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. 2024 Sep 2;7(1):101200.
doi: 10.1016/j.jhepr.2024.101200. eCollection 2025 Jan.

Quantification of alcohol intake in patients with steatotic liver disease and excessive alcohol intake

Emil Deleuran Hansen  1   2 , Nikolaj Torp  1   2 , Stine Johansen  1   2 , Johanne Kragh Hansen  1   2 , Marianne Lerbæk Bergmann  3 , Camilla Dalby Hansen  1   2 , Sönke Detlefsen  2   4 , Peter Andersen  1 , Ida Villesen  1   2 , Katrine Bech  1 , Katrine Thorhauge  2 , Gitte Hedegaard Jensen  4 , Katrine Prier Lindvig  1   2 , Torben Hansen  5 , Emmanuel A Tsochatzis  1   6 , Jonel Trebicka  1   7   8 , Maja Thiele  1   2 , Aleksander Krag  1   2 , Mads Israelsen  1 ; GALAXY and MicrobLiver consortia
Affiliations

Quantification of alcohol intake in patients with steatotic liver disease and excessive alcohol intake

Emil Deleuran Hansen et al. JHEP Rep. .

Erratum in

Abstract

Background & aims: Quantifying alcohol intake is crucial for subclassifying participants with steatotic liver disease (SLD) and interpreting clinical trials of alcohol-related liver disease (ALD) and metabolic and alcohol-related liver disease (MetALD). However, the accuracy of self-reported alcohol intake is considered imprecise. We compared the diagnostic and prognostic utility of self-reported alcohol intake with blood-based biomarkers of alcohol intake: phosphatidylethanol (PEth) and carbohydrate-deficient transferrin (CDT).

Methods: We studied 192 participants from two randomized controlled trials on MetALD and ALD, all with current or former excessive alcohol intake (≥24/36 [♀/♂] grams daily for at least 1 year) and biopsy-proven liver disease. We assessed self-reported alcohol intake, PEth, and CDT at four time points. We collected follow-up data on hepatic decompensation and death manually through electronic medical records.

Results: Most participants were male (n = 161, 84%) with a mean age of 59 (SD 9) years and 73 participants reported 1-week abstinence before inclusion; the remaining reported a median alcohol intake of 43 g/day. Median PEth was 0.5 μmol/L (IQR: 0.0-1.3) and %CDT = 1.9 (IQR: 1.6-2.3). Of 32 patients reporting at least 6 months of abstinence; 27 (84%) was confirmed by PEth <0.05 μmol/L. Self-reported alcohol intake correlated well with PEth (r = 0.617) and moderately with CDT (r = 0.316). Self-reported alcohol intake, PEth, and CDT all predicted hepatic decompensation and death. However, PEth showed the highest prediction, surpassing self-reported alcohol intake (Harrel's C, PEth = 0.80 vs. self-reported = 0.68, p = 0.026).

Conclusions: Self-reported abstinence can be considered reliable in clinical trials. However, PEth is superior in predicting hepatic decompensation and death in patients with MetALD and ALD.

Impact and implications: An accurate quantification of alcohol intake is crucial in the clinical phenotyping of patients with steatotic liver disease and when designing clinical trials. This study found self-reported abstinence to be reliable but phosphatidylethanol was a more accurate prognostic biomarker of hepatic decompensation and death in a clinical trial setting. Findings may inform the design of future trials in patients with steatotic liver disease.

Keywords: alcohol use disorder; alcohol-related liver disease; biomarker; cirrhosis; steatotic liver disease.

