Prognostic Performance of Phosphatidylethanol With Noninvasive Liver Fibrosis Tests in Alcohol-Related Liver Disease

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.