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


CONCLUSIONS
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.
Department of Pediatric Oncology, Emma Children's Hospital/Academic Medical Center, Amsterdam, The Netherlands. r.l.mulder@amc.uva.nl
Renée L
RL
Mulder
Leontien C M
LC
Kremer
Bart G P
BG
Koot
Marc A
MA
Benninga
Sebastiaan L
SL
Knijnenburg
Helena J H
HJ
van der Pal
Caro C E
CC
Koning
Foppe
F
Oldenburger
James C H
JC
Wilde
Jan A J M
JA
Taminiau
Huib N
HN
Caron
Elvira C
EC
van Dalen
D000293:Adolescent; D000328:Adult; D000410:Alanine Transaminase / Q000032:analysis; D000970:Antineoplastic Agents / Q000009:adverse effects; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008107:Liver Diseases / Q000453:epidemiology* / Q000209:etiology*; D008297:Male; D009369:Neoplasms / Q000628:therapy*; D015995:Prevalence; D012307:Risk Factors; D017741:Survivors / Q000706:statistics & numerical data*; D005723:gamma-Glutamyltransferase / Q000032:analysis
D000970:Antineoplastic Agents; D005723:gamma-Glutamyltransferase; D000410:Alanine Transaminase