Burden of Liver Disease Among Individuals With Turner Syndrome and Klinefelter Syndrome: A Comprehensive Perspective.

The liver is increasingly recognized as a major regulator of systemic cardio-renal-metabolic health. Evidence is mounting that sex-chromosome dosage per se itself, independent of gonadal sex hormones, modulates hepatic physiology and liver disease risk. Turner syndrome (TS; monosomy X) and Klinefelter syndrome (KS; 47, XXY and variants) are the two most common sex-chromosome aneuploidies and carry a clinically relevant, yet often under-appreciated, burden of liver disease. Population studies show that individuals with TS have 2- to sixfold higher odds of raised liver enzymes, steatotic liver disease, advanced fibrosis, and even hepatocellular malignancy compared with to sex- and age-matched controls. In KS, the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) reaches approximately 45%, with testosterone deficiency, visceral adiposity, and systemic inflammation acting as key drivers. Pathogenetic mechanisms converge on vascular dysgenesis and estrogen deficiency in TS, and on hypogonadism-related metabolic derangements in KS, together accelerating steatosis, inflammation, and fibrogenesis. This concise review/Comprehensive perspective reviews discusses historical background, epidemiology, hepatic phenotypes, pathophysiology, and current diagnostic and management recommendations. It also highlights critical knowledge gaps, including the need for prospective cohorts, optimized hormone-replacement protocols, and trials of emerging pharmacological approaches anti-MASH agents. Raising awareness among all stakeholders, endocrinologists, hepatologists, and primary-care physicians is essential for early detection, multidisciplinary management, and improved hepatic and extra-hepatic outcomes in these vulnerable patient populations.