Phosphatidylethanol versus clinical criteria to diagnose alcohol use relapse after liver transplantation: a prospective cohort study

BACKGROUND: Alcohol-associated liver disease (ALD) with concomitant alcohol use disorder (AUD) is a leading indication for liver transplantation (LT). Return to alcohol use after LT (RAULT) affects a considerable proportion of recipients but lacks an objective diagnostic standard. We evaluated blood phosphatidylethanol (PEth) as a direct biomarker of RAULT and compared it with conventional clinical criteria (ClinC). METHODS: We prospectively studied adult patients who underwent LT for ALD between 2008 and 2023. Since 2020, RAULT has been assessed quarterly using both ClinC and PEth (cut-off > 0.05 µg/L). Discordant results were interpreted using PEth as a biochemical comparator, given its higher objectivity and specificity compared with ClinC, although it was not considered a definitive diagnostic standard. RESULTS: Among 143 patients (median age 56 years; 29% female; median post-LT follow-up 72 months), during a 3-year comparative study interval, RAULT was identified in 46 patients (32.2%) by PEth and in 69 patients (48.3%) by ClinC. Concordance between the two methods was observed in 98 cases (68.5%): in 63 cases (44.0%) for absence of RAULT and in 35 cases (24.5%) for presence of RAULT. Discordance occurred in 45 cases (31.5%), including 34 ClinC-positive/PEth-negative cases (23.8%) and 11 ClinC-negative/PEth-positive cases (7.7%). Quarterly and semi-annual PEth testing yielded comparable overall RAULT detection rates; however, quarterly testing identified a higher proportion of severe RAULT (16.1% vs. 12.6%). Time since LT independently predicted RAULT according to PEth (OR = 1.17; 95% CI 1.08-1.27; p = 0.0002). CONCLUSIONS: Clinical criteria may overestimate the occurrence of RAULT after liver transplantation. Quarterly or semi-annual PEth testing provides additional objective insight into post-transplant alcohol use dynamics and may enhance monitoring of patients with AUD following LT.