Blood phosphatidylethanol (PEth) positivity associates with unfavorable waitlist-related outcomes for patients medically appropriate for liver transplant

Abstract

Background:

Excessive alcohol use is a leading etiology of liver disease and indication for liver transplantation. Accurate determination of alcohol use remains a challenge in the management of patients in the pre-, peri- and post-liver transplant setting. Blood 16:0-18:1 phosphatidylethanol (PEth) is a sensitive and specific biomarker of binge and moderate, chronic alcohol use. As it has the longest detection window of available blood-based direct alcohol biomarkers for moderate to heavy drinking, it shows promise in indicating patterns and chronicity of drinking. The utility of PEth, however, in clinical liver transplant remains understudied. This study explores the association of PEth results with liver transplant 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 transplant 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 to objectively determine alcohol use patterns (86.3%) and to diagnostically assess alcohol as a putative etiology of liver injury (13.7%). Of the 109 patients, 56 were medically appropriate for liver transplant. Medically acceptable transplant candidates with unfavorable transplant 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 transplant waitlist-related outcomes (Odds Ratio 3.41, CI 3.41- ∞, p=0.001).

Conclusion:

This unicentric study reporting a comprehensive account of PEth utilization at a liver transplant center demonstrates that liver transplant waitlist-related outcomes associate with PEth test results.

Introduction

Alcohol-associated liver diseases (ALD), such as alcohol-associated cirrhosis (AC) and acute alcohol-associated hepatitis (AH), are the leading causes of liver failure and indications for liver transplantation globally (Lee et al., 2019). A shorter duration of pre-transplant abstinence has been shown to be associated with alcohol relapse following liver transplant for alcohol-related liver disease (Tandon et al., 2009, Chuncharunee et al., 2019). Until recently, liver transplant centers across the United States have utilized a “six-month rule,” requiring a total abstinence from alcohol for six months before listing for transplant (Mellinger and Volk, 2018). To this end, liver transplant centers routinely use interviews and questionnaires to understand a patient’s lifetime and recent drinking history (Allen et al., 2013). The sensitivity of these techniques in accurately determining alcohol use may be dependent on the training of the administering professional (Donnadieu-Rigole et al., 2017). While alcohol use screening can be performed by asking “have you drank alcohol in prior six months,” the use of standardized questionnaires (i.e. the Cut-back, Annoyed, Guilty, Eye-opener [CAGE]) (Weinrieb, 2019) is more effective for accurately determining drinking patterns. CAGE can be administered to determine if a patient has concerning alcohol use, prompting assessment by mental health or addiction subspeciality providers. Chronic alcohol use can also be assessed by the well-validated questionnaire, LifeTime Drinking History (LTDH) (Skinner and Sheu, 1982), which reveals cumulative alcohol and variations of alcohol consumption. LTDH is a reliable assessment among alcohol drinkers with chronic (Jeon et al., 2019) as well as acute organ injury (Zhou et al., 2019). Timeline follow-back (TLFB) of alcohol drinking is another well-validated tool which captures patterns of drinking, including heavy and frequent episodes (Sobell and Sobell, 1992). Recent publications have shown robust association between the patterns of alcohol drinking (derived from TLFB) and onset of ALD (Vatsalya et al., 2016). Finally, alcohol use disorders identification test (AUDIT) captures drinking patterns of the year prior (Saunders et al., 1993). AUDIT has also been effective in predicting ALD especially at an acute and advanced stage (Vatsalya et al., 2019). Major drawbacks in these interview-based assessments are that they are not universally used by transplant centers or standard of care (SOC) in clinical practice of ALD.

A recent survey of hepatologists at liver transplant centers underscored the lack of addictions-trained personnel working in the field of liver transplantation (Im et al., 2020). This study uncovered that transplant professionals, often lacking time and addiction medicine training, use alcohol biomarkers as surrogates for the detection of alcohol use in patients (Im et al., 2020). Historically, indirect biomarkers of alcohol use have limited utility. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), mean corpuscular volume (MCV) and carbohydrate-deficient transferrin (CDT) have been reported previously (Cabezas et al., 2016) with low sensitivity and specificity. Direct alcohol biomarkers appear more accurate and include blood alcohol concentration (BAC) (Andresen-Streichert et al., 2018, Bean et al., 2001), ethyl glucuronide (Staufer et al., 2011, Armer et al., 2016, Helander et al., 2008, Shukla et al., 2017, Staufer and Yegles, 2016, Sterneck et al., 2014, Stewart et al., 2013, Wurst et al., 2002), and ethyl sulfate (Helander et al., 2008, Shukla et al., 2017, Stewart et al., 2013). For the detection of alcohol use, these biomarkers have variable temporal windows of detection, sensitivity, and specificity; transplant centers integrate them into their protocols at their own discretion.

