Head‐to‐Head Comparison Between Phosphatidylethanol Versus Indirect Alcohol Biomarkers for Diagnosis of MetALD Versus MASLD: A Prospective Study

ABSTRACT Background The current subclassification of steatotic liver disease (SLD) relies on validated questionnaires, such as Alcohol Use Disorders Identification Test (AUDIT) and Lifetime Drinking History (LDH), which, while useful, are impractical and lack precision for their use in routine clini...

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Vydáno v:	Alimentary pharmacology & therapeutics Ročník 61; číslo 6; s. 1043 - 1054
Hlavní autoři:	Tavaglione, Federica, Amangurbanova, Maral, Yang, Alexander H., Tincopa, Monica A., Ajmera, Veeral, Richards, Lisa, Butcher, Christian, Hernandez, Christie, Madamba, Egbert, Singh, Seema, Bettencourt, Ricki, Sirlin, Claude B., Loomba, Rohit
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	England Wiley Subscription Services, Inc 01.03.2025
Témata:	Adult Aged Alanine transaminase Alcohol Alcohol Drinking Alcohol use ALD Aspartate aminotransferase Biomarkers Biomarkers - blood Body weight California - epidemiology Clinical medicine Cross-Sectional Studies Diagnosis, Differential Drinking behavior Fatty Liver - blood Fatty Liver - diagnosis Female Glycerophospholipids - blood Humans Liver diseases Liver Diseases, Alcoholic - diagnosis Magnetic resonance imaging Male Metabolism Middle Aged NAFLD Obesity Obesity - complications Overweight Prospective Studies Questionnaires Sensitivity and Specificity SLD California alcohol ALD NAFLD SLD biomarkers
ISSN:	0269-2813, 1365-2036, 1365-2036
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Abstract	ABSTRACT Background The current subclassification of steatotic liver disease (SLD) relies on validated questionnaires, such as Alcohol Use Disorders Identification Test (AUDIT) and Lifetime Drinking History (LDH), which, while useful, are impractical and lack precision for their use in routine clinical practice. Phosphatidylethanol (PEth) is a quantitative, objective alcohol biomarker with high sensitivity and specificity. Aims To assess the diagnostic accuracy of PEth for differentiating metabolic dysfunction and alcohol‐associated liver disease (MetALD) from metabolic dysfunction‐associated steatotic liver disease (MASLD) in a large, population‐based, prospective, multiethnic cohort of individuals with overweight or obesity. Methods This is a cross‐sectional analysis of a prospective study including 374 adults with overweight or obesity residing in Southern California who had SLD as defined by MRI‐PDFF ≥ 5%. The clinical research visit included medical history, biochemical and PEth testing, standardised validated questionnaires (including AUDIT and LDH), physical examination, and advanced imaging using MRI‐PDFF and MRE. Results Among 374 adults with SLD, the prevalence of MASLD, MetALD, and ALD was 90.1%, 6.4%, and 3.5%, respectively. PEth had a robust diagnostic accuracy in the detection of MetALD (AUROC 0.81, 95%CI 0.73–0.89) and the Youden cut‐off was 25 ng/mL. In head‐to‐head comparative efficacy analysis, PEth was both statistically and clinically superior to all previously used indirect alcohol biomarkers for diagnosing MetALD, including aspartate aminotransferase/alanine aminotransferase ratio, mean corpuscular volume, gamma glutamyltransferase, and ALD/NAFLD index (p < 0.05). Conclusions PEth outperforms previously used non‐invasive tests in differentiating MetALD from MASLD and has the potential to change clinical practice by enhancing the subclassification of SLD. Using a well‐phenotyped prospective cohort with systematic assessment through MRI‐PDFF, MRE, and PEth testing, this study demonstrates that PEth is an accurate, quantitative, objective alcohol biomarker for detecting and differentiating MetALD from MASLD, and outperforms previously available indirect alcohol biomarkers.
