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.
Berson
A
A
Unité de Recherche de Physiopathologie Hépatique (INSERM U24), Hôpital Beaujon, Clichy, France.
Fréneaux
E
E
Larrey
D
D
Lepage
V
V
Douay
C
C
Mallet
C
C
Fromenty
B
B
Benhamou
J P
JP
Pessayre
D
D
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