High-level mixed-type hyperbilirubinaemia due to rifampicin

Abstract

Rifampicin, a highly colephilic antibiotic, is rarely toxic: its toxicity has predominantly minor hepatic and immunological effects. A 42-year-old man was admitted to our institution because of hepatotoxicity as a result of anti-tuberculosis therapy. He complained of jaundice, nausea, vomiting, and fever. At first presentation, he exhibited the following: plasma unconjugated bilirubin, 5.1 mg/dl; conjugated bilirubin, 1.9 mg/dl; SGOT, 180 IU/l; SGPT, 472 IU/l; alkaline phosphatase, 222 IU/l; LDH, 1,656 U/l. He had no peripheral blood eosinophilia. No evidence for haemolytic anaemia or viral hepatitis was observed. Four days later, transaminases and bilirubin levels had returned to normal. Anti-tuberculosis therapy was restarted, but the patient became jaundiced after an episode of chills, fever (39.5°C), nausea and abdominal pain. Transaminases and alkaline phosphatase levels gradually continued to decrease, however, LDH and unconjugated and conjugated bilirubin levels increased to a maximum of; 1,240 U/l, 15.1 mg/dl and 5.5 mg/dl, respectively. Gamma-glutamyl transpeptidase level was stable during the course of these febrile episodes. There was no cholelithiasis or hepatic lesion on abdominal computerised tomography. Rifampicin was excluded, and the patient was treated with isoniazid, streptomycin, ethambutol, and morphozinamide. He was cured after 9 months of anti-tuberculosis therapy. Because it impairs uptake and excretion of bilirubin by hepatocytes, rifampicin can cause high-level mixed-type hyperbilirubinaemia in sensitised patients.