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. 2023 Jul 31;14:1213145. doi: 10.3389/fmicb.2023.1213145

Table 1.

Common mutations in HBV preS/S and preC/C.

Mutation Outcome References
PreS/S mutants
sW172stop (aa) Generates a stop codon in the HBsAg
Impairs secretion of HBsAg
Reduces viral fitness
Increases the risk of HCC
Sheldon and Soriano (2008), Yeh et al. (2011), Lai and Yeh (2008)
C3116T (nt) /T31C (aa) combo mutation The frequency of the single mutation is very low compared to the combo mutation
Promoting hepatocarcinogenesis by inducing ER stress, and STAT3 pathways
Increases the risk of HCC in patients without antiviral therapy
Liu W. et al. (2022)
A2962G (nt)
C2964A (nt)
Associated with an increased risk of HCC
Higher tumor cccDNA level
Also reported as A2962G/C2964A combo mutation
Wang et al. (2015)
T53C (aa) Associated with an increased risk of HCC Yin et al. (2010), Jiang et al. (2009), Sung et al. (2008)
C7A (aa) Increases risk of HCC Qu et al. (2014), Thi Cam Huong et al. (2022), Rivière et al. (2019)
C105T (aa) Higher tumor cccDNA levels Wang et al. (2015)
W4P/R (aa) This male-specific mutation is significantly related to HCC Thi Cam Huong et al. (2022), Caligiuri et al. (2016)
PreC/C mutants
G1896A (nt) *known as the most important mutation in HBV-related HCC
Prevents expression of HBeAg protein
Increases HCC tumor growth in vivo via enhancing HBV replication and activating the ERK/MAPK pathways
Strongly associated with HCC
Wei et al. (2017), Zhao et al. (2023)
C1766T (nt)
T1768A (nt)
Increases viral replication and viral infectivity
Associated with acute liver failure and CHB progression
C1766T/T1768A combo mutants were associated with higher HBV-DNA levels and increased liver disease
Liu Y. et al. (2022), Kitab et al. (2012), Dong et al. (2008)
A1762T (nt) or K130M (aa)
G1764A (nt) or V131I (aa)
Contributes to an inefficient immune response that leads to hepatocarcinogenesis
A1762T/G1764A mutants are associated with the increased HCC risk
Wei et al. (2017)
T1753V (nt) Increases risk of HCC
Associated with severe clinical outcome
Linked with enhanced viral replication and/or reduced HBeAg expression and related with acute liver failure in some instances
Kitab et al. (2012), Parekh et al. (2003)
C1914G (nt) Associated with HCC Asim et al. (2010)

(nt), for nucleotide change/name; (aa), for amino acid change/name.