Blood 16:0-18:1 phosphatidylethanol (PEth) has emerged as a promising direct alcohol biomarker (Schrock et al., 2017) and is increasingly used as a tool for determining etiology of liver injury and detecting recent alcohol use (Aradottir et al., 2006, Ulwelling and Smith, 2018b, Ulwelling and Smith, 2018a). PEth is a unique phospholipid formed only in the presence of alcohol. The physiologic mechanism of PEth formation portends its high specificity (Andresen-Streichert et al., 2017), sensitivity (Aradottir et al., 2006), and extended window of detection of up to 12 days after a single large ingestion of alcohol (Schrock et al., 2017) and up to 28 days after chronic, moderate to heavy alcohol intake (Fleming et al., 2017, Wurst et al., 2010). Reports of false positives are rare (Hartmann et al., 2007, Ulwelling and Smith, 2018b), and PEth accuracy is not affected by gender, age, liver disease severity, and non-alcohol-related liver diseases (Wurst et al., 2010, Stewart et al., 2009, Viel et al., 2012, Stewart et al., 2014). Studies show that blood PEth concentration correlates with the quantity of alcohol consumed (Stewart et al., 2014) and does not exceed positivity thresholds (20ng/dL) with routine use of alcohol-containing mouthwashes (Reisfield et al., 2020).

Recent studies (Andresen-Streichert et al., 2017, Fleming et al., 2017, Lindenger et al., 2018) suggest PEth is an effective tool for assessing alcohol use in liver transplant candidates and recipients; however, data detailing associations between PEth results and patient liver transplant waitlist-related outcomes are limited. While the use of PEth is not FDA approved as a sole means to diagnose active alcohol use, it may be used with other patient data for clinical decision-making. As such, we hypothesized that PEth results associate with patient liver transplant waitlist-focused outcomes. We retrospectively studied PEth testing and patient outcomes for a one-year period at a tertiary care medical center with an active liver transplantation program and found that patients with positive PEth tests have a higher likelihood of unfavorable transplant waitlist-focused outcomes.

Patients and Methods

Patients and Study Paradigm

This study was approved by the University of Nebraska Medical Center Institutional Review Board (54-19-EP). Retrospective data were abstracted from the medical records of all individuals with one or more PEth tests performed between October 1, 2018, and September 23, 2019. Patient data were abstracted onto a secure, standardized form. No personal identifiers were recorded. Data included non-identifiable subject demographic information (age, sex, height, weight, body mass index [BMI]) and medical information pertaining to liver disease and/or liver transplant, including liver biopsy pathology reports, documentation of patient self-reported alcohol use in clinical notes, date of PEth test(s), PEth result(s), the indication for PEth testing, medical decision making/outcomes occurring after PEth test(s), encounter type (inpatient vs outpatient) and the specialty of the PEth ordering provider. PEth was ordered at the providers’ discretion, and there was no formalized protocol regarding criteria under which it was ordered. At the time of this study, this center adhered to the “six-month sobriety rule” for listing an individual for liver transplantation. Upon consideration of liver transplantation evaluation, a diagnosis of alcohol-associated liver disease including AC or AH, positive BAC or patient self-reported alcohol use in the prior 6 months prompted further assessment by a licensed clinical social worker with subspecialty addiction certification. Notes from those assessments were protected within the Epic medical record system by a “break the glass” restriction and were not available for this study.