AbstractList	The current subclassification of steatotic liver disease (SLD) relies on validated questionnaires, such as Alcohol Use Disorders Identification Test (AUDIT) and Lifetime Drinking History (LDH), which, while useful, are impractical and lack precision for their use in routine clinical practice. Phosphatidylethanol (PEth) is a quantitative, objective alcohol biomarker with high sensitivity and specificity. To assess the diagnostic accuracy of PEth for differentiating metabolic dysfunction and alcohol-associated liver disease (MetALD) from metabolic dysfunction-associated steatotic liver disease (MASLD) in a large, population-based, prospective, multiethnic cohort of individuals with overweight or obesity. This is a cross-sectional analysis of a prospective study including 374 adults with overweight or obesity residing in Southern California who had SLD as defined by MRI-PDFF ≥ 5%. The clinical research visit included medical history, biochemical and PEth testing, standardised validated questionnaires (including AUDIT and LDH), physical examination, and advanced imaging using MRI-PDFF and MRE. Among 374 adults with SLD, the prevalence of MASLD, MetALD, and ALD was 90.1%, 6.4%, and 3.5%, respectively. PEth had a robust diagnostic accuracy in the detection of MetALD (AUROC 0.81, 95%CI 0.73-0.89) and the Youden cut-off was 25 ng/mL. In head-to-head comparative efficacy analysis, PEth was both statistically and clinically superior to all previously used indirect alcohol biomarkers for diagnosing MetALD, including aspartate aminotransferase/alanine aminotransferase ratio, mean corpuscular volume, gamma glutamyltransferase, and ALD/NAFLD index (p < 0.05). PEth outperforms previously used non-invasive tests in differentiating MetALD from MASLD and has the potential to change clinical practice by enhancing the subclassification of SLD. ABSTRACT Background The current subclassification of steatotic liver disease (SLD) relies on validated questionnaires, such as Alcohol Use Disorders Identification Test (AUDIT) and Lifetime Drinking History (LDH), which, while useful, are impractical and lack precision for their use in routine clinical practice. Phosphatidylethanol (PEth) is a quantitative, objective alcohol biomarker with high sensitivity and specificity. Aims To assess the diagnostic accuracy of PEth for differentiating metabolic dysfunction and alcohol‐associated liver disease (MetALD) from metabolic dysfunction‐associated steatotic liver disease (MASLD) in a large, population‐based, prospective, multiethnic cohort of individuals with overweight or obesity. Methods This is a cross‐sectional analysis of a prospective study including 374 adults with overweight or obesity residing in Southern California who had SLD as defined by MRI‐PDFF ≥ 5%. The clinical research visit included medical history, biochemical and PEth testing, standardised validated questionnaires (including AUDIT and LDH), physical examination, and advanced imaging using MRI‐PDFF and MRE. Results Among 374 adults with SLD, the prevalence of MASLD, MetALD, and ALD was 90.1%, 6.4%, and 3.5%, respectively. PEth had a robust diagnostic accuracy in the detection of MetALD (AUROC 0.81, 95%CI 0.73–0.89) and the Youden cut‐off was 25 ng/mL. In head‐to‐head comparative efficacy analysis, PEth was both statistically and clinically superior to all previously used indirect alcohol biomarkers for diagnosing MetALD, including aspartate aminotransferase/alanine aminotransferase ratio, mean corpuscular volume, gamma glutamyltransferase, and ALD/NAFLD index (p < 0.05). Conclusions PEth outperforms previously used non‐invasive tests in differentiating MetALD from MASLD and has the potential to change clinical practice by enhancing the subclassification of SLD. Using a well‐phenotyped prospective cohort with systematic assessment through MRI‐PDFF, MRE, and PEth testing, this study demonstrates that PEth is an accurate, quantitative, objective alcohol biomarker for detecting and differentiating MetALD from MASLD, and outperforms previously available indirect alcohol biomarkers. The current subclassification of steatotic liver disease (SLD) relies on validated questionnaires, such as Alcohol Use Disorders Identification Test (AUDIT) and Lifetime Drinking History (LDH), which, while useful, are impractical and lack precision for their use in routine clinical practice. Phosphatidylethanol (PEth) is a quantitative, objective alcohol biomarker with high sensitivity and specificity.BACKGROUNDThe current subclassification of steatotic liver disease (SLD) relies on validated questionnaires, such as Alcohol Use Disorders Identification Test (AUDIT) and Lifetime Drinking History (LDH), which, while useful, are impractical and lack precision for their use in routine clinical practice. Phosphatidylethanol (PEth) is a quantitative, objective alcohol biomarker with high sensitivity and specificity.To assess the diagnostic accuracy of PEth for differentiating metabolic dysfunction and alcohol-associated liver disease (MetALD) from metabolic dysfunction-associated steatotic liver disease (MASLD) in a large, population-based, prospective, multiethnic cohort of individuals with overweight or obesity.AIMSTo assess the diagnostic accuracy of PEth for differentiating metabolic dysfunction and alcohol-associated liver disease (MetALD) from metabolic dysfunction-associated steatotic liver disease (MASLD) in a large, population-based, prospective, multiethnic cohort of individuals with overweight or obesity.This is a cross-sectional analysis of a prospective study including 374 adults with overweight or obesity residing in Southern California who had SLD as defined by MRI-PDFF ≥ 5%. The clinical research visit included medical history, biochemical and PEth testing, standardised validated questionnaires (including AUDIT and