BACKGROUND & AIMS The occurrence of acute decompensation (AD) worsens the prognosis of advanced chronic liver disease (ACLD). Various insults leading to increased systemic inflammation trigger acute-on-chronic liver failure (ACLF) with dramatically increased short-term mortality. During acute conditions such as sepsis, high-density lipoprotein cholesterol (HDL-C) levels decrease rapidly and HDL particles undergo profound changes in their composition and function. Indices of HDL quantity and quality may therefore associate with progression and survival in patients with advanced liver disease. METHODS We studied levels of HDL-cholesterol (HDL-C), its subclasses HDL2-C and HDL3-C, and apolipoprotein(apo)A-I as indices of HDL quantity and HDL cholesterol efflux capacity as a metric of HDL functionality in 508 patients with compensated or decompensated cirrhosis including ACLF and 40 age- and gender-matched controls. RESULTS Baseline levels of HDL-C and apoA-I were significantly lower in stable cirrhosis compared to control and further decreased in AD and ACLF. In stable cirrhosis (n=228), both HDL-C and apoA-I predicted the development of liver-related complications independently of MELD. In patients with AD with or without ACLF (n=280) both HDL-C and apoA-I were MELD-independent predictors of 90-day mortality. On ROC analysis, high diagnostic accuracies for 90-day mortality in AD patients were found for HDL-C (AUROC 0.79) and apoA-I (AUROC 0.80), very similar to that of MELD (AUROC 0.81). On Kaplan-Meier analysis, HDL-C <17 mg/dl and apoA-I <50 mg/dl indicated poor short-term survival. The prognostic accuracy of HDL-C was validated in a large external validation cohort of 985 patients with portal hypertension due to ACLD (AUROCs HDL-C: 0.81 vs. MELD: 0.77). CONCLUSION HDL-related biomarkers are robust predictors of disease progression and survival in chronic liver failure.

中文翻译：

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HDL 相关生物标志物是慢性肝功能衰竭患者生存的有力预测因子

背景与目的 急性失代偿（AD）的发生使晚期慢性肝病（ACLD）的预后恶化。导致全身炎症增加的各种损伤引发急性加慢性肝衰竭 (ACLF)，短期死亡率显着增加。在败血症等急性疾病中，高密度脂蛋白胆固醇 (HDL-C) 水平迅速下降，HDL 颗粒的组成和功能发生了深刻变化。因此，HDL 数量和质量的指标可能与晚期肝病患者的进展和生存相关。方法 我们研究了 HDL-胆固醇 (HDL-C) 及其亚类 HDL2-C 和 HDL3-C 的水平，和载脂蛋白（apo）AI 作为 HDL 数量的指标，HDL 胆固醇流出能力作为 508 名代偿性或失代偿性肝硬化患者（包括 ACLF 和 40 名年龄和性别匹配的对照）的 HDL 功能指标。结果 与对照组相比，稳定期肝硬化患者的 HDL-C 和 apoA-I 基线水平显着降低，而 AD 和 ACLF 患者的基线水平进一步降低。在稳定期肝硬化 (n=228) 中，HDL-C 和 apoA-I 均可独立于 MELD 预测肝脏相关并发症的发生。在伴有或不伴有 ACLF 的 AD 患者（n=280）中，HDL-C 和 apoA-I 都是 MELD 独立的 90 天死亡率预测因子。在 ROC 分析中，发现 HDL-C (AUROC 0.79) 和 apoA-I (AUROC 0.80) 对 AD 患者 90 天死亡率的诊断准确度很高，与 MELD (AUROC 0.81) 非常相似。在 Kaplan-Meier 分析中，HDL-C <17 mg/dl 和 apoA-I <50 mg/dl 表明短期存活率较差。HDL-C 的预后准确性在 985 名 ACLD 导致的门静脉高压患者的大型外部验证队列中得到验证（AUROC HDL-C：0.81 vs. MELD：0.77）。结论 HDL 相关生物标志物是慢性肝功能衰竭疾病进展和生存的有力预测因子。