The Relationship Between Liver Iron Content and Hepatocellular Carcinoma and the Mediating Role of NAFLD: A Study Based on Mediation Mendelian Randomization Method

Objective To explore the causal relationship between liver iron content and hepatocellular carcinoma(HCC)mediated by non-alcoholic fatty liver disease(NAFLD).Methods Mendelian randomization(MR)method was employed,using single nucleotide polymorphisms(SNPs)as instrumental variables.The inverse variance weighted(IVW),MR-Egger,and weighted median methods were used for MR analysis to assess the potential causal relationships among liver iron content,NAFLD,and HCC.Sensitivity analyses were conducted to verify the robustness of the results.Results The IVW results showed a significant causal effect of higher liver iron content on the risk of HCC(OR=2.746,95%CI:1.822~4.139,P=1.39E-06).Liver iron content was positively correlated with NAFLD(OR=1.245,95%CI:1.107~1.401,P=0.000264534),and NAFLD significantly increased the risk of HCC(OR=9.207,95%CI:6.540~12.962,P=4.47E-37).NAFLD played a partial mediating role between liver iron content and HCC,with a mediation effect proportion of 48.14%.Conclusions This study confirms a causal relationship between liver iron content and HCC, with NAFLD playing a partial mediating role.