影响因子：
24.1
作者：
通讯作者：
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影响因子：
12.4
作者：
Hu, Yiming;Zhang, Haohao;Xie, Ningxia;Liu, Dandan;Jiang, Yuhang;Liu, Zhi;Ye, Deji;Liu, Sanhong;Chen, Xi;Li, Cuifeng;Wang, Qi;Huang, Xingxu;Liu, Yongzhong;Shi, Yufang;Zhang, Xiaoren
通讯作者：
Zhang, Xiaoren