Elevation of S2-bound α1-acid glycoprotein is associated with chronic hepatitis C virus infection and hepatocellular carcinoma

J Viral Hepat. 2024 Jul;31(7):383-390. doi: 10.1111/jvh.13943. Epub 2024 Apr 12.

Abstract

There is an urgent need for new high-quality markers for the early detection of hepatocellular carcinoma (HCC). Åström et al. suggested that S2-bound α1-acid glycoprotein (AGP) might be a promising marker. Consequently, we evaluated the predictive advantage of S2-bound AGP in the early detection of HCC. In a retrospective case-control study of patients chronically infected with hepatitis C virus (HCV) and treated with direct-acting antiviral agents (n = 93), we measured S2-bound AGP using the HepaCheC® ELISA kit (Glycobond AB, Linköping, SE) at the start of treatment, end of treatment and follow-up (maximum: 78 months). Patients were retrospectively propensity score matched (1:2). Thirty-one patients chronically infected with HCV developed HCC after a sustained virological response, while 62 did not. In addition, samples of patients with chronic hepatitis B virus infection, metabolic dysfunction-associated steatotic liver disease and HCC of different etiologies were analysed. S2-bound AGP elevation in HCC patients was confirmed. However, we did not observe a predictive advantage of S2-bound AGP for the early detection of HCC during treatment and follow-up. Interestingly, S2-bound AGP levels correlated with aspartate aminotransferase (ρ = .56, p = 9.5×10-15) and liver elastography (ρ = .67, p = 2.2×10-16). Of note, S2-bound AGP decreased in patients chronically infected with HCV after treatment-induced HCV clearance. Fucosylated S2-bound AGP levels were elevated in patients with chronic HCV and HCC. The potential role of S2-bound AGP as a novel tumour marker requires further investigation.

Keywords: AST; HBV; HCC; HCV; MASLD; S2‐bound AGP; biomarker; cancer; elastography; surveillance.

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / therapeutic use
  • Biomarkers* / blood
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Hepatocellular* / diagnosis
  • Carcinoma, Hepatocellular* / etiology
  • Case-Control Studies
  • Early Detection of Cancer
  • Female
  • Hepacivirus
  • Hepatitis C, Chronic* / complications
  • Hepatitis C, Chronic* / diagnosis
  • Humans
  • Liver Neoplasms* / diagnosis
  • Liver Neoplasms* / etiology
  • Male
  • Middle Aged
  • Orosomucoid* / analysis
  • Orosomucoid* / metabolism
  • Retrospective Studies

Substances

  • Antiviral Agents
  • Biomarkers
  • Biomarkers, Tumor
  • Orosomucoid