Hepatocyte-derived biomarkers predict liver-related events at 2 years in Child-Pugh class A alcohol-related cirrhosis

肝细胞 肝硬化 肝病 内科学 胃肠病学 角蛋白 酒精性肝病 医学 化学 内分泌学 病理 生物化学 体外
作者
Laure Elkrief,Nathalie Ganne‐Carrié,Hana Manceau,Marion Tanguy,Shantha Valainathan,Alix Riescher‐Tuczkiewicz,Louise Biquard,Nathalie Barget,Cendrine Chaffaut,Alexandre Louvet,Valérie Paradis,Marianne Ziol,Rikke Bæk,Maléne Møller Jørgensen,Guillaume van Niel,Pierre‐Michaël Coly,Adel Hammoutène,Fanny Dujardin,Katell Peoc’h,Thierry Poynard
出处
期刊:Journal of Hepatology [Elsevier BV]
卷期号:79 (4): 910-923 被引量:8
标识
DOI:10.1016/j.jhep.2023.05.025
摘要

In patients with compensated alcohol-related cirrhosis, reliable prognostic biomarkers are lacking. Keratin-18 and hepatocyte-derived large extracellular vesicles (lEVs) concentrations reflect disease activity, but their ability to predict liver-related events is unknown. Methods We measured plasma keratin-18 and hepatocyte lEVs concentrations in 500 patients with Child-Pugh class A alcohol-related cirrhosis. Ability of these hepatocyte-derived biomarkers, alone or combined with MELD and FibroTest, to predict liver-related events at 2 years was analyzed, taking into account the alcohol consumption at inclusion and during the follow-up. Results Keratin-18 and hepatocyte lEVs concentrations increased with alcohol consumption. In patients without active alcohol consumption at enrollment (n=419), keratin-18 concentration predicted liver-related events at 2 years, independently of FibroTest and MELD. Patients with both keratin-18 concentration >285 U/L and FibroTest >0.74 had a 24% cumulative incidence of liver-related events at 2 years, versus 5% to 14% in other groups of patients. Similar results were obtained when combining keratin-18 concentration >285 U/L with MELD >10. In patients with active alcohol consumption at enrollment (n=81), hepatocyte lEVs predicted liver-related events at 2 years, independently of FibroTest and MELD. Patients with both hepatocyte lEVs concentration >50 U/L and FibroTest>0.74 had a 62% cumulative incidence of liver-related events at 2 years, versus 8% to 13% in other groups of patients. Combining hepatocyte lEVs concentration >50 U/L with MELD >10 had a lower discrimination ability. Similar results were obtained using as endpoint decompensation of cirrhosis defined according Baveno VII criteria. Conclusion In patients with Child-Pugh class A alcohol-related cirrhosis, combining hepatocyte-derived biomarkers with FibroTest or MELD score identifies patients at high-risk of liver-related events, and could be used for risk stratification and patient selection in clinical trials.
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