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Somatische complicaties van risicovol alcoholgebruik

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Detectie overmatig en zwaar alcoholgebruik

Beoordeeld: 10-09-2025

Uitgangsvraag

Wat is de waarde van een laboratoriumtest om patiënten met overmatig of zwaar alcoholgebruik te detecteren?

Aanbeveling

Gebruik voor het screenen op overmatig en zwaar alcoholgebruik eerst een gevalideerde vragenlijst, zoals de AUDIT-C.

 

Overweeg de inzet van phosphatidylethanol (PEth) voor de detectie van overmatig en zwaar alcoholgebruik in de acute of poliklinische setting bij een negatieve AUDIT-C en een vermoeden op overmatig of zwaar alcoholgebruik.

 

Wees terughoudend met de inzet van ethylglucuronide (EtG) en carbohydrate-deficient transferrin (%CDT) voor de detectie van overmatig of zwaar alcoholgebruik, aangezien er geen uitspraak gedaan kan worden over de waarde hiervan in verband met het ontbreken van literatuur.

Overwegingen

Voor- en nadelen van de interventie en de kwaliteit van het bewijs

Voor deze module is een literatuuranalyse gedaan naar de diagnostische accuratesse van phosphatidylethanol (PEth), ethylglucuronide (EtG) en carbohydrate-deficient transferrin (%CDT) in het detecteren van overmatig en zwaar alcoholgebruik, afgezet tegen de Alcohol Use Disorder Identification Test-Consumption (AUDIT-C).

De AUDIT-C is een verkorte versie van de AUDIT en bevat alleen drie vragen over alcoholconsumptie. Hiermee wordt de mate van gebruik van alcohol duidelijk. In tegenstelling tot de volledige AUDIT worden alcohol gerelateerde problemen niet geïnventariseerd met de AUDIT-C. Aangezien het in deze module gaat over de hoeveelheid alcohol en niet over de impact van het alcoholgebruik op het leven de patiënt, is het gebruik van de AUDIT-C passend bij de vraagstelling van deze module. Een andere belangrijke overweging om de AUDIT-C te gebruiken is dat de afnametijd korter is dan die van de AUDIT en daarmee beter haalbaar is in de (acute) klinische praktijk.

De bewijskracht van de resultaten voor de diagnostische accuratesse van PEth was zeer laag vanwege risico op bias en indirectheid. De bewijskracht van de resultaten voor EtG kon niet worden bepaald, vanwege grote heterogeniteit. Daarnaast is het goed om te benoemen dat beide geïncludeerde studies die keken naar de diagnostische waarde van EtG zijn uitgevoerd bij zwangere vrouwen. Er zijn geen studies gevonden die naar de diagnostische accuratesse van %CDT hebben gekeken, vergeleken met de AUDIT-C. De uiteindelijke bewijskracht is daarmee zeer laag. Er is dus sprake van een kennisvraag.

Het is belangrijk om te benoemen dat er geen gouden standaard beschikbaar is voor het bepalen van de mate van alcoholgebruik. De huidige studieresultaten zijn afgezet tegen de AUDIT-C, waarbij de antwoorden op de vragen door de patiënt zelf worden gegeven. 

 

PEth, EtG en %CDT verschillen in hoe lang ze na ingestie alcoholgebruik kunnen detecteren. Een overzicht van de laboratoriumtesten in het Nederlands Tijdschrift voor Geneeskunde (NTvG, Bergkamp, 2021) geeft de volgende normalisatietijden:

  • PEth: 1-3 weken
  • EtG: 4-80 uur
  • %CDT: 2-3 weken
  • Bloedalcoholconcentratie (BAC): 1-5 uur

Voor het aantonen van een alcoholpromillage kan de BAC worden bepaald in bloed of in uitgeademde lucht. Deze test is goedkoop (Bergkamp, 2021; <5 euro). De BAC toont echter alleen zeer recent (uren voorafgaand aan afname) alcoholgebruik aan en is niet bruikbaar voor het aantonen van langdurig alcoholgebruik. Detectie van langdurig alcoholgebruik is ook mogelijk door middel van een EtG-bepaling uit haar. Echter deze test is in veel laboratoria niet beschikbaar en het is een dure bepaling (>400 euro). Om deze redenen is ervoor gekozen om deze tests niet mee te nemen in de literatuuranalyse en daarmee in deze module. 

 

Behalve voor het detecteren van overmatig of zwaar alcoholgebruik om gezondheidsredenen, kunnen de tests worden ingezet om te detecteren of er überhaupt alcoholgebruik is geweest. Dit kan bijvoorbeeld van waarde zijn bij een al bekende stoornis in het gebruik van alcohol om daarmee abstinentie van alcohol te monitoren (zie ook overwegingen in module screening, classificatie, diagnostiek, indicatiestelling, monitoring en evaluatie uit de richtlijn Stoornissen in het gebruik van alcohol).

In deze situaties wordt vaak gebruik gemaakt van EtG, sneltesten of blaastesten (BAC). Hierbij is soms de diagnostische accuratesse minder van belang en hoeft er geen onderscheid gemaakt te worden tussen eenmalig alcoholgebruik en overmatig of zwaar alcoholgebruik. In dat geval kan worden overwogen om een eenvoudig uitvoerbare of goedkopere test in te zetten, of een test die minder lang positief blijft na gebruik, zoals een EtG- of BAC-bepaling.

 

Waarden en voorkeuren van patiënten (en evt. hun verzorgers)

De inzet van een laboratoriumtest gericht op het gebruik van alcohol kan een negatief effect hebben op de behandelrelatie tussen zorgverlener en patiënt vanwege het controlerende aspect, met name in de vrijwillige zorg. Zelfrapportage van alcoholgebruik lijkt in het geval van een stoornis in het gebruik van alcohol een grotere therapeutische waarde te hebben vanwege het minder controlerende karakter en heeft daarmee mogelijk tevens een positief effect op de behandelrelatie. Echter, wanneer overmatig of zwaar alcoholgebruik wordt vermoed en de patiënt dit blijft ontkennen, kan het aantonen hiervan door middel van een laboratoriumtest de patiënt alsnog motiveren om het gesprek aan te gaan over het alcoholgebruik. Een doel hiervan kan zijn om toe te leiden naar een behandeling van de stoornis in het gebruik van alcohol of het eerder signaleren van (lange termijn) complicaties van alcoholgebruik.

De aanvraag van een laboratoriumtest dient met goedkeuring van de patiënt te gebeuren. Het is denkbaar dat een patiënt die op dat moment schaamte ervaart over het alcoholgebruik en/of nog niet open staat voor behandeling, geen toestemming zal geven voor het uitvoeren van het onderzoek. Hierdoor kan overmatig of zwaar alcoholgebruik onopgemerkt blijven. Anderzijds kan het weigeren van een laboratoriumtest door de patiënt op zichzelf al opening geven voor een gesprek over alcoholgebruik, waarmee de mate van alcoholgebruik alsnog aan het licht kan komen door zelfrapportage. 

 

Kosten (middelenbeslag)

De kosten per test variëren per laboratorium. Een overzicht van laboratoriumtesten in het NTvG (Bergkamp, 2021) geeft de volgende kosten:

  • PEth: relatief duur (>50 euro)*
  • EtG: gemiddeld (20-40 euro) tot relatief duur (>50 euro)
  • %CDT: gemiddeld (20-40 euro) tot relatief duur (>50 euro)

Hieruit blijkt dat PEth een duurdere bepaling is om in te zetten, zeker in vergelijking met andere methoden voor het aantonen en kwantificeren van alcoholgebruik.

 

* Bij navraag bij enkele laboratoria door leden van de werkgroep blijkt dat de kosten veelal >100 euro per aanvraag liggen.

 

Aanvaardbaarheid, haalbaarheid en implementatie

Hoewel veel laboratoria de bepaling van EtG en %CDT kunnen uitvoeren, is het aanvragen van PEth niet bij alle laboratoria mogelijk of kan er vertraging zijn, omdat het monster moet worden opgestuurd naar een ander laboratorium. In Nederland is er op dit moment nog een beperkt aanbod van laboratoria die PEth kunnen bepalen. De verwachting is dat dit aanbod in de toekomst zal toenemen. In België en de Scandinavische landen is dit aanbod aanzienlijk groter.

Hoewel het wenselijk en van belang is om screening uit te voeren en continue afname daarvan te stimuleren, blijkt uit studies dat routinescreening op overmatig en zwaar alcoholgebruik door middel van vragenlijsten op de spoedeisende hulp (SEH) vaak niet haalbaar is om uiteenlopende redenen, onder andere omdat personeel er vaak onvoldoende tijd en rust voor heeft en niet alle patiënten kunnen of willen meewerken (Van Loon, 2020). Laboratoriumtests die screenen op overmatig en zwaar alcoholgebruik zouden kunnen bijdragen aan een betere detectie hiervan. Een dergelijke test zou tegelijk met ander bloedonderzoek dat wordt ingezet na binnenkomst op de SEH bepaald kunnen worden. Het is op de SEH meestal van belang dat de bepaling snel (cito) uitgevoerd kan worden en de uitslag binnen een tot twee uren bekend kan zijn, om deze mee te kunnen nemen bij het bepalen van het behandelbeleid. Als cito bepaling niet mogelijk is, kan dat een belemmering zijn voor de implementatie. Het aanvragen van een cito PEth-bepaling is op dit moment in Nederland niet mogelijk. Voor CDT en EtG is dit wel mogelijk, indien dit met immunoassay wordt gemeten.

 

Aanbeveling

Rationale van de aanbeveling: weging van argumenten voor en tegen de diagnostische procedure

PEth

De bewijskracht van de resultaten over de diagnostische accuratesse van PEth in het aantonen van overmatig en zwaar alcoholgebruik ten opzichte van de AUDIT-C is zeer laag. Vanwege de hogere kosten en de minder goede beschikbaarheid van de PEth test kan de toepasbaarheid beperkt zijn.

 

EtG

Uit de literatuur wordt niet duidelijk wat de meerwaarde is van de inzet van EtG in het opsporen van overmatig en zwaar alcoholgebruik. De gevonden literatuur bestond enkel uit studies bij zwangere vrouwen met heterogene resultaten. Derhalve konden geen conclusies worden geformuleerd. De beschikbaarheid van laboratoria die testen op EtG is groter dan PEth en de kosten zijn lager.

 

%CDT

Voor %CDT zijn er geen studies gevonden die voldeden aan de inclusiecriteria. Derhalve konden hierover geen conclusies worden geformuleerd. De beschikbaarheid van laboratoria die testen op %CDT is groter dan PEth en de kosten zijn lager.

 

De AUDIT-C is een accurate screener (zie overwegingen in module Screening, Classificatie, Diagnostiek, Indicatiestelling, Monitoring en evaluatie uit de richtlijn Stoornissen in het gebruik van alcohol en Bisschop, 2025) . De uitvoer brengt slechts beperkte kosten met zich mee. Ondanks de geringe afnametijd kan de daadwerkelijke inzet op de SEH en poliklinieken wisselend zijn vanwege onder andere aanwezige tijdsdruk en/of onvoldoende scholing bij het zorgpersoneel en de toestand waarin de patiënt verkeert, die screening kan bemoeilijken.

Onderbouwing

In clinical practice, there may be various reasons for detecting alcohol use. The amount of alcohol use that needs to be detected depends on the patient’s situation and the treatment plan. For example, to determine a possible candidate for liver transplantation after chronic alcohol use and for monitoring abstinence after an alcohol use disorder, the use of any amount of alcohol needs to be detected. However, when trying to prevent long-term health risks, detection of only excessive or heavy alcohol use is necessary. In this module, we only focus on the accuracy of three laboratory tests in determining excessive or heavy alcohol use, in comparison to the AUDIT-C questionnaire. The accuracy of these laboratory tests in detecting any amount of alcohol use is not evaluated in this module.

 

For this question two different settings were distinguished:

 

Emergency department:

Alcohol-related health problems are common in the emergency department (ED). However, excessive and heavy alcohol use is not always apparent. Not every healthcare professional routinely asks patients about alcohol use, routine screening is not always feasible in the ED and patients are sometimes hesitant to answer the questions about alcohol use truthfully. Therefore, there is a need for a reliable tool that can help determine the extent to which patients use alcohol. Knowledge of the extent to which patients use alcohol is not only relevant in the diagnostic process, it is also important for considering treatment options, as several medications used and prescribed in the ED can interact with alcohol. In addition, excessive and heavy alcohol use can have a detrimental effect on the recovery from many conditions and interventions. This has to be taken into account when deciding whether or not to carry out a treatment and to properly inform patients about the risks. Hence, for successful and safe treatment of health issues, it is crucial that the healthcare professional is informed about the patient’s alcohol use.

When excessive and heavy alcohol use can be detected by an accurate, reliable laboratory test, patients can subsequently be educated about risks, the treatment plan can be adapted to reduce risks of the drug-alcohol interactions, and if necessary, a referral for treatment of an alcohol use disorder can be made in order to prevent further harm.

 

Outpatient setting:

In the outpatient setting, screening for excessive or heavy alcohol use is mainly intended for the detection of an alcohol use disorder, for solving unexplained medical complaints and for early detection of long-term health risks associated with alcohol use. Recently, alcohol screening has received more attention. Especially self-reporting screening questionnaires are increasingly used. One of these questionnaires is the AUDIT-C, a validated and accurate screening tool for excessive and heavy alcohol use (zie overwegingen in module Screening, Classificatie, Diagnostiek, Indicatiestelling, Monitoring en evaluatie uit de richtlijn Stoornissen in het gebruik van alcohol en Bisschop, 2025).

However, self-reporting questionnaires carry the risk of acquiring socially desirable answers. Therefore, there is a need for an objective screening tool such as a laboratory test, detecting not only excessive or heavy alcohol use during the last few hours but also for longer periods.

Phosphatidylethanol (PEth)

Very low

GRADE

The evidence is very uncertain about the diagnostic accuracy of PEth bloodconcentration in determining (severe) alcohol misuse in adults, as compared to AUDIT-C.

 

Sources: Gerbase, 2021; Afshar, 2018; Schröck, 2017

 

Ethylglucuronide (EtG)

No

GRADE

No conclusion was drawn on the diagnostic accuracy of EtG concentration in urine of pregnant women to determine alcohol misuse, as the results were too heterogenous.

 

Sources: Ceci, 2022; Ferraguti, 2017

 

Carbohydrate-deficient transferrin (%CDT)

No

GRADE

No evidence was found on the diagnostic accuracy of %CDT in the detection of (chronic) excessive alcohol use in adult patients who are suspected of (chronic) excessive alcohol use.

 

Source: -

Description of studies

Gerbase (2021) performed a study on the diagnostic performance of phosphatidylethanol (PEth) for detection of alcohol misuse. They included 238 injured patients at the emergency department (ED). Whole blood samples were collected to determine PEth levels (16:0/18:1 fatty acids). Cut-offs of 18.3 ng/ml and 23.9 ng/ml were the most optimal cut-offs to indicate respectively alcohol misuse and severe alcohol misuse. The Alcohol Use Disorders Identification Test – Consumption (AUDIT-C) was used as a reference standard. Alcohol misuse was defined as AUDIT-C ≥3 (women)/ ≥4 (men) and severe alcohol misuse as AUDIT-C ≥6. Prevalences of alcohol misuse and severe alcohol misuse were respectively 26.9% and 13.9%. Mean (95CI%) age was 41.7 (39.3 to 44) years and 67.6% of the patients was male. Time interval between blood sampling and filling out the AUDIT-C was not reported.

