Lipidomics of HIV/HCV-related liver decompensation: association between plasma lipid depletion and immune dysregulation.

INTRODUCTION

Globally, 15-30% of patients with chronic hepatitis C develop compensated advanced chronic liver disease (cACLD). cACLD may further advance to decompensated ACLD (dACLD), which is associated with higher liver-related mortality, even after successful antiviral treatment. This progression is accelerated by HIV coinfection, yet its underlying molecular mechanisms remain poorly understood.

METHODS

In this cross-sectional study, we characterized the plasma lipidomic profiles of 58 HIV/HCV-coinfected patients using untargeted liquid chromatography-mass spectrometry. Multivariate (OPLS-DA) and univariate (GLM) statistical models were employed to identify lipid species associated with disease severity.

RESULTS

We identified a signature of 28 lipids-predominantly phosphatidylcholines, phosphatidylethanolamines, and triglycerides- that were significantly depleted in patients with dACLD (17.2% of the cohort). This systemic lipid depletion showed relevant correlations with the pro-inflammatory chemokine IP-10 and soluble immune checkpoint proteins.

DISCUSSION: Our findings indicate that dACLD in HIV/HCV-coinfection is defined by a profound collapse in plasma lipids. This metabolic failure correlates with markers of inflammation and immune activation, suggesting that lipid dysregulation plays a critical role in the pathogenesis of liver decompensation.