Abstract
BACKGROUND: In adults living with HIV, non-invasive biomarkers have been described for the early identification of metabolic dysfunction-associated steatotic liver diseases (MASLD). However, this issue remains unexplored in children and young people with vertical HIV (YWVH), among whom MASLD prevalence is around 30%. METHODS: To identify biomarkers associated with MASLD in YWVH under sustained viral suppression with antiretroviral therapy, we analysed plasma lipid species, plasma bile acid profile, and gut microbiome composition in a cross-sectional cohort of 10 YWVH with MASLD and 19 YWVH without clinical evidence of MASLD (control). RESULTS: Here we show that YWVH with MASLD have significantly increased circulating levels of eight specific lipid molecules and one bile acid, ursodeoxycholic acid (UDCA). UDCA and two triglycerides (TG54:5 and TG56:7) are identified as key biomolecules with strong discriminatory potential. The regression model incorporating these markers, along with hepatic steatosis index (HSI) and triglycerides-glucose index (TyG), demonstrates the highest predictive accuracy for MASLD (AUC of 0.932). UDCA correlates positively with Blautia and Collinsella genus (p = 0.040 and p = 0.021, respectively), and negatively with Faecalibacterium (p = 0.030). Notably, principal component analysis based on bile acid levels reveals two possible subpopulations within the control group, one potentially at higher risk for MASLD. CONCLUSIONS: Combining UDCA, TG54:5 and TG56:7 with the validated HSI score provides a potential model with high specificity and sensitivity for predicting MASLD in YWVH. Moreover, early alterations in the bile acid profile may help identify YWVH at risk of developing MASLD.