Ethyl Glucuronide in Hair Is an Accurate Biomarker of Chronic Excessive Alcohol Use in Patients With Alcoholic Cirrhosis

Verbeek, Jef; Crunelle, Cleo L.; Leurquin‐Sterk, Gil; Michielsen, Peter; Doncker, Mireille De; Monbaliu, Diethard; Pirenne, Jacques; Roskams, Tania; Merwe, Schalk van der; Cassiman, David; Neels, Hugo; Nevens, Frederik

doi:10.1016/j.cgh.2017.08.019

Cited by 14 publications

(16 citation statements)

References 8 publications

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“…It can be detected in urine for only up to two to three days, and due to its high sensitivity, urinary EtG may be positive after accidental consumption of foods containing alcohol. Scalp hair EtG is a highly sensitive and specific biomarker of chronic excessive alcohol use [26]. Ethyl sulfate (EtS), another liver side product of EtOH, has a detection period of even less (30 h).Phosphatidylethanol is generated from a phospholipid in presence of EtOH and can be detected in blood up to three weeks.…”

Section: Elucidating the Downstream Effects Of Etoh Exposurementioning

confidence: 99%

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Review and gap analysis: molecular pathways leading to fetal alcohol spectrum disorders

et al. 2018

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Alcohol exposure during pregnancy affects the development of the fetus in various ways and may lead to Fetal Alcohol Spectrum Disorders (FASD). FASD is one of the leading preventable forms of neurodevelopmental disorders. In the light of prevention and early intervention, knowledge on how ethanol exposure induces fetal damage is urgently needed. Besides direct ethanol and acetaldehyde toxicity, alcohol increases oxidative stress, and subsequent general effects (e.g., epigenetic imprinting, gene expression, and metabolite levels). The current review provides an overview of the existing knowledge about specific downstream pathways for FASD that affects e.g., the SHH pathway, cholesterol homeostasis, neurotransmitter signaling, and effects on the cytoskeleton. Available human data vary greatly, while animal studies with controlled ethanol exposition are only to a certain limit transferable to humans. The main deficits in knowledge about FASD are the lack of pathophysiological understanding and dose-response relationships, together with the lack of reliable biomarkers for either FASD detection or estimation of susceptibility. In addition to single outcome experiments, omics data should be generated to overcome this problem. Therefore, for future studies we recommend holistic data driven analysis, which allows integrative analyses over multiple levels of genetic variation, transcriptomics and metabolomics data to investigate the whole image of FASD development and to provide insight in potential drug targets for intervention.

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Section: Elucidating the Downstream Effects Of Etoh Exposurementioning

confidence: 99%

Section: Elucidating the Downstream Effects Of Etoh Exposurementioning

confidence: 99%

Review and gap analysis: molecular pathways leading to fetal alcohol spectrum disorders

et al. 2018

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“…Hair and nail analyses with EtG and fatty acid ethyl ester also exist and have been reported to accurately identify alcohol use within the last several months, with higher specificity than urine testing, but these tests are not yet routinely used in LT centers …”

Section: Monitoring Alcohol Use After Lt: Tools Exist But There Is Lmentioning

confidence: 99%

Return to Alcohol Use After Liver Transplant: Patterns and Surveillance

Lee

Terrault

2018

Clinical Liver Disease

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“…Following the implementation of high‐performance LC–MS/MS as a routine apparatus in bioanalytical laboratories, analysis of phase II metabolites of medical drugs and illicit substances has gained importance in clinical and forensic toxicology . This includes the glucuronides and sulfates of small polar molecules, for example ethanol and γ‐hydroxybutanoic acid in blood, urine and hair . Ethyl glucuronide (EtG), formed by glucuronidation of ethanol by uridine diphosphate glucuronosyltransferases (UGTs), has proved suitable as a direct biomarker for ethanol consumption …”

Section: Introductionmentioning

confidence: 99%

“…48 This includes the glucuronides and sulfates of small polar molecules, for example ethanol and γ-hydroxybutanoic acid in blood, urine and hair. [49][50][51][52] Ethyl glucuronide (EtG), formed by glucuronidation of ethanol by uridine diphosphate glucuronosyltransferases (UGTs), has proved suitable as a direct biomarker for ethanol consumption. 53 However, so far the glucuronides of two of the most important alcohols in clinical toxicology, methanol and EG, have not been investigated.…”

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confidence: 99%

Ethylene glycol: Evidence of glucuronidation in vivo shown by analysis of clinical toxicology samples

Pedersen

Bélanger

Frykman

et al. 2019

Drug Testing and Analysis

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In the search for improved laboratory methods for the diagnosis of ethylene glycol poisoning, the in vivo formation of a glucuronide metabolite of ethylene glycol was hypothesized. Chemically pure standards of the β‐O‐glucuronide of ethylene glycol (EG‐GLUC) and a deuterated analog (d4‐EG‐GLUC) were synthesized. A high‐performance liquid chromatography and tandem mass spectrometry method for determination of EG‐GLUC in serum after ultrafiltration was validated. Inter‐assay precision (%RSD) was 3.9% to 15.1% and inter‐assay %bias was −2.8% to 12.2%. The measuring range was 2–100 μmol/L (0.48–24 mg/L). Specificity testing showed no endogenous amounts in routine clinical samples (n = 40). The method was used to analyze authentic, clinical serum samples (n = 31) from patients intoxicated with ethylene glycol. EG‐GLUC was quantified in 15 of these samples, with a mean concentration of 6.5 μmol/L (1.6 mg/L), ranging from 2.3 to 15.6 μmol/L (0.55 to 3.7 mg/L). In five samples, EG‐GLUC was detected below the limit of quantification (2 μmol/L) and it was below the limit of detection in 11 samples (1 μmol/L). Compared to the millimolar concentrations of ethylene glycol present in blood after intoxications and potentially available for conjugation, the concentrations of EG‐GLUC found in clinical serum samples are very low, but comparable to concentrations of ethyl glucuronide after medium dose ethanol intake. In theory, EG‐GLUC has a potential value as a biomarker for ethylene glycol intake, but the pharmacokinetic properties, in vivo/vitro stability and the biosynthetic pathways of EG‐GLUC must be further studied in a larger number of patients and other biological matrices.

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Ethyl Glucuronide in Hair Is an Accurate Biomarker of Chronic Excessive Alcohol Use in Patients With Alcoholic Cirrhosis

Cited by 14 publications

References 8 publications

Review and gap analysis: molecular pathways leading to fetal alcohol spectrum disorders

Review and gap analysis: molecular pathways leading to fetal alcohol spectrum disorders

Return to Alcohol Use After Liver Transplant: Patterns and Surveillance

Ethylene glycol: Evidence of glucuronidation in vivo shown by analysis of clinical toxicology samples

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