High plasma interleukin‐6 level, but not IL‐6 gene variants, as a predictive marker for the development of hepatocellular carcinoma in a Moroccan population

Chronic inflammation triggered by hepatitis B (HBV) and hepatitis C (HCV) viruses elevates interleukin 6 (IL‐6) levels, activating pathways that cause liver damage and contribute to hepatocellular carcinoma (HCC) development. In this study, we assessed IL‐6 levels and explored the correlation between the rs1800795 and rs1800797 variants of the IL‐6 gene and the risk of developing HCC. We conducted a case–control study involving 314 participants. Among them, 157 were HCC patients (94 anti‐HCV, 22 HBsAg and 41 metabolic dysfunction‐associated steatotic liver disease [MASLD]) and 157 controls. Genotyping for IL‐6 rs1800795 and rs1800797 polymorphisms was performed using real‐time polymerase chain reaction (PCR). Additionally, plasma IL‐6 levels were determined using enzyme‐linked immunosorbent assay. The IL‐6 levels were notably higher in patients compared to controls ( p < .0001). Among HCC patients, those with MASLD exhibited higher plasma IL‐6 levels than those with HCV and HBV ( p = .003). In male HCC patients, IL‐6 levels were significantly elevated compared to controls ( p < .0001). Similarly, female patients showed significantly higher IL‐6 levels compared to female controls, though still lower than in male HCC patients ( p = .023). However, no significant difference was observed in IL‐6 levels between male and female HCC patients ( p = .129). Contrastingly, the genotype and allele distributions of the rs1800795 and rs1800797 polymorphisms in the IL‐6 gene displayed no association with HCC development (all p > .05). In Moroccan HCC patients, chronic liver inflammation is characterized by elevated levels of IL‐6, potentially playing a role in the progression of liver disease and tumourigenesis.