Direct alcohol biomarkers in alcohol use disorder rehabilitation: Analytical challenges, longitudinal interpretation, and clinical utility

Direct alcohol biomarkers can strengthen monitoring during alcohol use disorder rehabilitation, but their clinical value depends on the question being asked, specimen quality, and interpretation over time. This critical narrative review examines phosphatidylethanol (PEth) in blood and ethyl glucuronide and ethyl sulfate in urine, with hair ethyl glucuronide considered as a complementary retrospective measure. Targeted literature searches and reference tracing identified analytical investigations, longitudinal treatment studies, consensus documents, and trials incorporating biomarker feedback. Study designs were appraised with explicit descriptors of evidence strength. PEth offers an extended observation window, whereas urinary metabolites are better suited to investigating more recent exposure. Neither a single concentration nor a fixed detection window reliably reconstructs drinking behavior. Residual PEth after cessation, erythrocyte turnover, transfusion, post-collection formation, urine dilution, renal dysfunction, and laboratory differences can materially affect interpretation. PEth harmonization cannot be assumed and external quality assessment is limited. Serial measurements anchored to baseline, collection dates, and temporally matched self-report are therefore more informative than isolated positive or negative classifications. Trials of biomarker-supported contingency management provide evidence for treatment packages, but do not isolate the benefit of testing itself or establish improvement in social recovery. We propose a laboratory-clinical interpretation framework that links test selection and analytical verification to collaborative treatment review, while assessing psychological and social outcomes separately. Priorities include harmonized reporting, external validation of longitudinal decision rules, and pragmatic trials measuring retention, functioning, costs, and unintended consequences. Direct biomarkers are valuable measures of alcohol exposure; their contribution to rehabilitation depends on an appropriate clinical response to the result.