Abstract / Summary
Hepatitis B virus (HBV) infection remains a significant global public health concern. Data suggest that HBV genotypes/sub-genotypes and virulence-associated mutations can influence the natural history and treatment outcomes of HBV infection. However, the dearth of full-length HBV genome sequences in Kenya limits complete understanding of emerging variants and recombination events. Here, we sequenced and analyzed 165 HBV DNA whole-genome sequences from HBsAg-positive serum samples of voluntary blood donors across different geographic regions of Kenya between 2019 and 2023 to provide deeper insights into the virus’s genomic diversity, virulence-associated mutations, recombinations, and drug resistance profiles. Genomic analysis revealed a predominance of HBV genotype A in Kenya (77.0%), followed by genotype D (19.4%) and genotype E (3.6%) during the study period. Within genotype A, sub-genotype A1 predominated (99%), while A2 was a minority. Among genotype D, sub-genotype D7 was most common (97%), followed by D1 (3%). Recombination was detected in 4.2% of the sequenced isolates and involved genotype A/D, A/E, D/A, and D/E recombinant forms. None of the sequenced isolates harbored mutations linked to resistance to approved nucleos(t)ide analogues in the reverse transcriptase region of the polymerase gene. However, genetic variation associated with a higher risk of hepatocellular carcinoma (HCC), vaccine immune escape, and occult hepatitis B virus infection (OBI) were detected across genomic regions, including HCC-linked mutations G1896A in 81.3% (26/32; 95% CI: 63.6–92.8) of genotype D and 50% (3/6; 95% CI: 11.8–88.2) of genotype E isolates (FDR-adjusted p < 0.001); and G1899A in 17.0% (28/165; 95% CI: 11.6–23.6, FDR-adjusted p < 0.05) in the precore gene region of all isolates. Additionally, those present in the basal core promoter region included C1773T in 80.0% (132/165; 95% CI: 73.1–85.8, FDR-adjusted p < 0.001) and A1762T/G1764-double mutation in 29.1% (48/165; 95% CI: 22.3–36.7) of all isolates. Immune escape-linked amino acid variation within the “a” determinant of the major hydrophilic region (MHR) in the S gene region, included T131N in 99.2% (126/127; 95% CI: 95.7–100, FDR-adjusted p < 0.001) of genotype A and T126A/S in 16.7% (1/6; 95% CI, 0.4–64.1, FDR-adjusted p > 0.05) of genotype E isolates, while those related to occult-HBV infection (OBI) included P127H/L in 3.6% (6/165; 1.3–7.7, FDR-adjusted p < 0.001) of all isolates. Overall, our findings indicate that HBV genotype A (sub-genotype A1) predominates in Kenya, followed by genotypes D (sub-genotype D7) and E. Moreover, the detection of HBV variants harboring genetic markers associated with immune escape, occult hepatitis B (OBI), and liver disease complications highlights the need for public health countermeasures such as immunization of infants and scaling up of adult vaccination to reduce infections. Furthermore, wider integration of molecular real-time PCR testing into the national blood screening algorithm is advised to reduce the risk of horizontal transmission from asymptomatic HBV blood donors harboring occult HBV infection mutations and ensure the safety of blood and blood products.