Lab values and dates were also abstracted when available, including BAC, cancer antigen (CA) 19-9, GGT, MCV, total bilirubin, AST, and ALT. If multiple values were available for a single lab test, the test performed temporally closest to PEth testing was utilized for analyses. For patients deemed medically appropriate candidates for transplant (age <75, BMI <40, non-preclusive surgical anatomy, lacking active malignancy, and without major cardio-pulmonary co-morbid conditions) (Murray et al., 2005), comparisons of PEth results were made between groups with favorable and unfavorable transplant waitlist-related outcomes. Favorable transplant listing-related outcomes included: a) remaining actively listed for transplant (for individuals already listed prior to their first PEth test), b) undergoing transplant evaluation and being placed on the liver transplant waitlist, and c) undergoing liver transplantation. Unfavorable transplant listing-related outcomes included: a) delisting from the transplant waiting list (for individuals already listed prior to their first PEth), b) deferment of transplant evaluation or listing for transplant until completion of recommended alcohol rehabilitation, and c) being deemed not a transplant candidate due to compliance concerns (i.e. multiple no-shows or leaving against medical advice) or active alcohol and/or drug use. The individuals in the latter category may have also had insufficient alcohol rehabilitation or demonstrated subjective lack of insight into alcohol or substance use.

Individuals with a clinical diagnosis of ALD were identified by review of provider notes explicitly stating this diagnosis, a liver biopsy not excluding ALD, and corroborating documented ICD-9 or ICD-10 codes consistent with ALD including any of the following: 571.0-571.3, K70.0-K70.4, and K70.9.

Laboratory Assessments

PEth testing was performed as a send out to MedTox (St. Paul, MN) and was performed by liquid chromatography/tandem mass spectrometry (LC/MS-MS). All specimens met quality control parameters set forth by MedTox. PEth tests negative for the detection of “moderate to heavy ethanol consumption” were reported as <20 ng/ml (with no further quantification provided for this range). PEth tests positive for moderate to heavy ethanol consumption were reported as >20 ng/mL, with quantification provided for values ranging from 20-1000 mg/ml (Ulwelling and Smith, 2018). Concentrations of >1000 ng/ml were not further quantified but reported as such.

Statistical Analysis

Continuous variables are presented as mean ± standard deviation (SD) and categorical variables are presented as frequency and percentage. Group comparisons were performed using the Student’s t-test for continuous variables and the Fisher’s exact test for categorical data. Correlations were performed using the Pearson method for parametric testing (N > 30) and the Spearman method for non-parametric testing (N < 30). P values were based on two-tail testing and statistical significance was accepted at P<0.05. All analyses were performed with GraphPad Prism 8 software version 8.1.2 for Mac OS X (San Diego, CA, USA).

Results

All Subjects

One hundred and nine individuals had a total of 153 PEth tests and the follow up period surveilling transplant-related outcomes ranged from 7 – 259 days. There were 107 negative PEth tests (<20ng/dL) and 46 positive PEth tests (mean concentration 321.84 ng/dL, range 27-1000). For these positive tests, mean PEth concentration did not differ significantly among sexes or patient groups (Figure 1).

Figure 1. Mean blood phosphatidylethanol (PEth) concentrations by appropriateness for transplant and sex.

Mean blood PEth (ng/dL) in all, male and female subjects were further classified by pre- and post (OLTx) liver transplant status. Pre-transplant subjects were deemed medically appropriate (MA) or medically inappropriate (MI) for transplant (see Methods). One way ANOVA showed no significant difference between groups (p=0.8609). Error bars denote one standard deviation.

One-way ANOVA, multiple comparisons, P=0.8609

Most tests (N=95) were performed in the outpatient setting whereas 58 tests were performed inpatient. The most common ordering service was Transplant Hepatology (N=129), followed by Gastroenterology (N=13), and Transplant Surgery (N=8).The two primary reasons for PEth testing were objective detection of alcohol use (86.3%, N=132) and diagnostic evaluation of change in medical status, abnormal liver function tests, or liver disease etiology (13.7%, N=21). Of the 132 tests performed to objectively detect alcohol use, 73 tests were used to assess individuals not listed or not currently under formal evaluation for liver transplant, 50 tests were performed as part of a pre-transplant alcohol abstinence compliance program, and nine tests were performed in post-transplant patients as part of an alcohol abstinence compliance program. Of the 21 tests done for diagnostic purposes, 14 were in non-transplanted individuals and seven were in post-liver transplant patients.

Among all subjects (N=109), 36 individuals had at least one positive PEth (Group “Any Positive PEth”) and 73 individuals had all negative PEth tests (Group “All Negative PEth”). There were no differences in age, sex, BMI or co-morbid conditions among the Any Positive PEth and All Negative PEth groups with the exception that the diagnosis of alcoholic cirrhosis was more common in the All Negative PEth group (64.4% vs 38.9% P=0.014) (Supplemental Table 1).

