The clinical significance of nucleotide G1613A and C1653T mutations in the core promoter region of hepatitis B virus / 解放军医学杂志

ABSTRACT

Objective To evaluate the impact of hepatitis B virus (HBV) genome G1613A and C1653T mutations on disease progression, viral replication capacity, and transcription activity of HBV core promoter (CP). Methods A total of 258 patients were enrolled in the present study, including 65 patients with acute hepatitis B (AHB), 120 with chronic hepatitis B (CHB), and 73 with acute on chronic liver failure (ACLF). Serum HBV DNA was extracted from patients, and full-length HBV genome was amplified by PCR. The incidences of G1613A, C1653T and G1613A+C1653T in different groups were compared, and through functional experiments, the impact of mutants and wild-type virus on viral replication capacity and CP transcription activity was assessed. Results Genotype B, C and D were the three detected genotypes in 285 patients, with detection rates of 22.2%, 76.2% and 1.6%, respectively. The incidences of G1613A, C1653T and G1613A+C1653T mutations increased with the disease exacerbation, and they were 13.70%, 31.80% and 45.20% in AHB patients (P<0.01), 2.30%, 16.30% and 27.40% in CHB patients (P<0.01), and 2.29%, 12.07% and 23.29% in ACLF patients (P<0.05). Compare with wild-type strain, the G1613A mutant strain of HBV increased the viral replication capacity by 6%, reduced HBsAg level and core promoter activity by 15% and 16.2%, and reduced HBeAg to undetectable level; the C1653T mutant strain increased the viral replication capacity, HBsAg level, and core promoter activity by 10%, 55% and 17.1%, respectively, and the HBeAg level was comparable to that of wild-type strain; the G1613A+C1653T mutant strain increased viral replication capacity, HBsAg level and HBeAg level by 7%, 66% and 227%, respectively, while it had no influence on core promoter activity. Conclusion The G1613A and C1653T mutation in CP region may increase HBV replication capacity and alter CP activity and HBV antigens expression, the doublet mutation of G1613A+C1653T shows synergic effect on these changes, suggesting these mutations are associated with liver disease progression.