Identification of amino acid substitutions in the hepatitis C virus core region associated with the development of hepatocellular carcinoma in treatment-naive patients in Cameroon - a 10-year retrospective cross-sectional study

In Cameroon, infection with the hepatitis C virus (HCV) is a major factor in hepatocellular carcinoma (HCC). Cirrhotic patients, even when treated with direct-acting antivirals (DAAs), may still be at risk of developing HCC. The aim of this study was to identify mutations associated with the development of HCC in treatment-naive HCV-infected patients, in order to understand the molecular mechanisms involved in this local context. From 2013 to 2023. 1065 HCV-infected Cameroonian patients provided blood samples. Plasma, isolated and stored at -80 °C, was used to amplify the Core gene using specific primers. Nucleotide sequences obtained by Sanger sequencing were analyzed with IQ-Tree for phylogenetic studies. Sequences were edited and aligned using Mega and MAFFT, and mutation searches were performed manually using AliView software. Three genotypes (1, 2, 4) were identified, with genotype 4 predominating. Several mutations known to play an oncogenic role were detected: K10R (0.66 %), R70Q (10.52 %), T72E (80.56 %), K74R (82.82 %), G77A (70.53 %) and C/L91M (0.09 %). A hundred other mutations potentially linked to response to AADs were also observed. The analysis revealed mutations significantly related to sex and year, such as (K115R, N106S, T48A) with p-values of (0.0023; 0.0006), (0.0012; 0.0004) and (0.0045; 0.0058) respectively. This study provides the first comprehensive mapping of HCV core mutations in Cameroon, identifying variants potentially linked to HCC. Although limited by the lack of clinical follow-up, it underscores the urgency of monitoring these mutations in national HCV elimination programs, in line with the WHO's goals for 2030.