LDH), physical examination, and advanced imaging using MRI-PDFF and MRE.METHODSThis is a cross-sectional analysis of a prospective study including 374 adults with overweight or obesity residing in Southern California who had SLD as defined by MRI-PDFF ≥ 5%. The clinical research visit included medical history, biochemical and PEth testing, standardised validated questionnaires (including AUDIT and LDH), physical examination, and advanced imaging using MRI-PDFF and MRE.Among 374 adults with SLD, the prevalence of MASLD, MetALD, and ALD was 90.1%, 6.4%, and 3.5%, respectively. PEth had a robust diagnostic accuracy in the detection of MetALD (AUROC 0.81, 95%CI 0.73-0.89) and the Youden cut-off was 25 ng/mL. In head-to-head comparative efficacy analysis, PEth was both statistically and clinically superior to all previously used indirect alcohol biomarkers for diagnosing MetALD, including aspartate aminotransferase/alanine aminotransferase ratio, mean corpuscular volume, gamma glutamyltransferase, and ALD/NAFLD index (p < 0.05).RESULTSAmong 374 adults with SLD, the prevalence of MASLD, MetALD, and ALD was 90.1%, 6.4%, and 3.5%, respectively. PEth had a robust diagnostic accuracy in the detection of MetALD (AUROC 0.81, 95%CI 0.73-0.89) and the Youden cut-off was 25 ng/mL. In head-to-head comparative efficacy analysis, PEth was both statistically and clinically superior to all previously used indirect alcohol biomarkers for diagnosing MetALD, including aspartate aminotransferase/alanine aminotransferase ratio, mean corpuscular volume, gamma glutamyltransferase, and ALD/NAFLD index (p < 0.05).PEth outperforms previously used non-invasive tests in differentiating MetALD from MASLD and has the potential to change clinical practice by enhancing the subclassification of SLD.CONCLUSIONSPEth outperforms previously used non-invasive tests in differentiating MetALD from MASLD and has the potential to change clinical practice by enhancing the subclassification of SLD. BackgroundThe current subclassification of steatotic liver disease (SLD) relies on validated questionnaires, such as Alcohol Use Disorders Identification Test (AUDIT) and Lifetime Drinking History (LDH), which, while useful, are impractical and lack precision for their use in routine clinical practice. Phosphatidylethanol (PEth) is a quantitative, objective alcohol biomarker with high sensitivity and specificity.AimsTo assess the diagnostic accuracy of PEth for differentiating metabolic dysfunction and alcohol‐associated liver disease (MetALD) from metabolic dysfunction‐associated steatotic liver disease (MASLD) in a large, population‐based, prospective, multiethnic cohort of individuals with overweight or obesity.MethodsThis is a cross‐sectional analysis of a prospective study including 374 adults with overweight or obesity residing in Southern California who had SLD as defined by MRI‐PDFF ≥ 5%. The clinical research visit included medical history, biochemical and PEth testing, standardised validated questionnaires (including AUDIT and LDH), physical examination, and advanced imaging using MRI‐PDFF and MRE.ResultsAmong 374 adults with SLD, the prevalence of MASLD, MetALD, and ALD was 90.1%, 6.4%, and 3.5%, respectively. PEth had a robust diagnostic accuracy in the detection of MetALD (AUROC 0.81, 95%CI 0.73–0.89) and the Youden cut‐off was 25 ng/mL. In head‐to‐head comparative efficacy analysis, PEth was both statistically and clinically superior to all previously used indirect alcohol biomarkers for diagnosing MetALD, including aspartate aminotransferase/alanine aminotransferase ratio, mean corpuscular volume, gamma glutamyltransferase, and ALD/NAFLD index (p < 0.05).ConclusionsPEth outperforms previously used non‐invasive tests in differentiating MetALD from MASLD and has the potential to change clinical practice by enhancing the subclassification of SLD.
Author	Yang, Alexander H. Butcher, Christian Tincopa, Monica A. Loomba, Rohit Ajmera, Veeral Hernandez, Christie Amangurbanova, Maral Sirlin, Claude B. Madamba, Egbert Richards, Lisa Bettencourt, Ricki Tavaglione, Federica Singh, Seema
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Notes	Funding VA is supported by NIDDK (K23DK119460). RL receives funding support from NCATS (5UL1TR001442), NIDDK (U01DK061734, U01DK130190, R01DK106419, R01DK121378, R01DK124318, P30DK120515), NHLBI (P01HL147835), John C Martin Foundation (RP124) and NIAAA (U01AA029019). ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
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Snippet	ABSTRACT Background The current subclassification of steatotic liver disease (SLD) relies on validated questionnaires, such as Alcohol Use Disorders... The current subclassification of steatotic liver disease (SLD) relies on validated questionnaires, such as Alcohol Use Disorders Identification Test (AUDIT)... BackgroundThe current subclassification of steatotic liver disease (SLD) relies on validated questionnaires, such as Alcohol Use Disorders Identification Test...
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SubjectTerms	Adult Aged Alanine transaminase Alcohol Alcohol Drinking Alcohol use ALD Aspartate aminotransferase Biomarkers Biomarkers - blood Body weight California - epidemiology Clinical medicine Cross-Sectional Studies Diagnosis, Differential Drinking behavior Fatty Liver - blood Fatty Liver - diagnosis Female Glycerophospholipids - blood Humans Liver diseases Liver Diseases, Alcoholic - diagnosis Magnetic resonance imaging Male Metabolism Middle Aged NAFLD Obesity Obesity - complications Overweight Prospective Studies Questionnaires Sensitivity and Specificity SLD
Title	Head‐to‐Head Comparison Between Phosphatidylethanol Versus Indirect Alcohol Biomarkers for Diagnosis of MetALD Versus MASLD: A Prospective Study
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