Title: 544 Liver Cirrhosis Increases Long-Term Risk for Autoimmunity: A Nationwide Population-Based Cohort Study
Abstract: Background: The etiology of autoimmune diseases is multifactorial but includes a dysregulated self-tolerance and a dysfunctional communication between the sympathetic nervous system (SNS) and the immune system.Regulatory T-cells are required to induce tolerance and prevent autoimmune disease.In cirrhosis, increased SNS-activity may shift cytokineresponse towards Th2-cytokines, suppressing cellular but incrementing humoral, B-cellmediated immune response.These immune modulations, and the peripheral T-cell depletion known to occur in cirrhosis, may support development of autoimmunity.We therefore aimed to investigate whether cirrhosis confers an increased risk of autoimmune disease.Methods: We used the Danish National Patient Registry (NPR) to identify all Danish citizens diagnosed with cirrhosis in 1977-2009.For each of them we sampled five gender-and agematched population controls.Competing-risks regression was used to compare the risk of rheumatoid arthritis, multiple sclerosis, or inflammatory bowel disease (identified through NPR) between cirrhosis patients and controls.Results: We included 38,394 cirrhotic patients.During 217,558 total years of follow-up 442 of them developed rheumatoid arthritis (N= 206), multiple sclerosis (N=20), or inflammatory bowel disease (N=216).In the first 10 years after cirrhosis diagnosis their risk did not exceed that of the population controls (Fig. 1), but after that their risk was markedly higher (HR >10 years after cirrhosis was diagnosed).Conclusion: Liver cirrhosis associates with an increased long-term risk for multiple sclerosis, inflammatory bowel disease and/or rheumatoid arthritis.This may indicate a general enhancement in susceptibility for autoimmune phenomena in liver cirrhosis and the underlying mechanisms should be delineated.