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Childhood Liver Cancer Treatment (PDQ®): Treatment - Health Professional Information [NCI] - General Information

Table 1. Risk Factors Associated With Hepatoblastoma and Hepatocellular Carcinoma continued...

In the absence of APC germline mutations, childhood hepatoblastomas do not have somatic mutations in the APC gene; however, they frequently have mutations in the beta-catenin gene, the function of which is closely related to APC.[40]

Hepatitis B and hepatitis C infection

Hepatocellular carcinoma is associated with hepatitis B and hepatitis C infection in adults,[23,24,25] while in children there is an association with perinatally acquired hepatitis B virus. Widespread hepatitis B immunization has decreased the incidence of hepatocellular carcinoma in Asia.[9] Compared with adults, the incubation period from hepatitis virus infection to the genesis of hepatocellular carcinoma is extremely short in a small subset of children with perinatally acquired virus. Mutations in the met/hepatocyte growth factor receptor gene occur in childhood hepatocellular carcinoma, and this could be one mechanism that results in a shortened incubation period. Hepatitis C infection is associated with development of cirrhosis and hepatocellular carcinoma that takes decades to develop and is generally not seen in children.[41]

Several specific types of nonviral liver injury and cirrhosis are associated with hepatocellular carcinoma in children, including tyrosinemia and biliary cirrhosis. Tyrosinemia patients should be screened for hepatocellular carcinoma on a regular basis, whether or not they are treated with 2-(2 nitro-4-3 trifluoro-methylbenzoyl)-1, 3-cyclohexanedione.[30] Hepatocellular carcinoma may also arise in very young children with mutations in the bile salt export pump ABCB11, which causes progressive familial hepatic cholestasis.[27] Despite these findings, cirrhosis in children, compared with cirrhosis in adults, is much less commonly involved in the development of hepatocellular carcinoma, and is found in only 20% to 35% of livers bearing childhood hepatocellular carcinoma tumors.


A biopsy of the tumor is always indicated to secure the diagnosis of a liver tumor except:

  • In infants with hepatic hemangiomas or hemangioendotheliomas that can be diagnosed by imaging.
  • In infantile hepatic choriocarcinoma, which can be diagnosed by imaging and markedly elevated beta-human chorionic gonadotropin (beta-hCG).[42]

The AFP and beta-hCG tumor markers are very helpful in diagnosis and management of liver tumors. Although AFP is elevated in most children with hepatic malignancy, it is not pathognomonic for a malignant liver tumor.[43] The AFP level can be elevated due to a benign tumor, as well as a malignant solid tumor. AFP is very high in neonates and steadily falls after birth. The half-life of AFP is 5 to 7 days, and by age 1 year, it should be less than 10 ng/ml.[44]

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