Hepatitis B virus infecting Peruvian patients with hepatocellular carcinoma

In Peru, Hepatocellular carcinoma (HCC) is characterized by an unusual bimodal distribution for age and the absence of fibrotic/cirrhotic process in the liver. The main etiological factor in Peruvians with HCC is chronic infection with Hepatitis B virus (HBV). We decided to explore HBV genomes present in 65 younger and older Peruvian patients with HCC, with half of them positive for HBV surface antigen. All HBV strains isolated from Peruvians patients with HCC (n=50) were belonging to sub-genotype F1b. We observed very low viral loads both in tumor and non-tumor liver tissues, with only a fraction of the cells potentially bearing a copy of HBV genome (median value: 1-1.5 copy of HBV for 100 cells). HBV DNA was more abundant in young patients than in elder ones and in non-tumor livers (NTL) than in tumor parts. Viral DNA isolated from young patients was significantly less mutated than isolates from older patients but presented changes affecting monotonous dipyrimidines (TpT or CpC). Microfluidic analysis of gene expression (n=120) on 40 pairs of tumors and NTL revealed drastic differences in DNA repair pathway gene expression between young and older patients. Considering the young age of many patients, our observations are at odds with the common vision that associates high HBV loads and faster tumor development. We consider that in Peru, HBV-associated liver tumorigenesis differs significantly from that generally observed in the rest of the world.