Comparison of Metabolic Dysfunction-Associated Steatotic Liver Disease Between Individuals With Werner Syndrome and Those With Insulin-Resistant Type 2 Diabetes: Hepatic Steatosis and Fibrosis Indices

AIM: This study compared metabolic dysfunction-associated steatotic liver disease (MASLD) in individuals with Werner syndrome (WS) and individuals with insulin-resistant type 2 diabetes (T2D). It also examined the association with imaging findings of MASLD in individuals with WS, clarified the characteristics of MASLD that accompany WS, and identified useful indices for its diagnosis in addition to imaging. METHODS: Three hepatic steatosis and two hepatic fibrosis indices in 48 individuals enrolled in the Japanese Werner Syndrome Registry were compared with those in 101 Japanese individuals with insulin-resistant T2D from another clinical study. In individuals with WS, the liver/spleen ratio (L/S ratio) was calculated from computed tomography (CT) images, and its associations with each index were examined. Statistical analyses were performed using the Welch test and pairwise comparisons. RESULTS: Individuals with WS had lower hepatic steatosis and fibrosis index values than those with insulin-resistant T2D. The mean L/S ratio calculated from CT images was 1.05 ± 0.24 in individuals with WS. The L/S ratio, which is one of the indicators for diagnosing MASLD, was < 0.9 in 5 of 20 cases (25%). Among the various indices in individuals with WS, only the hepatic steatosis index (HSI) was correlated with the L/S ratio (r = -0.863, p = 0.0003). CONCLUSIONS: The prevalence of MASLD is lower in individuals with WS than in those with insulin-resistant T2D. The HSI was associated with the L/S ratio in individuals with WS, suggesting that HSI may reflect hepatic steatosis-related changes in this population. Further studies in larger cohorts are needed to validate these findings. TRIAL REGISTRATION: The study was registered at the UMIN Clinical Trial Registry (https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034058) on November 3, 2017 (ID: UMIN000029812).