Twenty-nine subjects had >1 PEth test with repeat tests occurring a median of 42 days apart (mean 56.28 days, range 1-140), whereas 80 subjects had a single test. Males and females underwent repeat testing at similar frequency (P=0.1129). Among subjects with an initial negative (N=75) or positive (N=34) test, there was no difference in the rate of repeat testing (17/75 - 22.7% vs 12/34 - 35.3% p=0.245, Fisher’s exact test). Among those who had multiple tests, there was no difference in the mean number of tests for those who had an initial negative test verses an initial positive test (2.29 vs 2.83, P=0.2456, Student’s t test). Among those with multiple tests, 22 had concordant results (negative->negative N=15, positive ->positive N=7) and seven had discordant results (negative->positive N=2, positive->negative N=5).

Medically inappropriate for transplant cohort

For all subjects without a prior liver transplant at the time of PEth testing (N=101), 45 were medically inappropriate for liver transplant due to death prior to preliminary transplant evaluation (N=10), disqualifying medical conditions (i.e., extreme age, metastatic cancer, severe cardiovascular disease) (N=5), or low-MELD/non-cirrhotic status (N=30).

Medically appropriate for transplant cohort

Among the 56 individuals who were medically appropriate for consideration of liver transplant, 38 had all negative PEth tests and 18 had at least one positive PEth test. Based on PEth status, there were no differences in age, sex, BMI or co-morbid conditions (Supplemental Table 2). Among this cohort, individuals with favorable transplant listing-related outcomes were at least 3.41 times more likely to have all negative PEth tests when compared to those with unfavorable transplant listing-related outcomes: (OR 3.41, CI 3.41 - _∞, p=0.001, Fisher’s Exact Test) (Table 1).

Table 1.

Transplant waitlist-related outcomes, subjects medically appropriate for transplant

	All Negative PEths	Any Positive PEth	Total	Odds Ratio	95% Confidence Interval	p-value
Transplanted	5	0	5
Remains listed	4	0	4
Placed on transplant list	7	0	7
Favorable outcomes	16	0	16	1	N/A	N/A
Delisted	0	1	1
Alcohol rehab recommended	17	3	20
Transplant evaluation deferred	5	14	19
Unfavorable outcomes	22	18	40	∞	3.41 - ∞	0.001
All outcomes	38	18	56

Post-transplant cohort

Eight post-transplant patients underwent 16 PEth tests. Due to the recent availability of PEth at this center, none of these individuals had testing prior to transplant. For seven of these subjects, the initial reason for PEth testing was workup of abnormal liver function or change in medical condition; for one individual it was to attempt objective quantification of self-reported light occasional alcohol use. Rationale for testing, PEth values and outcomes for these subjects are detailed in Supplemental Table 3. For these post-transplant patients, surreptitious alcohol use was corroborated by positive PEth testing (Patient [P] 019, P022, P029, P061). A mildly positive PEth in the setting of congenital short gut syndrome with no subjective evidence of alcohol use led to the consideration of auto-brewery syndrome (Dahshan and Donovan, 2001) in P025. Additionally, the limitation of PEth testing in the setting of increased RBC turnover, loss or transfusion was considered in P053.

Performance of PEth in the Determination of Allograft ALD

Four post-transplant individuals underwent allograft liver biopsy and PEth testing. Two of these individuals, both of whom were <1-year post-transplant, tested PEth positive and self-reported relapse to heavy drinking. One showed features of acute cellular rejection on a first liver biopsy which progressed to chronic rejection on a subsequent biopsy, and the other patient’s liver showed non-specific cholestasis. Typical features of alcohol-induced damage (steatosis, lobular necroinflammatory changes, Mallory bodies, and neutrophilic satellitosis) (Erard-Poinsot et al., 2016) were not present in these allografts. Discussions with these patients revealed that relapse to alcohol use contributed to decreased stringency in taking immunosuppressants and overall failure to thrive. The other two post-transplant individuals had negative PEth testing and liver histology consistent with alternative etiologies of liver injury: one presented with acute heart failure from Coxsackie virus and the other showed evidence of preservation injury <2 weeks post-transplant.

PEth and Indirect Biomarkers

Routine labs which show some efficacy as indirect biomarkers of alcohol use are routinely checked at this medical center. Studies have previously reported a significant correlation between PEth and GGT and MCV (Hartmann et al., 2007). Herein, we found a strong correlation between PEth and GGT (r = 0.746) but not with MCV (r = 0.24).ALT, AST, CA19-9, and total bilirubin showed no correlation to PEth values (r-value range: −0.14 – 0.35).

