title: Hepatic late adverse effects after antineoplastic treatment for childhood cancer.
abstract: BACKGROUND
  Survival rates have greatly improved as a result of more effective treatments for childhood cancer. Unfortunately the improved prognosis has resulted in the occurrence of late, treatment-related complications. Liver complications are common during and soon after treatment for childhood cancer. However, among long-term childhood cancer survivors the risk of hepatic late adverse effects is largely unknown. To make informed decisions about future cancer treatment and follow-up policies it is important to know the risk of, and associated risk factors for, hepatic late adverse effects.
  
  
  OBJECTIVE
  To evaluate the existing evidence on the association between antineoplastic treatment for childhood cancer and hepatic late adverse effects.
  
  
  METHODS
  We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, Issue 2), MEDLINE (1966 to June 2009) and EMBASE (1980 to June 2009). In addition, we searched reference lists of relevant articles and conference proceedings.
  
  
  METHODS
  All studies except case reports, case series and studies including less than 10 patients that examined the association between antineoplastic treatment for childhood cancer (aged 18 years or less at diagnosis) and hepatic late adverse effects (one year or more after the end of treatment).
  
  
  METHODS
  Two review authors independently performed the study selection, risk of bias assessment and data extraction.
  
  
  RESULTS
  We identified 20 cohort studies investigating hepatic late adverse effects after antineoplastic treatment for childhood cancer. All studies had methodological limitations. The prevalence of hepatic late adverse effects varied widely, between 0% and 84.2%. Selecting studies where the outcome of hepatic late adverse effects was well defined as alanine aminotransferase (ALT) above the upper limit of normal resulted in five studies. In this subgroup the prevalence of hepatic late adverse effects ranged from 8.0% to 52.8%, with follow-up durations varying from one to 27 years after the end of treatment. A more stringent selection process using the outcome definition of ALT as above twice the upper limit of normal resulted in three studies, with a prevalence ranging from 7.9% to 44.8%. Chronic viral hepatitis was identified as a risk factor for hepatic late adverse effects in univariate analyses. It is unclear which specific antineoplastic treatments increase the risk of hepatic late adverse effects
  
  
  CONCLUSIONS
  The prevalence of hepatic late adverse effects ranged from 7.9% to 52.8% when selecting studies with an adequate outcome definition. It has not been established which childhood cancer treatments result in hepatic late adverse effects. There is a suggestion that chronic viral hepatitis increases the risk of hepatic late adverse effects. More well-designed studies are needed to reliably evaluate the prevalence of, and risk factors for, hepatic late adverse effects after antineoplastic treatment for childhood cancer.
authors: Department of Paediatric Oncology, Emma Children's Hospital / Academic Medical Center, P.O. Box 22660, Amsterdam, Netherlands, 1100 DD.
authors: Renée L
authors: RL
authors: Mulder
authors: Elvira C
authors: EC
authors: van Dalen
authors: Malon
authors: M
authors: Van den Hof
authors: Dorine
authors: D
authors: Bresters
authors: Bart Gp
authors: BG
authors: Koot
authors: Sharon M
authors: SM
authors: Castellino
authors: Yoon
authors: Y
authors: Loke
authors: Edith
authors: E
authors: Leclercq
authors: Piet N
authors: PN
authors: Post
authors: Huib N
authors: HN
authors: Caron
authors: Aleida
authors: A
authors: Postma
authors: Leontien Cm
authors: LC
authors: Kremer
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000970:Antineoplastic Agents / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology*; D002648:Child; D015331:Cohort Studies; D006525:Hepatitis, Viral, Human / Q000150:complications; D006801:Humans; D008099:Liver / Q000187:drug effects; D009369:Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D000410:Alanine Transaminase