Non‐invasive diagnosis of alcohol‐related steatohepatitis in patients ongoing alcohol withdrawal based on cytokeratin 18 and transient elastography

Author:

Chalin Arnaud1,Turlin Bruno2,Ousmen Ahmad3,Michalak Sophie4,Mueller Johannes5,Mueller Sebastian56ORCID,Legros Ludivine7,Bardou‐Jacquet Edouard78,Viel Jean François9,Samson Michel1ORCID,Moirand Romain810

Affiliation:

1. Univ Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail) ‐ UMR_S 1085 Rennes France

2. Department of Pathology Université Rennes 1, INRAE, INSERM, Institut NUMECAN (Nutrition Metabolisms and Cancer) ‐ UMR_S 1241, CHU Rennes France

3. Department of Epidemiology and Public Health University Hospital Rennes France

4. Department of Pathology CHU Angers France

5. Center for Alcohol Research University of Heidelberg Heidelberg Germany

6. Bauchmedizin Viscera AG Bern Switzerland

7. Service des Maladies du Foie CHU Rennes Rennes France

8. Univ Rennes, INRAE, INSERM, CHU Rennes, Institut NUMECAN (Nutrition Metabolisms and Cancer) Rennes France

9. Univ Rennes, CHU Rennes, Inserm, EHESP, Irset (Institut de Recherche en Santé, Environnement et Travail) ‐ UMR_S 1085 Rennes France

10. UF Addictologie CHU Rennes Rennes France

Abstract

SummaryBackground and AimsThe diagnosis of alcoholic steatohepatitis (ASH) is based on liver biopsy, which is costly and invasive with non‐negligible morbidity. The aim of this study was to evaluate the accuracy of circulating cytokeratin 18 M65 fragment (K18‐M65) alone or in association with other markers for the non‐invasive diagnosis of ASH in patients ongoing alcohol withdrawal.MethodsThis study examined the serum level of K18‐M65 in a test cohort of 196 patients. All patients underwent liver biopsy, transient elastography (TE) and serum collection. The diagnostic accuracy of K18‐M65 alone or combined with clinico‐biological data was assessed and the best defined cut‐offs were validated in an independent validation cohort of 58 patients.ResultsK18‐M65 had an area under the curve (AUC) of 0.82 (test cohort) and 0.90 (validation cohort). Using two cut‐off decision points, K18‐M65 was able to classify 46.9% (test cohort) and 34.5% (validation cohort) of patients with 95% sensitivity or specificity. Combining K18‐M65, alpha‐2‐macroglobulin, TE, body mass index, and age, we created a score allowing accurate diagnosis of ASH with an AUC of 0.93 (test cohort) and 0.94 (validation cohort). This new score was able to rule out or rule in the diagnosis of steatohepatitis for probability ≤0.135 or ≥0.667 respectively in more than two‐thirds of patients.ConclusionsWe propose a new validated non‐invasive score for the diagnosis of ASH in patients ongoing alcohol withdrawal. This score can help to identify patients that may benefit from potential therapeutics or motivate them to reduce alcohol consumption.

Publisher

Wiley

Subject

Pharmacology (medical),Gastroenterology,Hepatology

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