X region mutations of hepatitis B virus related to clinical severity

Table 1 Mutations in the hepatitis B virus X region as related to clinical severity

Type of mutation	Mutations				Genotype	Clinical Significance			Region	Description	Ref.
	Amino acid		Nucleotide			HCC (%)	Non-HCC (%)	P value
	aa	mutations	nt	mutations
AS	4	NC	1383	A1383C	B/C	HCC (postoperative survival in patients with HBV-HCC) (P = 0.028)				Independent predictors of HCC survival	[65]
						52.8	25.8	0.003		miRNA binding site	[66]
AS	5	V5M/L	1386	G1386A/C	C	50.0	4.9	< 0.001			[27]
						47.8	0.0	< 0.001			[38]
						37.7	13.3	0.002			[67]
AS	30	NC	1461	G1461A/T/C	B/C	HCC (postoperative survival in patients with HBV-HCC) (P = 0.005)			B cell epitope	Independent predictors of HCC survival	[65]
AS	36	T36P/S/A	1479	A/G1479C/T/G	A/C/D	49.3	22.7	0.034	B cell epitope	B cell epitope	[66]
						15.3	7.8	< 0.001		B cell epitope	[66]
						80.0	17.1	< 0.010			[68]
AS	38	P38S	1485	C1485T	B/C	21.7	4.9	0.023	B cell epitope		[27]
						HCC (postoperative survival in patients with HBV-HCC) (P = 0.006)				Independent predictors of HCC survival	[65]
						48.7	13.9	0.001		Independent risk factor for the HCC	[69]
						29.9	16.8	0.001		B cell epitope	[66]
						30.4	15.0	0.038			[67]
AS	44	A44V	1504, 1505	C1504G, C1505G	A/D	35.9	6.9	0.012	B cell epitope		[70]
AS	50	G50R	1521	G1521A/C	A/D	60.0	4.3	< 0.010			[68]
AS	57	NC	1544	T1544A/C	B/C	HCC (postoperative survival in patients with HBV-HCC) (P = 0.039)				Independent predictors of HCC survival	[65]
AS	80	NC	1613	G1613A	B/C/C2	HCC (postoperative survival in patients with HBV-HCC) (P = 0.006)			Core promoter	Independent predictors of HCC survival	[65]
						54.7	28.3	0.001		Significance of association with HCC	[71]
						38.0	10.0	< 0.050			[72]
AS	81	NC	1613	G1613A	B/C	50.0	8.6	0.001	Core promoter		[73]
AS	86	NC	1631	C1631T	C	8.3	1.8	0.010	Core promoter	CP, NRE	[66]
AS	94	H94Y	1653	C1653T	B/C/C2	40.0	4.9	< 0.001	Box α, C/EBP,CCAAT/enhancing binding protein, Core promoter, EnhII		[27]
						HCC (postoperative survival in patients with HBV-HCC) (P = 0.015)				Independent predictors of HCC survival	[65]
						61.3	25.3	< 0.001		Significance of association with HCC	[71]
						56.0	30.0	0.0013			[74]
						45.0	19.0	< 0.050			[72]
						31.6	19.1	0.016		Box α	[75]
						35.4	18.6	< 0.001		Box α, CP, C/EBP, EnII	[66]
						41.2	13.3	< 0.001			[67]
						55.5	2.9	< 0.001			[73]
						8.9	2.2	0.017			[76]
AS	101	S101Stop	1675	C1675A	B/C	35.3	5.3	0.001	Core promoter, EnhII	EnhII	[77]
AS	106	S106T	1689	T1689A	C2	19.3	4.4	< 0.001	Core promoter, EnhII		[76]
AS	116	L/V116V/L	1719	T/G1719G/T	B/C	HCC (postoperative survival in patients with HBV-HCC) (P = 0.020)			BH3-like motif, Core promoter, EnhII, NRE	Independent predictors of HCC survival	[65]
