Frontiers in Pharmacology (Oct 2024)

Low plasma levels of BTLA and LAG-3 before HCV therapy are associated with metabolic disorders after HCV eradication in persons with HIV/HCV coinfection: a retrospective study

  • Rubén Martín-Escolano,
  • Rubén Martín-Escolano,
  • Ana Virseda-Berdices,
  • Ana Virseda-Berdices,
  • Juan Berenguer,
  • Juan Berenguer,
  • Juan Berenguer,
  • Juan González-García,
  • Juan González-García,
  • Juan González-García,
  • Oscar Brochado-Kith,
  • Oscar Brochado-Kith,
  • Amanda Fernández-Rodríguez,
  • Amanda Fernández-Rodríguez,
  • Cristina Díez,
  • Cristina Díez,
  • Cristina Díez,
  • Victor Hontañon,
  • Victor Hontañon,
  • Victor Hontañon,
  • The Marathon Study Group,
  • Salvador Resino,
  • Salvador Resino,
  • María Ángeles Jiménez-Sousa,
  • María Ángeles Jiménez-Sousa,
  • A. Arranz,
  • F. Arnalich,
  • J. R. Arribas,
  • E. Aznar,
  • T. Aldamiz-Echevarría,
  • J. Bermejo,
  • J. Berenguer,
  • J. M. Bellón,
  • I. Bernardino,
  • M. J. Bustinduy,
  • A. Carrero,
  • S. Carretero,
  • E. Casas,
  • J. L. Casado,
  • M. Crespo,
  • P. Crespo,
  • C. Díez,
  • M. Díaz,
  • J. de Miguel,
  • F. Dronda,
  • H. Esteban,
  • C. Fanciulli,
  • A. Ferrer,
  • M. J. Galindo,
  • J. González-García,
  • I. Gutiérrez,
  • . A. Iribarren,
  • V. Hontañón,
  • C. López,
  • P. Miralles,
  • M. L. Montes,
  • A. Moreno,
  • S. Moreno,
  • L. Ortiz,
  • E. Ortega,
  • B Padilla,
  • J. F. Parras,
  • L. Pérez-Latorre,
  • F. Pascual,
  • M. Pérez,
  • M. J. Pérez-Elías,
  • J. M. Peña,
  • C. Quereda,
  • M. Ramírez,
  • E. Ribera,
  • J. F. Rodríguez-Arrondo,
  • J. Sanz,
  • J. Sanz,
  • I. Santos,
  • M. A. Sanfrutos,
  • S. Schroeder,
  • F. Tejerina,
  • M. J. Téllez,
  • E. Van den Eynde,
  • J. Vergas,
  • M. A. Von-Wichmann,
  • M. Yllescas,
  • J. F. Zamora

DOI
https://doi.org/10.3389/fphar.2024.1341612
Journal volume & issue
Vol. 15

Abstract

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BackgroundUnderstanding the predictors of metabolic disorders in persons with HIV/HCV coinfection post-HCV therapy is crucial for improving patient outcomes. Since immune checkpoint proteins are usually upregulated in these persons with HIV/HCV coinfection, we aimed to evaluate the association between plasma immune checkpoint proteins at baseline (before HCV therapy) and metabolic disturbances during the follow-up (about 5 years after successful HCV treatment) in persons with HIV/HCV coinfection.MethodsWe performed a retrospective study on 80 persons with HIV/HCV coinfection with advanced fibrosis or cirrhosis who cleared HCV infection after successful HCV therapy and were followed for about 5 years after completion of HCV treatment. Plasma samples were collected at baseline. Immune checkpoint proteins were analyzed using a Luminex 200™ analyzer. Outcomes were the development of a metabolic event (type 2 diabetes mellitus and/or dyslipidemia) and the change in Triglycerides and glucose (TyG) index.ResultsDuring follow-up, 21 (26%) patients developed metabolic events (type 2 diabetes mellitus/dyslipidemia), and 29 (46.0%) patients had an increase in TyG during the follow-up. Low baseline values of BTLA and LAG-3, two immune checkpoint proteins, were associated with the development of metabolic events (aAMR = 0.69 and aAMR = 0.71, respectively) and with increases in TyG values (aAMR = 0.72 and aAMR = 0.70, respectively). In addition, other immune checkpoint proteins were also inversely associated with increases in TyG.ConclusionWe discovered that low plasma levels of BTLA and LAG-3 before HCV therapy significantly correlate with an increased risk of developing metabolic disorders after treatment.

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