Possible role of HLA in hepatotoxicity. An exploratory study in 71 patients with drug-induced idiosyncratic hepatitis.
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.
Unité de Recherche de Physiopathologie Hépatique (INSERM U24), Hôpital Beaujon, Clichy, France.
A
A
Berson
E
E
Fréneaux
D
D
Larrey
V
V
Lepage
C
C
Douay
C
C
Mallet
B
B
Fromenty
J P
JP
Benhamou
D
D
Pessayre
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000276:immunology*; D002746:Chlorpromazine / Q000009:adverse effects; D004008:Diclofenac / Q000009:adverse effects*; D005260:Female; D006680:HLA Antigens / Q000235:genetics / Q000502:physiology*; D015234:HLA-A Antigens / Q000737:chemistry / Q000235:genetics; D059870:HLA-A11 Antigen; D015795:HLA-B8 Antigen / Q000235:genetics / Q000502:physiology; D015802:HLA-DR2 Antigen / Q000235:genetics / Q000502:physiology; D015808:HLA-DR6 Antigen / Q000235:genetics / Q000502:physiology; D006221:Halothane / Q000009:adverse effects*; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009582:Nitrofurantoin / Q000009:adverse effects*; D010641:Phenotype
D006680:HLA Antigens; D015234:HLA-A Antigens; D059870:HLA-A11 Antigen; D015795:HLA-B8 Antigen; D015802:HLA-DR2 Antigen; D015808:HLA-DR6 Antigen; D004008:Diclofenac; D009582:Nitrofurantoin; D002746:Chlorpromazine; D006221:Halothane