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

Renée L. Mulder, Leontien C.M. Kremer, Bart G.P. Koot, Marc A. Benninga, Sebastiaan L. Knijnenburg, Helena J.H. Van Der Pal, Caro C.E. Koning, Foppe Oldenburger, James C.H. Wilde, Jan A.J.M. Taminiau, Huib N. Caron, Elvira C. Van Dalen

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22 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)185-193
Number of pages9
JournalEuropean Journal of Cancer
Issue number1
Publication statusPublished - Jan 2013
Externally publishedYes


  • Childhood cancer survivors
  • Hepatic late adverse effects
  • Prevalence
  • Risk factors


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