Incidence and Sequelae of Liver Injury Among Children Treated for Solid Tumors: Analysis of a Large Single-Center Prospective Cohort.

Objectives: Pediatric oncology patients are at risk of adverse drug events. The incidence and etiologies of liver injury in this population are not well characterized. We utilized a large, single-center pediatric oncology registry to investigate the incidence, causes, and outcomes of liver injury during treatment for solid tumor malignancies.

Methods: We reviewed all young individuals (age <25 years) who received treatment for any solid tumor at the University of Michigan between January 2004 and July 2016. Subjects with liver injury meeting predetermined laboratory criteria were identified. Cases were independently reviewed by 2 expert hepatologists to assign a cause of liver injury. Clinical characteristics of drug-induced liver injury (DILI) and non-DILI cases were compared. Cases of liver injury occurring after bone marrow or liver transplant were excluded.

Results: Of 1136 solid tumor patients, 160 (14%) experienced liver injury, and the overall frequency of DILI was 4%. DILI was the leading identified cause of liver injury (31%), followed by infection (17%), metastatic/malignant biliary disease (13%), and perioperative liver injury (13%). Most DILI cases (>90%) were mild acute hepatocellular injury episodes that did not result in modification to the chemotherapy plan, and all DILI eventually resolved. Severe presentations involving jaundice and/or prolonged hospital course were significantly more common among non-DILI versus DILI cases (23% vs 2%, P < 0.001).

Conclusions: DILI is the leading cause of liver injury events among pediatric solid tumor patients. In our registry, DILI was of mild severity and did not result in an alteration of the treatment plan in most patients. In contrast, non-DILI-related liver injury events, including infection, were more likely to have a more severe presentation and a complicated course with a greater mortality during follow-up.