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. 2023 Jul 29;24(15):12175. doi: 10.3390/ijms241512175

Table 1.

Main data extracted from the selected articles.

Study and Year Type of Study Number of Subjects Clinical Setting Subjects Stratification Type of Sample Form of Measured PEth Analytical Method LOQ * Cut-Off # AUC-ROC of PEth Other Markers
Aboutara et al., 2022 [27] Cross-sectional 234 patients attending a liver and kidney clinic Outpatients By self-reported alcohol intake and by period of time assessed DBS from EDTA-blood 16:0/18:1
16:0/18:2
16:0/20:4
18:0/18:1
18:0/18:2
18:1/18:1
LC/MS/MS

16:0/18:1: 8.6 ng/mL *
16:0/18:2: 6.0 ng/mL *
16:0/20:4: 7.7 ng/mL *
18:0/18:1: 6.1 ng/mL *
18:0/18:2: 7.5 ng/mL *
18:1/18:1: 6.6 ng/mL *

10 ng/mL #
For PEth cut-off ≥10 ng/mL and a consumption in the last 4 weeks:

≥24 g/week:
16:0/18:1: 0.78
16:0/18:2: 0.76
16:0/20:4: 0.71
18:0/18:1: 0.70
18:0/18:2: 0.70
18:1/18:1: 0.66

≥ 84 g/week:
16:0/18:1: 0.93
16:0/18:2: 0.89
16:0/20:4: 0.82
18:0/18:1: 0.82
18:0/18:2: 0.82
18:1/18:1: 0.78
uEtG
hEtG
CDT
AST
ALT
GGT
MCV
Afshar et al., 2022 [28] Prospective clinical 251 patients attending a trauma center Inpatients By AUDIT score:

“No unhealthy alchol use”
if AUDIT < 5 (F) or <8 (M)

“Unhealthy alcohol use” if AUDIT ≥ 5 (F) or ≥8 (M)
DBS from EDTA-blood 16:0/18:1 LC/MS/MS

8 ng/mL *

25 ng/mL #
For PEth cut-off 25 ng/mL:
0.93
(CI: 0.92–0.93)

In the external validation:
0.83
(CI: 0.72–0.94)
uEtS
uEtG
CDT
GGT
BAC
Afshar et al., 2017 [29] Cohort 122 subjects:
From medical and burn ICU (n = 33)
From alcohol detoxification unit (n = 51)
Healty volunteers (n = 38)

(93 M / 29 F)”
Inpatients

Outpatients
By AUDIT score:

“Any alcohol misuse” if AUDIT ≥5 (F) or ≥8 (M)

“Severe alcohol misuse” if AUDIT ≥13 (F) or ≥16 (M)
DBS from whole blood 16:0/18:1 LC/MS/MS

4 ng/mL *

250 ng/mL #

400 ng/mL #
By AUDIT
For PEth as a continuous measure for any alcohol misuse: 0.927
(CI: 0.877–0.977)

For PEth as a continuous measure for severe alcohol misuse: 0.906
(CI: 0.850–0.962)

By AUDIT-C
For PEth as a continuous measure for any alcohol misuse: 0.948
(CI: 0.910–0.956)

For PEth as a continuous measure for severe alcohol misuse: 0.913
(CI: 0.856–0.971)
BAC
Baggio et al., 2020 [30] Single-center with a cross-sectional design 233 subjects of army recrutiment centre

(233 M/0 F)
By AUDIT score:

“Low score” if AUDIT < 13

“High score” if AUDIT ≥ 13
DBS from whole blood 16:0/18:1 LC/MS/MS

90 ng/mL #

210 ng/mL # (excessive chronic drinking)
0.617 hEtG
Cherrier et al., 2020 [31] Cross-sectional 183 subjects

(121 M/62 F)
Outpatients By age:

Middle age subjects (35–59 years)
Older age subjects (over 60 years)


By AUDIT-C score:

