Meta-Analysis: Liver Disease Burden and Associated Factors in Turner Syndrome

The prevalence, incidence, and associated factors of liver disease (LD) in Turner syndrome (TS) remain uncertain.

A meta-analysis was performed to quantify LD burden in TS.

Four electronic databases were searched through June 2025 for observational studies involving karyotype-confirmed individuals with TS. LD was defined by raised serum liver enzymes (RLE), International Classification of Diseases codes, imaging, or histology. Pooled prevalence, incidence, and odds ratios (OR) with 95% confidence intervals (CI) were calculated.

Forty studies from 19 countries with aggregate data on 9728 young TS individuals (median age 25.5 years, IQR 16.8-30.7) were included. Prevalences of RLE, steatotic LD (SLD), and significant/advanced liver fibrosis were 26.9% (95% CI 19.7-35.6), 22.3% (9.9-42.9), and 12.2% (2.6-41.7), respectively. Incidence of RLE was 16.7 per 1000 person-years (7.6-36.8). Compared to age-matched healthy controls, TS individuals had higher odds of RLE (OR 3.96 [95% CI 1.45-10.84]), SLD (OR 4.03 [1.86-8.70]), and significant/advanced fibrosis (OR 5.74 [2.99-11.01]). Compared to X monosomy, isochromosome Xq conferred a higher risk of RLE (OR 1.55 [1.15-2.10]), while mosaicism without structural abnormalities was protective (OR 0.54 [0.32-0.89]). Ring X or Y chromosome material carried risks like X monosomy. Hormone replacement therapy was not associated with an increased risk of RLE (OR 1.10 [0.79-1.53]).

Liver disease is common in individuals with TS, with a 4-6 times higher risk than age-matched healthy females. X chromosome abnormalities are more strongly associated with an increased liver disease risk than hypogonadism.