title: Co-amoxiclav jaundice: clinical and histological features and HLA class II association.
abstract: OBJECTIVE
  Jaundice associated with co-amoxiclav has been increasingly recognised. We aimed to characterise its clinical and histological features and to investigate linkage with human leucocyte antigen class II haplotypes.
  
  
  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). Jaundice occurred a median of 17 days after drug commencement, with a median peak bilirubin level of 225 micromol/l (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 follow up. One death occurred in a frail elderly woman despite resolving jaundice. 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 with focal injury to interlobular bile ducts. Fourteen of 20 patients had DRB1*1501 compared with 27 of 134 controls (p<2.5 x 10(-6); odds ratio (OR) 9.25; relative risk (RR) 6.43). Of these, seven patients were homozygous for DRB1*1501(p< 10(-8); OR 35.54; RR=8.68) compared with two of 134 controls. All patients with DRB1*1501 had the extended haplotype DRB1*1501-DRB5*0101-DQA1*0102-DQB1*0602. There were no clinical or histological differences between genotypes.
  
  
  CONCLUSIONS
  Co-amoxiclav associated hepatotoxicity may have a genetic basis and be delayed, severe, and prolonged, although complete recovery is usual.
authors.affiliation: Department of Gastroenterology, Gartnavel General Hospital, Glasgow G12 0YN, UK. john.o'donahue@uhl.nhs.uk
authors.forename: J
authors.initials: J
authors.lastname: O'Donohue
authors.forename: K A
authors.initials: KA
authors.lastname: Oien
authors.forename: P
authors.initials: P
authors.lastname: Donaldson
authors.forename: J
authors.initials: J
authors.lastname: Underhill
authors.forename: M
authors.initials: M
authors.lastname: Clare
authors.forename: R N
authors.initials: RN
authors.lastname: MacSween
authors.forename: P R
authors.initials: PR
authors.lastname: Mills
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019980:Amoxicillin-Potassium Clavulanate Combination / Q000009:adverse effects*; D001663:Bilirubin / Q000097:blood; D001706:Biopsy; D016022:Case-Control Studies; D004359:Drug Therapy, Combination / Q000009:adverse effects*; D005260:Female; D006681:HLA-D Antigens / Q000276:immunology*; D006239:Haplotypes; D006801:Humans; D007565:Jaundice / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction
chemical_list: D006681:HLA-D Antigens; D015345:Oligonucleotide Probes; D019980:Amoxicillin-Potassium Clavulanate Combination; D001663:Bilirubin