 

Afshar (2018) performed a study on the diagnostic performance of PEth for detection of alcohol misuse. They included 122 patients, of whom 31 were critically ill patients. Other participants were patients with alcohol use disorder (AUD, n=51) and matched controls (healthy volunteers, n=38). Whole blood samples were taken, from which dried blood spots were collected and analyzed for PEth (16:0 and 18:1 fatty acids). Cut-offs of 250 ng/ml and 400 ng/ml were used to indicate respectively alcohol misuse and severe alcohol misuse. The AUDIT-C was used as a reference standard. Alcohol misuse was defined as AUDIT-C ≥3 (women)/ ≥4 (men) and severe alcohol misuse as AUDIT-C ≥8 (men) and ≥6 (women). Prevalences of moderate and severe alcohol misuse were respectively 11.5% and 40.2%. Median (IQR) age was 43.5 (36 to 50) years and 76.2% of the patients was male. Time interval between blood sampling and filling out the AUDIT-C was not reported.

 

Schröck (2017) performed a study on the diagnostic performance of PEth for detection of alcohol (mis)use. They included data from 300 healthy volunteers. Inclusion nor exclusion criteria were reported. Whole blood samples were obtained after blood donation at blood donation centers and analyzed within three days for PEth (16:0 and 18:1/18:2 fatty acids). A cut-off of 112ng/ml was used to indicate severe alcohol misuse. The AUDIT-C was used as a reference standard. Moderate alcohol use was defined as AUDIT-C ≤3 (women)/ ≤4 (men) and excessive alcohol use as AUDIT-C ≥5 (men) and ≥4 (women). Prevalences of moderate and severe alcohol use were respectively 71% and 25%. Mean (±SD) age was 47±13 years and 67.6% of the patients was male. Time interval between blood sampling and filling out the AUDIT-C was not reported.

 

Ceci (2022) performed a study on the diagnostic performance of ethylglucuronide (EtG) for the detection of alcohol misuse in pregnant women. They included 309 pregnant women, who had a follow-up visit at the ambulatory of the department Gynaecology and Obstetrics. A food diary interview was used to indirectly understand alcohol habits. Afterwards, women were asked to fill in three structured questionnaires (AUDIT-C, T-ACE and TWEAK) and to provide a urine sample (to determine the EtG-concentration). For this question, the AUDIT-C was used as a reference standard. Hazardous or harmful alcohol use was defined as AUDIT-C ≥3. A cut-off of 100 ng/ml was used to indicate exposure to alcohol. Median (range) age was 32 (17 to 44) years.

 

Ferraguti (2017) performed a study on the diagnostic performance of EtG for the detection of alcohol misuse in pregnant women. They included 70 pregnant women, who had a follow-up visit at the ambulatory of the Gynaecology and Obstetrics department. Per hospital guidelines, gynecologists first used motivational interviewing and supportive dialogue to talk about alcohol use with pregnant women. Afterwards, women were asked to provide a urine sample (to determine the EtG-concentration) and to fill in three structured questionnaires (AUDIT-C, T-ACE and TWEAK). For this question, the AUDIT-C was used as a reference standard. Hazardous or harmful alcohol use was defined as AUDIT-C ≥3. A cut-off of 100 ng/ml was used to indicate exposure to alcohol. Mean (±SD) age was 33±7 years.

 

Results

Phosphatidylethanol (PEth)

Three studies (Gerbase, 2021; Afshar, 2018 and Schröck, 2017) researched the diagnostic accuracy of PEth in determining (severe) alcohol misuse in adults compared to AUDIT-C. Schröck (2017) only reported results for severe alcohol misuse. Alcohol misuse was defined as ≥4 in men and ≥3 in women. Severe alcohol misuse was defined as ≥6 (Gerbase, 2021), ≥8 in men and ≥6 in women (Afshar, 2018) or ≥4 in women and ≥5 in men (Schröck, 2017).

 

Results on diagnostic accuracy of PEth are shown in Table 1 for detection of alcohol misuse and in Table 2 for detection of severe alcohol misuse. When interpreting the results, it is important to take into account that the cut-offs varied widely between the studies. In the consensus paper on the use of PEth for the assessment of abstinence and extent of alcohol consumption (Luginbühl, 2022) the following cut-offs were proposed:

  • <20 ng/mL: compatible with abstinence or low alcohol consumption;
  • ≥20 ng/mL but <200 ng/mL: alcohol consumption;
  • ≥200 ng/mL: strongly suggestive of chronic excessive alcohol consumption

In the studies of Gerbase (2021) and Schröck (2017) lower cut-offs were applied, while the cut-offs used by Afshar (2018) were relatively high.

 

Two studies did not report the confidence intervals for sensitivity or specificity, nor could they be calculated as the authors did not report the crude numbers (Gerbase, 2021 and Schröck, 2018). Two studies used whole blood to measure PEth (Gerbase, 2021; Schröck, 2017) and one study a dried blood sample (Afshar, 2018). However, this should not influence the results.

 

In short, sensitivity and specificity of PEth for the detection of alcohol misuse is <85%, apart from the specificity in Afshar’s study (2018). The results for PEth in the detection of severe alcohol misuse, compared with the AUDIT-C were heterogeneous, with sensitivity and specificity varying from respectively 22.9% to 91.2% and 78.4% to 96.6%. 

 

The results from Table 1 showed a small to moderate benefit for the posttest probability. In other words, using results from PEth increases the likelihood in determining alcohol use (LR+) or non-use (LR-). The results from Table 2 in determining severe alcohol use were similar. However, Schröck (2018) may indicate that PEth does not decrease the posttest probability in case of alcohol non-use (LR-).

However, the results could not be pooled, because confidence intervals were not mentioned in the studies by Gerbase (2021) and Schröck (2018).

 

Table 1 Results on diagnostic accuracy of PEth for detection of alcohol misuse, compared with AUDIT-C.

Parameter

Gerbase, 2021

Afshar, 2018

Number of participants

238

122

Cut-off

18.3 ng/ml

250 ng/ml

Sensitivity (95%CI)

73.4%

80.6% (69.2% to 88.6%)

Specificity (95%CI)

80.6%

91.7% (79.1% to 97.3%)

PPV (95%CI)

79%

93.5% (83.5% to 97.9%)

NPV (95%CI)

75%

75.9% (62.5% to 85.7%)

LR+

3.78

9.71

LR-

0.33

0.21

LR+: positive likelihood ratio; LR-: negative likelihood ratio; NPV: negative predictive value; PPV: positive predictive value

 

Table 2 Results on diagnostic accuracy of PEth for detection of severe alcohol misuse, compared with AUDIT-C.

Parameter

Gerbase, 2021

Afshar, 2018

Schröck, 2017

Number of participants

238

122

300

Cut-off

23.9 ng/ml

400 ng/ml

112 ng/ml

Sensitivity (95%CI)

91.2%

83.6% (70.7% to 91.8%)

22.9%

Specificity (95%CI)

78.4%

89.2% (78.5% to 95.2%)

96.6%

PPV (95%CI)

80.8%

86.8% (74.0% to 94.1%)

-

NPV (95%CI)

89.9%

86.6% (75.5% to 93.3%)

-

LR+

4.22

7.74

6.74

LR-

0.11

0.18

0.80

LR+: positive likelihood ratio; LR-: negative likelihood ratio; NPV: negative predictive value; PPV: positive predictive value

 

Ethylglucuronide (EtG)

Two studies (Ceci, 2022 and Ferraguti, 2017) researched the diagnostic accuracy of EtG concentration (cut-off 100 ng/ml) for alcohol misuse in pregnant women, with the reference standard AUDIT-C (cut-off ≥ 3). Ceci (2022) used the ethylglucuronide/creatinine ratio. The results are shown in Table 3.

As the results were only from two studies, the results were not pooled. Because of heterogenous results, no conclusion can be drawn on the diagnostic accuracy of EtG concentration in urine for detection of alcohol misuse in pregnant women. Both studies reported low sensitivity and specificity levels (<85%) of EtG in the detection of alcohol misuse in pregnant women.

 

Table 3: Results on diagnostic accuracy of EtG for detection of alcohol misuse, when compared with AUDIT-C.

Parameter

Ceci (2022)

Ferraguti (2017)

Number of participants

309

80

Sensitivity (95%CI)

21% (13% to 31%)

0% (0% to 98%)

Specificity (95%CI)

80% (74% to 85%)

65% (53% to 76%)

PPV (95%CI)

29% (20% to 39%)

0% (-)

NPV (95%CI)

72% (70% to 75%)

98% (97% to 98%)

LR+ (95%CI)

1.03 (0.63 to 1.67)

0 (-)

LR- (95%CI)

0.99 (0.87 to 1.13)

1.53 (1.29 to 1.82)

LR+: positive likelihood ratio; LR-: negative likelihood ratio; NPV: negative predictive value; PPV: positive predictive value

 

Carbohydrate-deficient transferrin (%CDT)

There was no study available which evaluated the diagnostic value of %CDT in the detection of (chronic) excessive alcohol use in adult patients who are suspected of (chronic) excessive alcohol use, using the AUDIT-C as a comparator.

 

Level of evidence of the literature

Phosphatidylethanol (PEth)

The level of evidence for all outcome measures was downgraded by three levels to very low, because of risk of bias (unclear whether the results of the tests were interpreted without knowledge of the other test, AUDIT-C is self-reported, optimal cut-offs are determined using highest Youden indices and cut-offs varied widely between the studies, downgraded two levels) and indirectness (no golden standard available, downgraded one level).

 

Ethylglucuronide (EtG)

The level of evidence was not assessed as the results were too heterogenous.

 

Carbohydrate-deficient transferrin (%CDT)

There was no study available that evaluated the diagnostic value of %CDT in the detection of (chronic) excessive alcohol use in adult patients who are suspected of (chronic) excessive alcohol use, using the AUDIT-C as a comparator. Therefore, the level of evidence could not be assessed.

A systematic review of the literature was performed to answer the following question: What is the diagnostic value of a laboratory test (EtG, CDT or PEth) in the detection of (chronic) excessive alcohol use in adult patients who are suspected of (chronic) excessive alcohol use?

P (Patients) adult patients who are suspected of excessive alcohol use
I (Intervention) ethyl glucuronide levels (EtG), % carbohydrate-deficient transferrin (%CDT), phosphatidylethanol (PEth)
C (Comparison)

alcohol screening questionnaire (Alcohol Use Disorders Identification Test-Consumption, AUDIT-C)
R (Reference) n.a.
O (Outcomes) sensitivity, specificity, negative likelihood ratio (LR-), positive likelihood ratio (LR+), AUC
T/S (Timing/Setting) emergency department or outpatient clinic

Relevant outcome measures

The guideline development group considered sensitivity and negative likelihood ratio as critical outcome measures for decision making; and specificity and positive likelihood ratio as important outcome measures for decision making.

 

Likelihood ratios

The LR is the likelihood that a given test result is expected in a patient with the disease/target condition compared to the likelihood that the same test result is expected in a patient without the disease/target condition. If LR >1: the test result is associated with the presence of the disease/target condition (LR+), while LR <1 means that the test result is associated with the absence of the disease/target condition (LR-). The further LRs are away from 1, there is increasing utility of the test in ruling in or out the disease/target condition.

 

The LR is calculated as follows:

  • LR+ = sensitivity / (1-specificity)
  • LR- = (1-sensitivity) / specificity

 

The working group defined the following values as clinically relevant:

  • LR+: five to 10 (moderate effect on post-test probability (Jeaschke, 1994))
  • LR-: 0.1 to 0.2 (moderate effect on post-test probability (Jeaschke, 1994))
  • Sensitivity and specificity: >85%

Search and select (Methods)

The databases Medline (via OVID) and Embase (via Embase.com) were searched with relevant search terms until July 30th, 2023. The detailed search strategy is depicted under the tab Methods. The systematic literature search resulted in 623 hits. Studies were selected based on the following criteria: comparative studies on the diagnostic value of laboratory tests (EtG, CDT or Peth) in the detection of (chronic) excessive alcohol use in adult patients, using AUDIT-C as a comparator. The following studies were excluded:

  • Studies which were performed in settings that differ substantially from the Netherlands (e.g. Africa);
  • Studies performed in patients using medication that might interact with values of EtG, %CDT or Peth (e.g. patients with psoriasis);
  • Studies performed in patients with HIV;
  • Studies performed in drivers (since it is often not clear whether there is an underlying disease/problem);
  • Studies which used hair to determine EtG value. 

92 studies were initially selected based on title and abstract screening. After reading the full text, 87 studies were excluded (see the table with reasons for exclusion under the tab Methods), and five studies were included.

 

Results

Five studies were included in the analysis of the literature (Afshar, 2017; Schröck, 2017; Ferraguti, 2017; Gerbase, 2021 and Ceci, 2022). Important study characteristics and results are summarized in the evidence tables. The assessment of the risks of bias is summarized in the risk of bias tables.

  1. Afshar M, Burnham EL, Joyce C, Clark BJ, Yong M, Gaydos J, Cooper RS, Smith GS, Kovacs EJ, Lowery EM. Cut-Point Levels of Phosphatidylethanol to Identify Alcohol Misuse in a Mixed Cohort Including Critically Ill Patients. Alcohol Clin Exp Res. 2017 Oct;41(10):1745-1753. doi: 10.1111/acer.13471. Epub 2017 Sep 13. PMID: 28792620; PMCID: PMC5626634.
  2. Bergkamp FJM and van Soest EJ. Biomarkers voor alcoholgebruik, een update. Ned Tijdschr Geneeskd. 2021. 165: D6116
  3. Bisschop JM, de Jonge HJM, Brunsveld-Reinders AH, van de Mheen DH, Mathijssen JJP, Rozema AD. Screening instruments to detect problematic alcohol use among adults in hospitals and their diagnostic test accuracy: A systematic review. Drug Alcohol Rev. 2025 Feb;44(2):505-531. doi: 10.1111/dar.13987. Epub 2025 Jan 19. PMID: 39828425; PMCID: PMC11814358.
  4. Ceci FM, Fiore M, Agostinelli E, Tahara T, Greco A, Ralli M, Polimeni A, Lucarelli M, Colletti R, Angeloni A, Tirassa P, Ceccanti M, Messina MP, Vitali M, Petrella C, Ferraguti G. Urinary Ethyl Glucuronide for the Assessment of Alcohol Consumption During Pregnancy: Comparison between Biochemical Data and Screening Questionnaires. Curr Med Chem. 2022;29(17):3125-3141. doi: 10.2174/0929867328666211125100329. PMID: 34823457.
  5. Ferraguti G, Ciolli P, Carito V, Battagliese G, Mancinelli R, Ciafrè S, Tirassa P, Ciccarelli R, Cipriani A, Messina MP, Fiore M, Ceccanti M. Ethylglucuronide in the urine as a marker of alcohol consumption during pregnancy: Comparison with four alcohol screening questionnaires. Toxicol Lett. 2017 Jun 5;275:49-56. doi: 10.1016/j.toxlet.2017.04.016. Epub 2017 Apr 25. PMID: 28455000.
  6. Gerbase FE, Tegner M, Krutzmann ME, Muller VV, Alff JA, da Silva VB, Sagrilo OP, Linden R, Antunes MV. Blood phosphatidyl ethanol levels as a tool to detect alcohol misuse in trauma patients. Clin Toxicol (Phila). 2021 May;59(5):418-425. doi: 10.1080/15563650.2020.1822531. Epub 2020 Oct 6. PMID: 33021410.
  7. Jaeschke R, Guyatt GH, Sackett DL. Users' guides to the medical literature. III. How to use an article about a diagnostic test. B. What are the results and will they help me in caring for my patients? The Evidence-Based Medicine Working Group. JAMA. 1994 Mar 2;271(9):703-7. doi: 10.1001/jama.271.9.703. PMID: 8309035.
  8. Schröck A, Wurst FM, Thon N, Weinmann W. Assessing phosphatidylethanol (PEth) levels reflecting different drinking habits in comparison to the alcohol use disorders identification test - C (AUDIT-C). Drug Alcohol Depend. 2017 Sep 1;178:80-86. doi: 10.1016/j.drugalcdep.2017.04.026. Epub 2017 Jun 13. PMID: 28645063.
  9. van Loon M, Van der Mast RC, van der Linden MC, van Gaalen FA. Routine alcohol screening in the ED: unscreened patients have an increased risk for hazardous alcohol use. Emerg Med J. 2020 Apr;37(4):206-211. doi: 10.1136/emermed-2019-208721. Epub 2020 Jan 13. PMID: 31932395.

