Evaluation of direct and indirect ethanol biomarkers using a likelihood ratio approach to identify chronic alcohol abusers for forensic purposes.

The detection of direct ethanol metabolites, such as ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEEs), in scalp hair is considered the optimal strategy to effectively recognize chronic alcohol misuses by means of specific cut-offs suggested by the Society of Hair Testing. However, several factors (e.g. hair treatments) may alter the correlation between alcohol intake and biomarkers concentrations, possibly introducing bias in the interpretative process and conclusions. 125 subjects with various drinking habits were subjected to blood and hair sampling to determine indirect (e.g. CDT) and direct alcohol biomarkers. The overall data were investigated using several multivariate statistical methods. A likelihood ratio (LR) approach was used for the first time to provide predictive models for the diagnosis of alcohol abuse, based on different combinations of direct and indirect alcohol biomarkers. LR strategies provide a more robust outcome than the plain comparison with cut-off values, where tiny changes in the analytical results can lead to dramatic divergence in the way they are interpreted. An LR model combining EtG and FAEEs hair concentrations proved to discriminate non-chronic from chronic consumers with ideal correct classification rates, whereas the contribution of indirect biomarkers proved to be negligible. Optimal results were observed using a novel approach that associates LR methods with multivariate statistics. In particular, the combination of LR approach with either Principal Component Analysis (PCA) or Linear Discriminant Analysis (LDA) proved successful in discriminating chronic from non-chronic alcohol drinkers. These LR models were subsequently tested on an independent dataset of 43 individuals, which confirmed their high efficiency. These models proved to be less prone to bias than EtG and FAEEs independently considered. In conclusion, LR models may represent an efficient strategy to sustain the diagnosis of chronic alcohol consumption and provide a suitable gradation to support the judgment.

[1]  T. Mieczkowski,et al.  Practical experiences in application of hair fatty acid ethyl esters and ethyl glucuronide for detection of chronic alcohol abuse in forensic cases. , 2012, Forensic science international.

[2]  R. Leardi,et al.  Chemometrics: From classical to genetic algorithms , 2002 .

[3]  F. Pragst.  Alcohol Biomarkers in Hair , 2015 .

[4]  F. Pragst,et al.  Determination of Fatty Acid Ethyl Esters (FAEE) and Ethyl Glucuronide (EtG) in Hair: A Promising Way for Retrospective Detection of Alcohol Abuse During Pregnancy? , 2008, Therapeutic drug monitoring.

[5]  Ronald Agius,et al.  Ethyl glucuronide in hair - A highly effective test for the monitoring of alcohol consumption. , 2012, Forensic science international.

[6]  V. Pirro,et al.  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 , 2011, Analytical and bioanalytical chemistry.

[7]  Heinz Stoewer,et al.  Challenges and Perspectives , 2006 .

[8]  V. Pirro,et al.  Direct and indirect alcohol biomarkers data collected in hair samples - multivariate data analysis and likelihood ratio interpretation perspectives , 2017, Data in brief.

[9]  Agnieszka Martyna,et al.  Wine authenticity verification as a forensic problem: an application of likelihood ratio test to label verification. , 2014, Food chemistry.

[10]  Agnieszka Martyna,et al.  Statistical Analysis in Forensic Science: Evidential Value of Multivariate Physicochemical Data , 2014 .

[11]  C. Aitken,et al.  A Two‐Level Model for Evidence Evaluation , 2007, Journal of forensic sciences.

[12]  F. Pragst,et al.  Workplace alcohol testing program by combined use of ethyl glucuronide and fatty acid ethyl esters in hair. , 2012, Alcohol and alcoholism.

[13]  S. Suesse,et al.  Fatty acid ethyl ester concentrations in hair and self-reported alcohol consumption in 644 cases from different origin. , 2010, Forensic science international.

[14]  P. Kintz,et al.  Testing for ethanol markers in hair: discrepancies after simultaneous quantification of ethyl glucuronide and fatty acid ethyl esters. , 2014, Forensic science international.

[15]  G. Zadora,et al.  Interpretation of FTIR spectra of polymers and Raman spectra of car paints by means of likelihood ratio approach supported by wavelet transform for reducing data dimensionality , 2015, Analytical and Bioanalytical Chemistry.

[16]  Grzegorz Zadora,et al.  Evaluation of glass samples for forensic purposes — An application of likelihood ratios and an information–theoretical approach , 2010 .

[17]  R Core Team,et al.  R: A language and environment for statistical computing. , 2014 .

[18]  Agnieszka Martyna,et al.  A likelihood ratio model for the determination of the geographical origin of olive oil. , 2015, Analytica chimica acta.

[19]  V. Pirro,et al.  Interpretation of group-level factors from a large population dataset in the determination of ethyl glucuronide in hair. , 2015, Drug testing and analysis.

[20]  Guido Viel,et al.  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 , 2014, Therapeutic drug monitoring.

[21]  A. Heinz,et al.  Detecting alcohol abuse: traditional blood alcohol markers compared to ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEEs) measurement in hair , 2013, Forensic Science, Medicine, and Pathology.

[22]  F. Musshoff,et al.  Comparison of ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEEs) concentrations in hair for testing abstinence , 2011, Analytical and bioanalytical chemistry.

[23]  B. Lendl,et al.  A rapid method for the differentiation of yeast cells grown under carbon and nitrogen-limited conditions by means of partial least squares discriminant analysis employing infrared micro-spectroscopic data of entire yeast cells , 2012, Talanta.

