Pharmacogenomics of drug-induced liver injury (DILI): Molecular biology to clinical applications

A 21-year old woman was admitted to hospital with a two-week history of painless jaundice, fatigue and anorexia having previously been fit and well. One month prior to presentation, the patient had taken a five-day course of amoxicillin-clavulanic acid for an infected skin cyst. Otherwise, she was only on the oral contraceptive pill and reported minimal alcohol intake. On examination, she was deeply jaundiced, but alert and oriented with no asterixis. She had no stigmata of chronic liver disease, but hepatomegaly extending 3 cm from below the right subcostal margin was evident. Investigations showed: white cell count 13.4 × 109/L (normal 3.6–9.3), haemoglobin 11.8 g/dl (normal 11–15), platelet count 356 × 109/L (normal 170–420), sodium 138 mmol/L (normal 134–144), potassium 3.5 mmol/L (normal 3.5–5.0), creatinine 32 µmol/L (normal 40–75), albumin 30 g/L (normal 35–48), alanine aminotransferase 707 IU/L (normal 15–54), alkaline phosphatase 151 IU/L (normal 30–130), bilirubin 384 µmol/L (normal 7–31) and prothrombin time 27.2 s (normal 11.7–14). Screening for hepatitis A, B, C, E, Epstein-Barr virus, cytomegalovirus and autoimmune hepatitis was negative. Tests for anti-smooth muscle, antinuclear, and anti-liver-kidney microsomal-1 antibodies were negative; immunoglobulin levels and ceruloplasmin levels were normal. Liver ultrasonography demonstrated a liver of normal contour with no biliary dilatation, a normal spleen size and patent vessels. Liver biopsy revealed severe portal interface hepatitis with lobular inflammation and scant plasma cells.