Serum markers for detecting histological features of autoimmune hepatitis and predicting prognosis in patients with antinuclear antibody‐positive drug‐induced liver injury

Although useful for distinguishing drug‐induced liver injury (DILI) from autoimmune hepatitis (AIH), liver biopsy is an invasive examination, and the presence of antinuclear antibody (ANA) positivity in patients with DILI could lead to excessive use of biopsy. Hence, we aimed to identify screening markers for histological features of AIH in patients with ANA‐positive DILI and verify their clinical outcomes after 1 year. This retrospective study included patients with ANA‐positive DILI, who underwent liver biopsy between January 2017 and April 2022. Two pathologists identified histological features of AIH. We detected the independent indicators associated with histological features of AIH using logistic regression. We evaluated their diagnostic ability for histological features of AIH using the receiver operating characteristic curve. The follow‐up period to determine clinical outcomes was 1 year after DILI onset. The χ2test or Fisher's exact test was used to compare categorical data and the Wilcoxon rank‐sum test was used to compare continuous variables. Two‐sided p< 0.05 was considered to indicate significance. The final analysis included 125 patients with ANA‐positive DILI, of whom 18 had AIH‐like histology. Factors independently associated with AIH‐like histology included globulin levels (odds ratio [OR] = 1.154, 95% confidence interval [CI] = 1.046–1.288; p= 0.006) and ANA titer ≥ 1:1000 (OR = 3.531, 95% CI = 1.136–11.303; p= 0.029). The optimal globulin cutoff indicating AIH‐like histology was 31.8 g/L. This globulin level in combination with ANA titer ≥ 1:1000 (area under the curve = 0.785, 95% CI = 0.738–0.832) provided a sensitivity of 100% and a specificity of 57% for indicating histological features of AIH in patients with ANA‐positive DILI. During follow‐up, more patients developed AIH in the group with AIH‐like histology than in the group without AIH‐like histology (35.3% vs. 0, p< 0.001). For patients with ANA‐positive DILI and ANA titer ≥ 1:1000 or globulin ≥ 31.8 g/L, liver biopsy is recommended to determine the presence of histological features of AIH and guide further monitoring. Serum markers for detecting histological features of autoimmune hepatitis (AIH) in patients with antinuclear antibody (ANA)‐positive drug‐induced liver injury (DILI) and their associations with the development of AIH are unclear. This retrospective cohort study identified serum globulin ≥ 31.8 g/L and ANA titer ≥ 1:1000 as potential screening markers. Patients with ANA‐positive DILI and histological features of AIH are more likely to develop AIH than those without these features. AIH, autoimmune hepatitis; ANA, antinuclear antibody; DILI, drug‐induced liver injury; HDS, herbal and dietary supplements; TCM, traditional Chinese medicines. Significant findings of the study Serum globulin ≥ 31.8 g/L and ANA titer ≥ 1:1000 could be screening markers for detecting histological features of autoimmune hepatitis (AIH) in patients with antinuclear antibody (ANA)‐positive drug‐induced liver injury. Patients with ANA‐positive DILI and histological features of AIH are more likely to develop autoimmune hepatitis than those without these features. What this study adds Some patients with ANA‐positive DILI present with histological features of AIH, which can be screened noninvasively by ANA titer ≥ 1:1000 and globulin ≥ 31.8 g/L before liver biopsy. Furthermore, patients who present with histological features of AIH should be followed up to monitor the development of AIH.