Cumulative exposure to integrase inhibitors and metabolic factors as independent predictors of severe hepatic steatosis in people with HIV
Francesca Panza, Manuel Crispo, Margherita Sambo, Alessandra Bailoni, Enrico Morelli, Gabriele Giuliano, Daniela Romano, Francesco Pippi, Michele Trezzi, Francesca Montagnani, Mario Tumbarello, Massimiliano FabbianiAbstract
Background
The progressive ageing of people living with HIV (PLWH) has increased hepatic and metabolic comorbidities.
Objectives
This study evaluates the impact of HIV-related, metabolic and behavioural factors on hepatic steatosis and fibrosis development using vibration-controlled transient elastography (VCTE).
Methods
This is a single-centre cross-sectional study evaluating an Italian cohort of PLWH at an academic medical centre. Steatosis (via CAP, dB/m) and fibrosis (kPa) were assessed using VCTE. Lifestyle habits were investigated through a structured questionnaire. Factors associated with severe steatosis (S3) and with fibrosis were analysed.
Results
Overall, 265 patients were included (median age 53.9 years; 89.4% with HIV-RNA < 50 copies/mL; median CD4 count 758 cells/mm3). Moderate-to-severe steatosis (S2–S3) affected 49% of the cohort (S3: 28.5%). In multivariate analysis, independent predictors of severe (S3) steatosis were longer cumulative integrase inhibitor (InSTI) exposure (aOR 1.19/year, P = 0.002), higher BMI (aOR 1.45 per kg/m2, P < 0.001), daily alcohol consumption (aOR 2.41, P = 0.031) and higher LDL cholesterol (aOR 1.20 per +10 mg/dL, P = 0.003). Regular physical activity was associated with lower CAP. Higher CAP values showed an independent association with increased liver stiffness (mean change +0.07 kPa per +10 db/m, P = 0.016), while virological suppression (HIV-RNA < 50 copies/mL) was significantly associated with reduced liver stiffness (mean change −1.61 kPa, P = 0.001).
Conclusions
Hepatic steatosis and fibrosis are highly prevalent in PLWH. Cumulative InSTI exposure and metabolic factors may drive severe steatosis, which may accelerate fibrotic damage, whereas effective virological suppression can significantly lower fibrosis risk. Strict metabolic monitoring and lifestyle interventions should be integrated into PLWH long-term care protocols.