Lipid and immune dysregulation and risk of metabolic disorders after HCV clearance in HIV/HCV-coinfected participants with cACLD: a retrospective study
Year: 2026
Type: article
Study design: Observational Study
Abstract: Introduction: People with HIV and chronic hepatitis C may develop metabolic complications after sustained virologic response (SVR), possibly due to persistent molecular alterations induced by HCV. This study aimed to identify baseline (pre-treatment) lipid and immune biomarkers associated with post-SVR metabolic events in HIV/HCV-coinfected participants with compensated advanced chronic liver disease (cACLD) receiving long-term suppressive antiretroviral therapy. Methods: We conducted a retrospective study of 56 HIV/HCV-coinfected participants with cACLD. Untargeted lipidomic profiling was performed on baseline plasma samples using a liquid-chromatography-mass spectrometer. The outcome was the development of metabolic events (diabetes mellitus and/or hyperlipidemia) during follow-up, up to seven years post-HCV treatment. Statistical analyses included orthogonal partial least squares discriminant analysis (OPLS-DA), Cox regressions models, and Spearman correlations with inflammation-related biomarkers and immune checkpoint proteins, with multiple comparison corrections using the false discovery rate. Results: 25% participants developed metabolic events after SVR. OPLS-DA identified 163 lipid species (VIP scores≥1) associated with these events, and adjusted Cox regression confirmed significant associations for 24 of them. Lysophosphatidylcholines (LPCs) were the most prevalent, with higher baseline levels linked to increased metabolic risk. Participants who developed events also had higher levels of plasmalogens LPC (O-LPC), lysophosphatidylethanolamine (LPE), lysophosphatidylinositol (LPI), lysophosphatidic acid (LPA), and phosphosphatidylcholine (PC). Several lipid species correlated positively with the pro-inflammatory cytokine IL-18, the anti-inflammatory suppressor IL-1RA, and the immune checkpoint proteins IDO and S100A8/A9. Discussion: Pre-treatment lipid and immune dysregulation was associated with post-SVR metabolic events in HIV/HCV-coinfected participants, suggesting that HCV may leave a lasting metabolic imprint that contributes to adverse outcomes after viral clearance.
Source: Frontiers in Immunology
Institutions: Instituto de Salud Carlos III, Centro Nacional de Microbiologia, Centro de Investigación Biomédica en Red, Centro de Investigación Biomédica en Red Enfermedades Infecciosas, Universidad San Pablo CEU, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Hospital Universitario La Paz, Hospital La Paz Institute for Health Research
Language: English
Topic: Hepatitis C virus research
Subfield: Hepatology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
Funder: Instituto de Salud Carlos III
Awards: Infecciones Agudas/Recientes y Reinfecciones por VHC en Hombres que tienen Sexo con Hombres con y sin VIH, G2136752990, Infecciones Agudas/Recientes y Reinfecciones por VHC en Hombres que tienen Sexo con Hombres con y sin VIH, Análisis multi-ómico para evaluar el impacto a largo plazo de la erradicación del VHC en pacientes coinfectados por VIH/VHC con cirrosis., Infecciones Agudas/Recientes y Reinfecciones por VHC en Hombres que tienen Sexo con Hombres con y sin VIH, Enfermedad hepática avanzada en pacientes cirróticos infectados por el VHC: Análisis metabolómico, G7616783251, Biomarcadores plasmáticos de envejecimiento y esteatohepatitis no alcohólica en personas que viven con VIH: un estudio de asociación con aleatorización mendeliana
OpenAlex ID: W7122729490