“Subjects at-risk for excessive alcohol consumption” if AUDIT-C ≥ 6
“Subjects without risk for excessive alcohol consumption” if AUDIT-C < 6
EDTA-Whole blood 16:0/18:1
16:0/18:2
Total PEth
LC/MS/MS

16:0/18:1: 0.009 μmol/L *

16:0/18:2: 0.03 μmol/L *
- GGT

AST

ALT
Bilirubin
Francis et al., 2015 [32] Cross-sectional 202 college students and casual labourers

(161 M/41 F)
Outpatients By AUDIT score:

“Low risk drinking” if AUDIT < 8

“Risk drinking” if AUDIT ≥ 8
By AUDIT-C score:
“No hazardous drinking” if AUDIT-C < 6

“Hazardous drinking” if AUDIT-C ≥ 6
By TLFB:
“Heavy alcohol intake” if were consumed ≥6 S.D. per drinking event
EDTA-Whole blood 16:0/18:1 LC/MS/MS

0.01 μmol/L *

0.01 μmol/L # (any alcohol intake)

0.30 μmol/L # (heavy alcohol intake)
AUDIT ≥ 8 use against PEth for heavy alcohol use: 0.89 (0.83–0.92)

AUDIT-C ≥ 6 use against PEth for heavy alcohol use: 0.89 (0.84–0.93)
-
Gerbase et al., 2020 [33] Prospective cross-sectional 238 adult patients presenting for trauma

(161 M/77 F)
ER department of Novo Hamburgo (population: 250,000) in South Brazil “By AUDIT-C score:

“No alcohol misuse” if AUDIT-C < 3 (F) or <4 (M)
“Any level of alcohol misuse” if AUDIT-C ≥ 3 (F) or ≥4 (M)
“Severe alcohol misuse” if AUDIT-C ≥ 6”
EDTA-Whole blood 16:0/18:1 LC-MS/MS

1.67 ng/mL *

18,3 ng/mL# (any alcohol misuse)

23,9 ng/mL# (severe alcohol misuse)
For PEth cut-off 18.3 ng/mL to detect any alcohol misuse based on AUDIT-C ≥ 3 (F) or ≥4 (M): 0.791 (CI: 0.722–0.860)

For PEth cut-off 29.3 ng/mL to detect severe alcohol misuse based on AUDIT-C ≥ 6: 0.885 (CI: 0.830–0.939)
-
Jorgenrud et al., 2021 [34] Cross-sectional 2874 patients in Oslo: 931 with AUDIT-QF data and PEth levels ≥ 0.030 μM

3009 patients in Moscow: 953 with AUDIT-QF data and PEth levels ≥ 0.030 μM
2 Hospitals in Oslo and Moscow By AUDIT-QF:
“Harmful alcohol use”: ≥5 (M)/≥4 (F)

By weekly grams of alcohol:
“Harmful alcohol use”: ≥350 g of alcohol
Whole blood 16:0/18:1 UHPLC-MS/MS

≥300 μmol/L # (excessive alcohol use)
For PEth as a continuous variable ≥ 0.030 μM (AUDIT-QF ≥ 5 (men)/4 (women) as cutoff for harmful alcohol use):
Oslo: 0.633 (CI: 0.596–0.669)
Moscow: 0.685 (CI: 0.651–0.718, p < 0.001)

For PEth as a continuous variable ≥ 0.030 μM (weekly grams of alcohol ≥ 350 as cutoff for harmful alcohol use):
Oslo: 0.856 (CI: 0.798–0.914)
Moscow: 0.746 (CI: 0.700–0.793, p < 0.001)
-
Kechagias et al., 2015
[35]
Prospective randomized 44 subjects

(12 M/32 F)
Department of Clinical Chemistry, University Hospital, Lund, Sweden Randomization to alcohol abstention or to alcohol consumption:

Abstention: avoid any sort of alcohol intake during the three study months

Consumption: 300 mL of red wine (32–33 g of alcohol) per 24 h (M);
150 mL of red wine (16–16.5 g of alcohol) per 24 h (F).
Whole blood 16:0/18:1 LC-MS/MS

