Treatment-related late effects on the liver in survivors of childhood cancer

Advances in the treatment of childhood cancer over the last decades have greatly improved the survival rates. Unfortunately, the improved prognosis has been accompanied by the occurrence of late, treatment-related complications. One of the adverse effects that can occur due to treatment of childhood cancer is damage to the liver. Hepatic adverse effects are common both during and soon after treatment. However, the evidence on adverse effects in the liver many years after treatment is still inconclusive. Liver injury as a result of childhood cancer treatment is most often subclinical (asymptomatic). If liver disease becomes symptomatic, a person's complaints may include fatigue, jaundice, nausea, weight loss and abdominal pain. The development of future treatment and follow-up policies should be based on high quality evidence on the risk of, and associated risk factors for, hepatic late adverse effects.

In this systematic review, 20 cohort studies examining hepatic late adverse effects after antineoplastic treatment for childhood cancer were included. The authors found that 8% to 53% of the childhood cancer survivors developed hepatic late adverse effects after their treatment. It is unclear which childhood cancer treatments increase the risk of hepatic late adverse effects. Childhood cancer survivors with chronic viral hepatitis seemed to have an increased risk of hepatic late adverse effects. The quality of the evidence was however limited. Therefore, more high quality research is needed.

Authors' 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.

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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.

Objectives: 

To evaluate the existing evidence on the association between antineoplastic treatment for childhood cancer and hepatic late adverse effects.

Search strategy: 

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.

Selection criteria: 

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).

Data collection and analysis: 

Two review authors independently performed the study selection, risk of bias assessment and data extraction.

Main 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

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