What’s in Metabolomics for Alcoholic Liver Disease?
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Alina M. Suciu1,2, Dana A. Crisan3, Bogdan D. Procopet1,2, Corina I. Radu1,2, Carmen Socaciu4, Marcel V. Tantau1,2, Horia O. Stefanescu2, Mircea Grigorescu1
1) 3rd Medical Clinic, Iuliu Hatieganu University of Medicine and Pharmacy;
2) Hepatology Unit, Regional Institute of Gastroenterology and Hepatology Cluj;
3) 5th Medical Clinic, Iuliu Hatieganu University of Medicine and Pharmacy;
4) RTD Center for Applied Biotechnology. BIODIATECH, SC Proplanta, Cluj-Napoca, Romania
Background & Aims: Current management of alcoholic liver disease (ALD), especially for alcoholic hepatitis (AH) is still driven by liver biopsy. Therefore, the identification of novel and accurate noninvasive biomarkers for the diagnosis and assessment of severity is important. Metabolomics, because it unravels changes closest to the phenotype, may represent the key for novel biomarkers. The aim of this study was to identify and characterize potential metabolomic biomarkers for diagnosis, staging and severity assessment of ALD.
Methods: 30 consecutive ALD patients and 10 healthy controls were included in this proof-of-concept crosssectional study. Baseline assessment consisted in evaluation of Maddrey’s Discriminant Function, Model for End-Stage Liver Disease (MELD) and ABIC scores as well as ASH-Test (Fibromax) as a surrogate for the confirmatory diagnosis of AH in suggestive clinical and biologic settings. Additionally, SOP metabolomics and lipidomics were performed from serum samples by liquid chromatography mass-spectrometry analysis.
Results: From the 127 and 135 serum/urine candidate metabolites initially identified, only 11/5 metabolites were characteristic for ALD patients. None of them correlated with alcohol intake, and only 5/1 metabolites could differentiate cirrhotic from non-cirrhotic patients. Of those, N-Lauroglycine (NLG) was the best for identifying cirrhosis (100% sensitivity and 90% negative predictive value, NPV) and decatrienoic acid (DTEA) was the best for assessing disease severity (evaluated by ABIC score) with 100% sensitivity and 100% NPV.
Conclusion: Due to their high NPV, NLG and DTEA could be used in conjunction in ALD patients to exclude cirrhosis or a severe disease. If further validated, they could become biomarkers for better management and risk assessment in ALD.
Key words: metabolomics − lipidomics − alcoholic liver disease − noninvasive.
Abbreviations: ABIC: age-bilirubin-INR-cholesterol; ALD: alcoholic liver disease; AH: alcoholic hepatitis; AST/ALT: aspartate/alanine aminotransferase; DF: Maddrey’s Discriminant Function; DTEA: decatrienoic acid; LC-MS: liquid chromatography–mass spectrometry; LRD: liver related clinical decompensation; MELD: Model for End-Stage Liver Disease; NLG: N-Lauroglycine; NPV: negative predictive value; PPV: positive predictive value; PT: prothrombin time; Se: sensibility; Sp: specificity