						82.6	57.6	0.010		BH3-like motif, CP, EnhII, HNF3, T cell epitope	[66]
AS	117	NC	1724	T1724C	B/C	41.1	2.6	0.000	BH3-like motif, Core promoter, EnhII, NRE	EnhII	[77]
AS	118	NC	1727	A1727G	D1	35.0	5.0	0.001	BH3-like motif, Core promoter, EnhII, NRE		[78]
AS	123	L123S	1741	T1741C	D1	30.0	7.5	0.006	BH3-like motif, Core promoter, EnhII, NRE		[78]
AS, DM	127	I127L/T/N/S	1753	T1753C/A	C	36.7	12.2	0.007	BH3-like motif, Core promoter, NRE		[27]
			1753	T1753C	B/C	HCC (postoperative survival in patients with HBV-HCC) (P = 0.047)				Independent predictors of HCC survival	[65]
			1752, 1753	A1752C + T1753A/C/G	D	52.2	20.0	0.033			[79]
			1753	T1753A/C/G	C2	50.7	16.0	< 0.001		Significance of association with HCC	[71]
			1753	T1753A/C/G	C2	50.0	24.0	0.001			[74]
			1753	T1753C/G	A/D	43.6	17.2	0.041			[70]
			1753	T1753A/C/G	B/C	30.9	17.6	0.006		EnhII/BCP	[75]
			1753	T1753A/C/G	C	29.0	5.0	< 0.001			[67]
AS	130	K130M	1762	A1762T	C2	94.7	74.7	0.001	BH3-like motif, Core promoter	Significance of association with HCC	[71]
					B/C	80.0	25.7	< 0.001			[73]
AS	131	V131I	1764	G1764A	C2	98.7	78.7	< 0.001	BH3-like motif, Core promoter	Significance of association with HCC	[71]
					B/C	95.0	31.4	< 0.001			[73]
AS, DM	134	NC	1773	C1773T	D1	95.0	52.5	0.000	Core promoter		[78]
			1773, 1775	C1773T + A1775G	D1	17.5	0.0	0.010			[78]
AS	143	C143R	1800	T1800C	C	3.5	0.3	0.008	Core promoter	CP	[66]
AS, DM	100, 102	NC	1673, 1679	C1673T + A1679G	D1	17.5	0.0	0.010	Core promoter		[78]
AS, TM	128, 131	NC + V131L	1757, 1764, 1766	G1757A, G1764C + C1766G	D1	37.5	12.5	0.010	Core promoter		[78]
AS, DM	130, 131	K130M + V131I	1762, 1764	A1762T + G1764A	C	86.7	24.4	< 0.001	Core promoter		[27]
					D	HCC (HBV-DNA ≥ 5 log copies/mL) vs CLD (HBV-DNA < 5 log copies/mL) (P < 0.05)					[79]
					C2	91.0	73.0	0.0035			[74]
					A/D	62.5	14.3	0.034			[80]
					A/D	64.1	20.7	0.000			[70]
					B/C	71.1	55.7	0.009		EnhII/BCP	[75]
					B/C	64.0	50.8	< 0.00001			[81]
					A/D	44.9	20.7	< 0.001			[82]
					C	91.5	53.3	< 0.001			[67]
					C2	60.7	22.2	< 0.001			[76]
Del, Ins	129-154, 120-148, 115-149, 135-154, 137-151	Deletion	93-94 (4aa), 79-80 (2aa), 93-94 (4aa), 151-152 (3aa)	Insertion	C2	HCC + LC (7.6%) vs CH + C (1.5%) (P = 0.017)					[30]

AA: Amino acid; AS: Amino acid substitution; BCP: Basal core promoter; C: Carrier; CH: Chronic hepatitis; CLD: Chronic liver disease; CP: Core protein; Del: Deletion; DM: Double mutation; EnhII: Enhancer II; HCC: Hepatocellular carcinoma; HNF3: Hepatocyte nuclear factor 3; Ins: Insertion; LC: Liver cirrhosis; miRNA: MicroRNA; NC: No change; NRE: Negative regulatory element; TM: Triple mutation.