Different pre-S deletion patterns and their association with hepatitis B virus genotypes

doi:10.3748/wjg.v22.i35.8041

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World Journal of Gastroenterology

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World J Gastroenterol. Sep 21, 2016; 22(35): 8041-8049
Published online Sep 21, 2016. doi: 10.3748/wjg.v22.i35.8041

Table 1 Characteristics of the study population classified according to the presence of pre-S deletion n (%)

Features	wild type pre-S(n = 147)	Pre-S deletion(n = 126)	P value
Age (mean ± STD)	45.4 ± 6.6	45.9 ± 7.0	0.540
Male	101 (68.7)	100 (79.4)	0.054
Genotype C	42 (28.6)	60 (47.6)	0.003
Genotype B	94 (63.9)	62 (49.2)
Mixed genotypes	11 (7.5)	4 (3.2)
HBV DNA ≥ 10⁵ copies/mL	67 (45.7)	92 (73.0)	< 0.001
BCP mutation (A1762T, G1764A)	80 (54.4)	98 (77.8)	< 0.001
PC mutation (G1896A)	87 (59.2)	86 (68.3)	0.132
Clinical categories
ASC	51 (34.7)	4 (3.2)
Progressive liver diseases	96 (65.3)	122 (96.8)	< 0.001
CH	24 (16.3)	31 (24.6)	0.098
LC	19 (12.9)	36 (28.6)	0.001
NC-HCC	29 (19.7)	24 (19.0)	1.000
LC-HCC	24 (16.3)	31 (24.6)	0.098

ASC: Asymptomatic carriers; CH: Chronic hepatitis; HBV: Hepatitis B virus; LC: Liver cirrhosis; LC-HCC: Liver cirrhotic hepatocellular carcinoma; NC-HCC: Noncirrhotic hepatocellular carcinoma; BCP: Basal core promoter; PC: Precore.

Full Size Table

Table 2 Clinical and virological characteristics of hepatitis B virus carriers with pre-S deletion n (%)

Features	HBV/B(n = 43)	HBV/C(n = 43)	P value
Age (mean ± STD)	44.5 ± 8.8	45.8 ± 7.6	0.464
Male	33 (76.7)	31 (72.1)	0.805
HBV DNA ≥ 10⁵ copies/mL	29 (67.4)	32 (74.4)	0.635
BCP mutation (A1762T, G1764A)	30 (69.8)	37 (86.0)	0.117
PC mutation (G1896A)	38 (88.4)	25 (58.1)	0.003
Clinical categories
ASC	2 (4.7)	2 (4.7)	1.000
Progressive liver diseases	41 (95.3)	41 (95.3)
CH	9 (20.9)	11 (25.6)	0.799
LC	8 (18.6)	14 (32.6)	0.216
NC-HCC	14 (32.6)	4 (9.3)	0.015
LC-HCC	10 (23.3)	12 (27.9)	0.805

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Table 3 Frequencies of different types of pre-S deletions in HBV/B- and HBV/C-infected carriers n (%)

Deletion	HBV/B(n = 43)	HBV/C(n = 43)	P value
N-terminal half of pre-S1 (aa 1-57)	17 (39.5)	17 (39.5)	1.000
C-terminal half of pre-S1 (aa 58-119)	37 (86.0)	30 (69.8)	0.117
N-terminus of pre-S2 (aa 1-31)	34 (79.1)	31 (72.1)	0.616
d183 M	10 (23.3)	9 (20.9)	1.000
Epitope Mapping
Pre-S1 region
pS1-T1 (aa 12-48 of pre-S1)	15 (34.9)	9 (20.9)	0.229
pS1-B1 (aa 12-53 of pre-S1)	15 (34.9)	9 (20.9)	0.229
pS1-B2 (aa 72-78 of pre-S1)	18 (41.9)	22 (51.2)	0.517
pS1-BT (aa 94-117 of pre-S1)	31 (72.1)	22 (51.2)	0.075
Pre-S2 region
pS2-B1 (aa 1-6 of pre-S2)	31 (72.1)	16 (37.2)	0.002
pS2-B2 (aa 3-15 of pre-S2)	33 (76.7)	27 (62.8)	0.240
pS2-B3 (aa 13-24 of pre-S2)	19 (44.2)	24 (55.8)	0.388
pS2-T1 (aa 21-48 of pre-S2)	11 (25.6)	21 (48.8)	0.044
Functional Mapping
Pre-S1 region (aa 1-119)
The start codon of L	4 (9.3)	9 (20.9)	0.228
HBS (aa 2-48)	16 (37.2)	15 (34.9)	1.000
S promoter (nt 3045-3189)	31 (72.1)	30 (69.8)	1.000
CBF (nt 3137-3147)	23 (53.5)	15 (34.9)	0.128
HSC70 (aa 74-118)	31 (72.1)	29 (67.4)	0.815
CAD (aa 81-105)	30 (69.8)	23 (53.5)	0.379
Pre-S1/S2 region (aa1-174)
NBS (aa 103-127)	39 (90.7)	27 (62.8)	0.004
Pre-S2 region (aa1-55)
The start codon of M¹	30 (69.8)	18 (41.9)	0.016
VS (aa 1-5 of pre-S2)	32 (74.4)	16 (37.2)	0.001
pHSA (aa 3-16 of pre-S2)	34 (79.1)	25 (58.1)	0.062

¹Deletion or mutation of the start codon of the M protein. HBS: Hepatocyte binding site; CBF: CCAAT binding factor; HSC70: Heat shock protein 70; CAD: Cytosolic anchorage determinant; NBS: Nucleocapsid binding site; VS: Viral secretion; pHSA: Polymerized human serum albumin.

