Hepatic Medicine: Evidence and Research (Nov 2023)
Confounders of Serum Phosphatidylethanol: Role of Red Blood Cell Turnover and Cirrhosis
Abstract
Marc Bartel,1,* Vanessa Hofmann,1,* Shijin Wang,2,3 Johannes Mueller,2 Tom R Sundermann,1 Sebastian Mueller2 1Institute of Forensic and Traffic Medicine, Heidelberg University Hospital, Heidelberg, Germany; 2Center for Alcohol Research, University Hospital Heidelberg, Heidelberg, Germany; 3Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Shandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Sebastian Mueller, Center for Alcohol Research, University Hospital Heidelberg, Im Neuenheimer Feld 350, Heidelberg, 69120, Germany, Tel +49 (0) 6221 567121, Email [email protected]: Ethyl glucuronide (EtG), ethyl sulfate (EtS) and phosphatidylethanol (PEth) are considered specific direct biomarkers for detecting alcohol consumption. However, PEth, which is produced in red blood cells (RBC), varies considerably between patients for unknown reasons. We here studied various confounders of PEth elimination including fibrosis after alcohol withdrawal.Patients and Methods: EtG, EtS and PEth together with routine laboratory and clinical parameters were studied in 100 Caucasian heavy drinkers prior and after alcohol detoxification. In addition, fibrosis stage and degree of steatosis were assessed by transient elastography (Fibroscan, Echosens, Paris).Results: All three biomarkers were highly correlated (0.61– 0.72) with initial serum alcohol levels, but only PEth correlated with daily alcohol consumption. After alcohol withdrawal, PEth significantly decreased within 6.1 days from 1708 to 810 ng/mL (half-life varied from 1.6 to 15.2 days). Both levels of serum alcohol but also EtG and EtS were higher in patients with liver cirrhosis as compared to patients without fibrosis despite comparable alcohol consumption suggesting a decreased alcohol elimination in patients with cirrhosis. PEth was also elevated in cirrhosis but not significantly. In contrast, PEth elimination rate was significantly higher in patients with enhanced RBC turnover and signs of alcohol-mediated hemolytic anemia with elevated ferritin, LDH and increased mean corpuscular volume (MCV).Conclusion: We here demonstrate that alcohol elimination is decreased in patients with liver cirrhosis. In patients with cirrhosis, PEth levels are both affected in opposite directions by enhanced red blood cell turnover and elevated alcohol levels. Our data have important implications for the use and interpretation of PEth in the clinical setting.Keywords: ethyl glucuronide, ethyl sulfate, alcohol-related liver disease, liver fibrosis, liver stiffness, alcohol consumption
