Martín-Escolano, RubénVirseda-Berdices, AnaBerenguer, JuanGonzález-García, JuanBrochado-Kith, OscarFernandez-Rodriguez, AmandaDíez, CristinaHontañón, VíctorMarathon Study GroupResino, SalvadorJimenez-Sousa, Maria Angeles2025-01-072025-01-072024-10Martín-Escolano R, Virseda-Berdices A, Berenguer J, González-García J, Brochado Kith O, Fernández-Rodríguez A, Díez C, Hontañon V, The Marathon Study Group, Resino S and Jiménez-Sousa MÁ. 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. Front Pharmacol. 2024 Oct 28:15:1341612.https://hdl.handle.net/20.500.12105/25938Background: 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.engVoRhttp://creativecommons.org/licenses/by/4.0/HCV therapyHIV/HCV-coinfectionTyG indexDyslipidemiaImmune checkpoint proteinsType 2 diabetes mellitusAttribution 4.0 International3953045715134161210.3389/fphar.2024.13416121663-9812Frontiers in pharmacologyopen access