Immune checkpoint proteins are associated with persistently high liver stiffness after successful HCV treatment in people with HIV: a retrospective study

Front Immunol. 2024 Dec 17:15:1505864. doi: 10.3389/fimmu.2024.1505864. eCollection 2024.

Abstract

Various immune checkpoint proteins have been linked to cirrhosis. This study aimed to explore the association between plasma levels of these proteins measured one year after successful HCV treatment and persistently liver stiffness (defined as liver stiffness measurement (LSM) ≥ 12.5 kPa) five years after HCV treatment in people with HIV (PWH). We conducted a retrospective study involving 39 patients with HIV/HCV-coinfection who had advanced fibrosis or cirrhosis and achieved sustained virologic response (SVR). Plasma samples were obtained one year after treatment, and levels of immune checkpoints along with inflammatory biomarkers were evaluated using a Luminex 200TM analyzer. Statistical analyses were performed using Generalized Linear Models (GLMs) with a gamma distribution. Spearman correlation tests were used to analyze the correlation between significant immune checkpoints and inflammatory biomarkers. Although LSM values showed a decreasing trend over the years following successful HCV treatment, this trend was not statistically significant due to substantial variability among PWH. Persistently high liver stiffness was observed in 61.5% of patients five years after HCV treatment. Elevated plasma levels of soluble BTLA, PD-1, and TIM-3 one year after HCV treatment were associated with persistently liver stiffness five years later. These significant immune checkpoints were found to correlate with inflammatory biomarkers in PWH with persistently high liver stiffness. In conclusion, increased plasma concentrations of immune checkpoints one year after successful HCV therapy were linked to persistently high liver stiffness five years later, particularly BTLA, PD-1, and TIM-3. This suggests a potential immunopathological mechanism in ongoing liver stiffness post-HCV eradication.

Keywords: HIV/HCV-coinfection; antiviral therapy; biomarkers; cirrhosis; liver stiffness.

MeSH terms

  • Adult
  • Antiviral Agents / therapeutic use
  • Biomarkers* / blood
  • Coinfection* / drug therapy
  • Coinfection* / immunology
  • Female
  • HIV Infections* / blood
  • HIV Infections* / complications
  • HIV Infections* / drug therapy
  • HIV Infections* / immunology
  • Hepacivirus / immunology
  • Hepatitis C / blood
  • Hepatitis C / complications
  • Hepatitis C / drug therapy
  • Hepatitis C / immunology
  • Hepatitis C / virology
  • Hepatitis C, Chronic / blood
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / drug therapy
  • Hepatitis C, Chronic / immunology
  • Humans
  • Immune Checkpoint Proteins* / blood
  • Liver / immunology
  • Liver / pathology
  • Liver Cirrhosis / blood
  • Liver Cirrhosis / etiology
  • Liver Cirrhosis / immunology
  • Liver Cirrhosis / virology
  • Male
  • Middle Aged
  • Retrospective Studies
  • Sustained Virologic Response

Substances

  • Immune Checkpoint Proteins
  • Biomarkers
  • Antiviral Agents

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by grants from Instituto de Salud Carlos III (ISCIII; grant numbers CP17CIII/00007, PI18CIII/00028 and PI21CIII/00033 to MJ-S, PI17/00657 and PI20/00474 to JB, PI17/00903 and PI20/00507 to JG-G, PI18CIII/00020 to AF-R, and PI17CIII/00003 and PI20CIII/00004 to SR) and Ministerio de Ciencia e Innovación (AEI, PID2021-126781OB-I00 to AF-R). The study was also funded by the CIBER -Consorcio Centro de Investigación Biomédica en Red-(CB 2021), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea -NextGenerationEU (CB21/13/00044). MAJ-S is Miguel Servet’s researcher supported and funded by ISCIII (grant numbers CP17CIII/00007). R.M.-E. is César Nombela researcher supported and funded by Comunidad de Madrid (grant number 2023-T1/SAL-GL-28980).