Mechanistic Pathways Linking Chronic Hepatitis B Infection to Hepatocellular Carcinoma in Nigerian Patients: A Molecular Epidemiological Contribution

Nigeria has one of the highest hepatitis B surface antigen prevalence rates globally, yet the molecular mechanisms linking chronic HBV infection to hepatocellular carcinoma in Nigerian patients, including the relative contributions of viral integration, HBx-mediated epigenetic silencing, and aflatoxin B1 co-mutagenesis, are poorly characterised at the genomic level. This study investigates the mechanistic pathways linking chronic HBV infection to hepatocellular carcinoma in a Nigerian molecular epidemiological study using surgical and biopsy-derived tumour specimens from six teaching hospitals across four geopolitical zones. The study recruits 180 HCC cases (140 HBV-positive, 40 HBV-negative controls) and collects matched tumour and non-tumour liver tissue. HBV genotyping is performed using Sanger sequencing of the S gene. Whole-exome sequencing of tumour DNA identifies somatic mutation profiles. HBX gene expression and promoter methylation analysis identifies epigenetic silencing signatures. Aflatoxin B1-specific TP53 codon 249 mutations are detected by allele-specific PCR. Unsupervised hierarchical clustering in R integrates multi-omic data to define molecular subtypes. The Cancer Hallmarks Theory and Viral Oncogenesis Framework provide the theoretical basis. The study makes an original molecular epidemiological contribution by characterising the dominant oncogenic pathway in Nigerian HBV-associated HCC, informing surveillance and targeted therapy strategies. Findings will support the Federal Ministry of Health hepatocellular carcinoma early detection policy. Keywords: hepatocellular carcinoma, hepatitis B, molecular epidemiology, TP53 mutation, Nigeria.