[24]  F. Pragst,et al.  Analysis of fatty acid ethyl esters in hair as possible markers of chronically elevated alcohol consumption by headspace solid-phase microextraction (HS-SPME) and gas chromatography-mass spectrometry (GC-MS). , 2001, Forensic science international.

[25]  P. Randall,et al.  Hair ethyl glucuronide is highly sensitive and specific for detecting moderate-to-heavy drinking in patients with liver disease. , 2013, Alcohol and alcoholism.

[26]  P. Mangin,et al.  Diagnostic performance of ethyl glucuronide in hair for the investigation of alcohol drinking behavior: a comparison with traditional biomarkers , 2012, International Journal of Legal Medicine.

[27]  Grzegorz Zadora,et al.  Evaluation of the evidential value of physicochemical data by a Bayesian network approach , 2010 .

[28]  John Fox,et al.  GETTING STARTED WITH THE R COMMANDER: A BASIC-STATISTICS GRAPHICAL USER INTERFACE TO R , 2005 .

[29]  Niko Brümmer,et al.  Application-independent evaluation of speaker detection , 2006, Comput. Speech Lang..

[30]  M. Savolainen,et al.  Biochemical markers of alcoholism , 2007, Clinical chemistry and laboratory medicine.

[31]  G. Zadora.  Classification of Glass Fragments Based on Elemental Composition and Refractive Index * , 2009, Journal of forensic sciences.

[32]  A. Polettini,et al.  Comparison of ethyl glucuronide in hair with carbohydrate-deficient transferrin in serum as markers of chronic high levels of alcohol consumption. , 2009, Forensic science international.

[33]  G. Zadora,et al.  Differentiation between weathered kerosene and diesel fuel using automatic thermal desorption-GC-MS analysis and the likelihood ratio approach , 2005 .

[34]  F. Pragst,et al.  Combined use of fatty acid ethyl esters and ethyl glucuronide in hair for diagnosis of alcohol abuse: interpretation and advantages. , 2010, Forensic science international.

[35]  V. Pirro,et al.  Determination of ethyl glucuronide levels in hair for the assessment of alcohol abstinence. , 2013, Forensic science international.

[36]  Pascal Kintz,et al.  2014 consensus for the use of alcohol markers in hair for assessment of both abstinence and chronic excessive alcohol consumption. , 2015, Forensic science international.

[37]  Matthias Otto,et al.  Chemometrics: Statistics and Computer Application in Analytical Chemistry , 1999 .

[38]  Grzegorz Zadora,et al.  Information-theoretical feature selection using data obtained by scanning electron microscopy coupled with and energy dispersive X-ray spectrometer for the classification of glass traces. , 2011, Analytica chimica acta.

[39]  G. Zadora,et al.  Application of a likelihood ratio approach in solving a comparison problem of Raman spectra recorded for blue automotive paints , 2015 .

[40]  G. Zadora,et al.  An effect of selection of a smoothing parameter on the performance of likelihood ratio models for solving classification task , 2015 .

[41]  A. S. Tippetts,et al.  Ethylglucuronide in Hair Is a Top Predictor of Impaired Driving Recidivism, Alcohol Dependence, and a Key Marker of the Highest BAC Interlock Tests , 2014, Traffic injury prevention.

[42]  Franco Taroni,et al.  Statistics and the Evaluation of Evidence for Forensic Scientists , 2004 .

[43]  G. Iannello,et al.  Chronic Excessive Alcohol Consumption Diagnosis: Comparison Between Traditional Biomarkers and Ethyl Glucuronide in Hair, a Study on a Real Population , 2011, Therapeutic drug monitoring.

[44]  Grzegorz Zadora,et al.  Evidential value of physicochemical data—comparison of methods of glass database creation , 2010 .

[45]  Colin Aitken,et al.  Evaluation of trace evidence in the form of multivariate data , 2004 .

[46]  Andrzej Parczewski,et al.  The evidential value of microspectrophotometry measurements made for pen inks , 2013 .

[47]  V. Pirro,et al.  Multivariate strategies for screening evaluation of harmful drinking. , 2013, Bioanalysis.

[48]  P. Marques.  Levels and types of alcohol biomarkers in DUI and clinic samples for estimating workplace alcohol problems. , 2012, Drug testing and analysis.

[49]  G. Koren,et al.  Agreement Between the Fatty Acid Ethyl Ester Hair Test for Alcohol and Social Workers' Reports , 2010, Therapeutic drug monitoring.

[50]  Johanna Smeyers-Verbeke,et al.  Handbook of Chemometrics and Qualimetrics: Part A , 1997 .

[51]  H. Neels,et al.  Hair ethyl glucuronide levels as a marker for alcohol use and abuse: a review of the current state of the art. , 2014, Drug and alcohol dependence.

[52]  Agnieszka Martyna,et al.  Analysis of lead isotopic ratios of glass objects with the aim of comparing them for forensic purposes. , 2013, Talanta.

[53]  Burkhard Madea,et al.  A SPME-GC/MS procedure for the determination of fatty acid ethyl esters in hair for confirmation of abstinence test results. , 2014, Journal of chromatographic science.

[54]  W R Mayr,et al.  DNA commission of the International Society of Forensic Genetics: Recommendations on the interpretation of mixtures. , 2006, Forensic science international.

[55]  M. Augsburger,et al.  Positive EtG findings in hair as a result of a cosmetic treatment. , 2012, Forensic science international.