Evidence table for diagnostic test accuracy studies

Study reference

Study characteristics

Patient characteristics

 

Index test

(test of interest)

Reference test

 

Follow-up

Outcome measures and effect size

Comments

Gerbase, 2021

Type of study:

Cohort study

 

Setting and country:

Emergency department, Brazil

 

Funding and conflicts of interest:

Non-commercial funding, no COI

Inclusion criteria:

Adult patients presenting at the

Emergency department with any type of trauma

 

Exclusion criteria:

Inability to give

informed written consent, more than 6 h between trauma

and blood sampling or decline to participate in the study.

 

N=238

 

Prevalence:*

Alcohol misuse: 26.9%

Severe alcohol misuse: 13.9%

*Based on AUDIT-C

 

Mean age (95%CI):

41.7 (39.3-44)

 

Sex: 67.6% M / 32.4% F

 

Other important characteristics:

 

 

Describe index test:

Blood Phosphatidylethanol 16:0/18:1 (PEth) in whole blood samples

 

Cut-off point(s):

Alcohol misuse

6.7/15/1/18.3*/21.8/30.0 ng/mL

Severe alcohol misuse

6.7/23.9*/30.5/34.9

 

* Optimal cut-point levels were derived using the highest Youden indices

 

Comparator test:

n.a.

Cut-off point(s):

n.a.

Describe reference test:

Alcohol Use Disorders Identifcation Test, AUDIT-C)

 

 

Cut-off point(s):

Alcohol misuse

≥4 in men and ≥3 in women

Sever alcohol misuse

≥6

 

Time between the index test en reference test:

Not reported

 

For how many participants were no complete outcome data available?

None

 

Reasons for incomplete outcome data described?

N.A.

Alcohol misuse

 

Sensitivity (%)

6.7 ng/mL: 76.6

15.1 ng/mL: 75

18.3 ng/mL: 73.4

21.8 ng/mL: 70.3

30.0 ng/mL: 64.0

 

Specificity (%)

6.7 ng/mL: 69

15.1 ng/mL: 71.9

18.3 ng/mL: 80.6

21.8 ng/mL: 81

30.0 ng/mL: 82.8

 

PPV (%)

6.7 ng/mL: 71.1

15.1 ng/mL: 72.7

18.3 ng/mL: 79

21.8 ng/mL: 78.7

30.0 ng/mL: 78.8

 

NPV (%)

6.7 ng/mL: 74.6

15.1 ng/mL: 74.2

18.3 ng/mL: 75.0

21.8 ng/mL: 73.1

30.0 ng/mL: 69.6

 

Severe alcohol misuse

 

Sensitivity (%)

6.7 ng/mL: 94.1

23.9 ng/mL: 91.2

30.5 ng/mL: 88.2

34.9 ng/mL: 82.4

 

Specificity (%)

6.7 ng/mL: 65.2

23.9 ng/mL: 78.4

30.5 ng/mL: 79.9

34.9 ng/mL: 81.9

 

PPV (%)

6.7 ng/mL: 73.0

23.9 ng/mL: 80.8

30.5 ng/mL: 81.4

34.9 ng/mL: 81.9

 

NPV (%)

6.7 ng/mL: 91.7

23.9 ng/mL: 89.9

30.5 ng/mL: 87.1

34.9 ng/mL: 82.3

 

Authors conclusion

In conclusion, our results indicate that blood PEth levels are positively correlated to the AUDIT-C score in the studied

population. This study corroborates the findings of underreporting on self-reported alcohol consumption questionnaires.

The use of blood PEth levels might provide additional and

objective evidence in the screening of alcohol misuse in trauma patients. Future studies with PEth and other direct alcohol biomarkers in injured patients area needed to identify the best alcohol screening tool and to provide interventions to reduce the burden of trauma recidivism.

 

Other remarks

Median time between trauma and blood sampling (median, range): 50 min (20 min – 5h 48 min)

 

Afshar, 2017

Type of study:

Cohort study/case control

 

Setting and country:

Burn or medical ICU, inpatient alcohol detoxification unit and healthy volunteers, USA

 

Funding and conflicts of interest:

Non-commercial funding, no COI

Inclusion criteria:

Burn ICU patients

Those >15% burn injury or suspected inhalation injury admitted to a burn ICU.

Medical ICU patients

Admitted to the medical ICU,  respiratory failure requiring invasive mechanical ventilation.

Ambulatory individuals (alcohol use disorders and healthy individuals)

Individuals with AUD (AUDIT score of ≥8 for men or ≥5 for women) who were otherwise healthy in comparison to healthy controls (no elevated AUDIT scores).

 

Exclusion criteria:

Burn ICU patients

< 18 years; expected to die within 48 hours of admission; admitted greater than 24 hours after injury; and pregnancy

 

Medical ICU patients

< 18 or > 90 years; pregnancy; organ transplant; chronic immunosuppression; prior respiratory disease; patients at-risk for increase intracranial pressure; or expected survival of less than six months

 

Ambulatory individuals (alcohol use disorders and healthy individuals)

liver disease, gastrointestinal bleeding, left ventricular ejection fraction <50%, myocardial infarction, severe valvular dysfunction, end-stage renal disease requiring dialysis, serum creatinine ≥2 mg/dl, diabetes mellitus, HIV, or lung disease defined as an abnormal chest radiograph; concurrent illicit drug use; pregnancy; or abnormal nutrition status

 

N= 122

Critically ill patients: N=33

AUD patients

N=51

Healthy controls

N=38

 

Prevalence:*

Alcohol misuse: 14/122 (11.5)%

Severe alcohol misuse: 49/122 (40.2%)

*Based on AUDIT-C

 

 

Age (median, IQR):

43.5 (36-50)

 

Sex: 76.2% M / 23.8% F

 

Other important characteristics:

 

Describe index test:

Peth 16:0 and 18:1 via dried blood spot collection (obtained from whole blood samples)

 

Cut-off point(s):

Alcohol misuse

250 ng/mL

Severe alcohol misuse

400 ng/mL

 

 

*Optimal cut-point levels were derived using the highest Youden indices

 

Comparator test:

N.A.

Cut-off point(s):

N.A.

Describe reference test:

AUDIT-C

 

 

Cut-off point(s):

Alcohol misuse

≥4 in men and ≥3 in women

Sever alcohol misuse

≥6 in women and ≥8 in men

 

Time between the index test en reference test:

Not reported

 

For how many participants were no complete outcome data available?
None

Reasons for incomplete outcome data described?
N.A.

Alcohol misuse

(cut-off: 250 ng/mL)

 

Sensitivity (%, 95%CI)

80.6 (69.2, 88.6)

 

Specificity (%, 95%CI)

91.7 (79.1, 97.3)

 

PPV (%, 95%CI)

93.5 (83.5, 97.9)

 

NPV (%, 95%CI)

75.9 (62.5, 85.7)

 

Severe alcohol misuse

(cut-off: 400 ng/mL)

 

Sensitivity (%, 95%CI)

83.6 (70.7, 91.8)

 

Specificity (%, 95%CI)

89.2 (78.5, 95.2)

 

PPV (%, 95%CI)

86.8 (74.0, 94.1)

 

NPV (%, 95%CI)

86.6 (75.5, 93.3)

 

*Diagnostic accuracy for critically ill patients is also available.

Authors conclusion

This is the first study to address the role of PEth in a cohort including critically ill patients. We demonstrate good diagnostic accuracy for PEth in discriminating alcohol misuse with useful cut-points to risk stratify patients. Further validation in a more representative sample of critically ill patients is needed prior to clinical and research application.

 

Other remarks

Blood was collected within 36 hours of hospital presentation.

 

Mixed cohort, AUD patients and healthy controls were matched for age, gender and smoking habits.

Schröck, 2017

Type of study:

Cohort study

 

Setting and country:

Healthy volunteers, Switzerland,

 

Funding and conflicts of interest:

No COI, non-commercial funding

Inclusion criteria:

NR

 

Exclusion criteria:

NR

N= 300

 

Prevalence: *

Abstinence: 12/300 (4%)

Moderate consumption: 214/300 (71%)

ive consumption: 74/300 (25%)

*Based on AUDIT-C

 

Age (mean± SD): 47±13

Abstinence: 46±13

Moderate consumption: 48±12

Excessive consumption: 44±14

 

Sex: 67.6% M / 31.4% F

(1% not specified)

Abstinence: 46±13

Moderate consumption: 48±12

Excessive consumption: 44±14

 

Other important characteristics:

 

Describe index test:

PEth 16:0/18:1 and PEth 16:0/18:2 in whole blood

 

Cut-off point(s):*

Abstainers/moderate consumption

PEth 16:0/18:1: < 112 ng/mL

PEth 16:0/18:2: < 67 ng/mL

 

Excessive consumption

PEth 16:0/18:1: ≥ 112 ng/mL

PEth 16:0/18:2: ≥ 67 ng/mL

 

Comparator test:

n.a.

 

Cut-off point(s):

n.a.  

 

*Cut-off points were chosen to differentiate between alcohol consumption groups with high sensitivity and specificity.

Describe reference test:

AUDIT-C

 

 

Cut-off point(s):

Abstainers

=0

Moderate consumption

≤4 in men and ≤3 in women

Excessive consumption

≥4 in women and ≥5 in men

 

 

Time between the index test en reference test:

Not clear

 

For how many participants were no complete outcome data available?

NR

 

Reasons for incomplete outcome data described?

NR

PEth 16:0/18:1: 112 ng/mL

 

Sensitivity (%)

22.9

 

Specificity (%)

96.6

 

PEth 16:0/18:2: 67 ng/mL

 

Sensitivity

22.1

 

Specificity

96.6

 

Authors conclusion

the alcohol biomarker PEth can be applied to confirm or to disprove self-reported alcohol consumption. In the present study a high correlation between PEth values and self-reports was found. PEth 16:0/18:1 values below the LOD of 10.0 ng/mL are strongly correlated with light drinking habits (≤10 g pure alcohol/day) or abstinence. As PEth 16:0/18:1 concentrations ranging from not detected to 112 ng/mL (for Peth 16:0/18:2 values from not detected to 67.0 ng/

mL) correspond to 95% of the tested persons in the group with AUDIT-C

scores representing moderate alcohol consumption, we suggest to employ these reference ranges as optimal indicators for alcohol consumption in a harmless way (≤20 g/day females, ≤ 40 g/day males, (WHO, 2000)). PEth values above this range point to recent excessive alcohol consumption (AUDIT-C score ≥4 females, AUDIT-C score ≥5 males).

 

Other remarks

Results on diagnostic accuracy are not very clear and reported in the discussion.

 

Ceci, 2022

Type of study:

Cohort study

 

Setting and country:

Ambulatory of Gynaecology and Obstetrics, Italy

 

Funding and conflicts of interest:

No relevant COI, no funding

Inclusion criteria:

Pregnant women visiting for a follow-up the ambulatory of Gynaecology and Obstetrics of a hospital in Italy between 2016-2020.

 

Exclusion criteria:

Impossibility to communicate

in Italian and complications in pregnancy, e.g. gestational diabetes and hypertension,

history of head injury, loss of consciousness, history of organic mental disorder, assumption of psychoactive legal and illegal drugs, and accessory criteria of exclusion

that can be correlated to alcohol abuse and alcoholism, use of mouthwashes containing alcohol

 

N= 309

 

Prevalence:

86/309 (27.8%) – based on AUDIT-C

 

Age (median – range):

32 (17-44)

 

Sex:

100%F

 

Other important characteristics:

Trimester (%)

1: 27

2: 29

3: 44

 

Describe index test:

EtG in urine (ng/mL) or EtG/CreU ratio (ng/mg)

 

Cut-off point(s):

100 ng/mL

100 ng/mg

 

 

Comparator test:

n.a.

 

Cut-off point(s):

 n.a.

Describe reference test:

AUDIT-C

 

 

Cut-off point(s):

Hazardous or harmful alcohol use

≥3

Time between the index test en reference test:

Urine sampling was done immediately after filling out the AUDIT-C

 

For how many participants were no complete outcome data available?

22 (7.2%)

 

Reasons for incomplete outcome data described?

Did not complete the four interviews or did not provide urine sample.

Patients at risk for hazardous alcohol consumption (n)

 

EtG/CreU

No

EtG/CreU

Yes

AUDIT-C no

176

45

AUDIT-C yes

68

18

 

Sensitivity

21% (13% to 31%)

 

Specificity

80% (74% to 85%)

 

PPV

29% (20% to 39%)

 

NPV

72% (70% to 75%)

 

Positive Likelihood Ratio

1.03 (0.63 to 1.67)

 

Negative Likelihood Ratio

0.99 (0.87 to 1.13)

Authors conclusion

Given the negative effects that alcohol consumption

has during pregnancy on fetus development, it is very

important to introduce periodic urinary EtG controls to identify alcohol use and to allow early management,

especially when alcohol-induced damage is higher.

Moreover, this study shows how the follow-up of patients throughout the pregnancy is of fundamental importance because those who tested negative on the first check can turn positive successively, mostly because of the limited time of the detection period of the EtG method.

Ferraguti, 2017 

Type of study:

Cohort study

 

Setting and country:

Ambulatory of Gynaecology and Obstetrics, Italy

 

Funding and conflicts of interest:

Non-commercial funding, no COI

Inclusion criteria:

Pregnant women visiting for a follow-up the ambulatory of Gynaecology and Obstetrics of a hospital in Italy in 2016.

 

Exclusion criteria:

History of head injury, loss of consciousness, history of organic mental disorder,

present assumption of psychoactive legal and illegal drugs, seizure disorders or central nervous system diseases, hypertension at the time of recruitment, use of mouthwash containing alcohol, Impossibility to communicate

in Italian

 

N=80

 

Prevalence: *

1/70 (1.4%)

*Based on AUDIT-C

 

Age (mean ± SD):

32.87 ± 7

 

Sex: 100% F

 

Other important characteristics:

Trimester (%)

1: 22.9

2: 24.3

3: 52.9

 

Describe index test:

EtG

 

Cut-off point(s):

100 ng/mL

 

Comparator test:

n.a.

 

Cut-off point(s):

 n.a.  

Describe reference test:

AUDIT-C

 

 

Cut-off point(s):

Hazardous or harmful alcohol use

≥3

 

Time between the index test en reference test:

Urine sampling was done immediately after filling out the AUDIT-C

 

 

For how many participants were no complete outcome data available?

10 (12.5%)

 

Reasons for incomplete outcome data described?

