Differences in the serum metabolomic profile of progressive alcohol-related liver disease in comparison to non-progressive alcohol-related liver disease: a cross sectional metabolomics study

Alcohol-related liver disease (ALD) is a major cause of mortality and disability adjusted life years. It is not fully understood why a small proportion of patients develop progressive forms of ALD (e.g. fibrosis, cirrhosis). Differences in the metabolic processes could be behind the individual progression of ALD. Our aim was to examine differences in serum metabolome between patients with non-progressive ALD and patients with an early form of progressive ALD. The study had three study groups: progressive ALD (alcohol-related steatohepatitis or early-stage fibrosis, n=50), non-progressive ALD (simple steatosis, n=50) and healthy controls (n=32). Both ALD groups took part in a voluntary alcohol rehabilitation program. A non-targeted metabolomics analysis and targeted analysis of short chain fatty acids was done to the serum samples taken on the day of admission. We found 111 significantly (p<0.0005) altered identified metabolites between the study groups. Our main finding was that levels of glycine conjugated bile acids, glutamic acid, 7-methylguanine and several phosphatidylcholines were elevated in the progressive ALD group in comparison to both the non-progressive ALD group and the controls. Glycine conjugated bile acid, glutamic acid and 7-methylguanine also positively correlated with increased levels of aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, cell death biomarker M65, and liver stiffness. Our results indicate that the enterohepatic cycle of glycine conjugated bile acids as well as lipid and energy metabolism are altered in early forms of progressive ALD. These metabolic processes could be a target for preventing progression of ALD.