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Immune mechanisms in tienilic acid associated hepatotoxicity

J Neuberger1, R Williams

  • 1Liver Unit, Queen Elizabeth Hospital, Queen Elizabeth Medical Centre, Birmingham.

Gut
|April 1, 1989
PubMed

Insights

Tienilic acid hepatotoxicity may be immune-mediated. Studies suggest drug-altered liver cell antigens trigger sensitization, leading to an immune attack on liver cells, evidenced by autoantibodies like anti-LKM2.

Area of Science:

  • Immunology
  • Hepatology
  • Pharmacology

Background:

  • Tienilic acid (Ticrynafen) is associated with hepatotoxicity.
  • The underlying mechanisms of drug-induced liver injury are not fully understood.

Purpose of the Study:

  • To investigate immune sensitization to drug-altered liver cell determinants in tienilic acid-induced hepatotoxicity.
  • To explore the role of autoantibodies in this adverse drug reaction.

Main Methods:

  • Indirect antibody-dependent cell-mediated cytotoxicity (ADCC) assay.
  • Hepatocytes isolated from rabbits pretreated with tienilic acid and enzyme inducers (phenobarbitone or B-naphthoflavone).
  • Sera analysis from patients with presumed tienilic acid hepatotoxicity, patients on tienilic acid without liver damage, normal controls, and patients with other liver diseases.

Main Results:

  • Sera from patients with presumed tienilic acid hepatotoxicity induced significant cytotoxicity to treated hepatocytes.
  • Cytotoxicity was also observed with sera from patients on tienilic acid without overt liver damage.
  • Anti-LKM2 autoantibodies were detected in association with tienilic acid-specific antibodies in affected patients.

Conclusions:

  • Tienilic acid-induced hepatotoxicity appears to be associated with immune sensitization to drug-altered liver cell antigens.
  • The findings suggest a potential immune-mediated mechanism involving drug-induced antigens breaking tolerance.
  • This immune response may lead to an attack on normal liver cell components.

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