AUTHOR=Martín-Escolano Rubén , Virseda-Berdices Ana , Berenguer Juan , González-García Juan , Brochado-Kith Oscar , Fernández-Rodríguez Amanda , Díez Cristina , Hontañon Victor , The Marathon Study Group , Resino Salvador , Jiménez-Sousa María Ángeles , Arranz A. , Arnalich F. , Arribas J. R. , Aznar E. , Aldamiz-Echevarría T. , Bermejo J. , Berenguer J. , Bellón J. M. , Bernardino I. , Bustinduy M. J. , Carrero A. , Carretero S. , Casas E. , Casado J. L. , Crespo M. , Crespo P. , Díez C. , Díaz M. , de Miguel J. , Dronda F. , Esteban H. , Fanciulli C. , Ferrer A. , Galindo M. J. , González-García J. , Gutiérrez I. , Iribarren . A. , Hontañón V. , López C. , Miralles P. , Montes M. L. , Moreno A. , Moreno S. , Ortiz L. , Ortega E. , Padilla B , Parras J. F. , Pérez-Latorre L. , Pascual F. , Pérez M. , Pérez-Elías M. J. , Peña J. M. , Quereda C. , Ramírez M. , Ribera E. , Rodríguez-Arrondo J. F. , Sanz J. , Sanz J. , Santos I. , Sanfrutos M. A. , Schroeder S. , Tejerina F. , Téllez M. J. , Van den Eynde E. , Vergas J. , Von-Wichmann M. A. , Yllescas M. , Zamora J. F. TITLE=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 JOURNAL=Frontiers in Pharmacology VOLUME=15 YEAR=2024 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1341612 DOI=10.3389/fphar.2024.1341612 ISSN=1663-9812 ABSTRACT=Background

Understanding 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.

Methods

We 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.

Results

During 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.

Conclusion

We 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.