Metabolic factors for liver cirrhosis: A Mendelian randomization study

Liver cirrhosis is a chronic disease caused by long-term inflammation and fibrosis of the liver. Early identification and intervention in liver cirrhosis have become an important goal for researchers to explore the influence of some metabolic factors on the risk of liver cirrhosis in terms of genetic susceptibility. Data from genome-wide association studies (GWASs) of fourteen metabolic factors and liver cirrhosis were obtained from publicly available databases. To make the results more credible, we selected 2 GWASs for liver cirrhosis to be validated separately. The causal effect of metabolic factors on liver cirrhosis was assessed separately using 2-sample Mendelian Randomization (MR). The inverse variance weighted (IVW) method was used as the main analysis method. The present MR analysis confirmed that fasting insulin level (IVW-OR = 2.89, 95% CI: 1.36-6.15, P = .006) and ALT (IVW-OR = 1.42, 95% CI: 1.11-1.80, P = .004) were positively causally associated with the risk of liver cirrhosis, and there was a negative causal relationship between hypertension and the risk of liver cirrhosis (IVW-OR = 0.40, 95% CI: 0.23-0.72, P = .002) in 1 liver cirrhosis GWAS. In replication analysis, our MR proved the positive causal effect between ALT (IVW-OR = 2.09, 95% CI: 1.61-2.72, P < .001) and BMI (IVW-OR = 1.44, 95% CI: 1.17-1.77, P < .001) and the risk of liver cirrhosis. A causal relationship between other metabolic factors and the risk of liver cirrhosis could not be established in the current selection of data. Our MR study revealed a causal and positive association between ALT and the risk of liver cirrhosis, suggesting an important role of effective control of ALT in liver cirrhosis prevention. The causal relationship between thirteen other metabolic factors and the risk of liver cirrhosis remains to be further verified.