Did not want to provide urine samples

Patients at risk for hazardous alcohol consumption (n)

 

 

EtG

No

EtG

Yes

AUDIT-C no

45

24

AUDIT-C yes

1

0

 

Sensitivity

0% (0% to 98%)

 

Specificity

65% (53% to 76%)

 

PPV

0% (-)

 

NPV

98% (97% to 98%)

 

Positive Likelihood Ratio

0 (-)

 

Negative Likelihood Ratio

1.53 (1.29 to 1.82)

Authors conclusion

Given the importance that alcohol consumption during pregnancy has in the determination of neonatal outcomes and development of FASD, it is very important to have suitable tools to assess the drinking habits of the mothers to raise awareness among women and for providing early interventions.

 

Based on the EtG data with a 100 ng/mL cutoff (Jatlow et al., 2014), we have shown that about the 34.28% of the enrolled women drank ethanol during gestation. Surprisingly, data obtained by AUDIT-C revealed quite different incidence of alcohol consumption (1.39%).

 

 

Risk of bias assessment diagnostic accuracy studies (QUADAS II, 2011)

Study reference

Patient selection

 

 

Index test

Reference standard

Flow and timing

Comments with respect to applicability

Gerbase, 2021

Was a consecutive or random sample of patients enrolled?

Yes

 

Was a case-control design avoided?

Yes

 

Did the study avoid inappropriate exclusions?

Yes

 

Were the index test results interpreted without knowledge of the results of the reference standard?

Unclear

 

If a threshold was used, was it pre-specified?

No

 

 

 

Is the reference standard likely to correctly classify the target condition?

No

 

Were the reference standard results interpreted without knowledge of the results of the index test?

Unclear

 

 

 

Was there an appropriate interval between index test(s) and reference standard?

Unclear

 

Did all patients receive a reference standard?

Yes

 

Did patients receive the same reference standard?

Yes

 

Were all patients included in the analysis?

Yes

 

Are there concerns that the included patients do not match the review question?

No

 

Are there concerns that the index test, its conduct, or interpretation differ from the review question?

No

 

Are there concerns that the target condition as defined by the reference standard does not match the review question?

No

 

 

CONCLUSION:

Could the selection of patients have introduced bias?

 

 

RISK: LOW

CONCLUSION:

Could the conduct or interpretation of the index test have introduced bias?

 

RISK: HIGH

Optimal cut-point levels were derived using the highest Youden indices.

CONCLUSION:

Could the reference standard, its conduct, or its interpretation have introduced bias?

 

RISK: HIGH

AUDIT-C is self-report

CONCLUSION

Could the patient flow have introduced bias?

 

 

RISK: UNCLEAR

Interval between index test(s) and reference standard is not reported.

Afshar, 2018

 

Was a consecutive or random sample of patients enrolled?

Yes/No

 

Was a case-control design avoided?

No

*Part of the cohort was case-control (AUD patients and healthy controls)

 

Did the study avoid inappropriate exclusions?

Yes

 

 

Were the index test results interpreted without knowledge of the results of the reference standard?

Unclear

 

If a threshold was used, was it pre-specified?

No

 

 

Is the reference standard likely to correctly classify the target condition?

No

 

Were the reference standard results interpreted without knowledge of the results of the index test?

Unclear

 

 

 

Was there an appropriate interval between index test(s) and reference standard?

Unclear

 

Did all patients receive a reference standard?

Yes

 

Did patients receive the same reference standard?

Yes

 

Were all patients included in the analysis?

Yes

Are there concerns that the included patients do not match the review question?

No

 

Are there concerns that the index test, its conduct, or interpretation differ from the review question?

Yes/No/Unclear

 

Are there concerns that the target condition as defined by the reference standard does not match the review question?

No

 

 

CONCLUSION:

Could the selection of patients have introduced bias?

 

 

RISK: HIGH

Part of the cohort was case-control (AUD patients and healthy controls)

CONCLUSION:

Could the conduct or interpretation of the index test have introduced bias?

 

RISK: HIGH

Optimal cut-point levels were derived using the highest Youden indices.

CONCLUSION:

Could the reference standard, its conduct, or its interpretation have introduced bias?

 

RISK: HIGH

AUDIT-C is self-report

CONCLUSION

Could the patient flow have introduced bias?

 

 

RISK: UNCLEAR

Interval between index test(s) and reference standard is not reported, but might be several days for the critically ill patients.

Schröck, 2017

 

Was a consecutive or random sample of patients enrolled?

Unclear

 

Was a case-control design avoided?

Yes

 

Did the study avoid inappropriate exclusions?

Unclear

 

 

Were the index test results interpreted without knowledge of the results of the reference standard?

Unclear

 

If a threshold was used, was it pre-specified?

No

 

 

 

Is the reference standard likely to correctly classify the target condition?

No

 

Were the reference standard results interpreted without knowledge of the results of the index test?

Unclear

 

 

 

Was there an appropriate interval between index test(s) and reference standard?

Unclear

 

Did all patients receive a reference standard?

Yes

 

Did patients receive the same reference standard?

Yes

 

Were all patients included in the analysis?

Yes

 

Are there concerns that the included patients do not match the review question?

No

 

Are there concerns that the index test, its conduct, or interpretation differ from the review question?

No

 

Are there concerns that the target condition as defined by the reference standard does not match the review question?

No

 

 

CONCLUSION:

Could the selection of patients have introduced bias?

 

 

RISK: UNCLEAR

Inclusion nor exclusion criteria were reported.

CONCLUSION:

Could the conduct or interpretation of the index test have introduced bias?

 

RISK: HIGH

Optimal cut-point levels were chosen based on highest specificity and sensitivity.

 

CONCLUSION:

Could the reference standard, its conduct, or its interpretation have introduced bias?

 

RISK: HIGH

AUDIT-C is self-report

CONCLUSION

Could the patient flow have introduced bias?

 

 

RISK: UNCLEAR

Interval between index test(s) and reference standard is not reported

Ceci, 2022

 

Was a consecutive or random sample of patients enrolled?

Yes

 

Was a case-control design avoided?

Yes

 

Did the study avoid inappropriate exclusions?

Yes

 

 

Were the index test results interpreted without knowledge of the results of the reference standard?

Unclear

 

If a threshold was used, was it pre-specified?

Yes

 

 

 

Is the reference standard likely to correctly classify the target condition?

No

 

Were the reference standard results interpreted without knowledge of the results of the index test?

Unclear

 

 

 

Was there an appropriate interval between index test(s) and reference standard?

Yes

 

Did all patients receive a reference standard?

Yes

 

Did patients receive the same reference standard?

Yes

 

Were all patients included in the analysis?

Yes

 

Are there concerns that the included patients do not match the review question?

No

 

Are there concerns that the index test, its conduct, or interpretation differ from the review question?

No

 

Are there concerns that the target condition as defined by the reference standard does not match the review question?

No

 

 

CONCLUSION:

Could the selection of patients have introduced bias?

 

 

RISK: LOW

CONCLUSION:

Could the conduct or interpretation of the index test have introduced bias?

 

RISK: LOW

It is unlikely that the interpretation of the EtG analysis was influenced by the results of the reference standard.

 

CONCLUSION:

Could the reference standard, its conduct, or its interpretation have introduced bias?

 

RISK: HIGH

AUDIT-C is self-report

CONCLUSION

Could the patient flow have introduced bias?

 

 

RISK: LOW

Ferraguti, 2017

 

Was a consecutive or random sample of patients enrolled?

Unclear

 

Was a case-control design avoided?

Yes

 

Did the study avoid inappropriate exclusions?

Yes

 

 

Were the index test results interpreted without knowledge of the results of the reference standard?

Unclear

 

If a threshold was used, was it pre-specified?

Yes

 

 

 

Is the reference standard likely to correctly classify the target condition?

No

 

Were the reference standard results interpreted without knowledge of the results of the index test?

Unclear

 

 

 

Was there an appropriate interval between index test(s) and reference standard?

Yes

 

Did all patients receive a reference standard?

Yes

 

Did patients receive the same reference standard?

Yes

 

Were all patients included in the analysis?

No, ten (13%) women refused to provide a urine sample.

 

 

Are there concerns that the included patients do not match the review question?

No (only pregnant women included)

 

Are there concerns that the index test, its conduct, or interpretation differ from the review question?

No

 

Are there concerns that the target condition as defined by the reference standard does not match the review question?

No

 

 

CONCLUSION:

Could the selection of patients have introduced bias?

 

 

RISK: LOW

CONCLUSION:

Could the conduct or interpretation of the index test have introduced bias?

 

RISK: LOW

It is unlikely that the interpretation of the EtG analysis was influenced by the results of the reference standard.

 

CONCLUSION:

Could the reference standard, its conduct, or its interpretation have introduced bias?

 

RISK: HIGH

AUDIT-C is self-report

CONCLUSION

Could the patient flow have introduced bias?

 

 

RISK: HIGH

 

Table of excluded studies

Reference

Reason for exclusion

 Afshar M, Baker K, Corral J, Ross E, Lowery E, Gonzalez R, Burnham EL, Callcut RA, Kornblith LZ, Hendrickson C, Kovacs EJ, Joyce C. Internal and External Validation of an Alcohol Biomarker for Screening in Trauma. Ann Surg. 2022 Dec 1;276(6):e961-e968. doi: 10.1097/SLA.0000000000004770. Epub 2021 Feb 1. PMID: 33534233; PMCID: PMC8429522.

wrong outcome

 Barrio P, Teixidor L, Rico N, Bruguera P, Ortega L, Bedini JL, Gual A. Urine Ethyl Glucuronide Unraveling the Reality of Abstinence Monitoring in a Routine Outpatient Setting: A Cross-Sectional Comparison with Ethanol, Self Report and Clinical Judgment. Eur Addict Res. 2016;22(5):243-8. doi: 10.1159/000445741. Epub 2016 May 26. PMID: 27220985.

Wrong comparison (nurse judgment vs EtG)

Berger L, Fendrich M, Jones J, Fuhrmann D, Plate C, Lewis D. Ethyl glucuronide in hair and fingernails as a long-term alcohol biomarker. Addiction. 2014 Mar;109(3):425-31. doi: 10.1111/add.12402. Epub 2013 Dec 13. PMID: 24524319; PMCID: PMC3927158.

wrong comparison (Self reported alcohol consumption)

Figlie NB, Benedito-Silva AA, Monteiro MG, Souza-Formigoni ML; WHO/ISBRA Study on State and Trait Markers of Alcohol Use and Dependence Investigators. Biological markers of alcohol consumption in nondrinkers, drinkers, and alcohol-dependent Brazilian patients. Alcohol Clin Exp Res. 2002 Jul;26(7):1062-9. PMID: 12170116.

Wrong comparison (extensive interview on alcohol consumption)

 Kim YG, Hwang J, Choi H, Lee S. Development of a Column-Switching HPLC-MS/MS Method and Clinical Application for Determination of Ethyl Glucuronide in Hair in Conjunction with AUDIT for Detecting High-Risk Alcohol Consumption. Pharmaceutics. 2018 Jul 4;10(3):84. doi: 10.3390/pharmaceutics10030084. PMID: 29973564; PMCID: PMC6161131.

Wrong comparison (AUDIT)

Lees R, Kingston R, Williams TM, Henderson G, Lingford-Hughes A, Hickman M. Comparison of ethyl glucuronide in hair with self-reported alcohol consumption. Alcohol Alcohol. 2012 May-Jun;47(3):267-72. doi: 10.1093/alcalc/ags010. Epub 2012 Feb 14. PMID: 22336766.

wrong comparison (AUDIT-c for past three months)

Madhubala V, Subhashree AR, Shanthi B. Serum carbohydrate deficient transferrin as a sensitive marker in diagnosing alcohol abuse: a case - control study. J Clin Diagn Res. 2013 Feb;7(2):197-200. doi: 10.7860/JCDR/2013/5137.2726. Epub 2012 Dec 24. PMID: 23542570; PMCID: PMC3592273.

wrong comparison (AUDIT or structured interview (not clear))

 Wurst FM, Wiesbeck GA, Metzger JW, Weinmann W. On sensitivity, specificity, and the influence of various parameters on ethyl glucuronide levels in urine--results from the WHO/ISBRA study. Alcohol Clin Exp Res. 2004 Aug;28(8):1220-8. doi: 10.1097/01.alc.0000134230.21414.11. PMID: 15318121.

wrong comparison (verbal assessment instruments)

 Allen JP, Litten RZ, Fertig JB, Sillanaukee P. Carbohydrate-deficient transferrin, gamma-glutamyltransferase, and macrocytic volume as biomarkers of alcohol problems in women. Alcohol Clin Exp Res. 2000 Apr;24(4):492-6. PMID: 10798585.

no systematic review

 Franceschetto L, Perilli M, Cinquetti A, Giraudo C, Gardi M, Cecchetto G, Viel G. Phosphatidylethanol in Maternal or Neonatal Blood to Detect Alcohol Exposure during Pregnancy: A Systematic Review. Life (Basel). 2022 Sep 30;12(10):1528. doi: 10.3390/life12101528. PMID: 36294962; PMCID: PMC9604963.

Narrative review (Pregnant women)

 Howlett H, Abernethy S, Brown NW, Rankin J, Gray WK. How strong is the evidence for using blood biomarkers alone to screen for alcohol consumption during pregnancy? A systematic review. Eur J Obstet Gynecol Reprod Biol. 2017 Jun;213:45-52. doi: 10.1016/j.ejogrb.2017.04.005. Epub 2017 Apr 5. PMID: 28426943.

wrong comparison (studies on other comparisons were included like comparison with TLFB, interviews etc. One study on AUDIT-C (Comasco), but was excluded based on ti/ab.)

 Aertgeerts B, Buntinx F, Ansoms S, Fevery J. Screening properties of questionnaires and laboratory tests for the detection of alcohol abuse or dependence in a general practice population. Br J Gen Pract. 2001 Mar;51(464):206-17. PMID: 11255902; PMCID: PMC1313952.

wrong comparison (CIDI (DSM III-R))

 Anton RF, Lieber C, Tabakoff B; CDTect Study Group. Carbohydrate-deficient transferrin and gamma-glutamyltransferase for the detection and monitoring of alcohol use: results from a multisite study. Alcohol Clin Exp Res. 2002 Aug;26(8):1215-22. doi: 10.1097/01.ALC.0000023986.42254.F5. PMID: 12198396.

wrong comparison (verbal report, breath analyzer and collateral report)

 Conigrave KM, Degenhardt LJ, Whitfield JB, Saunders JB, Helander A, Tabakoff B; WHO/ISBRA Study Group. CDT, GGT, and AST as markers of alcohol use: the WHO/ISBRA collaborative project. Alcohol Clin Exp Res. 2002 Mar;26(3):332-9. PMID: 11923585.

