Causal effect of autoimmune liver diseases on cancer: Meta-analyses of cohort studies and Mendelian randomization study

Background and Aims Prior studies suggested that patients with autoimmune liver diseases (AiLDs) had an increased risk of cancer, whereas the causal effect remained unclear. Methods Meta-analyses concerning the relationship between AiLD and cancer risk were performed to calculate the pooled relative risk (RR) and corresponding 95% confidence intervals (CIs). Then, the associations with a p value of A total of 37 cohort studies covering more than 34 558 patients were included, and we observed an increased risk of overall cancers (pooled RR = 3.64, 95% CI: 2.64-5.03, p < .001) and cancer-related death (pooled RR = 2.48, 95% CI: 1.73-3.53, p < .001) for patients with AiLD. Besides, overall and several site-specific cancers risk were found in patients with primary biliary cholangitis (PBC), autoimmune hepatitis (AIH), and primary sclerosing cholangitis (PSC) (p < .05). However, associations between genetically predisposed AIH, PBC, and PSC and the risk of specific cancers did not reach a significant level, except for PBC and gastric cancer (OR = 0.96, 95% CI: 0.93-0.99; p = .02). Conclusions In addition to hepatobiliary cancer, results from the meta-analyses suggest that patients with AiLD might have an increased risk of several extrahepatobiliary cancers. However, the causal role of AiLD in cancer development needs to be further investigated.