Programmed cell death-1 and interleukin-28B polymorphisms in autoimmune hepatitis.

BACKGROUND

Autoimmune hepatitis (AIH) is a relatively rare chronic liver disease of unknown etiology. The genetic background affects susceptibility, clinical phenotype, and prognosis. The polymorphism () has been associated with susceptibility to autoimmune diseases. The polymorphism has been associated with steatosis, inflammation, and fibrosis in liver diseases.

AIM

Our aim was to investigate for the first time the incidence and clinical significance of and in AIH.

METHODS

Two hundred patients with AIH were evaluated, while 100 healthy subjects were used as controls. Genotyping was performed with allelic discrimination End-Point PCR.

RESULTS

The SNP was present in 36/200 (18%) AIH patients compared to 28/100 (28%) healthy controls (p = 0.065). The AA/GA genotypes were not associated with the mode of presentation of AIH, the histological grade or stage, the presence of cirrhosis, risk of disease progression, response to treatment and survival. The genotype distribution was CC 79/200 (39.5%), TT 36/200 (18%) and CT 85/200 (42.5%), in similar rates with healthy controls (p = 0.878). Inflammatory activity and fibrosis stage did not differ between CC homozygotes and CT/TT carriers. LDL cholesterol was significantly higher in CC than CT/TT patients (P = 0.027), though no differences was found regarding the presence of steatosis or steatohepatitis. On-treatment response to immunosuppressive treatment was not affected by the polymorphism. However, CC homozygotes AIH patients achieved treatment withdrawal in significantly higher rates (OR 2.3, 95%CI: 1.1-4.7, P = 0.02) irrespective of the presence of steatosis or steatohepatitis.

CONCLUSIONS

The and variants are unlikely to contribute to AIH susceptibility, disease presentation and prognosis. The is not associated with the presence of concurrent steatosis or steatohepatitis. However, although on-treatment response rates to immunosuppression were not affected by the polymorphism, AIH patients with CC homozygosity were more likely to achieve complete treatment withdrawal. This novel finding needs validation and further clarification from larger multicenter studies.