Using Phosphatidylethanol as an Adjunct to Self-Reported Alcohol Use Improves Identification of Liver Fibrosis Risk

Pamela M Murnane^{1

2}, Majid Afshar³, Gabriel Chamie⁴, Robert L Cook⁵, Tekeda Ferguson^{6

7}, Lamia Y Haque⁸, Karen R Jacobson⁹, Amy C Justice^{10

11

12}, Theresa W Kim⁹, Mandana Khalili¹³, Evgeny Krupitsky^{14

15}, Kathleen A McGinnis¹⁰, Patricia Molina^{6

16}, Winnie R Muyindike¹⁷, Bronwyn Myers^{18

19

20}, Veronica L Richards²¹, Kaku So-Armah⁹, Scott Stewart²², Mark S Sulkowski²³, Phyllis C Tien^{4

24}, Judith A Hahn^{1

4}

Affiliations

¹ Department of Epidemiology and Biostatistics, University of California, San Francisco, California, USA.
² Institute for Global Health Sciences, University of California, San Francisco, California, USA.
³ Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
⁴ Department of Medicine, University of California, San Francisco, California, USA.
⁵ Department of Epidemiology, University of Florida, Gainesville, Florida, USA.
⁶ Comprehensive Alcohol-HIV/AIDS Research Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.
⁷ Epidemiology Program, School of Public Health, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.
⁸ Department of Internal Medicine (Section of Digestive Diseases) and Program in Addiction Medicine, Yale School of Medicine, New Haven, Connecticut, USA.
⁹ Department of Medicine, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts, USA.
¹⁰ United States Department of Veterans Affairs, VA Connecticut Healthcare System, West Haven, Connecticut, USA.
¹¹ Yale School of Medicine, New Haven, Connecticut, USA.
¹² Department of Health Policy and Management, Yale School of Public Health, New Haven, Connecticut, USA.
¹³ Department of Medicine, Division of Gastroenterology and Hepatology, University of California San Francisco, San Francisco, California, USA.
¹⁴ First Pavlov State Medical University, St. Petersburg, Russia.
¹⁵ V.M. Bekhterev National Medical Research Center for Psychiatry and Neurology, St. Petersburg, Russia.
¹⁶ Department of Physiology, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.
¹⁷ Department of Internal Medicine, Mbarara University of Science and Technology, Mbarara, Uganda.
¹⁸ Curtin EnAble Institute, Faculty of Health Sciences, Curtin University, Perth, Australia.
¹⁹ Mental Health, Alcohol, Substance Use and Tobacco Research Unit, South African Medical Research Council, Tygerberg, South Africa.
²⁰ Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.
²¹ TSET Health Promotion Research Center, University of Oklahoma Health Sciences Center, Tulsa, Oklahoma, USA.
²² Department of Family Medicine, Division of Addiction Medicine, University at Buffalo, Buffalo, New York, USA.
²³ Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
²⁴ Infectious Diseases Division, San Francisco VA Health Care System, San Francisco, California, USA .

PMID: 39480054
PMCID: PMC12041314
DOI: 10.14309/ajg.0000000000003178

Using Phosphatidylethanol as an Adjunct to Self-Reported Alcohol Use Improves Identification of Liver Fibrosis Risk

Pamela M Murnane et al. Am J Gastroenterol. 2024.

. 2024 Oct 31;120(7):1567-1575.

doi: 10.14309/ajg.0000000000003178.

Authors

Affiliations

¹ Department of Epidemiology and Biostatistics, University of California, San Francisco, California, USA.
² Institute for Global Health Sciences, University of California, San Francisco, California, USA.
³ Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
⁴ Department of Medicine, University of California, San Francisco, California, USA.
⁵ Department of Epidemiology, University of Florida, Gainesville, Florida, USA.
⁶ Comprehensive Alcohol-HIV/AIDS Research Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.
⁷ Epidemiology Program, School of Public Health, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.
⁸ Department of Internal Medicine (Section of Digestive Diseases) and Program in Addiction Medicine, Yale School of Medicine, New Haven, Connecticut, USA.
⁹ Department of Medicine, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts, USA.
¹⁰ United States Department of Veterans Affairs, VA Connecticut Healthcare System, West Haven, Connecticut, USA.
¹¹ Yale School of Medicine, New Haven, Connecticut, USA.
¹² Department of Health Policy and Management, Yale School of Public Health, New Haven, Connecticut, USA.
¹³ Department of Medicine, Division of Gastroenterology and Hepatology, University of California San Francisco, San Francisco, California, USA.
¹⁴ First Pavlov State Medical University, St. Petersburg, Russia.
¹⁵ V.M. Bekhterev National Medical Research Center for Psychiatry and Neurology, St. Petersburg, Russia.
¹⁶ Department of Physiology, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.
¹⁷ Department of Internal Medicine, Mbarara University of Science and Technology, Mbarara, Uganda.
¹⁸ Curtin EnAble Institute, Faculty of Health Sciences, Curtin University, Perth, Australia.
¹⁹ Mental Health, Alcohol, Substance Use and Tobacco Research Unit, South African Medical Research Council, Tygerberg, South Africa.
²⁰ Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.
²¹ TSET Health Promotion Research Center, University of Oklahoma Health Sciences Center, Tulsa, Oklahoma, USA.
²² Department of Family Medicine, Division of Addiction Medicine, University at Buffalo, Buffalo, New York, USA.
²³ Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
²⁴ Infectious Diseases Division, San Francisco VA Health Care System, San Francisco, California, USA .

