AbstractAutoimmune hepatitis (AIH) is an autoimmune liver disease and cirrhosis is sometimes complicated with AIH at diagnosis, influencing its prognosis.TNFAIP3gene encodes A20, an inhibitor of nuclear factor-κB pathway, and is a susceptibility gene for autoimmune diseases. We investigated deleterious variants in the coding regions ofTNFAIP3gene of Japanese AIH patients or those with cirrhosis. The deleterious variants in the coding regions ofTNFAIP3gene were analyzed by the cycle sequencing method and the frequencies of deleteriousTNFAIP3alleles of AIH or AIH with cirrhosis were compared with those of Japanese controls. The deleterious alleles inTNFAIP3were not associated with AIH. A significant association was shown for the deleterious alleles inTNFAIP3(P = 0.0180, odds ratio (OR) 4.28, 95% confidence interval (CI) 1.53–11.95) with AIH with cirrhosis at presentation. The serum IgM levels in AIH patients with deleterious alleles inTNFAIP3were tended to be lower than those without (P = 0.0152,Q = 0.1216). The frequency of deleterious alleles inTNFAIP3was higher in the AIH subset without theDRB1risk alleles than that with (P = 0.0052, OR 5.10, 95%CI 1.55–16.74). The deleterious alleles inTNFAIP3were associated with AIH with cirrhosis.