{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Hydroxysteroid 17β‐dehydrogenase 13 (HSD17B13) is a liver‐enriched, lipid droplet–associated protein that plays a central role in hepatic lipid metabolism and inflammation. Multiple genetic studies have shown that loss‐of‐function variants of HSD17B13—most notably the rs72613567:TA splice variant—are associated with lower serum liver enzyme levels, reduced hepatic inflammation, and a decreased risk of progression from steatosis to steatohepatitis, cirrhosis, and even hepatocellular carcinoma in diverse populations."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": " In experimental models, overexpression of HSD17B13 in the liver leads to a fatty liver phenotype with increased levels of key lipogenic proteins, whereas knockout mice develop hepatic steatosis accompanied by inflammation, indicating that HSD17B13 is critically involved in maintaining lipid homeostasis and modulating inflammatory pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Furthermore, carriers of the protective alleles exhibit reduced fibrosis and lower expression of inflammation‐related genes yet show alterations in hepatic phospholipid composition, suggesting that HSD17B13 may influence both the structural and immunometabolic aspects of liver disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Collectively, these observations support the concept that modulation of HSD17B13 activity could serve as a novel therapeutic strategy for chronic liver diseases such as nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH)"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ", and they are further corroborated by findings in both adult and pediatric cohorts that consistently demonstrate an ameliorated liver injury profile among carriers of the protective variants."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Noura S Abul-Husn, Xiping Cheng, Alexander H Li, et al. 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