KIR/HLA Genotypes Confer Susceptibility and Progression in Patients with Autoimmune Hepatitis

Abstract Background & Aims Natural killer (NK) cells are key members in the innate immune response. Killer cell immunoglobulin-like receptors (KIRs) are involved in the activation and inhibition of NK cells through the recognition of HLA class I molecules. We investigated the impact of KIR/HLA combinations on susceptibility and long-term clinical outcome in Japanese patients with type 1 autoimmune hepatitis (AIH). Methods A total of 154 cases of AIH were recruited at Shinshu University Hospital between 1974 and 2018. KIR genes and HLA class I and II alleles were genotyped in all patients along with 201 healthy subjects. Associations between KIR/HLA pairs and clinical outcomes (liver decompensation and liver-related death) were evaluated using the Cox proportional hazards model with stepwise method. Results After a median follow-up period of 11.1years, 12% of patients experienced liver decompensation and 8% died from liver disease. KIR3DL1/HLA-B Bw4-80Ile (P=0.0062) and the HLA-DRB1*04:05-DQB1*04:01 haplotype (P Conclusions This study revealed the impact of specific KIR/HLA pairs in AIH susceptibility and progression in the Japanese. KIR3DL1/HLA-B Bw4-negative AIH patients with cirrhosis at diagnosis are at high risk for adverse outcomes and require careful surveillance. Lay Summary Autoimmune hepatitis (AIH) is a disease of the liver that can present in acute or chronic hepatitis. We examined whether KIR/HLA pairs were associated with AIH susceptibility or disease progression. KIR3DL1/HLA-B Bw4 was a novel KIR/HLA pair related to a favorable clinical outcome, while cirrhosis at the initial diagnosis was a risk factor of a poor prognosis. Thus, frequent and careful surveillance is advised for KIR3DL1/HLA-B Bw4-negative AIH patients with cirrhosis.