HLA association of amoxicillin-clavulanate-induced hepatitis

Background & Aims: Drug-induced immunoallergic hepatitis typically affects a minority of patients exposed to a particular drug. Its rarity is believed to be due to metabolic or immunologic idiosyncrasy. The presence of an imm unologic idiosyncrasy might imply an HLA association. Previous studies repo rting an HLA association of drug-induced hepatitis included only small numb ers of patients and used serological HLA typing. Methods: We studied 35 pat ients with biopsy-documented amoxicillin-clavulanate-induced hepatitis. HLA -A and -B were typed using alloantisera and compared with those of 300 cont rols (volunteer bone marrow donors). HLA-DRB and -DWB were typed by polymer ase chain reaction-line probe assay, with 60 volunteer bone marrow donors s erving as controls. Results: The study group was characterized by a higher frequency of DRB1*1501-DRB5*0101-DQB1*0602 haplotype (57.1% vs. 11.7% in co ntrols, P < 0.000005; after correction for the large number of comparisons, P < 0.0002). Patients with DRB1*1501-DRB5*0101-DQB1*0602 haplotype were mo re likely than patients without it to have a cholestatic (70% vs. 60%) or m ixed (30% vs. 13%) than a hepatocellular pattern of hepatitis (0% vs. 27%) (P < 0.05). Conclusions: Amoxicillin-clavulanate-induced hepatitis is assoc iated with the DRB1*1501-DRB5*0101-DQB1*0602 haplotype. The data support th e view that an immunologic idiosyncrasy, mediated through HLA class II anti gens, plays a role in the pathogenesis of drug-induced immunoallergic hepat itis. HLA association has a limited impact on the expression of hepatitis.