PMID: 39480054
PMCID: PMC12041314
DOI: 10.14309/ajg.0000000000003178

Abstract

Introduction: Accurate assessment of alcohol use informs prevention and management of liver disease. We examined whether phosphatidylethanol (PEth, an alcohol metabolite) blood concentrations are associated with liver fibrosis risk independently of self-reported alcohol use, among persons with and without HIV.

Methods: We pooled individual-level data from 12 studies from the United States, Russia, Uganda, and South Africa with PEth, Alcohol Use Disorders Identification Test-Consumption (AUDIT-C), and fibrosis-4 (FIB-4) measurements. We conducted mixed-effects logistic regression of the relationship between PEth and AUDIT-C as continuous variables (after checking linearity), with high FIB-4 (≥2.67). We divided PEth (range 0-1,000) by 83.3 to put it on the same scale as AUDIT-C (0-12) to directly compare odds ratios. Adjusted models included sex, race/ethnicity, age, body mass index, HIV, and virologic suppression status.

Results: Among 4,644 adults, the median age was 49 years (interquartile range [IQR]: 40-55), 998 (21%) were female, and 3,520 (76%) were living with HIV, among whom 2,386 (68%) were virologically suppressed. Median PEth was 13 ng/mL (IQR: <8-132.0) and median AUDIT-C was 3 (IQR: 1-6); 554 (12%) had high FIB-4. The adjusted odds ratios per 83.3 ng/mL difference in PEth and one-unit difference in AUDIT-C with high FIB-4 were 1.15 (95%CI: 1.08-1.22) and 1.03 (95%CI: 1.00-1.07), respectively. Findings were similar when PEth and AUDIT-C were treated as categorical variables.

Discussion: PEth was independently associated with high FIB-4, with a larger odds ratio than that of the association of AUDIT-C. The use of PEth may improve identification of alcohol use and liver fibrosis prevention and management.

Keywords: alcohol use; biomarkers; liver fibrosis; screening.

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Conflict of interest statement

Guarantor of the article: Pamela M. Murnane, PhD and Judith A. Hahn, PhD.

Specific author contributions: P.M.M. and J.A.H. conceptualized the study and wrote the first draft of the statistical analysis plan and manuscript. P.M.M. conducted the analyses. J.A.H., M.A., G.C., T.F., K.R.C., A.C.J., T.W.K., E.K., K.A.M., P.M., W.R.M., B.M., V.L.R., K.S., S.S., and M.S.S. contributed previously collected data to this study. All co-authors substantially and critically reviewed and edited the concept, analysis plan, and manuscript.

Financial support: This work was supported by the following grants: NIH U01 AA026223 (J.A.H.), NIH U01 AA020776 (J.A.H.), NIH R01 AA018631 (J.A.H.), NIH K24 AA022586 (J.A.H.), NIH K01MH119910 (P.M.M.), NIH U01 AA026226 (G.C.), NIH R01 AI119037 (K.R.J.), NIH U01 AA020780 (K.S.-A.), NIH R01 DA016065 (M.S.S.), NIH U01 AA020797 (R.L.C.), NIH T32 DA017629 (V.L.R., MPIs: Lanza and Maggs), NIH P60 AA009803 (P.M.), NIH R01 AA017911 (S.S.), NIH K23 AA024503 (M.A.), NIH R24AA019661 (M.A.), NIH R01 DA051464 (M.A.), NIH P01 AA029545 (A.C.J.), NIH U24 AA020794 (A.C.J.), NIH U01 AA020790 (A.C.J.), NIH U01 AA020795 (A.C.J.), NIH U01 AA022001 (A.C.J.), NIH U10 AA013566 (A.C.J.), NIH K24 AA022523 (M.K.), NIH R01 AA029312 (M.K.), NIH R34MH122268 (Magidson/B.M.); NIH K23 AA031334 (L.Y.H.), NIH U01AA020784 (MPIs: Heeren and Kim) NIH U01 HL146242 (P.C.T.), NIH K24 AI108516 (P.C.T., NIH R01 DK109823 (P.C.T.).

Potential competing interests: None to report.

References

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Using Phosphatidylethanol as an Adjunct to Self-Reported Alcohol Use Improves Identification of Liver Fibrosis Risk

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Using Phosphatidylethanol as an Adjunct to Self-Reported Alcohol Use Improves Identification of Liver Fibrosis Risk

Authors

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Abstract

Conflict of interest statement

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