Dataset Information

Serum and Fecal Oxylipins in Patients with Alcohol-Related Liver Disease.

ABSTRACT: BACKGROUND:Alcohol-related liver disease is one of the most prevalent chronic liver diseases worldwide. Mechanisms involved in the pathogenesis of alcohol-related liver disease are not well understood. Oxylipins play a crucial role in numerous biological processes and pathological conditions. Nevertheless, oxylipins are not well studied in alcohol-related liver disease. AIMS:(1) To characterize the patterns of bioactive ?-3 and ?-6 polyunsaturated fatty acid metabolites in alcohol use disorder and alcoholic hepatitis patients and (2) to identify associations of serum oxylipins with clinical parameters in patients with alcohol-related liver disease. METHODS:We performed a comprehensive liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis of serum and fecal oxylipins derived from ?-6 arachidonic acid, ?-3 eicosapentaenoic acid, and docosahexaenoic acid in a patient cohort with alcohol-related liver disease. RESULTS:Our results show profound alterations in the serum oxylipin profile of patients with alcohol use disorder and alcoholic hepatitis compared to nonalcoholic controls. Spearman correlation of the oxylipins with clinical parameters shows a link between different serum oxylipins and intestinal permeability, aspartate aminotransferase, bilirubin, albumin, international normalized ratio, platelet count, steatosis, fibrosis and model for end-stage liver disease score. Especially, higher level of serum 20-HETE was significantly associated with decreased albumin, increased hepatic steatosis, polymorphonuclear infiltration, and 90-day mortality. CONCLUSIONS:Patients with alcohol-related liver disease have different oxylipin profiles. Future studies are required to confirm oxylipins as disease biomarker or to connect oxylipins to disease pathogenesis.

SUBMITTER: Gao B

PROVIDER: S-EPMC6588282 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Serum and Fecal Oxylipins in Patients with Alcohol-Related Liver Disease.

Gao Bei B Lang Sonja S Duan Yi Y Wang Yanhan Y Shawcross Debbie L DL Louvet Alexandre A Mathurin Philippe P Ho Samuel B SB Stärkel Peter P Schnabl Bernd B

Digestive diseases and sciences 20190510 7

<h4>Background</h4>Alcohol-related liver disease is one of the most prevalent chronic liver diseases worldwide. Mechanisms involved in the pathogenesis of alcohol-related liver disease are not well understood. Oxylipins play a crucial role in numerous biological processes and pathological conditions. Nevertheless, oxylipins are not well studied in alcohol-related liver disease.<h4>Aims</h4>(1) To characterize the patterns of bioactive ω-3 and ω-6 polyunsaturated fatty acid metabolites in alcohol ...[more]

PMID: 31076986

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Project description:Background & aimsMaintenance of abstinence in alcohol-related liver disease (ARLD) is a major unmet therapeutic need. Digital therapeutics can deliver ongoing behavioural therapy, in real-time, for chronic conditions. The aim of this project was to develop and clinically test AlcoChange, a novel digital therapeutic for ARLD.MethodsAlcoChange was developed using validated behaviour change techniques and a digital alcohol breathalyser. This was an open-label, single-centre study. Patients with ARLD, ongoing alcohol use (within 1 month) and possession of a suitable smartphone were eligible. Patients were recruited from inpatient and outpatient settings, and received AlcoChange therapy for 3 months. The primary outcome was reduction in alcohol use from baseline to 3 months, measured by timeline follow-back. Secondary outcomes included: (i) compliance with the AlcoChange app, (ii) alcohol-related and all-cause hospital re-admissions up to 1 year, (iii) qualitative analysis to determine factors associated with compliance.ResultsSixty-five patients were recruited, of whom 41 completed the study per protocol. Patients compliant with the intervention (>60 logins over 3 months) had a significant reduction in alcohol use from baseline compared to non-compliant patients (median [IQR]: -100% [100% to -55.1%] vs. -57.1% [-95.3% to +32.13%], p = 0.029). The proportion attaining abstinence at 3 months was higher in the compliant group (57.1% vs. 22.2%, p = 0.025). The compliant group had a significantly decreased risk of subsequent alcohol-related re-admission up to 12 months (p = 0.008). Qualitative analysis demonstrated that receiving in-app feedback and the presence of a health-related 'sentinel event' were predictors of compliance with the intervention.ConclusionsUse of the novel digital therapeutic, AlcoChange, was associated with a significant reduction in alcohol use and an increase in the proportion of patients with ARLD attaining abstinence. Definitive randomised trials are warranted for this intervention.Impact and implicationsAlcohol-related liver disease (ARLD) is an increasing health problem worldwide. The main cause of death and disability in ARLD is ongoing alcohol consumption, but few patients receive medications or talking therapy to maintain abstinence. This study demonstrated that a digital therapeutic, linked to a smartphone, may help reduce alcohol consumption and alcohol-related hospital admissions in these patients. If validated in larger, randomised, trials, digital therapeutics may have a role in the primary and secondary prevention of complicatons from ARLD.

Project description:Background & aimsAlcohol-related hepatitis (AH) and alcohol-related cirrhosis are grave conditions with poor prognoses. Altered hepatic lipid metabolism can impact disease development and varies between different alcohol-related liver diseases. Therefore, we aimed to investigate lipidomics and metabolomics at various stages of alcohol-related liver diseases and their correlation with survival.MethodsPatients with newly diagnosed alcohol-related cirrhosis, who currently used alcohol (ALC-A), stable outpatients with decompensated alcohol-related cirrhosis with at least 8 weeks of alcohol abstinence (ALC), and patients with AH, were compared with each other and with healthy controls (HC). Circulating lipids and metabolites were analysed using HPLC and mass spectrometry.ResultsForty patients with ALC, 95 with ALC-A, 30 with AH, and 42 HC provided plasma. Lipid levels changed according to disease severity, with generally lower levels in AH and cirrhosis than in the HC group; this was most pronounced for AH, followed by ALC-A. Nine out of 10 free fatty acids differed between cirrhosis groups by relative increases of 0.12-0.66 in ALC compared with the ALC-A group (p <0.0005). For metabolomics, total bile acids increased by 19.7, 31.3, and 80.4 in the ALC, ALC-A, and AH groups, respectively, compared with HC (all p <0.0001). Low sphingolipid ([d42:1] and [d41:1]) levels could not predict 180-day mortality (AUC = 0.73, p = 0.95 and AUC = 0.73, p = 0.95) more accurately than the model for end-stage liver disease score (AUC = 0.71), but did predict 90-day mortality (AUC d42:1 = 0.922, AUC d41:1 = 0.893; pd42:1 = 0.005, pd41:1 = 0.007) more accurately than the MELD score AUCMELD = 0.70, pMELD = 0.19).ConclusionsAlcohol-related severe liver disease is characterised by low lipid levels progressing with severity of liver disease, especially low sphingomyelins, which also associate to poor prognoses.Impact and implicationsLipidomics has the potential to diagnose and risk stratify patients with liver diseases. Lipidomics differed between patients with alcohol-related hepatitis and alcohol-related cirrhosis with and without recent alcohol use. Furthermore, lipidomics could predict short-term mortality and might be suitable as a prognostic tool in the future.Clinical trials registrationScientific Ethics Committee of the Capital Region of Denmark, journal no. H-21013476.

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Serum and Fecal Oxylipins in Patients with Alcohol-Related Liver Disease.

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Serum and Fecal Oxylipins in Patients with Alcohol-Related Liver Disease.

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