Serum interferon-gamma-induced protein-10 level and gene polymorphism in patients with drug-induced liver injury accompanied by autoimmune phenomena

Objective To investigate the single nucleotide polymorphism( SNP) and serum expression of interferon-gamma-induced protein 10( IP-10) in patients with drug-induced liver injury accompanied by autoimmune phenomena( AI-DILI). Methods A total of 168 patients with drug-induced liver injury( DILI) who were diagnosed and treated in Beijing YouAn Hospital,Capital Medical University,from October 2016 to June 2019 were enrolled and divided into AI-DILI group( n = 72) and non-AI-DILI group( n = 96). The SNP of IP-10 rs56061981 locus was detected and the serum level of IP-10 was measured. The two groups were compared in terms of IP-10 level and SNP genotype,and their association with the development of AI-DILI was analyzed. Allele frequency was calculated based on genotype results,and the chi-square test was used for Hardy-Weinberg equilibrium analysis. The t-test and the Mann-Whitney U test were used for comparison between two groups; a repeated measures analysis of variance was used for comparison between different time points; the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups. The Pearson correlation analysis was used to investigate correlation. The receiver operating characteristic( ROC) curve was used to analyze the value of baseline IP-10 level in predicting AI-DILI. Results There was a significant difference in the positive rate of autoantibody between the AI-DILI group and the non-AI-DILI group( 91. 67% vs 12. 5%,χ2= 103. 8,P < 0. 05). Compared with the non-AI-DILI group,the AI-DILI group had significantly higher distribution frequency of CC genotype( 77. 78% vs 62. 50%,χ2= 4. 592,P = 0. 03) and frequency of C allele( 86. 11% vs 72. 92%,χ2= 4. 41,P = 0. 04). The AI-DILI group had a significantly higher baseline IL-10 level than the non-AI-DILI group( 627. 99 ± 198. 07 pg/ml vs 378. 13 ± 218. 45 pg/ml,t = 7. 34,P < 0. 05),and baseline IL-10 level was positively correlated with baseline aspartate aminotransferase level and AIH score( r = 0. 67 and 0. 79,both P < 0. 05). At the optimal cut-off value of 527. 03 pg/ml,baseline IP-10 level had a sensitivity of 0. 846,a specificity of 0. 867,and an area under the ROC curve of 0. 832 in predicting AI-DILI. CC genotype combined with a baseline IP-10 level of ≥527. 03 pg/ml had a positive predictive value of 92. 84% and a negative predictive value of 86. 33% in predicting the development of AI-DILI. Conclusion CC genotype of IP-10 rs56061981 is associated with the development of AI-DILI and affects the serum expression of IP-10,and the combination of CC genotype and IP-10 expression has a high value in predicting AI-DILI.