Wrong comparison (Interview on alcohol consumption)

 Dahl H, Hammarberg A, Franck J, Helander A. Urinary ethyl glucuronide and ethyl sulfate testing for recent drinking in alcohol-dependent outpatients treated with acamprosate or placebo. Alcohol Alcohol. 2011 Sep-Oct;46(5):553-7. doi: 10.1093/alcalc/agr055. Epub 2011 May 26. PMID: 21616946.

wrong comparison (Self reported alcohol consumption)

 Fendrich M, Fuhrmann D, Berger L, Plate C, Lewis D, Jones J. The utility of collateral student drinking reports: Evidence from a biomarker study. Addict Behav. 2015 Nov;50:213-6. doi: 10.1016/j.addbeh.2015.06.028. Epub 2015 Jun 11. PMID: 26160524; PMCID: PMC4535420.

wrong comparison (TLFB)

Ferraguti G, Merlino L, Battagliese G, Piccioni MG, Barbaro G, Carito V, Messina MP, Scalese B, Coriale G, Fiore M, Ceccanti M. Fetus morphology changes by second-trimester ultrasound in pregnant women drinking alcohol. Addict Biol. 2020 May;25(3):e12724. doi: 10.1111/adb.12724. Epub 2019 Feb 27. PMID: 30811093.

overlapping study population with Ceci (2022)

 Kechagias S, Dernroth DN, Blomgren A, Hansson T, Isaksson A, Walther L, Kronstrand R, Kågedal B, Nystrom FH. Phosphatidylethanol Compared with Other Blood Tests as a Biomarker of Moderate Alcohol Consumption in Healthy Volunteers: A Prospective Randomized Study. Alcohol Alcohol. 2015 Jul;50(4):399-406. doi: 10.1093/alcalc/agv038. Epub 2015 Apr 15. PMID: 25882743.

wrong study design (randomized to alcohol consumption vs abstinence)

Lowe JM, McDonell MG, Leickly E, Angelo FA, Vilardaga R, McPherson S, Srebnik D, Roll J, Ries RK. Determining ethyl glucuronide cutoffs when detecting self-reported alcohol use in addiction treatment patients. Alcohol Clin Exp Res. 2015 May;39(5):905-10. doi: 10.1111/acer.12699. Epub 2015 Apr 10. PMID: 25866234; PMCID: PMC4400217.

wrong comparison (TLFB and self reported alcohol consumption)

McDonald H, Borinskya S, Kiryanov N, Gil A, Helander A, Leon DA. Comparative performance of biomarkers of alcohol consumption in a population sample of working-aged men in Russia: the Izhevsk Family Study. Addiction. 2013 Sep;108(9):1579-89. doi: 10.1111/add.12251. Epub 2013 Jul 5. PMID: 23692391; PMCID: PMC3992900.

wrong comparison (Interview on alcohol consumption)

 Staufer K, Andresen H, Vettorazzi E, Tobias N, Nashan B, Sterneck M. Urinary ethyl glucuronide as a novel screening tool in patients pre- and post-liver transplantation improves detection of alcohol consumption. Hepatology. 2011 Nov;54(5):1640-9. doi: 10.1002/hep.24596. PMID: 21809364.

Wrong comparison (Interview on alcohol consumption)

 Aboutara N, Müller A, Jungen H, Szewczyk A, van Rüth V, Bertram F, Püschel K, Heinrich F, Iwersen-Bergmann S. Investigating the use of PEth, CDT and MCV to evaluate alcohol consumption in a cohort of homeless individuals- A comparison of different alcohol biomarkers. Forensic Sci Int. 2022 Feb;331:111147. doi: 10.1016/j.forsciint.2021.111147. Epub 2021 Dec 10. PMID: 34920332.

wrong comparison (questionnaire on alcohol consumption  )

 Andresen-Streichert H, Beres Y, Weinmann W, Schröck A, Müller A, Skopp G, Pischke S, Vettorazzi E, Lohse A, Nashan B, Sterneck M. Improved detection of alcohol consumption using the novel marker phosphatidylethanol in the transplant setting: results of a prospective study. Transpl Int. 2017 Jun;30(6):611-620. doi: 10.1111/tri.12949. Epub 2017 Apr 17. PMID: 28295675.

Wrong comparison (Adapted AUDIT elements)

Andresen-Streichert H, von Rothkirch G, Vettorazzi E, Mueller A, Lohse AW, Frederking D, Seegers B, Nashan B, Sterneck M. Determination of Ethyl Glucuronide in Hair for Detection of Alcohol Consumption in Patients After Liver Transplantation. Ther Drug Monit. 2015 Aug;37(4):539-45. doi: 10.1097/FTD.0000000000000160. PMID: 25525763.

wrong comparison (self report (written questionnaire))

Anttila P, Järvi K, Latvala J, Blake JE, Niemelä O. A new modified gamma-%CDT method improves the detection of problem drinking: studies in alcoholics with or without liver disease. Clin Chim Acta. 2003 Dec;338(1-2):45-51. doi: 10.1016/j.cccn.2003.07.016. PMID: 14637264.

wrong comparison (TLFB)

Anttila P, Järvi K, Latvala J, Niemelä O. Method-dependent characteristics of carbohydrate-deficient transferrin measurements in the follow-up of alcoholics. Alcohol Alcohol. 2004 Jan-Feb;39(1):59-63. doi: 10.1093/alcalc/agh021. PMID: 14691076.

wrong comparison (TLFB)

Armer JM, Gunawardana L, Allcock RL. The Performance of Alcohol Markers Including Ethyl Glucuronide and Ethyl Sulphate to Detect Alcohol Use in Clients in a Community Alcohol Treatment Programme. Alcohol Alcohol. 2017 Jan;52(1):29-34. doi: 10.1093/alcalc/agw072. Epub 2016 Oct 7. PMID: 27998921.

wrong comparison (alcohol diary)

Azurmendi-Funes ML, Martínez-Villanueva M, Delgado-Marín JL, Ramis R, Sánchez-Sauco MF, López-Hernández FA, Sánchez-Solís M, Monteagudo-Piqueras O, Noguera-Velasco JA, Claudio L, Ortega-García JA. An Integrative Screening Tool of Alcohol Exposure During Early Pregnancy: Combining of the CDT Biomarker with Green Page Questionnaire. Alcohol Alcohol. 2019 Dec 1;54(6):599-608. doi: 10.1093/alcalc/agz073. PMID: 31612211.

wrong comparison (Green page questionnaire and interview)

Barrio P, Gual A, Lligoña A, Teixidor L, Weinmann W, Yegles M, Wurst FM. Phosphatidylethanol for Monitoring Alcohol Use in Liver Transplant Candidates: An Observational Study. J Clin Med. 2020 Sep 22;9(9):3060. doi: 10.3390/jcm9093060. PMID: 32971960; PMCID: PMC7564451.

wrong comparison (AUDIT and TLFB)

Beach SRH, Ong ML, Gibbons FX, Gerrard M, Lei MK, Dawes K, Philibert RA. Epigenetic and Proteomic Biomarkers of Elevated Alcohol Use Predict Epigenetic Aging and Cell-Type variation Better Than Self-Report. Genes (Basel). 2022 Oct 18;13(10):1888. doi: 10.3390/genes13101888. PMID: 36292773; PMCID: PMC9601579.

wrong comparison (Self reported alcohol consumption)

Bean P, Brown G, Hallinan P, Becerra S, Lewis D. Improved recovery of repeat intoxicated drivers using fingernails and blood spots to monitor alcohol and other substance abuse. Traffic Inj Prev. 2017 Jan 2;18(1):9-18. doi: 10.1080/15389588.2016.1190014. Epub 2016 Jun 10. PMID: 27285956.

Wrong comparison (self report during assessment interviews, using different questionnaires)

Bertholet N, Winter MR, Cheng DM, Samet JH, Saitz R. How accurate are blood (or breath) tests for identifying self-reported heavy drinking among people with alcohol dependence? Alcohol Alcohol. 2014 Jul-Aug;49(4):423-9. doi: 10.1093/alcalc/agu016. Epub 2014 Apr 15. PMID: 24740846; PMCID: PMC4060735.

wrong comparison (Interview on alcohol consumption)

Bracero LA, Maxwell S, Nyanin A, Seybold DJ, White A, Broce M. Improving screening for alcohol consumption during pregnancy with phosphatidylethanol. Reprod Toxicol. 2017 Dec;74:104-107. doi: 10.1016/j.reprotox.2017.09.007. Epub 2017 Sep 19. PMID: 28939493.

wrong comparison  (self report and urine ethanol vs self report and PETh)

de Beaurepaire R, Lukasiewicz M, Beauverie P, Castéra S, Dagorne O, Espaze R, Falissard B, Giroult P, Houery M, Mahuzier G, Matheron I, Niel P, Padovani P, Poisson N, Richier JP, Rocher J, Ruetsh O, Touzeau D, Visinoni A, Molimard R. Comparison of self-reports and biological measures for alcohol, tobacco, and illicit drugs consumption in psychiatric inpatients. Eur Psychiatry. 2007 Nov;22(8):540-8. doi: 10.1016/j.eurpsy.2007.05.001. Epub 2007 Jun 26. PMID: 17596918.

wrong comparison/outcome (no diagnostic accuracy )

Erim Y, Böttcher M, Dahmen U, Beck O, Broelsch CE, Helander A. Urinary ethyl glucuronide testing detects alcohol consumption in alcoholic liver disease patients awaiting liver transplantation. Liver Transpl. 2007 May;13(5):757-61. doi: 10.1002/lt.21163. PMID: 17457868.

wrong comparison (Classification in high risk, risk and no risk patients)

Fleming M, Mundt M. Carbohydrate-deficient transferrin: validity of a new alcohol biomarker in a sample of patients with diabetes and hypertension. J Am Board Fam Pract. 2004 Jul-Aug;17(4):247-55. doi: 10.3122/jabfm.17.4.247. PMID: 15243012.

wrong comparison (TLFB)

Ghosh S, Jain R, Rao R, Mishra AK, Jhanjee S. Does ethyl glucuronide in hair correlate with alcohol consumption? A comparative study with other traditional biomarkers among individuals with alcohol dependence syndrome. Alcohol. 2023 Feb;106:55-60. doi: 10.1016/j.alcohol.2022.10.005. Epub 2022 Nov 14. PMID: 36395967.

Wrong comparison (beverage-specific Quantity-Frequency (QF))

Godart B, Mennetrey L, Schellenberg F, Pages JC, Bacq Y. Carbohydrate-deficient transferrin and gamma-glutamyl transpeptidase in the evaluation of alcohol consumption. A five-year retrospective study of 633 outpatients in a single center. Gastroenterol Clin Biol. 2005 Feb;29(2):113-6. doi: 10.1016/s0399-8320(05)80712-2. PMID: 15795656.

wrong comparison (Interview on alcohol consumption)

Gómez A, Conde A, Aguiar JA, Santana JM, Jorrín A, Betancor P. Diagnostic usefulness of carbohydrate-deficient transferrin for detecting alcohol-related problems in hospitalized patients. Alcohol Alcohol. 2001 May-Jun;36(3):266-70. doi: 10.1093/alcalc/36.3.266. PMID: 11373266.

Wrong comparison (no AUDIT-C)

Gundlach JP, Braun F, Mötter F, Bernsmeier A, Barrio P, Ehmke N, Günther R, Hinrichsen H, Becker T, Weinmann W, Schröck A, Yegles M, Wurst FM. Phosphatidylethanol (PEth) for Monitoring Sobriety in Liver Transplant Candidates: Preliminary Results of Differences Between Alcohol-Related and Non-Alcohol-Related Cirrhosis Candidates. Ann Transplant. 2022 Jun 7;27:e936293. doi: 10.12659/AOT.936293. PMID: 35668618; PMCID: PMC9188289.

Wrong comparison (Waiting list active/inactive, no waiting list. Besides results available for AUDIT and TLFB)

Gutierrez HL, Hund L, Shrestha S, Rayburn WF, Leeman L, Savage DD, Bakhireva LN. Ethylglucuronide in maternal hair as a biomarker of prenatal alcohol exposure. Alcohol. 2015 Sep;49(6):617-23. doi: 10.1016/j.alcohol.2015.06.002. Epub 2015 Jul 21. PMID: 26260252; PMCID: PMC4555093.

Wrong comparison (Categorization based on AUDIT ánd TLFB)

Hock B, Schwarz M, Domke I, Grunert VP, Wuertemberger M, Schiemann U, Horster S, Limmer C, Stecker G, Soyka M. Validity of carbohydrate-deficient transferrin (%CDT), gamma-glutamyltransferase (gamma-GT) and mean corpuscular erythrocyte volume (MCV) as biomarkers for chronic alcohol abuse: a study in patients with alcohol dependence and liver disorders of non-alcoholic and alcoholic origin. Addiction. 2005 Oct;100(10):1477-86. doi: 10.1111/j.1360-0443.2005.01216.x. PMID: 16185209.

Wrong comparison (Interview and AUDIT)

Høiseth G, Morini L, Polettini A, Christophersen A, Mørland J. Ethyl glucuronide in hair compared with traditional alcohol biomarkers--a pilot study of heavy drinkers referred to an alcohol detoxification unit. Alcohol Clin Exp Res. 2009 May;33(5):812-6. doi: 10.1111/j.1530-0277.2009.00900.x. Epub 2009 Mar 6. PMID: 19298326.

Wrong comparison (Interview)

Kabashi S, Vindenes V, Bryun EA, Koshkina EA, Nadezhdin AV, Tetenova EJ, Kolgashkin AJ, Petukhov AE, Perekhodov SN, Davydova EN, Gamboa D, Hilberg T, Lerdal A, Nordby G, Zhang C, Bogstrand ST. Harmful alcohol use among acutely ill hospitalized medical patients in Oslo and Moscow: A cross-sectional study. Drug Alcohol Depend. 2019 Nov 1;204:107588. doi: 10.1016/j.drugalcdep.2019.107588. Epub 2019 Sep 25. Erratum in: Drug Alcohol Depend. 2020 Aug 1;213:108073. PMID: 31590131.

wrong comparison (Audit 4)

Kollmann D, Rasoul-Rockenschaub S, Steiner I, Freundorfer E, Györi GP, Silberhumer G, Soliman T, Berlakovich GA. Good outcome after liver transplantation for ALD without a 6 months abstinence rule prior to transplantation including post-transplant CDT monitoring for alcohol relapse assessment - a retrospective study. Transpl Int. 2016 May;29(5):559-67. doi: 10.1111/tri.12756. Epub 2016 Mar 1. PMID: 26865285.

