Kronborg Thit Mynster, Gao Qian, Trošt Kajetan, Ytting Henriette, O'Connell Malene Barfod, Werge Mikkel Parsberg, Thing Mira, Gluud Lise Lotte, Hamberg Ole, Møller Søren, Moritz Thomas, Bendtsen Flemming, Kimer Nina
Gastro Unit, Medical Division, University Hospital Hvidovre, Hvidovre, Denmark.
Novo Nordisk Foundation Centre for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
JHEP Rep. 2023 Nov 1;6(2):100953. doi: 10.1016/j.jhepr.2023.100953. eCollection 2024 Feb.
BACKGROUND & AIMS: Alcohol-related hepatitis (AH) and alcohol-related cirrhosis are grave conditions with poor prognoses. Altered hepatic lipid metabolism can impact disease development and varies between different alcohol-related liver diseases. Therefore, we aimed to investigate lipidomics and metabolomics at various stages of alcohol-related liver diseases and their correlation with survival.
Patients with newly diagnosed alcohol-related cirrhosis, who currently used alcohol (ALC-A), stable outpatients with decompensated alcohol-related cirrhosis with at least 8 weeks of alcohol abstinence (ALC), and patients with AH, were compared with each other and with healthy controls (HC). Circulating lipids and metabolites were analysed using HPLC and mass spectrometry.
Forty patients with ALC, 95 with ALC-A, 30 with AH, and 42 HC provided plasma. Lipid levels changed according to disease severity, with generally lower levels in AH and cirrhosis than in the HC group; this was most pronounced for AH, followed by ALC-A. Nine out of 10 free fatty acids differed between cirrhosis groups by relative increases of 0.12-0.66 in ALC compared with the ALC-A group ( <0.0005). For metabolomics, total bile acids increased by 19.7, 31.3, and 80.4 in the ALC, ALC-A, and AH groups, respectively, compared with HC (all <0.0001). Low sphingolipid ([d42:1] and [d41:1]) levels could not predict 180-day mortality (AUC = 0.73, = 0.95 and AUC = 0.73, = 0.95) more accurately than the model for end-stage liver disease score (AUC = 0.71), but did predict 90-day mortality (AUC = 0.922, AUC = 0.893; = 0.005, = 0.007) more accurately than the MELD score AUC = 0.70, = 0.19).
Alcohol-related severe liver disease is characterised by low lipid levels progressing with severity of liver disease, especially low sphingomyelins, which also associate to poor prognoses.
Lipidomics has the potential to diagnose and risk stratify patients with liver diseases. Lipidomics differed between patients with alcohol-related hepatitis and alcohol-related cirrhosis with and without recent alcohol use. Furthermore, lipidomics could predict short-term mortality and might be suitable as a prognostic tool in the future.
Scientific Ethics Committee of the Capital Region of Denmark, journal no. H-21013476.
酒精性肝炎（AH）和酒精性肝硬化是预后不良的严重病症。肝脏脂质代谢的改变会影响疾病发展，且在不同的酒精性肝病中有所不同。因此，我们旨在研究酒精性肝病各个阶段的脂质组学和代谢组学及其与生存率的相关性。
将新诊断的酒精性肝硬化且目前仍在饮酒的患者（ALC-A）、戒酒至少8周的失代偿性酒精性肝硬化稳定门诊患者（ALC）以及AH患者相互比较，并与健康对照者（HC）进行比较。使用高效液相色谱法和质谱法分析循环脂质和代谢物。
40例ALC患者、95例ALC-A患者、30例AH患者和42例HC提供了血浆。脂质水平根据疾病严重程度而变化，AH和肝硬化患者的脂质水平通常低于HC组；AH患者最为明显，其次是ALC-A患者。与ALC-A组相比，肝硬化组中10种游离脂肪酸中有9种相对增加0.12 - 0.66（<0.0005）。对于代谢组学，与HC相比，ALC组、ALC-A组和AH组的总胆汁酸分别增加了19.7、31.3和80.4（均<0.0001）。低鞘脂（[d42:1]和[d41:1]）水平预测180天死亡率（AUC = 0.73，= 0.95和AUC = 0.73，= 0.95）并不比终末期肝病评分模型（AUC = 0.71）更准确，但预测90天死亡率（AUC = 0.922，AUC = 0.893；= 0.005，= 0.007）比终末期肝病模型评分（AUC = 0.70，= 0.19）更准确。
酒精性严重肝病的特征是脂质水平随着肝病严重程度的增加而降低，尤其是鞘磷脂水平低，这也与预后不良相关。
脂质组学有潜力对肝病患者进行诊断和风险分层。酒精性肝炎患者与近期饮酒或未饮酒的酒精性肝硬化患者的脂质组学存在差异。此外，脂质组学可以预测短期死亡率，未来可能适合作为一种预后工具。
丹麦首都地区科学伦理委员会，期刊编号H-21013476。
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