What are the risk factors for Hepatoblastoma (liver cancer)?

From the Guidelines

Hepatoblastoma is strongly associated with genetic syndromes, particularly overgrowth syndromes.

Risk Factors

• Genetic syndromes: such as Beckwith–Wiedemann syndrome (BWS), Simpson–Golabi–Behmel syndrome, and Sotos syndrome, which confer a high relative risk of developing hepatoblastoma, with BWS conferring a 2,280-fold relative risk 1
• Familial adenomatous polyposis (FAP): although the risk is elevated, it is presumed to be less than 1% for APC mutation carriers 1
• Constitutional trisomy 18: carries a risk of hepatoblastoma, along with other major anomalies 1
• Metabolic genetic syndromes: such as tyrosinemia type I, fumarylacetoacetate hydroxylase deficiency, and glycogen storage diseases, which lead to liver damage and cirrhosis, and may predispose to liver tumors, including hepatoblastoma 1

Surveillance and Screening

• Abdominal ultrasonography every 3 months until age 4 is recommended for children with BWS and other overgrowth syndromes to screen for hepatoblastoma and Wilms tumor 1
• Periodic measurement of serum alpha-fetoprotein (AFP) every 3 months may also be recommended in some centers 1

From the Research

Risk Factors for Hepatoblastoma

The risk factors for hepatoblastoma can be categorized into constitutional and environmental factors.

• Constitutional risk factors include:
  • Beckwith-Wiedemann Syndrome 2
  • Familial Adenomatous Polyposis 3, 2
  • Isolated hemihyperplasia syndrome 2
  • Adenomatous polyps of the colon 2
  • Hemochromatosis 2
  • Hereditary Tyrosinemia Type 1 2
  • a-1-antitrypsin deficiency 2
  • Porphyrias 2
  • Cirrhosis 2
  • Nonalcoholic steatosis 2
  • Primary sclerosing cholangitis 2
• Environmental risk factors include:
  • Hepatitis B virus (HBV) and C virus (HCV) 2
  • B1 aflatoxin (B1AF) 2
  • Ionizing radiation 2
  • Alcohol 2
  • Hormonal treatments 2
  • Occupational exposure to pesticides, solvents, vinyl chloride, and metals 2
  • Smoking 3, 2
  • Arsenic 2
  • Prematurity and very low birth weight 3, 2, 4
  • Trematodes 2

Birth Characteristics and Risk of Hepatoblastoma

Birth characteristics that increase the risk of hepatoblastoma include:

• Low birth weight (<1500g) 3, 4
• Very low birth weight (<1500g) 3, 4
• Preterm birth (<33 weeks) 4
• Small size for gestational age 4
• Multiple birth pregnancies 4

Prognostic Factors for Hepatoblastoma

Prognostic factors for hepatoblastoma include:

• Advanced PRETEXT group 5
• Macrovascular venous or portal involvement 5
• Contiguous extrahepatic disease 5
• Primary tumor multifocality 5, 6
• Tumor rupture at enrollment 5
• Higher age (≥ 8 years) 5
• Low AFP (<100 ng/ml) 5, 6
• Metastatic disease 5, 6
• Vascular involvement 6
• Distant metastasis 6
• Platelet count > 400 × 10^9/L 6