PEth and Other Direct Biomarkers

At this transplant center, non-random BAC is employed to objectively detect alcohol use on a case-by-case basis. There were 64 PEth tests with subject-matched BACs available within a 28-day window of PEth testing. Among negative PEth tests (N=50), all subject-matched BAC tests were negative. Among positive PEth tests (N=14), only 2 matched patients BAC tests were positive.

Discussion

Prior to the work herein, there were three previous studies exploring the utility of PEth testing in the liver transplant setting. The University of Hamberg-Eppendorf in Germany studied PEth in outpatient pre-transplant cirrhotic and post-transplant follow-up patients, all with a primary disease etiology of ALD. This study found an overall PEth positivity of around 20% within these populations with 100% specificity and 96% sensitivity for detecting alcohol use when compared to self-reporting of alcohol consumption via a modified AUDIT questionnaire. This study, however, did not share the clinical impacts of PEth positivity on medical decision making or associations of PEth results with patient waitlist outcomes (Andresen-Streichert et al., 2017). A second study reported PEth testing in patients previously transplanted for all etiologies of liver disease at two US liver transplant centers and employed patient interview (the Sobell follow-back method (Sobell et al., 1992)) as the gold standard to detect alcohol use. Twenty-four percent of individuals transplanted for ALD and 16% transplanted for non-alcohol liver disease had PEth positivity despite denying alcohol consumption. Only 46% of individuals reporting recent alcohol use had a positive PEth (Fleming et al., 2017). A third study from Sahlgrenska University Hospital in Gothenburg, Sweden employed PEth in a clinical algorithm to detect alcohol use, but specific data regarding its utilization, sensitivity and specificity were not presented (Lindenger et al., 2018). Despite its promise as a robust alcohol biomarker (Andresen-Streichert et al., 2017), the PEth test has not been integrated into SOC at most transplant centers (Staufer and Yegles, 2016) and more studies of centers’ experiences are needed.

This report herein describes the experience of a single US liver transplant center during the first year after integration of PEth testing as a tool for the detection of alcohol use in patients at the providers’ discretion. A strength of this study lies in the conclusion of the primary aim which determined that favorable and unfavorable transplant waitlist-related outcomes associate with negative and positive PEth results, respectively. Among patients tested, we found no differences in PEth concentration based on sex or medical appropriateness for liver transplant.

Next, this study revealed an important limitation of PEth testing in the immediate post-transplant setting as encountered in a patient who made a statement suggesting surreptitious heavy drinking in the days prior to transplant. As there was concern for delirium in the patient, blood PEth testing was performed one day after the transplant to corroborate the statement; it was negative (<20ng/dL). Even if the patient truly had a significant alcohol exposure prior to transplant, the patient’s RBC localized PEth was likely diminished as he had substantial operative blood loss and transfusions. Likewise, in individuals with severe acute alcohol hepatitis and concurrent Zieve’s syndrome (Abughanimeh et al., 2019, Choudhry et al., 2019, Gotor Delso et al., 2019, Senatore and McDonald, 2016), RBC destruction may be responsible for negative PEth testing despite recent alcohol intake and we suspect this occurred in one of our patients. As EtG and EtS have been detected in hair samples, these hair biomarkers may be most appropriate in such scenarios (Cappelle et al., 2018, Crunelle et al., 2014, Sterneck et al., 2014). Therefore, we propose cautious interpretation of PEth results in individuals with bleeding or increased RBC consumption as blood PEth may be falsely negative. Similar caution should be used in interpreting positive PEth tests results in individuals who have had recent RBC transfusion; it is feasible (Aradottir et al., 2004) that a blood donor’s drinking pattern could impact PEth results in a transfusion recipient.

Limitations of this study include its retrospective nature, modest sample size and short time frame of follow up for these subjects. Lack of patient-matched BAC testing within a 28-day window of PEth testing was also a limitation as we only had matched data for 64 of 109 patients, the majority of which were outpatient. One reason for this discrepancy is the consultative nature of the inpatient transplant hepatology service at this center. Due to the time lapse from admission until subspecialty consultation, the window of opportunity for informative BAC testing (<6-12 hours since drinking) (Bean et al., 2001, Andresen-Streichert et al., 2017, Andresen-Streichert et al., 2018) had often passed. Although the topic has been well reviewed (Donroe and Tetrault, 2017), studies are limited examining the rates of patients within the window of positive BAC at outpatient visits. Anecdotal evidence suggests that individuals tend to abstain from alcohol in the preceding 12-24 hours prior to outpatient visits, likely accounting for the low rates of BAC positivity in this study.