Wrong comparison (structured interviews)

Kwak HS, Han JY, Choi JS, Ahn HK, Ryu HM, Chung HJ, Cho DH, Shin CY, Velazquez-Armenta EY, Nava-Ocampo AA. Characterization of phosphatidylethanol blood concentrations for screening alcohol consumption in early pregnancy. Clin Toxicol (Phila). 2014 Jan;52(1):25-31. doi: 10.3109/15563650.2013.859263. PMID: 24400931.

wrong comparison (self reported alcohol consumption)

Lee J, Min S, Ahn JS, Kim H, Cha YS, Oh E, Moon JS, Kim MH. Identifying alcohol problems among suicide attempters visiting the emergency department. BMC Psychiatry. 2019 Nov 8;19(1):350. doi: 10.1186/s12888-019-2347-5. PMID: 31703656; PMCID: PMC6842213.

wrong comparison (psychiatric interview)

Marques P, Tippetts S, Allen J, Javors M, Alling C, Yegles M, Pragst F, Wurst F. Estimating driver risk using alcohol biomarkers, interlock blood alcohol concentration tests and psychometric assessments: initial descriptives. Addiction. 2010 Feb;105(2):226-39. doi: 10.1111/j.1360-0443.2009.02738.x. Epub 2009 Nov 16. PMID: 19922520; PMCID: PMC2825139.

wrong comparison/outcome (Correlation)

Marques PR, Tippetts AS, Yegles M. Ethylglucuronide in hair is a top predictor of impaired driving recidivism, alcohol dependence, and a key marker of the highest BAC interlock tests. Traffic Inj Prev. 2014;15(4):361-9. doi: 10.1080/15389588.2013.824569. PMID: 24471360.

wrong comparison (DSM-IV diagnosis, based on TLFB, AUDIT and DRINC)

May PA, Hasken JM, De Vries MM, Marais AS, Stegall JM, Marsden D, Parry CDH, Seedat S, Tabachnick B. A utilitarian comparison of two alcohol use biomarkers with self-reported drinking history collected in antenatal clinics. Reprod Toxicol. 2018 Apr;77:25-32. doi: 10.1016/j.reprotox.2018.02.002. Epub 2018 Feb 6. PMID: 29425712; PMCID: PMC5878131.

wrong comparison (AUDIT)

McAleer MA, Mason DL, Cunningham S, O'Shea SJ, McCormick PA, Stone C, Collins P, Rogers S, Kirby B. Alcohol misuse in patients with psoriasis: identification and relationship to disease severity and psychological distress. Br J Dermatol. 2011 Jun;164(6):1256-61. doi: 10.1111/j.1365-2133.2011.10345.x. PMID: 21457207.

wrong comparison (AUDIT, MAST and CAGE)

McDonell MG, Skalisky J, Leickly E, McPherson S, Battalio S, Nepom JR, Srebnik D, Roll J, Ries RK. Using ethyl glucuronide in urine to detect light and heavy drinking in alcohol dependent outpatients. Drug Alcohol Depend. 2015 Dec 1;157:184-7. doi: 10.1016/j.drugalcdep.2015.10.004. Epub 2015 Oct 9. PMID: 26475403; PMCID: PMC4663163.

wrong comparison (Self reported alcohol consumption)

Morini L, Politi L, Acito S, Groppi A, Polettini A. Comparison of ethyl glucuronide in hair with carbohydrate-deficient transferrin in serum as markers of chronic high levels of alcohol consumption. Forensic Sci Int. 2009 Jul 1;188(1-3):140-3. doi: 10.1016/j.forsciint.2009.04.003. Epub 2009 May 1. PMID: 19410394.

wrong comparison (questionnaire on alcohol consumption in last 2 weeks and 3 months)

Morini L, Politi L, Polettini A. Ethyl glucuronide in hair. A sensitive and specific marker of chronic heavy drinking. Addiction. 2009 Jun;104(6):915-20. doi: 10.1111/j.1360-0443.2009.02535.x. Epub 2009 Apr 9. PMID: 19392911.

wrong comparison (TLFB)

Neumann T, Helander A, Dahl H, Holzmann T, Neuner B, Weiss-Gerlach E, Müller C, Spies C. Value of ethyl glucuronide in plasma as a biomarker for recent alcohol consumption in the emergency room. Alcohol Alcohol. 2008 Jul-Aug;43(4):431-5. doi: 10.1093/alcalc/agn035. Epub 2008 May 25. PMID: 18503080.

wrong comparison (AUDIT)

Niemelä O, Niemelä S, Ritvanen A, Gissler M, Bloigu A, Vääräsmäki M, Kajantie E, Werler MM, Surcel HM. Assays of Gamma-Glutamyl Transferase and Carbohydrate-Deficient Transferrin Combination from Maternal Serum Improve the Detection of Prenatal Alcohol Exposure. Alcohol Clin Exp Res. 2016 Nov;40(11):2385-2393. doi: 10.1111/acer.13207. Epub 2016 Sep 21. PMID: 27650665.

wrong comparison (Unexposed vs exposed subjects based on alcohol questionnaire)

Peña S, Mäkelä P, Härkänen T, Heliövaara M, Gunnar T, Männistö S, Laatikainen T, Vartiainen E, Koskinen S. Measurement error as an explanation for the alcohol harm paradox: analysis of eight cohort studies. Int J Epidemiol. 2021 Jan 23;49(6):1836-1846. doi: 10.1093/ije/dyaa113. PMID: 32995840.

wrong study design

Piano S, Marchioro L, Gola E, Rosi S, Morando F, Cavallin M, Sticca A, Fasolato S, Forza G, Chiara Frigo A, Plebani M, Zanus G, Cillo U, Gatta A, Angeli P. Assessment of alcohol consumption in liver transplant candidates and recipients: the best combination of the tools available. Liver Transpl. 2014 Jul;20(7):815-22. doi: 10.1002/lt.23881. Epub 2014 May 26. PMID: 24692331.

wrong comparison (self report (ROC UETG vs Audit C available))

Pirro V, Valente V, Oliveri P, De Bernardis A, Salomone A, Vincenti M. Chemometric evaluation of nine alcohol biomarkers in a large population of clinically-classified subjects: pre-eminence of ethyl glucuronide concentration in hair for confirmatory classification. Anal Bioanal Chem. 2011 Oct;401(7):2153-64. doi: 10.1007/s00216-011-5314-7. Epub 2011 Sep 4. PMID: 21901464.

wrong comparison (medical records)

 Sonmez MB, Cinar RK, Gorgulu Y, Kilic EK & Unal A. Evaluation of phosphatidylethanol by ELISA for detection of excessive alcohol use compared with traditional biomarkers: a case-control study, Psychiatry and Clinical Psychopharmacology, 2017 27:1, 41-46, DOI: 10.1080/24750573.2017.1293249

wrong comparison (AUDIT)

Staufer K, Huber-Schönauer U, Strebinger G, Pimingstorfer P, Suesse S, Scherzer TM, Paulweber B, Ferenci P, Stimpfl T, Yegles M, Datz C, Trauner M. Ethyl glucuronide in hair detects a high rate of harmful alcohol consumption in presumed non-alcoholic fatty liver disease. J Hepatol. 2022 Oct;77(4):918-930. doi: 10.1016/j.jhep.2022.04.040. Epub 2022 May 20. Erratum in: J Hepatol. 2023 May;78(5):1080-1083. PMID: 35605744.

wrong comparison (SIAC)

Stewart SH, Koch DG, Burgess DM, Willner IR, Reuben A. Sensitivity and specificity of urinary ethyl glucuronide and ethyl sulfate in liver disease patients. Alcohol Clin Exp Res. 2013 Jan;37(1):150-5. doi: 10.1111/j.1530-0277.2012.01855.x. Epub 2012 Jun 22. PMID: 22725265; PMCID: PMC3459172.

wrong comparison (TLFB)

Stewart SH, Koch DG, Willner IR, Randall PK, Reuben A. Hair ethyl glucuronide is highly sensitive and specific for detecting moderate-to-heavy drinking in patients with liver disease. Alcohol Alcohol. 2013 Jan-Feb;48(1):83-7. doi: 10.1093/alcalc/ags109. Epub 2012 Sep 25. PMID: 23015609; PMCID: PMC3523385.

wrong comparison (TLFB)

Stewart SH, Law TL, Randall PK, Newman R. Phosphatidylethanol and alcohol consumption in reproductive age women. Alcohol Clin Exp Res. 2010 Mar 1;34(3):488-92. doi: 10.1111/j.1530-0277.2009.01113.x. Epub 2009 Dec 17. PMID: 20028353; PMCID: PMC2858230.

wrong comparison (TLFB)

Uljas E, Jalkanen V, Kuitunen A, Hynninen M, Hästbacka J. Prevalence of risk-drinking in critically ill patients, screened with carbohydrate-deficient transferrin and AUDIT-C score: A retrospective study. Acta Anaesthesiol Scand. 2020 Feb;64(2):216-223. doi: 10.1111/aas.13484. Epub 2019 Oct 10. PMID: 31541613.

wrong comparison/wrong population (no diagnostic accuracy )

van de Luitgaarden IAT, Beulens JWJ, Schrieks IC, Kieneker LM, Touw DJ, van Ballegooijen AJ, van Oort S, Grobbee DE, Bakker SJL. Urinary Ethyl Glucuronide Can Be Used as a Biomarker of Habitual Alcohol Consumption in the General Population. J Nutr. 2019 Dec 1;149(12):2199-2205. doi: 10.1093/jn/nxz146. PMID: 31268139; PMCID: PMC6887922.

wrong comparison (Self reported alcohol consumption)

van de Luitgaarden IAT, Schrieks IC, Kieneker LM, Touw DJ, van Ballegooijen AJ, van Oort S, Grobbee DE, Mukamal KJ, Kootstra-Ros JE, Muller Kobold AC, Bakker SJL, Beulens JWJ. Urinary Ethyl Glucuronide as Measure of Alcohol Consumption and Risk of Cardiovascular Disease: A Population-Based Cohort Study. J Am Heart Assoc. 2020 Apr 7;9(7):e014324. doi: 10.1161/JAHA.119.014324. Epub 2020 Mar 21. PMID: 32200717; PMCID: PMC7428618.

wrong comparison (Self reported alcohol consumption)

van Pelt J, Leusink GL, van Nierop PW, Keyzer JJ. Test characteristics of carbohydrate-deficient transferrin and gamma-glutamyltransferase in alcohol-using perimenopausal women. Alcohol Clin Exp Res. 2000 Feb;24(2):176-9. PMID: 10698369.

wrong comparison (no AUDIT-C)

Verbeek J, Crunelle CL, Leurquin-Sterk G, Michielsen PP, De Doncker M, Monbaliu D, Pirenne J, Roskams T, van der Merwe S, Cassiman D, Neels H, Nevens F. Ethyl Glucuronide in Hair Is an Accurate Biomarker of Chronic Excessive Alcohol Use in Patients With Alcoholic Cirrhosis. Clin Gastroenterol Hepatol. 2018 Mar;16(3):454-456. doi: 10.1016/j.cgh.2017.08.019. Epub 2017 Aug 19. PMID: 28830836.

Wrong publication type (research correspondence)

Whitfield JB, Dy V, Madden PA, Heath AC, Martin NG, Montgomery GW. Measuring carbohydrate-deficient transferrin by direct immunoassay: factors affecting diagnostic sensitivity for excessive alcohol intake. Clin Chem. 2008 Jul;54(7):1158-65. doi: 10.1373/clinchem.2007.101733. Epub 2008 May 16. PMID: 18487284.

wrong comparison (Self reported alcohol consumption)

Wurst FM, Alexson S, Wolfersdorf M, Bechtel G, Forster S, Alling C, Aradóttir S, Jachau K, Huber P, Allen JP, Auwärter V, Pragst F. Concentration of fatty acid ethyl esters in hair of alcoholics: comparison to other biological state markers and self reported-ethanol intake. Alcohol Alcohol. 2004 Jan-Feb;39(1):33-8. doi: 10.1093/alcalc/agh005. PMID: 14691072.

wrong comparison (TLFB)

Wurst FM, Haber PS, Wiesbeck G, Watson B, Wallace C, Whitfield JB, Halter C, Weinmann W, Conigrave KM. Assessment of alcohol consumption among hepatitis C-positive people receiving opioid maintenance treatment using direct ethanol metabolites and self-report: a pilot study. Addict Biol. 2008 Sep;13(3-4):416-22. doi: 10.1111/j.1369-1600.2007.00076.x. Epub 2007 Aug 15. PMID: 17711559.

wrong comparison (AUDIT and drinking diary)

Wurst FM, Thon N, Aradottir S, Hartmann S, Wiesbeck GA, Lesch O, Skala K, Wolfersdorf M, Weinmann W, Alling C. Phosphatidylethanol: normalization during detoxification, gender aspects and correlation with other biomarkers and self-reports. Addict Biol. 2010 Jan;15(1):88-95. doi: 10.1111/j.1369-1600.2009.00185.x. PMID: 20002024.

wrong comparison (AUDIT and TLFB)

Wurst FM, Vogel R, Jachau K, Varga A, Alling C, Alt A, Skipper GE. Ethyl glucuronide discloses recent covert alcohol use not detected by standard testing in forensic psychiatric inpatients. Alcohol Clin Exp Res. 2003 Mar;27(3):471-6. doi: 10.1097/01.ALC.0000057942.57330.E2. PMID: 12658113.

wrong comparison (self reported alcohol consumption)

Youn K, Kim JS, Kim SS, Yoon SJ, Woo DJ. Carbohydrate-Deficient Transferrin as a Biomarker for Screening At-Risk Drinking in Elderly Men. Korean J Fam Med. 2017 Sep;38(5):291-295. doi: 10.4082/kjfm.2017.38.5.291. Epub 2017 Sep 22. PMID: 29026490; PMCID: PMC5637221.

wrong comparison (data from medical records)

Zou L, Lonne-Rahm SB, Helander A, Stokkeland K, Franck J, Nordlind K. Alcohol intake measured by phosphatidylethanol in blood and the lifetime drinking history interview are correlated with the extent of psoriasis. Dermatology. 2015;230(4):375-80. doi: 10.1159/000380818. Epub 2015 Mar 21. PMID: 25823412.

Wrong comparison (AUDIT and LDH)

Boscolo-Berto R, Favretto D, Cecchetto G, Vincenti M, Kronstrand R, Ferrara SD, Viel G. Sensitivity and specificity of EtG in hair as a marker of chronic excessive drinking: pooled analysis of raw data and meta-analysis of diagnostic accuracy studies. Ther Drug Monit. 2014 Oct;36(5):560-75. doi: 10.1097/FTD.0000000000000063. PMID: 24577122.

wrong comparison (self reported daily alcohol intake of at least one month before EtG analysis (hair))

Hahn JA, Murnane PM, Vittinghoff E, Muyindike WR, Emenyonu NI, Fatch R, Chamie G, Haberer JE, Francis JM, Kapiga S, Jacobson K, Myers B, Couture MC, DiClemente RJ, Brown JL, So-Armah K, Sulkowski M, Marcus GM, Woolf-King S, Cook RL, Richards VL, Molina P, Ferguson T, Welsh D, Piano MR, Phillips SA, Stewart S, Afshar M, Page K, McGinnis K, Fiellin DA, Justice AC, Bryant K, Saitz R. Factors associated with phosphatidylethanol (PEth) sensitivity for detecting unhealthy alcohol use: An individual patient data meta-analysis. Alcohol Clin Exp Res. 2021 Jun;45(6):1166-1187. doi: 10.1111/acer.14611. Epub 2021 May 7. PMID: 33837975; PMCID: PMC8254773.

Wrong population (e.g. Included studies in patients with HIV)

Koch H, Meerkerk GJ, Zaat JO, Ham MF, Scholten RJ, Assendelft WJ. Accuracy of carbohydrate-deficient transferrin in the detection of excessive alcohol consumption: a systematic review. Alcohol Alcohol. 2004 Mar-Apr;39(2):75-85. doi: 10.1093/alcalc/agh031. PMID: 14998820.

wrong comparison (Self reported alcohol consumption (converted to g/day))

Berner MM, Bentele M, Kriston L, Mänz C, Clement HW, Härter M, Mundle G. DOVER and QUVER-new marker combinations to detect and monitor at-risk drinking. Alcohol Clin Exp Res. 2006 Aug;30(8):1372-80. doi: 10.1111/j.1530-0277.2006.00163.x. PMID: 16899040.

wrong comparison (AUDIT)

Zierau F, Hardt F, Henriksen JH, Holm SS, Jørring S, Melsen T, Becker U. Validation of a self-administered modified CAGE test (CAGE-C) in a somatic hospital ward: comparison with biochemical markers. Scand J Clin Lab Invest. 2005;65(7):615-22. doi: 10.1080/00365510500333445. PMID: 16271993.

Wrong comparison (CAGE)

Baggio S, Trächsel B, Rousson V, Rothen S, Studer J, Marmet S, Heller P, Sporkert F, Daeppen JB, Gmel G, Iglesias K. Identifying an accurate self-reported screening tool for alcohol use disorder: evidence from a Swiss, male population-based assessment. Addiction. 2020 Mar;115(3):426-436. doi: 10.1111/add.14864. Epub 2019 Dec 12. PMID: 31656049.

wrong comparison (DIGS-AUD)

Cherrier MM, Shireman LM, Wicklander K, Yeung W, Kooner P, Saxon AJ, Simpson T, Terman G, Shen D. Relationship of Phosphatidylethanol Biomarker to Self-Reported Alcohol Drinking Patterns in Older and Middle-Age Adults. Alcohol Clin Exp Res. 2020 Dec;44(12):2449-2456. doi: 10.1111/acer.14475. Epub 2020 Nov 9. PMID: 33038267; PMCID: PMC8476046.

