Chinese Hepatolgy ›› 2021, Vol. 26 ›› Issue (3): 237-242.

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The association between antinuclear antibody titers with the clinical features and prognosis of drug induced liver injury

WANG Yan1, WANG Yu1, WANG Lan2, TIAN Qiu-ju3, YANG Rui-yuan4, LI Ke-xin1, LIU Li-wei1, LU Yi-da5, WANG Xiao-ming1, WANG Yu1, OU Xiao-juan1, JIA Ji-dong1, ZHAO Xin-yan1   

  1. 1. Liver Research Center, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases,Beijing 100050, China;
    2. Department of gastroenterology, Affiliated Chuiyangliu Hospital of Tsinghua University;
    3. Liver Research Center, the Affiliated Hospital of Qingdao University;
    4. China Medical Tribune;
    5. The Second Clinical Medical College, Capital Medical University
  • Received:2021-01-07 Published:2021-04-21
  • Contact: ZHAO Xin-yan, Email: zhao_xinyan@ccmu.edu.cn

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Abstract: Objective To study the clinical characteristics and outcomes of patients with drug-induced liver injury (DILI) and different titers of antinuclear antibodies (ANA). Methods The clinical and prognostic data of DILI patients who were hospitalized in Liver Research Center, Beijing Friendship Hospital, Capital Medical University from January 2009 to January 2019 were collected. They were divided into ANA negative, titers of 1:80, 1:160 and ≥ 1:320 groups. The clinical manifestations, laboratory indexes, and prognosis among each group were compared. ANOVA test, Kruskal Wallis H test was used for continuous variables. Chi Square test was used for categorical variables. Bonferroni correction was used for multiple comparisons. P<0.05 was statistically significant. Results A total of 602 patients was enrolled, with 177 in ANA negative group, 281 in ANA 1:80 group, 99 in ANA 1:160 group, and 45 cases in ANA ≥ 1:320 group. The majority of patients were female (76.8%-87.9%), and the median age was 56.0 years old. There was no significant difference in the peak value of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), glutamyl transpeptidase (GGT) and total bilirubin (TBIL) among these four groups of patients. However, with the increase of ANA titer, serum albumin (Alb) (37.2 ± 5.5g/L, 36.5 ± 5.0 g/L, 36.2 ± 5.1 g/L, 34.6 ± 4.9 g/L in these four groups, respectively, P=0.030) and prothrombin activity (PTA) (86.1 ± 22.9%, 82.5 ± 23.5%, 78.6 ± 24.1%, 75.7 ± 27.4%, P=0.016) significantly decreased, whereas serum globulin (GLB) (27.5 ± 4.6 g/L, 29.5 ± 5.2 g/L, 29.2 ± 5.8 g/L, 32.3 ± 6.4 g/L, P<0.001) and Immunoglobulin G (IgG) [1240.0 (1080.0, 1420.0)mg/dL, 1380.0 (1140.0, 1670.0) mg/dL, 1440.0 (1180.0, 1840.0) mg/dL, 1740.0 (1380.0, 2110.0) mg/dL, P=0.001] significantly increased. The proportion of connective tissue diseases increased successively along with the increased titers of ANA (0.6%, 2.8%, 5.0%, 13.3%, respectively, P<0.001). The hospitalization time also significantly prolonged, which were 11.0 (8.0, 14.0) days, 11.0 (8.0, 14.0) days, 12.0 (9.0, 15.0) days and 15.0 (10.0, 20.0) days, respectively (P<0.001). The proportion of normalization of liver biochemical indexes decreased, whereas the proportion of progression of chronicity, cirrhosis, death or liver transplantation significantly increased (P=0.006). Conclusion Higher ANA titer in DILI patients is associated with an increase of connective tissue diseases, prolonged hospitalization time, impaired liver synthetic function, worsened immune function, less normalization of liver biochemical indexes. It is also related to significant progression of chronicity, cirrhosis, death or liver transplantation. Our data suggests that the higher titer of ANA, the worse of outcomes of DILI patients, which warrant clinical awareness.

Key words: Drug-induced liver injury (DILI), Antinuclear antibody (ANA), Prognosis, Connective tissue diseases