Positive blood phosphatidylethanol concentration is associated with unfavorable waitlist‐related outcomes for patients medically appropriate for liver transplantation

Abstract

Background Excessive alcohol use is a leading etiology of liver disease and indication for liver transplantation. Accurate measurement of alcohol use remains a challenge in the management of patients in the pre‐, peri‐, and post‐liver transplant settings. Blood 16:0‐18:1 phosphatidylethanol (PEth) concentration is a sensitive and specific biomarker of binge and moderate, chronic alcohol use. As PEth has the longest detection window of available blood‐based direct alcohol biomarkers for moderate to heavy drinking, it shows promise as an indicator of patterns and chronicity of drinking. However, the utility of PEth in clinical liver transplantation is understudied. This study examines the association of PEth results with liver transplantation waitlist‐focused patient outcomes. Methods Retrospective data for all patients tested for PEth for a one‐year period at a tertiary care medical center with an active liver transplantation program were abstracted. Indications for PEth testing, liver transplantation waitlist‐related outcomes (e.g., listing and delisting) following testing and associations of PEth results with other parameters were analyzed. Results Over a one‐year period, 153 PEth tests were performed on 109 individuals. The most frequent indications for PEth testing were as an objective indicator of alcohol use patterns (86.3%) and to assess alcohol as a putative etiology of liver injury (13.7%). Of the 109 patients, 56 were medically appropriate for liver transplantation. Medically acceptable candidates with unfavorable transplantation waitlist‐related outcomes (delisting, deferment of transplant evaluation, deferment of listing until completion of recommended alcohol rehabilitation, and being deemed not a transplant candidate) were at least 3.41 times more likely to have a positive PEth test than those with favorable transplantation waitlist‐related outcomes (odds ratio 3.41, confidence interval 3.41 to ∞, p = 0.001). Conclusion This single‐center study reporting a comprehensive account of PEth utilization at a liver transplant center demonstrates that liver transplantation waitlist‐related outcomes are associated with PEth test results. Patients with positive PEth tests were more likely to have unfavorable transplant waitlist‐related outcomes. PEth testing has not been validated as a predictor of relapse to drinking in post‐transplant patients and because its utility in the pre‐transplant setting is unclear its use could lead to disparities in the selection of patients for liver transplantation.

Role of Biomarkers to Assess the Use of Alcohol

“…PEth can be detected for up to 28 days from the last alcohol drink in patients with chronic alcohol use, whereas in patients with ALD who averaged 4 or more drinks per day, PEth was 96% specific for drinking within the last 30 days 42,43 . Unlike other biomarkers discussed here, PEth is not affected by age, gender, BMI, or severity of liver disease 16,43 . Given the PEth’s presence on erythrocytes, the replacement of a patient’s erythrocytes after a blood transfusion will decrease the reliability of that patient’s PEth results.…”

Protocolized screening and detection of occult alcohol use before and after liver transplant: Lessons learned from a quality improvement initiative

“…19 One recent study showed that the availability of PEth testing at a LT center resulted in a higher rates of LT evaluation termination or de-listing, while another reported that positive PEth tests were associated with unfavorable LT waitlist outcomes. 20,21 Quality improvement (QI) is an important cornerstone of LT programs as centers seek to continually improve processes of care and patient outcomes. 22,23 A recent national survey showed that most programs do not have alcohol screening protocols in the post-LT setting despite widespread monitoring in the pre-LT setting, making this an ideal target for a QI initiative.…”

“…PEth can detect alcohol ingestion up to 3 weeks prior with heavy use and levels do not vary with age, sex, liver or kidney function 19 . One recent study showed that the availability of PEth testing at a LT center resulted in a higher rates of LT evaluation termination or de‐listing, while another reported that positive PEth tests were associated with unfavorable LT waitlist outcomes 20,21 …”

Blood phosphatidylethanol testing and liver transplant eligibility selection: A step closer

“…It should be noted that the window of detection of alcohol use and accuracy of biomarkers vary based on the amount of alcohol consumed by the individual and the cut-off used to adjudicate abnormal test results. Although a promising biomarker, data on PEth use in LT centers remain limited.In the April issue of this journal, Faulkner et al report on a retrospective study that examined the association of positive PEth results (≥20 ng/dL) with waitlist outcomes among patients either listed or being evaluated for LT(Faulkner et al, 2022). Whole blood was tested for PEth levels and the waitlist outcomes were studiedfor a period of 7 to 259 days from the date of PEth testing.…”

“…In the April issue of this journal, Faulkner et al report on a retrospective study that examined the association of positive PEth results (≥20 ng/dL) with waitlist outcomes among patients either listed or being evaluated for LT (Faulkner et al, 2022). Whole blood was tested for PEth levels and the waitlist outcomes were studied for a period of 7 to 259 days from the date of PEth testing.…”