The Causal Relationship between Inflammatory Cytokines and Liver Cirrhosis in European Descent: A Bidirectional Two-Sample Mendelian Randomization Study and the First Conclusions.

Abstract

Observational studies have highlighted the pivotal role of inflammatory cytokines in cirrhosis progression. However, the existence of a causal link between inflammatory cytokines and cirrhosis remains uncertain. In this study, we conducted a bidirectional Mendelian randomization (MR) analysis at a summarized level to illuminate the potential causal relationship between the two variables. This study utilized genetic variance in cirrhosis and inflammatory cytokines from a genome-wide association study (GWAS) of European descent. The MR-PRESSO outlier test, Cochran's Q test, and MR-Egger regression were applied to assess outliers, heterogeneity, and pleiotropy. The inverse variance weighted method and multiple sensitivity analyses were used to evaluate causalities. Furthermore, the validation set was used for simultaneous data validation. The inflammatory cytokine monocyte chemoattractant protein 3 (MCP-3) was supposedly associated with a greater risk of cirrhosis. And cirrhosis was significantly correlated with increased levels of hepatocyte growth factor (HGF). This study suggests that MCP-3 might be associated with the etiology of cirrhosis, while several inflammatory cytokines could potentially play a role in its downstream development. Additionally, the progression of cirrhosis was associated with elevated levels of HGF, suggesting a possible role for liver repair functions.