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Conflict of interest statement

JKH has received a speaking fee from Norgine. KPL has received a speaking fee, support for travels from Siemens, and is a co-founder and board member for Evido. ET has received speaking fees from Echosens, NovoNordisk, Orphalan, and Dr Falk and participated in advisory boards for Boehringer, NovoNordisk, Pfizer, Orphalan, Univar, Alexion, and Siemens Healthineers. JT has received speaking and/or consulting fees from Versantis, Gore, Boehringer-Ingelheim, Falk, Grifols, Genfit, and CSL Behring. MT has received speaking fees from Siemens Healthcare, Norgine, Echosens, Tillotts pharma, Takeda and Madrigal; consulting fees from GE Healthcare, Boehringer Ingelheim and GSK, is vice chair on the board of Alcohol & Society (NGO) and co-founder and board member for Evido. AK has served as speaker for Novo Nordisk, Norgine, Siemens, and Nordic Bioscience and participated in advisory boards for Norgine, Siemens, Resalis Therapeutics, Boehringer Ingelheim, and Novo Nordisk. Research support: Norgine, Siemens, Nordic Bioscience, AstraZeneca, Echosens. Board member and co-founder Evido. EDH, NT, SJ, MLB, CDH, SD, PA, IV, KB, KT, GHJ, and TB declare no conflicts of interest. Please refer to the accompanying ICMJE disclosure forms for further details.

Figures

Image 1
Graphical abstract
Fig. 1
Fig. 1
Self-reported alcohol intake and blood-based biomarkers of alcohol intake. Box plots of baseline PEth and CDT according to the defined self-reported alcohol intake groups: an intake corresponding to MASLD <20/30 g (♀/♂); MetALD, 20-50 g/30–60 g (♀/♂), and ALD, >50/60 g (♀/♂) with p values obtained using the Wilcoxon rank-sum test. Levels of alcohol intake are corresponding to the limits of MetALD and ALD. PEth was measured in 184 patients, while %CDT was measured in 120 patients. ALD, alcohol-related liver disease; MASLD, metabolic-dysfunction associated steatotic liver disease; MetALD, metabolic dysfunction and ALD.
Fig. 2
Fig. 2
Sankey plot over the flow of participants between self-reported alcohol intake and PEth groups over the study time. Self-reported alcohol intake group is defined as an intake corresponding to MASLD <20/30 g (♀/♂); MetALD, 20–50 g/30–60 g (♀/♂), and ALD >50/60 g (♀/♂). Levels of PEth corresponding to the limits of MetALD and ALD. PEth groups defined as low <0.21 μmol/L, MetALD 0.21–0.42 μmol/L, and ALD >0.42 μmol/L. Only participants with complete data for PEth and self-reported alcohol intake are included in the Sankey plot. ALD, alcohol-related liver disease; MetALD, metabolic dysfunction and ALD; MASLD, metabolic-dysfunction associated steatotic liver disease; PEth, phosphatidylethanol.
Fig. 3
Fig. 3
Harrel’s C statistic with 95% CIs for baseline self-reported alcohol intake, PEth, and CDT on prognostic performance to predict hepatic decompensation and death. PEth had the highest (Harrell’s C = 0.80, 95% CI 0.69-0.91) followed by CDT (Harrell’s C = 0.73, 95% CI 0.61–0.86) and self-reported alcohol intake (Harrell’s C = 0.68, 95% CI 0.58–0.79). PEth was significantly better than self-reported alcohol intake (p = 0.026) to predict hepatic decompensation and death. No difference between PEth and CDT or CDT and self-reported. CDT, carbohydrate-deficient transferrin; PEth, phosphatidylethanol.
Fig. 4
Fig. 4
Kaplan–Meier plot of decompensation-free survival using baseline levels. Cut-offs at (A) self-reported alcohol intake ≥60 g/day for men and ≥50 g/day for women, Peth ≥0.42 μmol/L and CDT ≥2.08 %CDT (B) by Youden’s index: self-reported alcohol intake ≥8 g/day, PEth ≥1.06 μmol/L and CDT ≥2.1 %CDT. p values are obtained by log-rank test between the high and low group for each assessment. CDT, carbohydrate-deficient transferrin; PEth, phosphatidylethanol.
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