The progression of chronicity and autoimmune hepatitis in recurrent drug-induced liver injury

Clin Res Hepatol Gastroenterol. 2022 Dec;46(10):102009. doi: 10.1016/j.clinre.2022.102009. Epub 2022 Aug 14.


Background and aims: Recurrent drug-induced liver injury (DILI) is not well documented. We retrospectively analysed the characteristics of patients who had a history of two separate DILI episodes due to different drugs.

Methods: We collected data from 57 patients with recurrent DILI from 9582 confirmed DILI cases. Demographic, laboratory, and clinical data from both episodes were collected and analysed to determine the relationship between recurrent DILI, chronic DILI, and autoimmune hepatitis (AIH).

Results: The incidence rate of recurrent DILI in our cohort was 0.59%. Most of the 57 patients with recurrent DILI were female (73.68%). The latency period of the initial episode was 30 days, whereas that of the second episode was 13 days (P = 0.003). The pattern of liver injury was not significantly different between episodes (P = 0.52). Laboratory indicators, such as alanine aminotransferase, aspartate transaminase, alkaline phosphatase, and total bilirubin, were significantly lower in the second episode than in the initial episode (P < 0.05). The incidence of chronic DILI was 43.86% during the initial episode and increased to 63.16% during the second episode. After the initial episode, 15 patients developed AIH during the second episode.

Conclusions: The latency period of recurrent DILI was gradually shortened. The clinical indices of liver injury tended to be less elevated during the second episode. Female post-menopausal patients with abnormal serum immunoglobulin G levels may be predisposed to AIH. The second DILI episode was more likely to have features of AIH.

Keywords: Autoimmune hepatitis; Chronic DILI; Clinical features; Prognosis; Recurrent DILI.

MeSH terms

  • Alanine Transaminase
  • Aspartate Aminotransferases
  • Chemical and Drug Induced Liver Injury* / epidemiology
  • Chemical and Drug Induced Liver Injury* / etiology
  • Chemical and Drug Induced Liver Injury, Chronic*
  • Female
  • Hepatitis, Autoimmune* / epidemiology
  • Hepatitis, Autoimmune* / etiology
  • Humans
  • Male
  • Retrospective Studies


  • Alanine Transaminase
  • Aspartate Aminotransferases