Wrong population, wrong outcomes (Patients should refrain from alcohol for 24 hours prior to study visit, no diagnostic accuracy)

Coulton S, Drummond C, James D, Godfrey C, Bland JM, Parrott S, Peters T; Stepwice Research Team. Opportunistic screening for alcohol use disorders in primary care: comparative study. BMJ. 2006 Mar 4;332(7540):511-7. doi: 10.1136/bmj.38743.421574.7C. Epub 2006 Feb 17. PMID: 16488896; PMCID: PMC1388125.

wrong comparison (TLFB)

Forsberg L, Halldin J, Ekman S, Rönnberg S. Screening of binge drinking among patients on an emergency surgical ward. Alcohol. 2002 Jun;27(2):77-82. doi: 10.1016/s0741-8329(02)00202-1. PMID: 12106826.

wrong comparison (TLFB and AUDIT)

Neumann T, Gentilello LM, Neuner B, Weiss-Gerlach E, Schürmann H, Schröder T, Müller C, Haas NP, Spies CD. Screening trauma patients with the alcohol use disorders identification test and biomarkers of alcohol use. Alcohol Clin Exp Res. 2009 Jun;33(6):970-6. doi: 10.1111/j.1530-0277.2009.00917.x. Epub 2009 Mar 19. PMID: 19302090.

wrong comparison (interviews (ICD-10, WHO definition and quantity-frequency method))

Verheij C, Haagsma JA, Koch BCP, Segers AEM, Schuit SCE, Rood PPM. Screening for hazardous alcohol use in the Emergency Department: Comparison of phosphatidylethanol with the Alcohol Use Disorders Identification Test and the Timeline Follow-back. Alcohol Clin Exp Res. 2022 Dec;46(12):2225-2235. doi: 10.1111/acer.14958. Epub 2022 Dec 15. PMID: 36520053; PMCID: PMC10107187.

Wrong outcomes (Correlation)

Beoordelingsdatum en geldigheid

Laatst beoordeeld  : 10-09-2025

De Nederlandse Vereniging van Spoedeisende Hulp Artsen (NVSHA) autoriseert de richtlijn onder voorbehoud van goedkeuring tijdens de ALV in december 2025.

Initiatief en autorisatie

Initiatief:
  • Nederlandse Vereniging van Maag-Darm-Leverartsen
Geautoriseerd door:
  • Nederlandse Vereniging van Maag-Darm-Leverartsen
  • Nederlandse Vereniging van Spoedeisende Hulp Artsen
  • Nederlandse Vereniging voor Heelkunde
  • Nederlandse Vereniging voor Klinische Geriatrie
  • Nederlandse Vereniging voor Psychiatrie
  • Nederlandse Vereniging voor Klinische Chemie en Laboratoriumgeneeskunde
  • Nederlandse Vereniging voor Intensive Care
  • Vereniging voor Verslavingsgeneeskunde Nederland
  • Nederlandse Leverpatiënten Vereniging

Algemene gegevens

De ontwikkeling/herziening van deze richtlijnmodule werd ondersteund door het Kennisinstituut van de Federatie Medisch Specialisten (www.demedischspecialist.nl/kennisinstituut) en werd gefinancierd uit [de Kwaliteitsgelden Medisch Specialisten (SKMS). De financier heeft geen enkele invloed gehad op de inhoud van de richtlijnmodule.

Samenstelling werkgroep

Voor het ontwikkelen van de richtlijnmodule is in 2022 een multidisciplinaire werkgroep ingesteld, bestaande uit vertegenwoordigers van alle relevante specialismen (zie hiervoor de Samenstelling van de werkgroep) die betrokken zijn bij de zorg voor patiënten met somatische complicaties als gevolg van risicovol alcoholgebruik.

 

Werkgroep

  • Dr. H. van Soest, MDL-arts, Haaglanden MC, NVMDL (voorzitter)
  • Dr. M.A. Lantinga, MDL-arts, Amsterdam UMC, NVMDL (vice-voorzitter)
  • Dr. R.B. Takkenberg, MDL-arts, Amsterdam UMC, NVMDL
  • Dr. H.J.M. de Jonge, MDL-arts, Jeroen Bosch Ziekenhuis, NVMDL
  • Prof. dr. A.F.A. Schellekens, psychiater, Radboudumc, NVVP
  • Drs. T. van Grinsven, verslavingsarts, Novadic Kentron, VVGN
  • Dr. M. van Loon, spoedeisende hulparts, Haaglanden MC, NVSHA
  • Drs. H. Lam, levertransplantatiechirurg, LUMC, NVvH (vanaf 2024)
  • Drs. J.A. Willemse, directeur, Nederlandse Leverpatienten Vereniging
  • Drs. P.J. van Dongen, ervaringsdeskundige en vrijwilliger, Hersenletsel.nl (tot 2023)
  • H.M. Luttikhuis Msc, ziekenhuisapotheker, Slingeland Ziekenhuis, NVZA (vanaf 2023)
  • Dr. R.A. Weersink, ziekenhuisapotheker, Deventer Ziekenhuis (tot 2024), NVZA (vanaf 2023)
  • Dr. J. Blokzijl, MDL-arts, UMCG, NTV/LOL (vanaf 2025, specifiek voor module levertransplantatie)

Klankbordgroep

  • J.E. de Haan, intensivist, Erasmus MC, NVIC
  • Drs. A.T. Timmer, klinisch geriater, Tjongerschans Ziekenhuis, NVKG
  • Dr. J.M.W. van den Ouweland, klinische chemie en endocrinologie, Canisius Wilhelmina Ziekenhuis, NVKC
  • Dhr. A. van den Berg, ervaringsdeskundige, Stichting het Zwarte Gat (vanaf 2024)

Met ondersteuning van

  • H. Olthuis-van Essen MSc, adviseur, Kennisinstituut van de Federatie Medisch Specialisten
  • J.M.H. van der Hart MSc, adviseur, Kennisinstituut van de Federatie Medisch Specialisten

Belangenverklaringen

Een overzicht van de belangen van werkgroepleden en het oordeel over het omgaan met eventuele belangen vindt u in onderstaande tabel. De ondertekende belangenverklaringen zijn op te vragen bij het secretariaat van het Kennisinstituut van de Federatie Medisch Specialisten via secretariaat@kennisinstituut.nl.

 

Tabel 1 Gemelde (neven)functies en belangen werkgroep

Werkgroeplid

Functie

Nevenfuncties

Gemelde belangen

Ondernomen actie

Dr. H. van Soest (voorzitter)

MDL-arts, Haaglanden MC

Voorzitter commissie hepatologie NVMDL; Voorzitter richtsnoer hepatitis C; Lid richtsnoer commissie hepatitis B; Lid medisch advies raad NLV; Lid visitatiecommissie NVMDL; Lid adviesraad MLDS/NAFLD-NL (initiation of a Dutch NAFLD consortium), lid werkgroep portale hypertensie

Geen

Geen restricties

Dr. M.A. Lantinga (vice-voorzitter)

MDL-arts, Amsterdam UMC, locatie VUmc

Post Doc, Radboudumc (onbetaald), copromotor. Co-voorzitter portale hypertensie werkgroep, Nederlandse Vereniging van Hepatologie (NVH), onbetaald.

Advisory Board - ERN RARE-LIVER // Training and Education Committee, onbetaald.

Geen

Geen restricties

Dr. R.B. Takkenberg

MDL-arts, Amsterdam UMC

Deelname werkgroep tweede lijn, lid alcoholalliantie, gesprekken in het kader van nationaal preventieakkoord, deelname adviesraad over hepatitis Delta, Gilead

ZonMw, Prevention of hepatic Encephalopathy by Administration of in patients with l, projectleider; Fonds-LVC, Neurofilament light chain and glial fibrillary acidic protein for

hepatic encephalopathy, projectleider;

KWF, Validation of a Short and Effective MRI Surveillance protocol for Hepatocellular Carcinoma Scr;

MLDS, Initiation of a Dutch NAFLD consortium, geen projectleider

Geen restricties (adviesraad betreft onderwerp dat niet relevant is voor deze richtlijnmodules)

Dr. H.J.M. de Jonge

MDL-arts, Jeroen Bosch Ziekenhuis

Lid AIH werkgroep, lid werkgroep portale hypertensie, deelname werkgroep tweede lijn

Geen

Geen restricties

Prof. dr. A.F.A. Schellekens

Psychiater, Radboudumc

Nationaal rapporteur verslavingen, adviescommissie alcohol van Gezondheidsraad

ZonMw, onderzoek over verslaving, projectleider; NWO, onderzoek over verslaving, geen projectleider

Geen restricties

Drs. T. van Grinsven

Verslavingsgeneeskundige, Novadic-Kentron

Geen

Dienstverband bij verslavingszorg Novadic-Kentron

Geen restricties

Dr. M. van Loon

SEH-arts in Haaglanden MC; onderzoeker bij LUMC, afdeling Public Health en Eerstelijnsgeneeskunde

Promotieonderzoek naar effectiviteit screening/haalbaarheid op SEH (afgerond); lid werkgroep 2e Lijn, samenwerkingsverband Vroegsignalering Alcoholstoornissen, onbetaald;

Lid sectie Geriatrische Spoedzorg, NVSHA, scholing geven aan collega's m.b.t. acute geriatrie, betaald;

de NVSHA vertegenwoordigen op landelijke bijeenkomsten, waarbij gesproken en beleid gemaakt wordt over geriatrische zorg in de acute keten, onbetaald;

Instructeur voor aantal medische cursussen.

Geen

Geen restricties

Drs. J.A. Willemse

Directeur Nederlandse Leverpatienten Vereniging (betaald, tot 2024); bestuurslid/penningmeester Liver Patients International (onbetaald);

bestuurslid ERN RARE LIVER (onbetaald)

Deelname diverse commissies op gebied van leverziekten (onbetaald)

Geen

Geen restricties

Drs. P.J. van Dongen (tot 2023)

Patiëntenvertegenwoordiger bij Hersenletsel.nl (onbetaald)

Geen

Geen

Geen restricties

H.M. Luttikhuis Msc (vanaf 2023)

Ziekenhuisapotheker in Slingelandziekenhuis

Mede-eigenaar bij cooperatie Herenboerderij De Groote Modderkolk

Geen

Geen restricties

Dr. R.A. Weersink (vanaf 2023)

Ziekenhuisfarmacie, Deventer Ziekenhuis (tot 2024)

Geen

Geen

Geen restricties

Drs. H. Lam (vanaf 2024)

Levertransplantatiechirurg, LUMC

Geen

Geen

Geen restricties

Dr. J. Blokzijl (vanaf 2025)

MDL-arts, UMCG

Geen

Geen

Geen restricties

 

Klankbordgroeplid

Functie

Nevenfuncties

Gemelde belangen

Ondernomen actie

J.E. de Haan

Internist-intensivist

Geen

Geen

Geen restricties

Drs. A.T. Timmer

Klinisch geriater in het Tjongerschans Ziekenhuis

Geen

Geen

Geen restricties

Dr. J.M.W. van den Ouweland

Klinisch chemicus Dicoon, locatie Canisius-Wilhelmina Ziekenhuis, Nijmegen

Geen

Geen

Geen restricties
  1. Van den Berg

Lid algemeen bestuur Stichting het Zwarte Gat

Lid cliëntenraad verslavingszorg;

Lid werkgroepen Verslavingskunde Nederland;

Lid expertcommissie MIND/LpGgz;

Cliëntdeskundige bij twee zorgstandaarden, twee werkwijzers/richtlijnen voor alcohol/verslaving en werk en/of leefstijl, etc.

Bij werken aan herstel van verslaving is er baat voor familie vanwege werk aan herstel.

Verder zijn de uitkomsten altijd van nut bij naasten (b.v. cliënten die ik vertegenwoordig)

Geen restricties

Inbreng patiëntenperspectief

De werkgroep besteedde aandacht aan het patiëntenperspectief door het uitnodigen van patiëntenverenigingen voor de invitational conference, focusgroep en afgevaardigde patiëntenverenigingen in de werkgroep. Het verslag van de invitational conference is besproken in de werkgroep. De verkregen input is meegenomen bij het opstellen van de uitgangsvragen, de keuze voor de uitkomstmaten en bij het opstellen van de overwegingen. De conceptrichtlijn is tevens voor commentaar voorgelegd aan Hersenletsel.nl, de Nederlandse Leverpatienten Vereniging en Stichting het Zwarte Gat en de eventueel aangeleverde commentaren zijn bekeken en verwerkt.

 

Kwalitatieve raming van mogelijke financiële gevolgen in het kader van de Wkkgz

Bij de richtlijnmodule is conform de Wet kwaliteit, klachten en geschillen zorg (Wkkgz) een kwalitatieve raming uitgevoerd om te beoordelen of de aanbevelingen mogelijk leiden tot substantiële financiële gevolgen. Bij het uitvoeren van deze beoordeling is de richtlijnmodule op verschillende domeinen getoetst (zie het stroomschema op de Richtlijnendatabase).

 

Module

Uitkomst raming

Toelichting

Module Detectie risicovol alcoholgebruik

geen financiële gevolgen

Hoewel uit de toetsing volgt dat de aanbevelingen breed toepasbaar zijn (>40.000 patiënten), volgt ook uit de toetsing dat het geen nieuwe manier van zorgverlening of andere organisatie van zorgverlening betreft, het geen toename in het aantal in te zetten voltijdsequivalenten aan zorgverleners betreft en het geen wijziging in het opleidingsniveau van zorgpersoneel betreft. Er worden daarom geen substantiële financiële gevolgen verwacht.

Werkwijze

Voor meer details over de gebruikte richtlijnmethodologie verwijzen wij u naar de Werkwijze. Relevante informatie voor de ontwikkeling/herziening van deze richtlijnmodule is hieronder weergegeven.

Zoekverantwoording

Literature search strategy

 

Algemene informatie

Richtlijn:  Richtlijnmodules somatische complicaties van alcoholstoornissen

Wat is de diagnostische waarde van een laboratoriumtest (EtG, CDT of Peth) voor de detectie van (chronisch) risicovol alcoholgebruik bij volwassen patiënten met een vermoeden op (chronisch) risicovol alcoholgebruik, vergeleken met vragenlijsten?

Database(s): Ovid/Medline, Embase

Datum: 28-7-2023, 30-7-2023

Periode: 2000-heden

Talen: nvt

Literatuurspecialist: Eugenie Delvaux

BMI zoekblokken: voor verschillende opdrachten wordt (deels) gebruik gemaakt van de zoekblokken van BMI-Online https://blocks.bmi-online.nl/ Bij gebruikmaking van een volledig zoekblok zal naar de betreffende link op de website worden verwezen.

Toelichting:

Voor deze vraag is gezocht met de volgende concepten:

  • Alcoholism OR alcohol intoxiation EN (ethylglucuronide OF 'carbohydrate deficient transferrin' OF  phosphatidylethanolamine)

Gezien het feit dat het een diagnostische vraag is kunnen we waarschijnlijk niet naar de RCT’s kijken maar alleen naar de SR’s en de Observationele studies. Aangezien de RCT’s ook worden gevraagd in het zoekformulier is deze set ook in Rayyan gezet.

Het artikel van (Finanger T,2022) komt niet uit de search aangezien hier niet over een test wordt gesproken.