0.005 μmol/L * (3.5 ng/mL)
For PEth to descriminate between abstention and moderate daily consumption of red wine for 3 months: 0.92 (CI: 0.82–1) CDT
MCV
GGT
AST
ALT
Lowery et al., 2018 [36] Cross-sectional 140 brain dead organ donors

62% (n = 87) from the Gift of Hope (GOH) donor cohort
38% (n = 53) from the Loyola University Medical Center (LUMC) cohort
Itasca, IL. Loyola University Medical Center (LUMC) By UNOS definition:
“Heavy alcohol use” consumption ≥ 2 S.D./day

By CDC definition:
“Heavy alcohol use”: >1 S.D. per day on average or ≥4 S.D. consumed on one occasion in one month (F)
or >2 S.D. per day on average or ≥5 S.D. consumed on one occasion in one month (M)
Whole blood 16:0/18:1 Online-SPE-LC-MS/MS

8 ng/mL *
LOD: 2 ng/mL
For PEth cut-off ≥84 ng/mL to detect alcohol misuse: 0.86 (CI: 0.76–0.94) AST
ALT
GGT
CDT
Piano et al., 2015 [37] Cross-sectional 103 subjects

(36 M/67 F)
Participants of a larger ongoing study examinating the cardiovascular effects of binge drinking By Alcohol Intake Questionaire (AIQ)

“Alcohol abstainers”: ≤1 S.D. per month in the last 2–3 years (and abstention cannot be due to a medical illness or prior alcohol abuse)

“Moderate or social drinkers”: ≤3 S.D. per sitting with ≤1–2 times per week (M);
≤2 S.D. per sitting with ≤1–2 times in a given week in the last 5 years (F).
“Binge drinkers”: ≥5 S.D. either on one occasion or within a 2-h period in the last 30 days (M);
≥4 S.D. on one occasion or in a 2-h period in the last 30 days (F);
binge drinkers must have had ≥2 binge drinking episodes in the last month.
Venous whole blood

Venous DBS
16:0/18:1 HPLC LC/MS/MS

Whole blood:
20 ng/mL *
>20 ng/mL # (moderate to heavy drinking)

DSB:
8 ng/mL *
>8 ng/mL # (moderate to heavy drinking)
- -
Schrock et al., 2017 [9] Cross-sectional study 300 subjects

(203 M/94 F/3 not specified)
Outpatients By AUDIT-C:
Group A “Abstinence” (Group A) if AUDIT-C is 0

Group B “Moderate consumption” (Group B) if AUDIT-C is 1–3 (F) or 1–4 (M)
Group C “Excessive consumption” (Group C) if AUDIT-C is ≥4 (F) or ≥5 (M)
Whole blood 16:0/18.1
16:0/18:2
Online-SPE-LC–MS/MS
20 ng/mL *
LOD: 10 ng/mL
112 ng/mL # (for PEth 16:0/18:1, to distinguish moderate from excessive consumers)
67 ng/mL # (for PEth 16:0/18:2, to distinguish moderate from excessive consumers)
- -

PEth: Phosphatidylethanol. S.D.: Standard Drink. AUDIT: Alcohol Use Disorders Identification Test. DBS: dried blood spot. Online-SPE-LC–MS/MS: online solid-phase extraction and liquid chromatography-tandem mass spectrometry. LC MS/MS: Liquid chromatography–mass spectrometry. UHPLC-MS/MS: ultra-high performance liquid chromatography–mass spectrometry. BAC: blood alcohol concentration. uEtG: urinary ethylglucuronid. hEtG: hair ethylglucuronid. CDT: Carbohydrate-deficient transferrin. AST: aspartate aminotransferase. ALT: alanine aminotransferase. GGT: gamma-glutamyl transferase. MCV: mean corpuscular volume. In the 8th column the symbol * identifies the Limit of Quantitation (LOQ) while the symbol # identifies the interpretative cut-off chosen by the authors.