Long-term effects of HCV eradication on lipid profiles associated with MASLD among people with HIV with advanced fibrosis or cirrhosis

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BACKGROUND: Despite successful hepatitis C virus (HCV) clearance, some individuals continue to experience liver disease progression. Metabolic dysfunction-associated steatotic liver disease (MASLD) may play a key role in this ongoing progression. This study aims to characterize the lipidomic profiles associated with MASLD in individuals coinfected with human immunodeficiency virus (HIV) and HCV with advanced fibrosis or cirrhosis after sustained virologic response (SVR). METHODS: We conducted cross-sectional studies in fifty-two HIV/HCV-coinfected individuals. Untargeted lipidomics was performed on plasma samples collected at 1 year and 6 years post-SVR using liquid chromatography-mass spectrometry. The primary outcome was MASLD. Statistical analyses included orthogonal partial least squares discriminant analysis (OPLS-DA) and generalized linear models (GLM), with corrections for multiple comparisons. RESULTS: The prevalence of MASLD was 28.9 % one year after SVR, increasing to 44.8 % six years after SVR. OPLS-DA models identified 225 lipids at 1 year and 167 at 6 years, with a VIP score ≥ 1, distinguishing individuals based on MASLD status. Adjusted GLMs confirmed significant associations between MASLD and 116 lipids at 1 year and 49 at 6 years. At 1 year, most significant lipids were glycerophospholipids (GP), with increased phosphatidylcholines (PC) and phosphatidylethanolamines (PE), and decreased lysophosphatidylcholines (LPC) and lysophosphatidylethanolamines (LPE). By 6 years, LPC was the most abundant differential lipid, while triglycerides increased significantly. CONCLUSIONS: MASLD was common during follow-up, with changes in lipidomic profiles over time suggesting ongoing metabolic disturbances that may contribute to liver disease progression despite SVR. These findings highlight the need for long-term metabolic and liver health monitoring after HCV eradication in these individuals.

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