Chronic liver disease (CLD) is a growing global health challenge, accounting for millions of deaths each year. Its major contributors include metabolic dysfunction-associated steatohepatitis (MASH), alcoholic liver disease (ALD), and hepatitis C virus infection. These conditions are closely tied to hepatic steatosis, a condition characterized by the abnormal accumulation of fat in the liver.
Recent genome-wide association studies have identified the 17-beta-hydroxysteroid dehydrogenase 13 (HSD17B13) gene and its loss-of-function variant rs72613567, as a significant protective factor against CLD progression, particularly in MASH and ALD. The review highlights the importance of understanding this gene's function to unravel new therapeutic targets. Role of HSD17B13 in liver disease HSD17B13, primarily expressed in the liver, is associated with lipid metabolism within hepatic lipid droplets (LDs).
The enzyme belongs to a family of proteins that regulate steroid hormone activity and lipid processing. Despite its structural similarities with other dehydrogenases, HSD17B13's primary function lies in modulating liver lipid metabolism. Importantly, the gene is linked to hepatocyte lipid accumulation and, by extension, to conditions like hepatic steatosis.
Its loss-of-function mutation , rs72613567, results in a truncated, inactive protein that appears to protect against liver fat buildup and fibrosis, marking it as a key protective factor in CLD. Genetic interaction and disease progre.