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

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.