PEth data alone were not used to make major clinical decisions in the subjects included in this study but we acknowledge the likelihood of selection bias that may have occurred as the use of PEth testing at the time of this study was not protocolized at this center. While we cannot discern the scenarios that led to initial PEth testing, we demonstrate the initial PEth testing results (positive and negative) did not associate with repeat testing based on sex or transplant-candidate status. While providers were not blinded to PEth results during interdisciplinary patient assessments, review of provider notes affirms that PEth data were corroborated with additional data including subjective alcohol use reporting from the patient or their associates. In the experience of this center, discussing PEth testing (rationale for and results) opened the door for frank conversations about alcohol use patterns and helped facilitate triage to mental health providers for care of alcohol use disorder and alcohol relapse after transplantation.

A major caveat of this study is that standardized, formal drinking history assessments were not available to compare with PEth results. This caveat, however, does not affect the applicability of this study to other centers as universal protocols and personnel for assessing patient alcohol use vary widely and are not standardized across transplant centers. While integration of addiction specialists on liver transplant teams with dedicated time and expertise to administer well-validated interview-based instruments for alcohol use is associated with decreased alcohol relapse after transplant (Addolorato et al., 2013), the liver transplant community acknowledges that many centers lack such dedicated personnel and identify this as a critical investment for centers (Asrani et al., 2020). Transplant Hepatologists and Gastroenterologists self-report deficiencies in discerning alcohol use in patients citing “lack of time” as the most common barrier (Im et al., 2020), thus the PEth test may be perceived as an attractive, time-saving surrogate for detecting alcohol use.

It is unknown how many transplant centers routinely use or have formal protocols regarding PEth testing as there are no requirements for such transparency. Likewise, the United Network for Organ Sharing has no formal protocol or recommendations for the use of PEth or other alcohol biomarkers. As such, it is our hope that the study herein serves as a cautionary tale to the transplant community. Given the high stakes of liver transplant, our data demonstrating that PEth results associate with transplant waitlist-related outcomes contribute to the growing body of literature supporting the need for validation, universalization and transparency of alcohol biomarker and addiction protocols used by transplant centers. If not protocolized and universal for all patients, there is risk of selection bias with PEth testing. Further, if PEth testing were to be performed universally and at regular intervals in all patients (regardless of presumed etiology of liver disease) during the liver transplantation evaluation process, substantive alcohol use may be detected in more individuals. For many centers, this may open Pandora’s box. Do centers have the bandwidth of mental health and addiction personnel to address every positive PEth that may occur with a universal PEth testing protocol? Does a positive PEth test truly represent problem drinking in an individual with a proven, non-alcohol primary etiology of liver disease? Would universal PEth testing create another barrier to transplant for vulnerable populations? Prospective studies aimed at these questions are needed to validate the use of PEth testing in the transplant setting.

In summary, we describe the experience of a single US liver transplant center during the first year after the integration of PEth testing into patient care. We found unfavorable transplant waitlist-related outcomes are associated with positive PEth results. Without validation and protocolization of testing, transplant centers must carefully interpret PEth data on an individual basis as unique caveats exist in pre- and post-liver transplant patients.

Abbreviations:

AC

Alcohol-associated cirrhosis

AH

Acute alcohol-associated hepatitis

ALD

Alcohol-associated liver disease

ALT

Alanine aminotransferase

AST

Aspartate aminotransferase

AUDIT

Alcohol use disorders identification test

BAC

Blood alcohol concentration

BMI

Body mass index

CA 19-9

Cancer antigen 19-9

CAGE

Cut-down, Annoyed, Guilty, and Eye-opener

CDT

Carbohydrate-deficient transferrin

CI

Confidence interval

GGT

Gamma-glutamyl transferase

LFT

Liver function test

LTDH

LifeTime Drinking History

MCV

Mean corpuscular volume

MELD

Model for end-stage liver disease

NAFLD

Non-alcoholic fatty liver disease

OR

Odds ratio

PEth

Phosphatidylethanol

RBC

Red blood cells

SD

Standard deviation

SOC

Standard of care

TLFB

TimeLine follow-back