Serum HMGB1 associates with liver disease and predicts readmission and mortality in patients with alcohol use disorder.
Serum HMGB1 associates with liver disease and predicts readmission and mortality in patients with alcohol use disorder.
复制标题
血清 HMGB1 与肝脏疾病相关，可预测酒精使用障碍患者的再入院和死亡率。
DOI：
10.1016/j.alcohol.2021.05.003
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Luther,Jay
中科院分区：
文献类型：
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作者：
Vannier,AugustinGL;Wardwell,Ben;Fomin,Vladislav;PeBenito,Amanda;Wolczynski,Nicholas;Piaker,Samuel;Kedrin,Dmitriy;Chung,RaymondT;Schaefer,Esperance;Goodman,Russell;Patel,SurajJ;Luther,Jay
确定少数酒精使用障碍（AUD）患者发展为广泛的酒精相关性肝病（ALD），并对这些患者进行风险分层至关重要。高迁移率族蛋白1（HMGB 1）是一种与多种肝脏疾病的发病机制有关的警报蛋白。其作为AUD患者肝脏疾病的生物标志物的用途尚未研究。在这份报告中，我们研究了血清HMGB 1和ALD的存在，严重程度和进展之间的关系，在两个良好的特征性队列的AUD患者。在我们的80例患者的发现队列中，我们发现与仅患有AUD的患者相比，患有AUD和ALD的患者表现出更高的血清HMGB 1水平（p= 0.0002）。此外，血清HMGB 1水平与肝病严重程度呈正相关（p< 0.0001）。我们发现，指数血清HMGB 1水平与肝脏疾病进展相关，定义为120天时MELD评分增加（p= 0.0397）。血清HMGB 1以其诊断和预后能力而闻名;在我们的发现队列（AUC = 0.8199，p = 0.0003）和74例AUD患者的独立验证队列（AUC = 0.8818，p < 0.0001）中，它被证明能够准确区分重度和非重度ALD。此外，血清HMGB 1水平能有效预测90天时肝脏相关再入院（AUC = 0.8849，p < 0.0001）和移植/死亡（AUC = 0.8614，p = 0.0002）。HMGB 1的预测潜力也在一个独立的AUD患者队列中得到验证。综上所述，我们的研究结果表明，血清HMGB 1有望成为AUD患者ALD的生物学相关生物标志物。
Identifying the minority of patients with alcohol use disorder (AUD) who develop the wide spectrum of alcohol-associated liver disease (ALD), and risk-stratifying these patients, is of critical importance. High-Mobility Group Box 1 protein (HMGB1) is an alarmin that has been implicated in the pathogenesis of multiple liver diseases. Its use as a biomarker for liver disease in those with AUD has not been studied. In this report, we investigated the association between serum HMGB1 and the presence, severity, and progression of ALD in two well-characterized cohorts of patients with AUD. In our discovery cohort of 80 patients, we found that patients with AUD and ALD exhibited higher serum HMGB1 levels compared to patients with AUD only (p= 0.0002). Additionally, serum HMGB1 levels were positively associated with liver disease severity (p< 0.0001). We found that index serum HMGB1 levels were associated with liver disease progression, defined by an increase in MELD score at 120 days (p= 0.0397). Serum HMGB1 was notable for its diagnostic and prognostic ability; it proved able to distinguish accurately between severe and non-severe forms of ALD in both our discovery cohort (AUC = 0.8199,p= 0.0003) and an independent validation cohort of 74 patients with AUD (AUC = 0.8818,p< 0.0001). Moreover, serum HMGB1 levels effectively predicted both liver-related readmission (AUC = 0.8849,p< 0.0001) and transplantation/death (AUC = 0.8614,p= 0.0002) at 90 days. The predictive potential of HMGB1 was also validated in an independent cohort of patients with AUD. Taken together, our results suggest that serum HMGB1 shows promise as a biologically relevant biomarker for ALD in patients with AUD.