Published online Mar 27, 2026. doi: 10.4254/wjh.v18.i3.112850
Revised: September 29, 2025
Accepted: December 24, 2025
Published online: March 27, 2026
Processing time: 230 Days and 14.8 Hours
The human leukocyte antigen (HLA) system represents one of the most genetically diverse and densely packed genomic regions, playing a fundamental role in orchestrating immune responses. Among molecular markers linked to viral pathogenesis and immune modulation are insulin-like growth factor 2 (IGF-2) and intestinal fatty-acid-binding protein (I-FABP).
To investigate the influence of the HLA variant rs1131500, together with IGF-2 and I-FABP, on susceptibility to hepatitis C virus (HCV), coronavirus disease 2019 (COVID-19), and their co-occurrence, to identify predictive biomarkers and potential therapeutic targets.
The study involved quantifying circulating levels of IGF-2, I-FABP, and interferon-gamma (IFN-γ) and genotyping HLA rs1131500 using real-time polymerase chain reaction. Participants provided nasopharyngeal swabs for detection of severe acute respiratory syndrome coronavirus 2 RNA and blood samples for HCV RNA analysis and biomarker assessment.
Levels of IGF-2 and I-FABP were notably higher in all patient categories, with the highest values observed in co-infected individuals (P < 0.0001). A moderate positive correlation was observed between I-FABP and IFN-γ in COVID-19 cases (r = 0.261, P = 0.05). IGF-2 had the most substantial predictive value (odds ratio [OR]: 4.5-5.5), while IFN-γ showed a protective trend (OR < 1) when combined with IGF-2 and I-FABP.
IGF-2 emerged as the most consistent and reliable biomarker across all patient groups, particularly in COVID-19 and co-infections. I-FABP was a strong marker for co-infection, less so for COVID-19, and ineffective for HCV alone. Genetically, the CC genotype was more common in the HCV and Control groups, whereas the TT genotype was associated with COVID-19 and co-infection, suggesting potential diagnostic value.
Core Tip: This study identifies insulin-like growth factor 2 as a robust molecular biomarker for distinguishing between coronavirus disease 2019 (COVID-19), hepatitis C virus, and co-infection, with the highest diagnostic performance in co-infected individuals. Intestinal fatty-acid-binding protein showed selective utility in coinfections, while interferon-gamma displayed a protective association. Genotyping of human leukocyte antigen rs1131500 revealed the TT genotype as more frequent in COVID-19 and coinfection cases, suggesting a potential immunogenetic risk factor. These findings provide new insight into host immune responses and offer clinically relevant biomarkers for the diagnosis and personalized management of viral infections.