Clinical significance of hepatitis B surface antigen mutants

Table 1 Mutations reported in the hepatitis B surface antigen regions

Codon	Type mutation	Mutation	Phenotypic consequence	HBV genotype	Ref.
Wt1 atg, Mt1 acg, Wt2/3 tac, Mt2 tgc, Mt3 cac, Wt4 ttt, Mt4 ttg	AAS	M197T1, Y206C2/H3, F220L4	Low serum HBV DNA	D	[23]
Wt1 gga	AAS	G145A1	Immune escape1	A-B-C-D	[24,31,47]
Mt1 gca			Lamivudine resistance1
	AAS	G145R	Immune escape	A, B-C-D	[28,35,36,40,41,45,47-50]
Wt tgc	AAS	C121W	Immune escape	A	[25]
Mt tgg
Wr tgc, Mt tgg	AAS	C147W	Immune escape	D	[25,26]
Wt act, Mt att	AAS	T189I	Immune escape, reducing HBsAg detection signal	E-A	[27,28,33]
WT act, Mt aat	AAS	I126N	Immune escape	C	[29]
WtCaa, Mt cga	AAS	Q129R	Vaccine escape	B	[30,34]
Wt ttc, Mt tac	AAS	F161Y	Immune escape	C	[31,51]
Wt atg, Mt atc	AAS	M103I	Immune escape	D	[24,52]
Wt ttg, Mt tcg	AAS	L94S	HCC	D	[32]
WT gac, Mt gaa	AAS	D144E	Immune escape	D, C, A	[28,33,40,52]
Wt cct, Mt Tct	AAS	P127S	Immune escape	B, D	[33,34,39]
Wt act, Mt agt	AAS	T126S	Immune escape	B	[33,34,38]
WT act, MT atc	AAS	T126I	Immune escape	C, D	[28,34,53]
WT act, Mt agc	AAS	T143S	Immune escape	C, A	[34,53]
WTcca, Mt aca	AAS	P120T	Immune escape	B, D	[34,53]
Wt gca, Mt Gta	AAS	A184V	Immune escape	E	[27]
Wt gta, Mt gca	AAS	V184A	Immune escape	E	[27]
Wt Tcg, Mt acg	AAS	S143t	Immune escape	E	[25,27,53]
Wt tgt, Mt ttc	AAS	C76F	Immune escape	E	[27]
Wt cct, Mt act	AAS	P70T	Immune escape	E	[27]
Wt ata, Mt act	AAS	I82T	Immune escape	E	[27]
Wt att, Mt ctt	AAS	I110L	Immune escape	A, C	[25,53]
Wt tat, Mt ttt	AAS	Y134F	Immune escape	D	[25,55]
Wt agt, Mt aac	AAS	S207N	Immune escape	D	[25,56]
Wt tat, Mt cat	AAS	Y134H	Immune escape	D	[52]
Wt acg, Mt aat	AAS	T125N	Increased HBsAg reactivity in immunological diagnostic assays	D	[43]
Wt atg, Mt atc, WT aag, Mt agg	AAS	M103I-K122R	Immune escape	A-C-D	[24]
Wt tat, Mt tgt	AAS	Y100C	Immune escape	B-C	[45]
Wt ccc, Mt ctc, MtQ caa, MtS tcg, Mtt acc	AAS	P120L/Q/S/T	Immune escape	B-C	[45]
Wt tcg, Mt cta	AAS	S143L	Immune escape	D	[52]
Wt ctt, Mt cct	AAS	L127P	Immune escape	E	[27]
Wt cct, Mt ctt	AAS	P127L	Immune escape	A	[27]
Mutations in pre-S1 region
Wt tct, Mt aca	AAS	S98T	Significant association with disease progression (LF, LC, HCC)	D	[57]
Wt aac, Mt act	AAS	N48T	Reduced HBsAg detection signals	C	[27]
Wt cag, Mt cct	AAS	Q82P	Reduced HBsAg detection signals	C	[27]
Wt acc, Mt aat	AAS	T97N	HBsAg not detected	C	[27]
Wt aat, Mt acc	AAS	N97T	HBsAg not detected	E	[27]
Wt cct, Mt cag	AAS	P93Q	HBsAg not detected	E, C	[27]
Deletion size (bp) 39	D	Region (nt) 3046-3084	Progression to advanced liver disease	C	[58]
Deletion size (bp) 108	D	Region (nt) 2959-3066	Progression to advanced liver disease	C	[58]
Deletion size (bp) 39	D	Region (nt) 3046-3084	Progression to advanced liver disease	C	[58]
Deletion size (bp) 108	D	Region 2959-3066	Progression to advanced liver disease	C	[58]
104th codon	AAS	Q104Stop	HCC development and immune escape	C	[59]
preS1 start	D	Not specified	HCC development and immune escape	C	[59]
Wt ucc, Mt gcc	AAS	S17A	Immune escape	C	[59]
Wt cct, Mt ctt	AAS	P32L	Immune escape	C	[59]
Wt tgg, Mt ctg, Mt agg	AAS	W43L/R	Immune escape	C	[59]
104th codon	AAS	Q104Stop	HCC development and immune escape	C	[59]
Mutations in pre-S2 region
Not specified	AAS	preS2-W3Stop	Immune escape	C	[59]
From 8th codon to 23rd codon	D		Immune escape	C	[59]

AAS: Amino acid substitution; D: Deletion; HBV: Hepatitis B virus; HCC: Hepatocellular carcinoma; HBsAg: Hepatitis B surface antigen; LC: Liver cirrhosis; LF: Liver fibrosis.