Possible role of HLA in hepatotoxicity. An exploratory study in 71 patients with drug-induced idiosyncratic hepatitis

J Hepatol. 1994 Mar;20(3):336-42. doi: 10.1016/s0168-8278(94)80004-9.


Possible associations between particular human leucocyte antigen molecules and immunoallergic hepatitis have been suggested previously (HLA-A11 in halothane hepatitis, HLA-DR6 and DR2 in nitrofurantoin hepatitis, HLA-B8 in clometacin hepatitis). In this study the HLA haplotype was determined in 71 patients with idiosyncratic hepatitis due to different drugs. The prevalence of HLA-A11 was twice as high in the 71 patients in the study (23%) as in controls (12%), but p-values were not significant when corrections were made for the large number of comparisons (n = 39). The prevalences of HLA-DR2, DR6, and B8 were similar in the 71 patients and in controls. When hepatitis due to particular drugs was considered, HLA-A11 was found to be present in six of 12 patients (50%) with hepatitis caused by tricyclic antidepressants, and three of four patients (75%) with diclofenac hepatitis, compared to 12% in controls. HLA-DR6 was present in four of five patients (80%) with chlorpromazine hepatitis, compared to 22% in controls. In conclusion, the HLA phenotype does not contribute significantly to idiosyncratic drug-induced hepatitis considered collectively. Possible associations between some HLA molecules and the hepatotoxicity of certain drugs require further confirmation.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Chemical and Drug Induced Liver Injury / etiology*
  • Chemical and Drug Induced Liver Injury / immunology*
  • Chlorpromazine / adverse effects
  • Diclofenac / adverse effects*
  • Female
  • HLA Antigens / genetics
  • HLA Antigens / physiology*
  • HLA-A Antigens / chemistry
  • HLA-A Antigens / genetics
  • HLA-A11 Antigen
  • HLA-B8 Antigen / genetics
  • HLA-B8 Antigen / physiology
  • HLA-DR2 Antigen / genetics
  • HLA-DR2 Antigen / physiology
  • HLA-DR6 Antigen / genetics
  • HLA-DR6 Antigen / physiology
  • Halothane / adverse effects*
  • Haplotypes
  • Humans
  • Male
  • Middle Aged
  • Nitrofurantoin / adverse effects*
  • Phenotype


  • HLA Antigens
  • HLA-A Antigens
  • HLA-A11 Antigen
  • HLA-B8 Antigen
  • HLA-DR2 Antigen
  • HLA-DR6 Antigen
  • Diclofenac
  • Nitrofurantoin
  • Chlorpromazine
  • Halothane