Abstract
INTRODUCTION: Hepatocellular carcinoma (HCC) remains the major challenge in the management of patients with hepatitis B virus (HBV) infection. To date, limited studies have been done on pediatric HBV-associated HCC specifically. METHODS: Pediatric patients younger than 16 years with HBV-associated HCC were included in the study. HBV integration detection was performed using a high-throughput viral integration detection (HIVID) method. RESULTS: Among the 13 included pediatric patients, boys predominated (10, 76.9%). The median age at diagnosis of HCC was 13 years and the youngest age was 6 years. Nine patients had initially seronegative hepatitis B e antigen (HBeAg) and 4 had seropositive HBeAg. All patients had cirrhosis and elevated alpha-fetoprotein. Splenomegaly was present in all patients. Intrahepatic HBsAg was not detected in any tumor tissues from 5 patients who underwent biopsy or excision, while it was positive in all matched non-tumor tissues. In the tumor and matched non-tumor tissues from 3 individuals, HBV integration was identified except in the neoplastic specimen from 1 patient. Integration into the reported genes associated with hepatocarcinogenesis was not found in the tumor tissues from the 3 patients. DISCUSSION: Hypervigilance for HCC development is required in HBeAg-negative cirrhotic children. The findings based on the immunohistochemical and genetic results expand the knowledge of pediatric HCC development.