Precore/core mutation relatedness to viral reactivation in patients undergoing targeted therapy for hepatitis B virus-related hepatocellular carcinoma

Table 2 A summary of the identified and published hepatitis B virus mutations

Mutation	Effect	Mechanism
G1896A in precore	Affects early prognosis and severity of HCC	The study compared results between ultra-deep pyrosequencing and cloning based sequencing using HBeAg-positive and negative sera infected, with either genotype D or E
A1762T/G1764A double mutation	HBcAg mutations might increase the risk for HCC; affect early prognosis and severity of HCC; a factor that independently predicts worse survival rates after surgery	When combined with HBx mutants, they upregulate SKP2, which then down-regulates the cyclin kinase inhibitor p21 via ubiquitin-mediated proteasomal degradation. Eventually mRNA precore inhibition; upregulation of pgRNA transcription, and ultimately HCC
A1762T; 1753-1757 jointly with A1762T/G1764A; 1766T jointly with 1768A	HBeAg seroconversion, liver inflammation; FH, HCC, ALT; FH	-
1766T and 1768A; jointly with A1762T/G1764A	Recurrent hepatitis B post liver transplantation	-
T127P, P153 L, and F170S	In hemodialysis patients with occult HBV	Mutation in the precore/core and s regions results in undetectable s region
1915, 2134, 2221, 2245, 2288 in precore/core	Independent predictors of HCC survival	-
S87 and P156	Cancer recurrence	-
E77, P79, E83, L84, and S87 in core	Shorter survival times and increased viral activity. The S87 mutation could interfere with the assembly of the core	-
x/precore of HBV genotype D1, T1673/G1679, G1727, C1741, C1761, A1757/T1764/G1766, T1773, T1773/G1775 and C1909	A marker of HCC	-
G1896A; G1899A, T1846A, G1862C, G1888A, T1821C, C1826T, A1827C, A1850T precore start codon Kozak and G1951T, G1957A, genotype A1 and D	HBeAg-negative chronic; HBV infection and a more severe outcome	-
A2051C	Associated with increased viral replication both in vivo and in vitro	-
P5H/L/T, E83D, I97F/L, L100I, and Q182K/stop	More prevalent in chronic HBV and cirrhotic patients	Evading the host-immune system
The stop codon of W28*(G1896A), precore; S21, E40 and 1105; the epitope substitutions (117-131)	Identified to correlate with the development of the inactive carrier state. Higher in the cirrhotic/HCC group than in the inactive and the chronic active HBV groups	Evading the host-immune system
T1938C (V13A) with A2051C (N51H) in core	Those substitutions in the core correlated with HBV-related HCC and disease progression in Alaskan natives	-
YMDD mutation at codons 203-206 of the HBV RT	It targets the catalytic site of the HBV polymerase, specially at rtM204V/I	-
M204S substitution in the YMDD motif	HBV DNA accumulates, and relapse occurs	-

HCC: Hepatocellular carcinoma; HBeAg: Hepatitis B e antigen; HBcAg: Hepatitis B core antigen; FH: Fulminant hepatitis; ALT: Alanine aminotransferase; HBx: Hepatitis B virus X protein; SKP2: S-phase kinase-associated protein 2; pgRNA: Pregenomic RNA; HBV: Hepatitis B virus; RT: Reverse transcriptase.