High doses of aminoglycosides did not produce liver toxicity in patients with cystic fibrosis

Abstract

Liver disease is common in patients with cystic fibrosis, but the pathogenesis is poorly understood. The chronic colonization of bacteria in the lower airways leads to repeated treatments with antibiotics, especially aminoglycosides in high dosages. To investigate the possible role of aminoglycoside treatment in the natural history of liver disease in cystic fibrosis, five patients were studied for 3 years. Four of the patients received repeated courses of antibiotics, in two of the patients at the time of the liver biopsies. One patient did not receive any aminoglycosides. Light and electron microscopical morphometry was done on liver biopsy specimens. The contents of fat and lysosomes were quantified and expressed as volume density of liver cell volume (%). The amount of fat calculated in this way (13-35%) was highest in one patient who had not received any aminoglycosides. The two patients being treated with aminoglycosides at the time of the biopsy showed small amounts of fat in their liver cells (0.2-1.5%); similar values were noted in some patients who had not been treated for years. The lysosomes did not show the specific changes previously reported to occur in the kidney, nor did the morphometrical quantitation reveal any abnormalities which could be related to the administration of aminoglycosides. The present study did not find liver toxicity related to aminoglycosides in repeated high therapeutic dosages given to patients with cystic fibrosis.