Alcohol-Related Liver Disease

Alcohol-related liver disease has been a central focus of my translational and clinical research. The work combines disease mechanisms, non-invasive diagnosis, genetics, biomarkers, therapeutic studies and long-term outcome assessment.

A prospective cohort of heavy drinkers, established in 2007 and followed through 2022, provides comprehensive longitudinal data on liver injury, fibrosis, alcohol withdrawal and mortality. Most importantly, long-term outcome analysis identified enhanced red blood cell turnover and alcohol-mediated hemolysis as major drivers of mortality. Studies from this program also established keratin-18 fragments as predictors of liver-related death, defined the effects of inflammation and detoxification on liver stiffness, and contributed to international genetic studies of alcohol-related cirrhosis and hepatocellular carcinoma.

These findings led to a new mechanistic concept of alcohol-related liver disease. We were the first to demonstrate that hepatocytes can directly ingest oxidized red blood cells by efferocytosis—an unexpected function of liver parenchymal cells that had not previously been recognized. Together with phosphatidylserine-dependent erythrocyte clearance by liver sinusoidal endothelial cells, this establishes a direct mechanistic link between alcohol-mediated hemolysis, erythrophagocytosis, anemia, AST elevation, hepatic iron overload, progressive liver injury and mortality.

Selected publications

Caspase-cleaved keratin-18 fragments increase during alcohol withdrawal and predict liver-related death in patients with alcoholic liver disease. Mueller S et al. Hepatology. 2017;66(1):96–107.
Genetic variation in HSD17B13 reduces the risk of developing cirrhosis and hepatocellular carcinoma in alcohol misusers. Stickel F et al. Hepatology. 2020;72(1):88–102.
Confounders of serum phosphatidylethanol: Role of red blood cell turnover and cirrhosis. Bartel M et al. Hepat Med. 2023;15:195–208.
Direct ingestion of oxidized red blood cells (efferocytosis) by hepatocytes. Zheng C et al. Hepat Med. 2024;16:65–77.
Evidence for alcohol-mediated hemolysis and erythrophagocytosis. Zheng C et al. Redox Biol. 2025;85:103742.
Phosphatidylserine-dependent clearance of damaged red blood cells by liver sinusoidal endothelial cells in alcohol-related liver disease. Li S et al. Biology (Basel). 2026;15(9):699.