Predictive plasma biomarkers of long-term increase in hepatic steatosis index after HCV eradication in HIV/HCV-coinfected patients

Biomed Pharmacother. 2023 Aug:164:114913. doi: 10.1016/j.biopha.2023.114913. Epub 2023 May 20.

Abstract

Hepatic steatosis is a common condition found in the liver of hepatitis C virus (HCV)-infected patients, contributing to more severe forms of liver disease. In addition, the human immunodeficiency virus (HIV) may accelerate this process. Alternatively, several immune checkpoint proteins have been reported to be upregulated and correlated with disease progression during HCV and HIV infections. In steatosis, a detrimental immune system activation has been established; however, the role of the immune checkpoints has not been addressed so far. Thus, this study aimed to evaluate the association between plasma immune checkpoint proteins at baseline (before antiviral therapy) with hepatic steatosis index (HSI) increase at the end of follow-up (∼ five years after sustained virologic response (SVR)). We performed a multicenter retrospective study in 62 patients coinfected with HIV/HCV who started antiviral therapy. Immune checkpoint proteins were analyzed at baseline using a Luminex 200TM analyzer. The statistical association analysis was carried out using Generalized Linear Models (GLM) and Partial Least Squares Discriminant Analysis (PLS-DA). Fifty-three percent of the patients showed HSI increase from baseline to the end of follow-up. Higher immune checkpoint protein levels of BTLA, CD137(4-1BB), CD80, GITR, LAG-3, and PD-L1 before HCV therapy were associated with a long-term increase in HSI after successful HCV therapy, suggesting a potential predictive role for early detection of progression towards steatosis in HIV/HCV-coinfected patients.

Keywords: DAAs therapy; HIS; HIV/HCV-coinfection; Plasma proteins; Predictive biomarkers; Steatosis.

Publication types

  • Multicenter Study

MeSH terms

  • Antiviral Agents / therapeutic use
  • Biomarkers
  • Coinfection* / drug therapy
  • Fatty Liver* / complications
  • Fatty Liver* / drug therapy
  • HIV Infections* / complications
  • HIV Infections* / drug therapy
  • Hepacivirus
  • Hepatitis C* / complications
  • Hepatitis C* / drug therapy
  • Hepatitis C, Chronic* / drug therapy
  • Humans
  • Immune Checkpoint Proteins
  • Retrospective Studies

Substances

  • Immune Checkpoint Proteins
  • Antiviral Agents
  • Biomarkers