Surveillance of hepatic late adverse effects in a large cohort of long-term survivors of childhood cancer: prevalence and risk factors

Eur J Cancer. 2013 Jan;49(1):185-93. doi: 10.1016/j.ejca.2012.07.009. Epub 2012 Aug 15.

Abstract

Background: Childhood cancer survivors (CCS) are a growing group of young individuals with a high risk of morbidity and mortality. We evaluated the prevalence and risk factors of hepatic late adverse effects, defined as elevated liver enzymes, in a large cohort of CCS.

Methods: The cohort consisted of all five-year CCS treated in the EKZ/AMC between 1966 and 2003, without hepatitis virus infection and history of veno-occlusive disease (VOD). Liver enzyme tests included serum levels of alanine aminotransferase (ALT) for hepatocellular injury and gamma-glutamyltransferase (γGT) for biliary tract injury. We performed multivariable linear and logistic regression analyses.

Results: The study population consisted of 1404 of 1795 eligible CCS, of whom 1362 performed liver enzyme tests at a median follow-up of 12 years after diagnosis. In total, 118 (8.7%) of 1362 CCS had hepatic late adverse effects defined as ALT or γGT above the upper limit of normal. Abnormal ALT and γGT levels were found in 5.8% and 5.3%, respectively. In multivariable regression analyses treatment with radiotherapy involving the liver, higher body mass index, higher alcohol intake and longer follow-up time were significantly associated with elevated ALT and γGT levels; older age at diagnosis was only significantly associated with elevated γGT levels (all p<0.05).

Conclusion: One in twelve CCS showed signs of hepatic late adverse effects after a median follow-up of 12 years. Several risk factors have been identified. Future studies should focus on the course of long-term liver related outcomes and on the influence of radiotherapy and chemotherapy dose.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alanine Transaminase / analysis
  • Antineoplastic Agents / adverse effects
  • Bone Marrow Transplantation / adverse effects
  • Child
  • Child, Preschool
  • Cohort Studies
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Liver Diseases / epidemiology*
  • Liver Diseases / etiology*
  • Male
  • Neoplasms / therapy*
  • Prevalence
  • Risk Factors
  • Survivors / statistics & numerical data*
  • gamma-Glutamyltransferase / analysis

Substances

  • Antineoplastic Agents
  • gamma-Glutamyltransferase
  • Alanine Transaminase