Co-amoxiclav jaundice: clinical and histological features and HLA class IIassociation

Background and aims-Jaundice associated with co-amoxiclav has been increasi ngly recognised. We aimed to characterise its clinical and histological fea tures and to investigate linkage with human leucocyte antigen class II hapl otypes. Methods-We identified cases in the west of Scotland in the period 1991-1997 and performed polymerase chain reaction amplification and oligonucleotide probing on whole blood. Results-Twenty two cases were identified (10 male, mean age 59.1 years). Ja undice occurred a median of 17 days after drug commencement, with a median peak bilirubin level of 225 mu mol/1 (range 84-598) and median duration of jaundice 69 days (range 29-150). Two patients had primary biliary cirrhosis and two other patients had persistently abnormal liver biochemistry on fol low up. One death occurred in a frail elderly woman despite resolving jaund ice. The frequency of jaundice was 1 in 78 209 co-amoxiclav prescriptions. Liver biopsy, available in 12 patients, showed perivenular bilirubinostasis , accompanying reactive ceroid laden macrophages, and portal inflammation w ith focal injury to interlobular bile ducts. Fourteen of 20 patients had DR B1*1501 compared with 27 of 134 controls (p<2.5x10(-6); odds ratio (OR) 9.2 5; relative risk (RR) 6.43). Of these, seven patients were homozygous for D RB1*1501(p< 10(-8); OR 35.54; RR=8.68) compared with two of 134 controls. A ll patients with DRB1*1501 had the extended haplotype DRB1*1501-DRB5*0101-D QA1*0102-DQB1*0602. There were no clinical or histological differences betw een genotypes. Conclusions-Co-amoxiclav associated hepatotoxicity may have a genetic basis and be delayed, severe, and prolonged, although complete recovery is usual .