Metabolic Dysfunction-Associated Steatotic Liver Disease and Alcohol-Associated Liver Disease: Liver DNA Methylation Analysis-A Systematic Review.

backgroundMetabolic dysfunction-associated liver disease (MASLD) and alcohol-associated liver disease (ALD) are among the leading causes of liver disease worldwide. The exact roles of epigenetic factors in both diseases remains largely unknown. In this context, liver DNA methylation remains a field that requires further exploration and understanding.

methodsWe performed a systematic review of liver DNA methylation in humans with MASLD or ALD using Ovid MEDLINE, Ovid Embase, and Cochrane Library. We included human studies where liver DNA methylation was assessed in patients with MASLD and/or ALD. The Rayyan platform was used to select studies. Risk of bias was assessed with the "risk of bias in non-randomized studies of interventions" tool, ROBINS-I. We performed pathway analysis using the most important differentially methylated genes selected in each article.

resultsFifteen articles were included in this systematic review. The risk of bias was moderate to serious in all articles and bias due to confounding and patient selection was high. Sixteen common pathways, containing differentially methylated genes, including cancer pathways, were identified in both diseases.

conclusionsThere are common pathways, containing differentially methylated genes, in ALD and MASLD, such as pathways in cancer and peroxisome proliferator-activated receptor (PPAR) signaling pathways. In MASLD, the insulin signaling pathway is one of the most important, and in ALD, the MAPK signaling pathway is the most important. Our study adds one more piece to the puzzle of the mechanisms involved in steatotic liver disease.