Review on hepatitis B virus precore/core promoter mutations and their correlation with genotypes and liver disease severity

Table 1 Qualitative and quantitative factors and the level of each factor associated with hepatitis B virus-related hepatocellular carcinoma

Patient group	Qualitative factors	Quantitative factors
Low risk	Genotype A/B	Low level of HBV-DNA in serum; low level of HBsAg in serum
High risk	Genotype C/D; BCP mutation (A1762T/G1764A); pre-S deletion	High level of HBV-DNA in serum; high level of HBsAg in serum

HBV: Hepatitis B virus; BCP: Basal core promoter; HBsAg: Hepatitis B surface antigen.

Table 2 Prevalent basal core promoter mutations and their clinical importance

Nucleotide position	Clinical applicability
A1762T + G1764A (BCP double mutant)	Chronic hepatitis; FH; decline in HBeAg formation and enhanced virus replication; high ALT; found in patients with HBV genotypes who have 1858C (i.e., genotype C)
A1762T	HBeAg seroconversion; histological inflammation
A1764A	Marginally decline in replication ability of the virus
1653T	Jointly with 1762T + 1764A in FH and HCC patients
1753-1757	Jointly with the 1762T + 1764A mutation in FH and HCC patients; ALT level changes and histological changes
1764A/T + 1766A/G	Jointly with 1810T + 1811T double mutation in active and inactive disease; 1762A1766A mutation, jointly with 1762T mutation, was observed in FH and HCC patients; 1764T + 1766G mutation was observed in a patient with recurrent FH after liver transplantation, although was not observed in FH patients
1766T + 1768A	FH; along with A1762T + G1764A, in recurrent hepatitis patients following liver transplantation; jointly with G1764A in HBeAg-negative asymptomatic carrier; exacerbation of HBV infection

ALT: Alanine aminotransferase; BCP: Basal core promoter; FH: Fulminant hepatitis; HBeAg: Hepatitis B e antigen; HBV: Hepatitis B virus; HCC: Hepatocellular carcinoma.

Table 3 Various precore/core promoter mutations and their clinical outcomes

Mutation type	Clinical symptoms	Particular mutation
PC/CP mutations	HBeAg-negative. Hepatitis	T1753C[52], A1762T[82], G1764A[82], C1766T[52], T1768A[52], G1896A[59,83], G1899A[59,83]
	HCC	C1653T[63], T1753C[63], A1762T[63,65,84], G1764A[63,65,84], G1896A[63], G1899A[63]
	Fulminant hepatitis	A1762T[85], G1764A[85], G1862T[71,85], G1896A[85]

PC: Precore; CP: Core promoter; HBeAg: Hepatitis B e antigen; HCC: Hepatocellular carcinoma.