Treatment for childhood cancer is commonly associated with acute and often reversible hepatotoxicity.
Long-term hepatic effects following chemotherapy alone are uncommon, but there is little follow-up on long-term liver health in survivors of adult or childhood cancer.
Acute or subacute hepato-biliary injury is seen after:
- Radiation therapy (RT)
- Hematopoietic stem cell transplantation (HSCT)
- Graft-versus-host-disease (GVHD)
- Supportive care measures:
- Transfusion-acquired hepatitis
- Transfusion associated iron overload
- Cholestatic disease from total parenteral nutrition (TPN)
Acute liver injury related to cancer therapy has varying pathophysiology including:
- Hepatocellular necrosis
- ductal injury
Histological ﬁndings include periportal and concentric ﬁbrosis and injury to sinusoidal endothelial cells
Chronic or delayed liver injury following childhood cancer is from hepatic ﬁbrosis secondary to :
- inﬂammation from chronic viral hepatitis
- drug-induced injury
- fatty inﬁltration
Chronic GVHD involving the liver after HSCT is associated with:
- Hepatocellular necroinﬂammatory changes
- Paucity of interlobular bile ducts
- Intrahepatic cholestasis
Progressive ﬁbrosis increases the risk of cirrhosis, portal hypertension, and hepatocellular carcinoma.
The Childhood Cancer Survivor Study (US study of 14,358 CCS diagnosed between 1970 and 1986) assessed rates of self-reported late GI complications (occurring 5 or more years after cancer diagnosis).
Compared with their siblings, survivors had increased relative risk of late-onset complications of:
- Gallbladder disease (RR, 2.0)
- Requiring liver biopsy (RR, 24.1)
- Developing cirrhosis (RR, 8.9)
They found that older age at diagnosis, increasing alkylating agent exposure, the use of anthracyclines, abdominal surgery and TBI were all independent risk factors for liver conditions.
Normal liver anatomy and function:
The liver is an essential organ which has many important functions:
- Detoxification of drugs
- Synthesis of:
- Production of biochemicals necessary for digestion
- Coagulation proteins
- Cholesterol and primary bile acids Conjugation of bilirubin
- Storage of fat soluble vitamins
- Hepatocytes responsible for gluconeogenesis and glycolysis
Liver function tests measure a number of liver enzymes. Elevated enzymes are associated with liver inflammation.