Enrichment in selected genotypes, basal core and precore mutations of hepatitis B virus in patients with hepatocellular carcinoma in Cameroon

Worldwide, the development of hepatocellular carcinoma (HCC) is known to be influenced by several hepatitis B viral factors. However, the effect of hepatitis B virus (HBV) genotypes and a landscape of nucleotide changes affecting the precore (PC) and basal core promoter (BCP) during infection leading to HCC remain largely unknown in the Central Africa region. Thus, we performed a case-control study on patients with HBV-related HCC and matched controls without HCC but with chronic HBV infection. Genotypes and mutation spectrums were evaluated using a hemi-nested amplification and sequencing analysis focused on the BCP and PC regions. We identified the co-circulation of HBV quasi-subgenotype A3 (QS-A3) and genotype E in both groups. Interestingly, HBV-QS-A3 was significantly more prevalent in patients with HCC (80.0%) than in controls (31.9%, P = 4.5 E-7, OR = 11.5, 95% CI: 3.8-38.5). HBV mutation spectra and nucleotide changes were significantly more polymorphic in patients with HCC. Remarkably, HCC patients infected with HBV-QS-A3 were significantly more mutated compared to patients infected with genotype E (P < 0.0001). In addition, G:C>T:A transversions, generally associated with aflatoxin B1 exposure in tropical regions, were significantly more prevalent in HCC patients infected either with HBV-QS-A3 or HBV genotype E (P = 2.2 E-05) when compared to controls. In conclusion, our results indicate that patients infected with HBV-QS-A3 are at increased risk to develop HCC. In addition, viral genomes isolated for patients with tumour are more heavily altered than those found in controls. Preferential targeting of these patients for antiviral treatment is of paramount importance to reduce future HCC incidence in Cameroon.