Background and purpose
Insulin resistance is a common extrahepatic manifestation of hepatitis C virus (HCV) infection (HCVi), but its mechanisms are poorly understood. Although systemic insulin resistance has been documented, portal venous insulin dynamics, a key regulator of hepatic metabolism, remain unexplored. This study aimed to investigate the relationship between insulin, the gut-liver axis, and immunometabolic changes in HCV patients.
method
HCV patients were evaluated before (HCVi; n = 29) and after (SVR, n = 23) sustained viral response (SVR) achieved with sofosbuvir/velpatasvir treatment (NCT02400216). Liver biopsy, portal blood, and peripheral blood were collected at both stages. To elucidate the impairment of insulin homeostasis in HCVi, statistical analyzes were performed using Wilcoxon rank sum test, Mann-Whitney test, and Pearson’s correlation coefficient to assess differences and associations across insulin, glucose, cytokines, metabolites, immune cells, and liver transcriptomics.
result
HCV patients had significantly decreased portal insulin compared to SVR (p = 0.02), peripheral insulin, portal glucose, and peripheral glucose remained unchanged. Portal insulin was positively correlated with pro-inflammatory cytokines and vascular injury markers and negatively correlated with CD8/CD62L/CD45RA/CD3 cells (naive cytotoxic T cells) and non-canonical nucleotides. Liver transcriptome analysis revealed that portal insulin was positively correlated with immunity and negatively correlated with amino acid pathways, reflecting the role of insulin in the disruption of immunometabolism during HCVi.
conclusion
Decreased portal insulin during HCVi is associated with changes in pancreatic insulin secretion and changes consistent with decreased hepatic insulin extraction. The observed correlation supports a potential relationship between immune responses and insulin kinetics and indicates an interaction between the immune system, metabolism, and insulin in HCVi, with clinical implications for the management of glycemic abnormalities.
sauce:
Reference magazines:
Menkart, M.G.; Others. (2026). Relationship between changes in portal insulin and immunometabolism during and after hepatitis C virus infection. Journal of Clinical and Translational Hepatology. DOI: 10.14218/jcth.2025.00498. https://www.xiahepublishing.com/2310-8819/JCTH-2025-00498
