Characteristics of hepatitis B virus-associated hepatocellular carcinoma in children: A multi-center study

Introduction: Pediatricians and liver specialists in the United States and Canada continue to encounter hepatitis B virus (HBV) infection in high-risk populations, including unvaccinated children, adopted children, and immigrants. Although hepatocellular carcinoma (HCC) is a known complication of HBV, there exists a paucity of data regarding the clinical presentation of HBV-associated HCC in children in these countries. Methods: Investigators at 4 medical centers with large numbers of HBV-positive children queried their pathology and/or oncology databases to identify all cases of HBV-infected children <18 years old presenting with HCC between 1990 and 2015. Clinical data were extracted from chart review. Results: The group identified 8 patients, 8 to 17 years old, including 6 (75%) males. All individuals were assumed to be infected through vertical transmission. Three (38%) presented initially to the emergency room, 2 (25%) to a general pediatrician, 1 (13%) to a hepatologist, and the initial location was not documented in 2 (25%) cases. Three patients were asymptomatic, but the most common symptoms were abdominal pain (50%) and fatigue (38%). Hepatomegaly was present in 5 (63%) patients. Viral load was not documented in any patient. Only 3 patients had their HBeAg status documented and all individuals were HBeAg(-) and anti-HBe(+). Aspartate aminotransferase (AST) ranged from 13 to 575IU/L, and alanine aminotransferase (ALT) ranged from 14 to 212IU/L; 4 patients had AST and ALT < 1.5 times the upper limit of normal. Three patients had elevated bilirubin and gamma glutamyl transpeptidase (GGT), and 3 had normal bilirubin and GGT; 1 patient had unknown bilirubin and a separate patient had unknown GGT. Alpha-fetoprotein (AFP) was elevated in 3 patients (range 2.556-7.600ng/mL), normal in 2 patients, and not documented in 3 patients. Ultrasound was initially used to identify the tumor in 5 patients whereas computerized axial tomography scan was used in 3 patients. Six patients had multiple nodules on initial imaging. Conclusions: Although rare, HBV-associated HCC occurs in young children, often with normal liver enzymes, bilirubin, GGT, and AFP. Only routine imaging with ultrasound or computerized axial tomography scan consistently identified the tumor. These data may help inform screening for HCC including age of initiation and the role for imaging over laboratory testing.