Clinical and virological implications of A1846T and C1913A/G mutations of hepatitis B virus genome in severe liver diseases

Abstract

Objective: Mutations occurring within different genes of hepatitis B virus (HBV) genome may have different clinical implications. This study aimed to observe the clinical and virological implications of the A1846T and C1913A/G mutations of HBV genome in the development and treatment outcome of severe liver diseases, which has not been previously determined.

Materials and methods: A total of 438 cases of patients with liver diseases were retrospectively reviewed, including 146 with mild chronic hepatitis B infection (CHB-M), 146 with severe chronic hepatitis B infection (CHB-S), and 146 with acute-on-chronic liver failure (ACLF). Partial or full-length HBV genome was directly sequenced. Replicons containing A1846T, C1913A or other mutant sequences, or the wild-type counterparts were constructed respectively, and then transfected into HepG2 cells for phenotype analysis.

Results: There was significant difference in the detection rates of A1846T (30.82%, 40.41% and 55.48%, respectively) and C1913A/G (15.52%, 28.77%, and 35.62%, respectively) among patients with CHB-M, those with CHB-S, and those with ACLF (p < .01). A1846T was significantly associated with the mortality of ACLF patients within six months after the disease onset (OR 1.704, p = .041). In vitro experiment revealed that A1846T mutant resulted in 3.20-fold and 1.85-fold increase of replication capacity and promoter activity, respectively compared with wild type counterpart (p < .001), while C1913A led to a significant decrease of core protein expression (p < .05).

Conclusion: Occurrence of A1846T and C1913A is positively associated with clinical presentations of severe liver disease. A1846T mutation is significantly associated with poor prognosis of ACLF.

Keywords:

• Hepatitis B virus
• genome
• mutation
• acute-on-chronic liver failure
• A1846T
• C1913A

Acknowledgments

We are grateful to Jiuzeng Dai and Zengtao Yao for their help in HBV genomic sequencing work.

Disclosure statement

The authors report no conflicts of interest.

Additional information

Funding

This study was supported by grants from the National Thirteenth Five-Year Special Grand Project for Infectious Diseases [No. 2017ZX10302201-001, DX; 2007ZX10203201-004, SX], and the National Natural Science Foundation of China [No. 81572010, DX].