Different age-modulated mutational processes affect HBV genome in Peruvian patients with Hepatocellular Carcinoma. HBV in HCC from Peru

In Peru, Hepatocellular carcinoma (HCC) is characterized by an unusual bimodal distribution for age with a first peak of incidence around 20-25 yo. Although, some hitherto unidentified risk factors are suspected to be involved in the patho-physiology of the disease, hepatitis B virus (HBV), found in almost 80% of cases, is known to play here a prominent role. We characterized HBV at the molecular level in 64 pairs of HCC and matching non-tumor liver tissues from Peruvian patients. All viral strains were belonging to F1b subtype, endemic to this region of South America. A striking feature was the extremely low viral loads observed both in tumor and non-tumor tissues a situation that challenges most observations considering high HBV loads as the key-risk factor for early HCC. The comparison of HBV DNA mutation spectra in young (n=34) and older (n=19) patients was performed on different region of HBV genome (PreS-S, HBx, HBe-HBc, ≈1500 nucleotides/isolate) and revealed significant differences., HBV DNA in young patients was displaying significantly higher rates of mutation at dypyrimidines (TT or CC). Oveall, them mutational signature as observed on HBV DNA was different in young and older patients. This situation suggests that liver tissue in young patients is the siege of a specific mutational process that contributes to virus restriction. Whether it is contributing or not in liver tumorigenesis is currently under investigation.