Antimitochondrial Rather than Antinuclear Antibodies Correlate with Severe Drug-Induced Liver Injury

Dig Dis. 2021;39(3):275-282. doi: 10.1159/000511635. Epub 2020 Sep 17.

Abstract

Introduction: A proportion of patients with drug-induced liver injury (DILI) present with autoantibodies, which has led to the current concept of autoimmune-like DILI. However, no standardized definition exists and the clinical relevance has not been studied in detail yet.

Methods: 143 patients with DILI enrolled in a prospective study were analyzed. DILI diagnosis was based on the monocyte-derived hepatocyte-like cell test and supported by Roussel Uclaf Causality Assessment Method (RUCAM) and expert adjudication. Testing for antinuclear antibodies (ANA) and antimitochondrial antibodies (AMA) was performed using immunofluorescence. ANA titers ≥1:100 were considered positive and ≥1:400 clinically relevant; AMA positivity was considered at titers ≥1:100.

Results: 67% exhibited ANA ≥1:100 and 29% ANA ≥1:400; 10% were AMA positive. There was no significant correlation between the ANA titers and the causative drug, while AMA positive patients had taken nonsteroidal anti-inflammatory drugs more frequently. No difference was seen regarding clinical characteristics or laboratory parameters in patients with ANA ≥1:400, while patients with positive AMA presented with higher aminotransferases, bilirubin, and international normalized ratio. Significantly higher proportions of patients with ANA ≥1:400 or AMA positivity exhibited elevated immunoglobulin G levels. AMA positivity but not elevated ANA titers correlated with a higher proportion of Hy's law positivity.

Conclusion: A closer look in a causality proven DILI cohort provided no evidence that presence of ANA titers is specific for DILI by a certain medication. AMA rather than ANA positivity was related to a more pronounced liver injury.

Keywords: Acute liver injury; Antimitochondrial antibodies; Antinuclear antibodies; Autoantibodies; Drug-induced liver injury.

Publication types

  • Clinical Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies, Antinuclear / immunology*
  • Autoantibodies / immunology
  • Autoimmune Diseases / immunology
  • Chemical and Drug Induced Liver Injury / immunology*
  • Humans
  • Male
  • Middle Aged
  • Mitochondria / immunology*
  • Prospective Studies
  • Young Adult

Substances

  • Antibodies, Antinuclear
  • Autoantibodies