Het artikel van  (Yersin B, 1995) komt niet uit de search aangezien er gezocht dient te worden vanaf 2000

Het artikel van ( Bergkamp FJM, 2021) komt niet uit de search aangezien dit niet het juiste studietype is. Dit artikel komt wel uit de totale set.

Alle andere referentieartikelen komen uit de search.

  

Zoekopbrengst

 

EMBASE

OVID/MEDLINE

Ontdubbeld

SRs

25

87

91

RCTs

66

88

78

Observationele studies

479

189

454

Totaal

 

 

623

 

Zoekstrategie

Embase

No.

Query

Results

#17

#12 AND #14

479

#16

#9 AND #14

66

#15

#8 AND #14

25

#14

#13 AND [1-1-2000]/sd NOT ('conference abstract'/it OR 'editorial'/it OR 'letter'/it OR 'note'/it) NOT (('animal'/exp OR 'animal experiment'/exp OR 'animal model'/exp OR 'nonhuman'/exp) NOT 'human'/exp)

736

#13

#6 AND #7

1257

#12

#10 OR #11

16130698

#11

'case control study'/de OR 'comparative study'/exp OR 'control group'/de OR 'controlled study'/de OR 'controlled clinical trial'/de OR 'crossover procedure'/de OR 'double blind procedure'/de OR 'phase 2 clinical trial'/de OR 'phase 3 clinical trial'/de OR 'phase 4 clinical trial'/de OR 'pretest posttest design'/de OR 'pretest posttest control group design'/de OR 'quasi experimental study'/de OR 'single blind procedure'/de OR 'triple blind procedure'/de OR (((control OR controlled) NEAR/6 trial):ti,ab,kw) OR (((control OR controlled) NEAR/6 (study OR studies)):ti,ab,kw) OR (((control OR controlled) NEAR/1 active):ti,ab,kw) OR 'open label*':ti,ab,kw OR (((double OR two OR three OR multi OR trial) NEAR/1 (arm OR arms)):ti,ab,kw) OR ((allocat* NEAR/10 (arm OR arms)):ti,ab,kw) OR placebo*:ti,ab,kw OR 'sham-control*':ti,ab,kw OR (((single OR double OR triple OR assessor) NEAR/1 (blind* OR masked)):ti,ab,kw) OR nonrandom*:ti,ab,kw OR 'non-random*':ti,ab,kw OR 'quasi-experiment*':ti,ab,kw OR crossover:ti,ab,kw OR 'cross over':ti,ab,kw OR 'parallel group*':ti,ab,kw OR 'factorial trial':ti,ab,kw OR ((phase NEAR/5 (study OR trial)):ti,ab,kw) OR ((case* NEAR/6 (matched OR control*)):ti,ab,kw) OR ((match* NEAR/6 (pair OR pairs OR cohort* OR control* OR group* OR healthy OR age OR sex OR gender OR patient* OR subject* OR participant*)):ti,ab,kw) OR ((propensity NEAR/6 (scor* OR match*)):ti,ab,kw) OR versus:ti OR vs:ti OR compar*:ti OR ((compar* NEAR/1 study):ti,ab,kw) OR (('major clinical study'/de OR 'clinical study'/de OR 'cohort analysis'/de OR 'observational study'/de OR 'cross-sectional study'/de OR 'multicenter study'/de OR 'correlational study'/de OR 'follow up'/de OR cohort*:ti,ab,kw OR 'follow up':ti,ab,kw OR followup:ti,ab,kw OR longitudinal*:ti,ab,kw OR prospective*:ti,ab,kw OR retrospective*:ti,ab,kw OR observational*:ti,ab,kw OR 'cross sectional*':ti,ab,kw OR cross?ectional*:ti,ab,kw OR multicent*:ti,ab,kw OR 'multi-cent*':ti,ab,kw OR consecutive*:ti,ab,kw) AND (group:ti,ab,kw OR groups:ti,ab,kw OR subgroup*:ti,ab,kw OR versus:ti,ab,kw OR vs:ti,ab,kw OR compar*:ti,ab,kw OR 'odds ratio*':ab OR 'relative odds':ab OR 'risk ratio*':ab OR 'relative risk*':ab OR 'rate ratio':ab OR aor:ab OR arr:ab OR rrr:ab OR ((('or' OR 'rr') NEAR/6 ci):ab)))

14291780

#10

'major clinical study'/de OR 'clinical study'/de OR 'case control study'/de OR 'family study'/de OR 'longitudinal study'/de OR 'retrospective study'/de OR 'prospective study'/de OR 'comparative study'/de OR 'cohort analysis'/de OR ((cohort NEAR/1 (study OR studies)):ab,ti) OR (('case control' NEAR/1 (study OR studies)):ab,ti) OR (('follow up' NEAR/1 (study OR studies)):ab,ti) OR (observational NEAR/1 (study OR studies)) OR ((epidemiologic NEAR/1 (study OR studies)):ab,ti) OR (('cross sectional' NEAR/1 (study OR studies)):ab,ti)

7761791

#9

'randomized controlled trial'/exp OR random*:ti,ab OR (((pragmatic OR practical) NEAR/1 'clinical trial*'):ti,ab) OR ((('non inferiority' OR noninferiority OR superiority OR equivalence) NEAR/3 trial*):ti,ab) OR rct:ti,ab,kw

2081650

#8

'meta analysis'/exp OR 'meta analysis (topic)'/exp OR metaanaly*:ti,ab OR 'meta analy*':ti,ab OR metanaly*:ti,ab OR 'systematic review'/de OR 'cochrane database of systematic reviews'/jt OR prisma:ti,ab OR prospero:ti,ab OR (((systemati* OR scoping OR umbrella OR 'structured literature') NEAR/3 (review* OR overview*)):ti,ab) OR ((systemic* NEAR/1 review*):ti,ab) OR (((systemati* OR literature OR database* OR 'data base*') NEAR/10 search*):ti,ab) OR (((structured OR comprehensive* OR systemic*) NEAR/3 search*):ti,ab) OR (((literature NEAR/3 review*):ti,ab) AND (search*:ti,ab OR database*:ti,ab OR 'data base*':ti,ab)) OR (('data extraction':ti,ab OR 'data source*':ti,ab) AND 'study selection':ti,ab) OR ('search strategy':ti,ab AND 'selection criteria':ti,ab) OR ('data source*':ti,ab AND 'data synthesis':ti,ab) OR medline:ab OR pubmed:ab OR embase:ab OR cochrane:ab OR (((critical OR rapid) NEAR/2 (review* OR overview* OR synthes*)):ti) OR ((((critical* OR rapid*) NEAR/3 (review* OR overview* OR synthes*)):ab) AND (search*:ab OR database*:ab OR 'data base*':ab)) OR metasynthes*:ti,ab OR 'meta synthes*':ti,ab

948899

#7

'sensitivity and specificity'/de OR sensitiv*:ab,ti OR specific*:ab,ti OR predict*:ab,ti OR 'roc curve':ab,ti OR 'receiver operator':ab,ti OR 'receiver operators':ab,ti OR likelihood:ab,ti OR 'diagnostic error'/exp OR 'diagnostic accuracy'/exp OR 'diagnostic test accuracy study'/exp OR 'inter observer':ab,ti OR 'intra observer':ab,ti OR interobserver:ab,ti OR intraobserver:ab,ti OR validity:ab,ti OR kappa:ab,ti OR reliability:ab,ti OR reproducibility:ab,ti OR ((test NEAR/2 're-test'):ab,ti) OR ((test NEAR/2 'retest'):ab,ti) OR 'reproducibility'/exp OR accuracy:ab,ti OR 'differential diagnosis'/exp OR 'validation study'/de OR 'measurement precision'/exp OR 'diagnostic value'/exp OR 'reliability'/exp OR 'predictive value'/exp OR ppv:ti,ab,kw OR npv:ti,ab,kw

9908204

#6

#1 AND #5

2170

#5

#2 OR #3 OR #4

33633

#4

'phosphatidylethanolamine'/exp OR '1, 2 diacylglycero 3 phosphoethanolamine':ti,ab,kw OR 'cefalin':ti,ab,kw OR 'cefaline':ti,ab,kw OR 'cephalin':ti,ab,kw OR 'cephaline':ti,ab,kw OR 'diacylethanolamine phosphoglyceride':ti,ab,kw OR 'diacylglycerophosphoethanolamine':ti,ab,kw OR 'diacylphosphatidylethanolamine':ti,ab,kw OR 'ethanolamine glycerophosphatide':ti,ab,kw OR 'ethanolamine glycerophospholipid':ti,ab,kw OR 'ethanolamine phosphatide':ti,ab,kw OR 'ethanolamine phosphoglyceride':ti,ab,kw OR 'glycerophosphoethanolamine diacyl ester':ti,ab,kw OR 'kephalin':ti,ab,kw OR 'phosphatidyl ethanolamine':ti,ab,kw OR 'phosphatidylethanolamine':ti,ab,kw OR 'phosphatidylethanolamines':ti,ab,kw OR 'phosphotidylethanolamine':ti,ab,kw OR phosphatidylethanol:ti,ab,kw

31453

#3

'carbohydrate deficient transferrin'/exp OR 'carbohydrate deficient transferrin':ti,ab,kw

1403

#2

'ethyl glucuronide'/exp OR 'ethyl glucuronide':ti,ab,kw OR 'ethylglucuronide':ti,ab,kw

1142

#1

'alcoholism'/exp OR 'alcohol intoxication'/exp OR 'drinking behavior'/exp OR (((alcohol* OR drinking OR ethanol) NEAR/4 (drinking OR pattern OR behaviour OR behavior OR habit* OR chronic OR addiction OR dependence* OR polyneuropathy OR 'use disorder*' OR individual OR neuropath* OR polyneuritis OR polyneuropathy OR intoxication OR intoxification OR poisoning OR drunkenness* OR toxicit*)):ti,ab,kw) OR 'dipsomania*':ti,ab,kw OR 'ethanol dependenc*':ti,ab,kw OR 'alcohol use*':ti,ab,kw OR 'excessive alcohol':ti,ab,kw OR 'controlled drinking':ti,ab,kw OR 'social drinking':ti,ab,kw OR 'inebriation':ti,ab,kw OR 'binge drink*':ti,ab,kw

387895

 

Ovid/Medline

#

Searches

Results

16

12 and 13

189

15

11 and 13

88

14

10 and 13

87

13

8 and 9

655

12

Epidemiologic studies/ or case control studies/ or exp cohort studies/ or Controlled Before-After Studies/ or Case control.tw. or cohort*.tw. or Cohort analy$.tw. or (Follow up adj (study or studies)).tw. or (observational adj (study or studies)).tw. or Longitudinal.tw. or Retrospective*.tw. or prospective*.tw. or consecutive*.tw. or Cross sectional.tw. or Cross-sectional studies/ or historically controlled study/ or interrupted time series analysis/

4537714

11

exp clinical trial/ or randomized controlled trial/ or exp clinical trials as topic/ or randomized controlled trials as topic/ or Random Allocation/ or Double-Blind Method/ or Single-Blind Method/ or (clinical trial, phase i or clinical trial, phase ii or clinical trial, phase iii or clinical trial, phase iv or controlled clinical trial or randomized controlled trial or multicenter study or clinical trial).pt. or random*.ti,ab. or (clinic* adj trial*).tw. or ((singl* or doubl* or treb* or tripl*) adj (blind$3 or mask$3)).tw. or Placebos/ or placebo*.tw.

2615479

10

meta-analysis/ or review/ or meta-analysis as topic/ or (metaanaly* or meta-analy* or metanaly*).ti,ab,kf. or systematic review/ or cochrane.jw. or (prisma or prospero).ti,ab,kf. or ((systemati* or scoping or umbrella or "structured literature") adj3 (review* or overview*)).ti,ab,kf. or (systemic* adj1 review*).ti,ab,kf. or ((systemati* or literature or database* or data-base*) adj10 search*).ti,ab,kf. or ((structured or comprehensive* or systemic*) adj3 search*).ti,ab,kf. or ((literature adj3 review*) and (search* or database* or data-base*)).ti,ab,kf. or (("data extraction" or "data source*") and "study selection").ti,ab,kf. or ("search strategy" and "selection criteria").ti,ab,kf. or ("data source*" and "data synthesis").ti,ab,kf. or (medline or pubmed or embase or cochrane).ab. or ((critical or rapid) adj2 (review* or overview* or synthes*)).ti. or (((critical* or rapid*) adj3 (review* or overview* or synthes*)) and (search* or database* or data-base*)).ab. or (metasynthes* or meta-synthes*).ti,ab,kf. or review*.ti,ab,kf.

4549044

9

exp "Sensitivity and Specificity"/ or (Sensitiv* or Specific*).ti,ab. or (predict* or ROC-curve or receiver-operator*).ti,ab. or (likelihood or LR*).ti,ab. or exp Diagnostic Errors/ or (inter-observer or intra-observer or interobserver or intraobserver or validity or kappa or reliability).ti,ab. or reproducibility.ti,ab. or (test adj2 (re-test or retest)).ti,ab. or "Reproducibility of Results"/ or accuracy.ti,ab. or Diagnosis, Differential/ or Validation Studies.pt. or exp "Predictive Value of Tests"/ or ppv.ti,ab,kf. or npv.ti,ab,kf.

7900191

8

7 not ((exp animals/ or exp models, animal/) not humans/) not (letter/ or comment/ or editorial/)

1093

7

limit 6 to yr="2000 -Current"

1160

6

1 and 5

1437

5

2 or 3 or 4

31044

4

exp Phosphatidylethanolamines/ or '1, 2 diacylglycero 3 phosphoethanolamine'.ti,ab,kf. or cefalin.ti,ab,kf. or cefaline.ti,ab,kf. or cephalin.ti,ab,kf. or cephaline.ti,ab,kf. or 'diacylethanolamine phosphoglyceride'.ti,ab,kf. or diacylglycerophosphoethanolamine.ti,ab,kf. or diacylphosphatidylethanolamine.ti,ab,kf. or 'ethanolamine glycerophosphatide'.ti,ab,kf. or 'ethanolamine glycerophospholipid'.ti,ab,kf. or 'ethanolamine phosphatide'.ti,ab,kf. or 'ethanolamine phosphoglyceride'.ti,ab,kf. or 'glycerophosphoethanolamine diacyl ester'.ti,ab,kf. or kephalin.ti,ab,kf. or 'phosphatidyl ethanolamine'.ti,ab,kf. or phosphatidylethanolamine.ti,ab,kf. or 'phosphatidylethanolamines'.ti,ab,kf. or 'phosphotidylethanolamine'.ti,ab,kf. or phosphatidylethanol.ti,ab,kf.

29118

3

('carbohydrate deficient transferrin' or 'c-d-transferrin').ti,ab,kf.

895

2

*Glycerophospholipids/ or ('ethyl glucuron*' or 'ethylglucuron*').ti,ab,kf.

1645

1

Drinking Behavior/ or exp Alcohol Drinking/ or Alcoholic Intoxication/ or (((alcohol* or drinking or ethanol) adj4 (drinking or pattern or behaviour or behavior or habit* or chronic or addiction or dependence* or polyneuropathy or 'use disorder*' or individual or neuropath* or polyneuritis or polyneuropathy or intoxication or intoxification or poisoning or drunkenness* or toxicit*)) or 'dipsomania*' or 'ethanol dependenc*' or 'alcohol use*' or 'excessive alcohol' or 'controlled drinking' or 'social drinking' or 'inebriation' or 'binge drink*').ti,ab,kf.

252426
Volgende:
Acute alcoholintoxicatie