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Table 4 Frequencies of different types of pre-S deletions in HBV/B- and HBV/C-infected carriers according to their clinical outcome

Deletion	ASC		P value¹	CH		P value¹	LC		P value¹	NC-HCC		P value¹	LC-HCC		P value¹
Deletion	B (n = 2)	C (n = 2)	P value¹	B (n = 9)	C (n = 11)	P value¹	B (n = 8)	C (n = 14)	P value¹	B (n = 14)	C (n = 4)	P value¹	B (n = 10)	C (n = 12)	P value¹
N-terminal half of pre-S1 (aa 1-57)	50.0%	50.0%		22.2%	27.3%		50.0%	50.0%		28.6%	50.0%		60.0%	33.3%
C-terminal half of pre-S1 (aa 58-119)	50.0%	0		88.9%	81.8%		87.5%	71.4%		92.9%	75.0%		80.0%	66.7%
N-terminus of pre-S2 (aa 1-31)	0	100.0%		88.9%	72.7%		62.5%	78.6%		78.6%	75.0%		100.0%	58.3%	0.040
d183 M	50.0%	0		33.3%	36.4%		25.0%	28.6%		28.6%	0		0	8.3%
Epitope Mapping
pS1-T1 (aa 12-48 of pre-S1)	50.0%	0		11.1%	18.2%		50.0%	28.6%		21.4%	25.0%		60.0%	16.7%	0.074
pS1-B1 (aa 12-53 of pre-S1)	50.0%	0		11.1%	18.2%		50.0%	28.6%		28.6%	25.0%		50.0%	16.7%
pS1-B2 (aa 72-78 of pre-S1)	50.0%	0		44.4%	54.5%		37.5%	57.1%		50.0%	25.0%		30.0%	58.3%
pS1-BT (aa 94-117 of pre-S1)	50.0%	0		88.9%	81.8%		62.5%	64.3%		71.4%	25.0%		70.0%	25.0%	0.084
pS2-B1 (aa 1-6 of pre-S2)	0	0		88.9%	45.5%	0.070	50.0%	42.9%		64.3%	50.0%		100.0%	25.0%	< 0.001
pS2-B2 (aa 3-15 of pre-S2)	0	100.0%		88.9%	54.5%		62.5%	64.3%		71.4%	75.0%		100.0%	58.3%	0.040
pS2-B3 (aa 13-24 of pre-S2)	0	100.0%		44.4%	45.5%		37.5%	64.3%		35.7%	50.0%		70.0%	50.0%
pS2-T1 (aa 21-48 of pre-S2)	0	100.0%		33.3%	36.4%		25.0%	57.1%		14.3%	50.0%		40.0%	41.7%
Functional mapping
The start codon of L	0	50.0%		11.1%	9.1%		12.5%	42.9%		0	25.0%		20.0%	0
HBS (aa 2-48)	50.0%	50.0%		22.2%	18.2%		50.0%	50.0%		21.4%	50.0%		60.0%	25.0%
S promoter (nt 3045-3189)	50.0%	0		88.9%	81.8%		75.0%	71.4%		64.3%	75.0%		70.0%	66.7%
CBF (nt 3137-3147)	50.0%	0		66.7%	54.5%		50.0%	42.9%		57.1%	0	0.092	40.0%	25.0%
HSC70 (aa 74-118)	50.0%	0		88.9%	81.8%		62.5%	71.4%		71.4%	50.0%		70.0%	66.7%
CAD (aa 81-105)	50.0%	0		88.9%	81.8%		62.5%	64.3%		64.3%	50.0%		70.0%	25.0%	0.084
NBS (aa 103-127)	50.0%	0		100.0%	90.9%		75.0%	64.3%		92.9%	50.0%		100.0%	50.0%	0.015
The start codon of M	0	0		77.8%	54.5%		50.0%	50.0%		71.4%	50.0%		90.0%	25.0%	0.004
VS (aa 1-5 of pre-S2)	0	0		88.9%	45.5%	0.070	50.0%	42.9%		71.4%	50.0%		100.0%	25.0%	< 0.001
pHSA (aa 3-16 of pre-S2)	0	100.0%		88.9%	36.4%	0.028	62.5%	64.3%		78.6%	75.0%		100.0%	58.3%	0.040

¹P < 0.1. ASC: Asymptomatic carriers; CH: Chronic hepatitis; HBV: Hepatitis B virus; LC: Liver cirrhosis; LC-HCC: Liver cirrhotic hepatocellular carcinoma; NC-HCC: Noncirrhotic hepatocellular carcinoma; HBS: Hepatocyte binding site; CBF: CCAAT binding factor; HSC70: Heat shock protein 70; CAD: Cytosolic anchorage determinant; NBS: Nucleocapsid binding site; VS: Viral secretion; pHSA: Polymerized human serum albumin.

Full Size Table

Citation: Chen BF. Different pre-S deletion patterns and their association with hepatitis B virus genotypes. World J Gastroenterol 2016; 22(35): 8041-8049
URL: https://www.wjgnet.com/1007-9327/full/v22/i35/8041.htm
DOI: https://dx.doi.org/10.3748/wjg.v22.i35.8041