Published online May 27, 2026. doi: 10.4254/wjh.v18.i5.116995
Revised: January 23, 2026
Accepted: March 4, 2026
Published online: May 27, 2026
Processing time: 181 Days and 15.9 Hours
Chronic hepatitis C (CHC) infection remains a significant global health burden often progressing to hepatic fibrosis and cirrhosis, which may ultimately result in hepatocellular carcinoma. Liver fibrosis development is governed by complex host-pathogen interaction, including genetic susceptibility and immune dysregulation. IFI16 and AIM2 inflammasomes serve as critical modulators of inflammation and pathogen pathways.
To determine the association of variants IFI16 (rs1057028) and AIM2 (rs2814770) with hepatic fibrosis progression in Pakistani CHC patients.
This study recruited 378 CHC patients from Lahore General Hospital (tertiary care hospital). Study participants were selected based on hepatitis C virus (HCV)-RNA positivity and transient elastography confirmed hepatic fibrosis. A total of 378 CHC patients for IFI16 genetic variant and 140 CHC patients for AIM2 variant were genotyped using amplification refractory mutation system assays. χ2 test, t-test, Mann-Whitney U test, combined genotype effect, and logistic regression analysis was performed determine association between target single nucleotide polymorphisms and progression of HCV-related fibrosis and cirrhosis.
Results of our study showed that only AIM2 rs2841770 variant genotype TT shows significant association with a higher risk of advanced stage of liver fibrosis (OR = 4.83, P = 0.05). Combined genotype analysis had shown that CHC patients having A allele of rs1057028 and T allele of rs2814770 are significantly associated with increased risk of hepatic fibrosis (OR = 2.6, 95%CI: 1.16-5.86, P = 0.022). Our findings also revealed a significant trend of increasing frequency of liver fibrosis with an increased number of risk alleles of IFI16 rs1057028 and AIM2 rs2814770. In univariate regression analysis, body mass index and alanine aminotransferase levels significantly associated with increased risk of liver fibrosis.
This study suggests that AIM2 rs2814770 and its combined effect with IFI16 rs1057028 may be increase susceptibility to hepatic fibrosis in CHC patients, highlighting immunogenetic modulation, warranting further research for predictive biomarkers.
Core Tip: Hepatic fibrosis progression in chronic hepatitis C (CHC) is influenced by complex immunogenetic factors. This study demonstrates that the AIM2 (rs2814770) TT genotype and combined carriage of variants rs1057028 (A allele) of IFI16 and rs2814770 (T allele) of AIM2 significantly increases the risk of advanced liver fibrosis in Pakistani CHC patients. A dose-dependent rise in fibrosis severity with increasing risk alleles further supports their pathogenic relevance. These findings suggest a potential role of IFI16 and AIM2 genetic variants as predictive biomarkers for fibrosis progression, underscoring the need for expanded studies to validate their clinical utility.