Chemotherapy induced liver toxicity in children with malignant diseases

A broad spectrum of chemotherapy is being used in the therapy of childhood cancers, which may induce liver injury, impairing quality of life and efficacy of the treatment. History of, especially viral, liver diseases may increase toxicity. The aim of the paper is to assess the incidence, type and grade, predisposing factors and treatment options of drug-induced liver injury in children with malignant diseases under cytostatic therapy at the Hemato-Oncology Department of the Pediatric Clinic 2 from Targu-Mures, over a time period spanning from 2012 to 2017. The results of the study may serve as a foundation for such treatment strategies which would enable optimal outcomes with fewer cases of liver toxicity.

During this period, we treated 26 patients with acute lymphoblastic leukemia (ALL), two patients with acute myeloblastic leukemia (AML), one patient with lymphoma and seven with solid tumors. We found liver toxicity in 77% of the patients treated for ALL, mainly during the maintenance therapy (65%) with oral 6-mercaptopurine and methotrexate. The most common clinical signs were anorexia, nausea, vomiting, abdominal pain and faltering weight gain. Cholestasis developed in two patients, while hepatocytolysis was the most common observed event (n = 24). Liver fibrosis, hypersplenism, portal hypertension and esophageal varices were found in two patients. One patient required endoscopic ligation of esophageal varices. Elevation of serum bilirubin appeared in two patients, while hypoproteinemia was observed in nine patients. None of the patients developed acute liver failure. We treated liver toxicity with hydration, alkalinization, i.v. Aspatofort, Aminosteril-N Hepa 8%, oral acetylcysteine, silymarin, ursodeoxycholic acid, Liv-52, Sargenor, and Essentiale forte.

We found hepatotoxicity in 77% of the ALL patients undergoing chemotherapy, similar results have been published by other authors.

Hepatotoxicity may develop through direct hepatic effects of cytostatics, or a preexisting liver disease impairs the metabolism and excretion of the drug, increasing its toxic effects. In our patients hepatotoxicity can be explained mainly by direct liver-injury, previous infections with hepatotropic viruses, such as cytomegalovirus, were detected only in three patients.

Liver injury appeared in 77% of our ALL patients; 65% occurred during maintenance therapy with oral 6-mercaptopurine and methotrexate. Close followup of liver function during chemotherapy is mandatory for optimal results.