The incidence of hepatocellular carcinoma in the United States is 0.8 in children between the ages of 0 and 14 years and 1.5 in adolescents aged 15 to 19 years per year per 1 million. In several Asian countries, the incidence of hepatocellular carcinoma in children is 10 times more than that in North America. The high incidence appears to be related to the incidence of perinatally acquired hepatitis B, which can be prevented in most cases by vaccination and administration of hepatitis B immune globulin to the newborn.
The overall 5-year survival rate for children with hepatoblastoma is 70%,[10,11,12] but is only 42% for those with hepatocellular carcinoma. The 5-year survival for hepatocellular carcinoma may be dependent on stage; in an Intergroup chemotherapy study conducted in the 1990s, seven of eight stage I patients survived and less than 10% of stage III and IV patients survived.[3,13]
Risk factors associated with hepatoblastoma and hepatocellular carcinoma are described in Table 1.
Table 1. Risk Factors Associated With Hepatoblastoma and Hepatocellular Carcinoma
|Associated Disorder||Hepatoblastoma||Hepatocellular Carcinoma|
|Alagille syndrome|| ||X|
|Familial adenomatous polyposis[17,18,19]||X|| |
|Glycogen storage diseases I–IV||X||X|
|Hepatitis B and C[21,22,23]|| ||X|
|Low-birth-weight infants[5,6,7]||X|| |
|Progressive familial intrahepatic cholestasis[24,25]|| ||X|
|Trisomy 18, other trisomies||X|| |
Beckwith-Wiedemann syndrome and hemihyperplasia
The incidence of hepatoblastoma is increased 1,000-fold to 10,000-fold in infants and children with Beckwith-Wiedemann syndrome.[15,16] Hepatoblastoma is also increased in hemihypertrophy, now termed hemihyperplasia, a condition that results in asymmetry between the right and left side of the body when a body part grows faster than normal.[28,29]
Beckwith-Wiedemann syndrome can be caused by genetic mutations and be familial, or much more commonly, by epigenetic changes and be sporadic. Either mechanism can be associated with an increased incidence of embryonal tumors, including Wilms tumor and hepatoblastoma. The gene dosage and ensuing increased expression of insulin-like growth factor 2 (IGF-2) has been implicated in the macrosomia and embryonal tumors in Beckwith-Wiedemann syndrome.[16,30] When sporadic, the types of embryonal tumors associated with Beckwith-Wiedemann syndrome have frequently also undergone somatic changes in the Beckwith-Wiedemann syndrome locus and IGF-2.[31,32] The genetics of tumors in children with hemihyperplasia have not been clearly defined.
All children with Beckwith-Wiedemann syndrome or isolated hemihyperplasia should be screened regularly by ultrasound to detect abdominal malignancies at an early stage. Screening using alpha-fetoprotein (AFP) levels, in addition to abdominal ultrasound, has helped in the early detection of hepatoblastoma in children with Beckwith-Wiedemann syndrome or hemihyperplasia. Other somatic overgrowth syndromes, such as Simpson-Golabi-Behmel syndrome, may also be associated with hepatoblastoma.