HDL-related biomarkers are robust predictors of survival in patients with chronic liver failure

JOURNAL OF HEPATOLOGY

卷:73

Article

Trieb, Markus^1,2  Rainer, Florian³  Stadlbauer, Vanessa³  Douschan, Philipp⁴  Horvath, Angela^3,5  Binder, Lukas³  Trakaki, Athina¹  Knuplez, Eva¹  Scharnagl, Hubert⁶  Stojakovic, Tatjana⁷  Heinemann, Akos¹  Mandorfer, Mattias^8,9  Paternostro, Rafael^8,9  Reiberger, Thomas^8,9  Pitarch, Carla¹⁰  Amoros, Alex¹⁰  Gerbes, Alexander¹¹  Caraceni, Paolo^10,12  Alessandria, Carlo^10,13  Moreau, Richard^10,14,15  Claria, Joan^10,16,17  Marsche, Gunther^1,2  Stauber, Rudolf E.³ 

[1] Med Univ Graz, Otto Loewi Res Ctr, Div Pharmacol, Univ Pl 4, A-8010 Graz, Austria

[2] BioTechMed Graz, Graz, Austria

[3] Med Univ Graz, Dept Internal Med, Div Gastroenterol & Hepatol, Auenbruggerpl 15, A-8036 Graz, Austria

[4] Med Univ Graz, Dept Internal Med, Div Pulmonol, Graz, Austria

[5] Ctr Biomarker Res Med CBmed, Graz, Austria

[6] Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, Graz, Austria

[7] Univ Hosp Graz, Clin Inst Med & Chem Lab Diagnost, Graz, Austria

[8] Med Univ Vienna, Dept Internal Med 3, Div Gastroenterol & Hepatol, Vienna, Austria

[9] Med Univ Vienna, Vienna Hepat Hemodynam Lab, Vienna, Austria

[10] European Fdn Study Chron Liver Failure EF Clif, Barcelona, Spain

[11] Ludwig Maximilians Univ Munchen, Univ Hosp, Dept Med 2, Munich, Germany

[12] Univ Bologna, Dept Med & Surg Sci, Bologna, Italy

[13] Univ Turin, Citta Salute & Sci Hosp, Div Gastroenterol & Hepatol, Turin, Italy

[14] Univ Paris, Ctr Rech Inflammat, INSERM, Paris, France

[15] Hop Beaujon, AP HP, Serv Hepatol, Clichy, France

[16] IDIBAPS, Hosp Clin, Barcelona, Spain

[17] CIBERehd, Barcelona, Spain

关键词: HDL;    apoA-I;    MELD score;    ACLF;    Inflammation;   

DOI  :  10.1016/j.jhep.2020.01.026

来源: Elsevier

【 摘 要 】

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. Methods: 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. Results: 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). Conclusion: HDL-related biomarkers are robust predictors of disease progression and survival in chronic liver failure. Lay summary: 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. (C) 2020 European Association for the Study of the Liver. Published by Elsevier B.V.

【 授权许可】

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