Division of Pharmacology, Otto Loewi Research Center, Medical University of Graz, Graz, Austria; BioTechMed-Graz, Graz, Austria.
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
J Hepatol. 2020 Jul;73(1):113-120. doi: 10.1016/j.jhep.2020.01.026. Epub 2020 Feb 14.
BACKGROUND & AIMS: High-density lipoprotein cholesterol (HDL-C) levels are reduced in patients with chronic liver disease and inversely correlate with disease severity. During acute conditions such as sepsis, HDL-C levels decrease rapidly and HDL particles undergo profound changes in their composition and function. We aimed to determine whether indices of HDL quantity and quality associate with progression and survival in patients with advanced liver disease.
HDL-related biomarkers were studied in 508 patients with compensated or decompensated cirrhosis (including acute-on-chronic liver failure [ACLF]) and 40 age- and gender-matched controls. Specifically, we studied levels of HDL-C, its subclasses HDL2-C and HDL3-C, and apolipoprotein A1 (apoA-I), as well as HDL cholesterol efflux capacity as a metric of HDL functionality.
Baseline levels of HDL-C and apoA-I were significantly lower in patients with stable cirrhosis compared to controls and were further decreased in patients with acute decompensation (AD) and ACLF. In stable cirrhosis (n = 228), both HDL-C and apoA-I predicted the development of liver-related complications independently of model for end-stage liver disease (MELD) score. 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, both HDL-C and apoA-I had high diagnostic accuracy for 90-day mortality in patients with AD (AUROCs of 0.79 and 0.80, respectively, similar to that of MELD 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 advanced chronic liver disease (AUROCs HDL-C: 0.81 vs. MELD: 0.77).
HDL-related biomarkers are robust predictors of disease progression and survival in chronic liver failure.
People who suffer from cirrhosis (scarring of the liver) have low levels of cholesterol carried by high-density lipoproteins (HDL-C). These alterations are connected to inflammation, which is a problem in severe liver disease. Herein, we show that reduced levels of HDL-C and apolipoprotein A-I (apoA-I, the main protein carried by HDL) are closely linked to the severity of liver failure, its complications and survival. Both HDL-C and apoA-I can be easily measured in clinical laboratories and are as good as currently used prognostic scores calculated from several laboratory values by complex formulas.
高密度脂蛋白胆固醇（HDL-C）水平在慢性肝病患者中降低，并与疾病严重程度呈负相关。在脓毒症等急性情况下，HDL-C 水平迅速下降，HDL 颗粒的组成和功能发生深刻变化。我们旨在确定 HDL 数量和质量的指标是否与晚期肝病患者的进展和生存相关。
在 508 例代偿性或失代偿性肝硬化（包括慢加急性肝衰竭[ACLF]）患者和 40 名年龄和性别匹配的对照者中研究了与 HDL 相关的生物标志物。具体而言，我们研究了 HDL-C、其亚类 HDL2-C 和 HDL3-C 以及载脂蛋白 A1（apoA-I）的水平，以及作为 HDL 功能的指标的 HDL 胆固醇外排能力。
与对照组相比，稳定肝硬化患者的基线 HDL-C 和 apoA-I 水平显著降低，急性失代偿（AD）和 ACLF 患者的水平进一步降低。在稳定肝硬化（n=228）中，HDL-C 和 apoA-I 均独立于终末期肝病模型（MELD）评分预测肝相关并发症的发生。在有或没有 ACLF 的 AD 患者（n=280）中，HDL-C 和 apoA-I 均是 90 天死亡率的 MELD 独立预测因子。在 ROC 分析中，HDL-C 和 apoA-I 在 AD 患者的 90 天死亡率诊断准确性均较高（AUROCs 分别为 0.79 和 0.80，与 MELD 0.81 相似）。在 Kaplan-Meier 分析中，HDL-C<17mg/dl 和 apoA-I<50mg/dl 表明短期生存率较差。在由晚期慢性肝病引起的门静脉高压的 985 例患者的大型外部验证队列中验证了 HDL-C 的预后准确性（AUROCs HDL-C：0.81 vs. MELD：0.77）。
HDL 相关生物标志物是慢性肝衰竭患者疾病进展和生存的可靠预测因子。
患有肝硬化（肝脏瘢痕）的人，其高密度脂蛋白（HDL）携带的胆固醇水平较低。这些改变与炎症有关，炎症是严重肝脏疾病的一个问题。在此，我们表明，HDL-C 和载脂蛋白 A-I（apoA-I，HDL 携带的主要蛋白质）水平降低与肝功能衰竭的严重程度、其并发症和生存率密切相关。HDL-C 和 apoA-I 均可在临床实验室中轻松测量，并且与目前使用的基于复杂公式从多个实验室值计算得出的预后评分一样好。
