HLA-A33/B44/DR6 is highly related to intrahepatic cholestasis induced by tiopronin.
In order to elucidate the immunogenetic predisposition of tiopronin (mercaptopropionylglycine)-induced intrahepatic cholestasis, human leukocyte antigen (HLA) was analyzed in patients with tiopronin-induced liver injury. HLA-A, -B, -C, and -DR loci of 14 patients (10 males and 4 females) with tiopronin-induced liver injury were compared with those of control subjects. The mean duration of tiopronin administration was 26 days and that of jaundice was 4.5 months. The elevation of biliary enzymes lasted from 2 months to up to 10 years. Most of the cases manifested intrahepatic cholestasis on liver biopsy. Lymphocyte transformation test with tiopronin was positive in 6 of 8 (75%) tested cases. Thirteen patients (92.9%) had HLA-A33, 10 (71.4%) had B44, and 9 (64.3%) patients had DR6. These are statistically higher in the patients with tiopronin-induced cholestasis than in the general population. Ten of those with tiopronin-induced liver dysfunction (71.4%) had A33/B44 and 8 (57.1%) had A33/B44/DR6 in their haplotype. In conclusion, long-lasting tiopronin-induced intrahepatic-cholestasis is highly linked to specific HLA-A33, -B44 and -DR6.
Kurosaki
M
M
First Department of Internal Medicine, Gunma University, School of Medicine, Maebashi, Japan.
Takagi
H
H
Mori
M
M
D000328:Adult; D000368:Aged; D002780:Cholestasis, Intrahepatic / Q000139:chemically induced* / Q000276:immunology* / Q000473:pathology; D005260:Female; D015234:HLA-A Antigens / Q000032:analysis*; D015235:HLA-B Antigens / Q000032:analysis*; D059948:HLA-B44 Antigen; D015808:HLA-DR6 Antigen / Q000032:analysis*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008625:Tiopronin / Q000009:adverse effects*
D015234:HLA-A Antigens; C082945:HLA-A*33 antigen; D015235:HLA-B Antigens; D059948:HLA-B44 Antigen; D015808:HLA-DR6 Antigen; D008625:Tiopronin