TY - JOUR
T1 - Prognostic Performance of Phosphatidylethanol With Noninvasive Liver Fibrosis Tests in Alcohol-Related Liver Disease
AU - Torp, Nikolaj
AU - Johansen, Stine
AU - Jensen, Ellen Lyngbeck
AU - Maagaard, Markus
AU - Semmler, Georg
AU - Andersen, Mette Lehmann
AU - Bech, Katrine
AU - Schnefeld, Helle
AU - Lindvig, Katrine Prier
AU - Thorhauge, Katrine Holtz
AU - Petersen, Ellen Elise
AU - Hansen, Johanne Kragh
AU - Villesen, Ida Falk
AU - Andersen, Peter
AU - Bergmann, Marianne Lerbæk
AU - Leeming, Diana Julie
AU - Karsdal, Morten
AU - Hansen, Camilla Dalby
AU - Thiele, Maja
AU - Israelsen, Mads
AU - Krag, Aleksander
N1 - Publisher Copyright:
© 2025 The Authors
PY - 2025/12/22
Y1 - 2025/12/22
N2 - Background & Aims: Alcohol is a key driver of liver-related mortality, and phosphatidylethanol (PEth) is a direct biomarker of alcohol intake. We investigated the prognostic performance of PEth with noninvasive liver fibrosis tests (NITs) for predicting hepatic decompensation in an alcohol-related liver disease (ALD) at-risk population. Methods: Prospective cohort study with 411 at risk of ALD without prior known chronic liver disease of whom 162 had a follow-up PEth. PEth was measured from whole blood by liquid chromatography-mass spectrometry. PEth, self-reported alcohol intake, and 3 NITs: enhanced liver fibrosis (ELF) test, an algorithm incorporating PRO-C3 (ADAPT), and transient elastography (TE) were assessed at baseline. By review of medical records, participants were followed for up to 5 years for hepatic decompensation. Results: Baseline PEth was 338 ng/mL (interquartile range [IQR]: 32–921 ng/mL) and median time to follow-up PEth was 26 months (IQR: 17–33). Baseline PEth was associated with decompensation (subdistribution hazard ratio [sHR] per 100 ng/mL, 1.04; 95% confidence interval [CI], 1.01–1.06), independently of NITs. Liver fibrosis NITs were the strongest individual predictors, but PEth added incremental 6-month prognostic value. Discriminatory accuracy of PEth declined with an area under the curve of 0.77 at 6 months to 0.62 at 2 years, whereas fibrosis-based NITs maintained an area under the curve of ∼0.90. Of those with a follow-up PEth, 79 (49%) had increased PEth levels compared with baseline, and 83 (51%) had stable or lowered PEth. An increased follow-up PEth was significantly associated with a higher risk of subsequent hepatic decompensation (sHR, 4.92; 95% CI, 1.09–22.34; P = .039). Conclusions: PEth predicts hepatic decompensation independently of fibrosis-based NITs in individuals at risk of ALD. Although its prognostic performance declines rapidly, repeated PEth measurements maintain prognostic discrimination.
AB - Background & Aims: Alcohol is a key driver of liver-related mortality, and phosphatidylethanol (PEth) is a direct biomarker of alcohol intake. We investigated the prognostic performance of PEth with noninvasive liver fibrosis tests (NITs) for predicting hepatic decompensation in an alcohol-related liver disease (ALD) at-risk population. Methods: Prospective cohort study with 411 at risk of ALD without prior known chronic liver disease of whom 162 had a follow-up PEth. PEth was measured from whole blood by liquid chromatography-mass spectrometry. PEth, self-reported alcohol intake, and 3 NITs: enhanced liver fibrosis (ELF) test, an algorithm incorporating PRO-C3 (ADAPT), and transient elastography (TE) were assessed at baseline. By review of medical records, participants were followed for up to 5 years for hepatic decompensation. Results: Baseline PEth was 338 ng/mL (interquartile range [IQR]: 32–921 ng/mL) and median time to follow-up PEth was 26 months (IQR: 17–33). Baseline PEth was associated with decompensation (subdistribution hazard ratio [sHR] per 100 ng/mL, 1.04; 95% confidence interval [CI], 1.01–1.06), independently of NITs. Liver fibrosis NITs were the strongest individual predictors, but PEth added incremental 6-month prognostic value. Discriminatory accuracy of PEth declined with an area under the curve of 0.77 at 6 months to 0.62 at 2 years, whereas fibrosis-based NITs maintained an area under the curve of ∼0.90. Of those with a follow-up PEth, 79 (49%) had increased PEth levels compared with baseline, and 83 (51%) had stable or lowered PEth. An increased follow-up PEth was significantly associated with a higher risk of subsequent hepatic decompensation (sHR, 4.92; 95% CI, 1.09–22.34; P = .039). Conclusions: PEth predicts hepatic decompensation independently of fibrosis-based NITs in individuals at risk of ALD. Although its prognostic performance declines rapidly, repeated PEth measurements maintain prognostic discrimination.
KW - Alcohol Abstinence
KW - Fibrosis Biomarkers
KW - Portal Hypertension
KW - Risk Stratification
KW - Sequential Testing
KW - Steatotic Liver Disease
UR - http://www.scopus.com/inward/record.url?scp=105025569991&partnerID=8YFLogxK
U2 - 10.1053/j.gastro.2025.10.005
DO - 10.1053/j.gastro.2025.10.005
M3 - Journal article
C2 - 41427910
AN - SCOPUS:105025569991
SN - 0016-5085
JO - Gastroenterology
JF - Gastroenterology
ER -