Title :

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

Author(s) :

Elkrief, Laure [Auteur]
Centre de recherche sur l'Inflammation [CRI (UMR_S_1149 / ERL_8252 / U1149)]
Ganne-Carrié, Nathalie [Auteur]
UFR Santé, Médecine et Biologie Humaine [UFR SMBH]
Manceau, Hana [Auteur]
Centre de recherche sur l'Inflammation [CRI (UMR_S_1149 / ERL_8252 / U1149)]
Tanguy, Marion [Auteur]
Centre de recherche sur l'Inflammation [CRI (UMR_S_1149 / ERL_8252 / U1149)]
Valainathan, Shantha Ram [Auteur]
Centre de recherche sur l'Inflammation [CRI (UMR_S_1149 / ERL_8252 / U1149)]
Riescher-Tuczkiewicz, Alix [Auteur]
Centre de recherche sur l'Inflammation [CRI (UMR_S_1149 / ERL_8252 / U1149)]
Biquard, Louise [Auteur]
Centre de recherche sur l'Inflammation [CRI (UMR_S_1149 / ERL_8252 / U1149)]
Barget, Nathalie [Auteur]
Centre de Ressources Biologiques [Paris]
Chaffaut, Cendrine [Auteur]
Epidemiology and Clinical Statistics for Tumor, Respiratory, and Resuscitation | Epidémiologie Clinique, STatistique, pour la Recherche en Santé [ECSTRRA [CRESS - U1153 / UMR_A 1125]]
Louvet, Alexandre [Auteur]
Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
Paradis, Valérie [Auteur]
Centre de recherche sur l'Inflammation [CRI (UMR_S_1149 / ERL_8252 / U1149)]
Ziol, Marianne [Auteur]
Université Sorbonne Paris Cité [USPC]
Bæk, Rikke [Auteur]
Jørgensen, Malene Møller [Auteur]
Van Niel, Guillaume [Auteur]
Institut de psychiatrie et neurosciences de Paris [IPNP - U1266 Inserm]
Coly, Pierre-Michael [Auteur]
Institut de psychiatrie et neurosciences de Paris [IPNP - U1266 Inserm]
Hammoutène, Adel [Auteur]
Centre de recherche sur l'Inflammation [CRI (UMR_S_1149 / ERL_8252 / U1149)]
Dujardin, Fanny [Auteur]
CHU Trousseau [Tours]
Peoc'h, Katell [Auteur]
Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)]
Poynard, Thierry [Auteur]
BioPredictive [Paris]
Chevret, Sylvie [Auteur]
Epidemiology and Clinical Statistics for Tumor, Respiratory, and Resuscitation | Epidémiologie Clinique, STatistique, pour la Recherche en Santé [ECSTRRA [CRESS - U1153 / UMR_A 1125]]
Rautou, Pierre-Emmanuel [Auteur]
Centre de recherche sur l'Inflammation [CRI (UMR_S_1149 / ERL_8252 / U1149)]

Journal title :

Journal of Hepatology

Abbreviated title :

J Hepatol

Volume number :

79

Pages :

P910-923

Publication date :

2023-06-13

ISSN :

1600-0641

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

In patients with compensated alcohol-related cirrhosis, reliable prognostic biomarkers are lacking. Keratin-18 and hepatocyte-derived large extracellular vesicle (lEV) concentrations reflect disease activity, but their ...
Show more >In patients with compensated alcohol-related cirrhosis, reliable prognostic biomarkers are lacking. Keratin-18 and hepatocyte-derived large extracellular vesicle (lEV) concentrations reflect disease activity, but their ability to predict liver-related events is unknown. Methods We measured plasma keratin-18 and hepatocyte lEV concentrations in 500 patients with Child-Pugh class A alcohol-related cirrhosis. The ability of these hepatocyte-derived biomarkers, alone or combined with model for end-stage liver disease (MELD) and FibroTest scores, to predict liver-related events at 2 years was analyzed, taking into account the alcohol consumption at inclusion and during follow-up. Results Keratin-18 and hepatocyte lEV 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 concentrations >285 U/L and FibroTest >0.74 had a 24% cumulative incidence of liver-related events at 2 years, vs. 5% to 14% in other groups of patients. Similar results were obtained when combining keratin-18 concentrations >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 lEV concentrations >50 U/L and FibroTest >0.74 had a 62% cumulative incidence of liver-related events at 2 years, vs. 8% to 13% in other groups of patients. Combining hepatocyte lEV concentrations >50 U/L with MELD >10 had a lower discriminative ability. Similar results were obtained when using decompensation of cirrhosis, defined according to Baveno VII criteria, as an endpoint. Conclusion In patients with Child-Pugh class A alcohol-related cirrhosis, combining hepatocyte-derived biomarkers with FibroTest or MELD scores identifies patients at high risk of liver-related events, and could be used for risk stratification and patient selection in clinical trials. Impact and implications In patients with compensated alcohol-related cirrhosis, reliable predictors of outcome are lacking. In patients with Child-Pugh class A alcohol-related cirrhosis, combining hepatocyte-derived biomarkers (keratin-18 and hepatocyte-large extracellular vesicles) with FibroTest or MELD scores identifies those at high risk of liver-related events at 2 years. The identified patients at high risk of liver-related events are the target-of-choice population for intensive surveillance (e.g., referral to tertiary care centers; intensive control of risk factors) and inclusion in clinical trials.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
Inserm
CHU Lille

Collections :

• Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286

Submission date :

2024-01-11T22:32:05Z
2024-02-05T10:09:48Z