Preliminary Evaluation of Phosphatidylethanol and Alcohol Consumption in Patients with Liver Disease and Hypertension

Scott H. Stewart, Adrian Reuben, Walter A. Brzezinski, David G. Koch, Jan Basile, Patrick K. Randall, Peter M. Miller

First Published: 30 September 2009 DIO: https://doi.org/10.1093/alcalc/agp039

Medical University of South Carolina, Charleston, 29425, USA.

Abstract

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AIMS:

This preliminary study aimed to evaluate the relationship between blood phosphatidylethanol (PEth) and recent drinking in patients with liver disease and hypertension.

METHODS:

Twenty-one patients with liver disease and 21 patients with essential hypertension were recruited at an academic medical center. Alcohol consumption was estimated using validated self-report methods, and blood PEth was measured by HPLC-MS/MS at a contracted laboratory. Nonparametric comparisons were made between abstainers/light drinkers, moderate drinkers consuming between 1 and 3 drinks per day, and those drinking above this level. Regression methods were used to estimate the effects of liver disease, gender, and age on the relationship between PEth and alcohol use and to estimate the strength of the linear relationship between PEth and drinking.

RESULTS:

PEth differed significantly between the three drinking groups (P < 0.001). The relationship between PEth and alcohol did not differ between hypertension and liver disease patients (P = 0.696), nor by gender and age. While there was substantial variability between subjects in the PEth concentration given a similar level of reported drinking, the amount of ethanol consumed was strongly associated with the PEth concentration (P < 0.001).

CONCLUSION:

Results support PEth measurement by HPLC-MS/MS as a promising marker of past 1- to 2-week moderate to heavy alcohol consumption in patients with and without liver disease. PEth appears useful for differentiating abstinence or light drinking from moderate to heavy consumption but may have limited utility for differentiating moderate from heavy alcohol use.

Summary

Chronic heavy drinking is a direct cause of many medical conditions due to the toxic effects of ethanol or its metabolism. Effective treatment requires abstinence or a sharp reduction in drinking. Assessment of alcohol consumption in clinical and research settings mainly relies on self-report. While very useful, self-report methods are generally subject to potential sources of bias, which may be magnified in patients with alcohol-associated illnesses. Such individuals may wish to conceal their heavy drinking or prior unsuccessful attempts to control their drinking due to associated stigma. They may suffer from cognitive impairment due to chronic alcohol abuse or other factors.

Biomarkers of alcohol consumption may aid detection and treatment efforts in patients with alcohol-related conditions by providing highly objective indicators of recent ethanol exposure. However, biomarkers typically do not have adequate sensitivity and specificity in medical populations, particularly with liver disease, where other factors besides alcohol can influence markers such as gamma-glutamyltransferase, aminotransferase, and red blood cell mean corpuscular volume. The only FDA-approved marker for heavy drinking is the percent carbohydrate-deficient transferrin (Anton, 2001), but this requires ∼60 g of ethanol per day (i.e. 4–5 standard drinks) to become elevated, has a sensitivity of 60–70%, and loses its otherwise very high specificity in advanced liver disease. Blood phosphatidyl ethanol (PEth) is a minor, non-oxidative product of ethanol elimination formed from phosphatidylcholine and ethanol via the action of phospholipase D, which can occur extra-hepatically such as in human erythrocytes. Given this formation mechanism, the relationship between PEth and drinking may be less influenced by liver function relative to other biomarkers.

Circulating PEth is found primarily in the red blood cell fraction, has a detection window of ∼1–3 weeks following drinking cessation, and seems highly sensitive and specific in differentiating known heavy drinkers from known social drinkers and abstainers when measured using an evaporative light scattering detector assay. For example, this PEth assay has been used to detect unreported drinking in emergency department patients. An alternative mass spectrometer-based assay may be more sensitive for detecting low PEth concentrations and may allow for the detection of even moderate consumption. As such, the latter assay may reveal less heavy but still harmful drinking in patients with alcohol-associated disorders and predict the amount of alcohol consumed. However, before use as a marker of alcohol consumption in clinical care or clinical research, the relationship between PEth and drinking must be characterized in relevant populations that show a wide range of recent alcohol exposure. This manuscript describes our pilot testing of PEth in patients with two conditions that can be caused or aggravated by frequent moderate to heavy drinking: liver disease and hypertension. Importantly, liver impairment, by influencing the major oxidative mechanisms for ethanol elimination that occur primarily in the liver, may modify the association between the amount of alcohol consumed and PEth. Since hypertension should not modify this association, hypertension patients were also viewed as a control group for exploring our hypothesis that PEth synthesis may be related to liver function.