Basic Study
Copyright ©The Author(s) 2016.
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 (%)
Featureswild type pre-S(n = 147)Pre-S deletion(n = 126)P value
Age (mean ± STD)45.4 ± 6.645.9 ± 7.00.540
Male101 (68.7)100 (79.4)0.054
Genotype C42 (28.6)60 (47.6)0.003
Genotype B94 (63.9)62 (49.2)
Mixed genotypes11 (7.5)4 (3.2)
HBV DNA ≥ 105 copies/mL67 (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
ASC51 (34.7)4 (3.2)
Progressive liver diseases96 (65.3)122 (96.8)< 0.001
CH24 (16.3)31 (24.6)0.098
LC19 (12.9)36 (28.6)0.001
NC-HCC29 (19.7)24 (19.0)1.000
LC-HCC24 (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.
Table 2 Clinical and virological characteristics of hepatitis B virus carriers with pre-S deletion n (%)
FeaturesHBV/B(n = 43)HBV/C(n = 43)P value
Age (mean ± STD)44.5 ± 8.845.8 ± 7.60.464
Male33 (76.7)31 (72.1)0.805
HBV DNA ≥ 105 copies/mL29 (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
ASC2 (4.7)2 (4.7)1.000
Progressive liver diseases41 (95.3)41 (95.3)
CH9 (20.9)11 (25.6)0.799
LC8 (18.6)14 (32.6)0.216
NC-HCC14 (32.6)4 (9.3)0.015
LC-HCC10 (23.3)12 (27.9)0.805
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.
Table 3 Frequencies of different types of pre-S deletions in HBV/B- and HBV/C-infected carriers n (%)
DeletionHBV/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 M10 (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 L4 (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 M130 (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.
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
B (n = 2)
C (n = 2)
B (n = 9)
C (n = 11)
B (n = 8)
C (n = 14)
B (n = 14)
C (n = 4)
B (n = 10)
C (n = 12)
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%088.9%81.8%87.5%71.4%92.9%75.0%80.0%66.7%
N-terminus of pre-S2 (aa 1-31)0100.0%88.9%72.7%62.5%78.6%78.6%75.0%100.0%58.3%0.040
d183 M50.0%033.3%36.4%25.0%28.6%28.6%008.3%
Epitope Mapping
pS1-T1 (aa 12-48 of pre-S1)50.0%011.1%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%011.1%18.2%50.0%28.6%28.6%25.0%50.0%16.7%
pS1-B2 (aa 72-78 of pre-S1)50.0%044.4%54.5%37.5%57.1%50.0%25.0%30.0%58.3%
pS1-BT (aa 94-117 of pre-S1)50.0%088.9%81.8%62.5%64.3%71.4%25.0%70.0%25.0%0.084
pS2-B1 (aa 1-6 of pre-S2)0088.9%45.5%0.07050.0%42.9%64.3%50.0%100.0%25.0%< 0.001
pS2-B2 (aa 3-15 of pre-S2)0100.0%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)0100.0%44.4%45.5%37.5%64.3%35.7%50.0%70.0%50.0%
pS2-T1 (aa 21-48 of pre-S2)0100.0%33.3%36.4%25.0%57.1%14.3%50.0%40.0%41.7%
Functional mapping
The start codon of L050.0%11.1%9.1%12.5%42.9%025.0%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%088.9%81.8%75.0%71.4%64.3%75.0%70.0%66.7%
CBF (nt 3137-3147)50.0%066.7%54.5%50.0%42.9%57.1%00.09240.0%25.0%
HSC70 (aa 74-118)50.0%088.9%81.8%62.5%71.4%71.4%50.0%70.0%66.7%
CAD (aa 81-105)50.0%088.9%81.8%62.5%64.3%64.3%50.0%70.0%25.0%0.084
NBS (aa 103-127)50.0%0100.0%90.9%75.0%64.3%92.9%50.0%100.0%50.0%0.015
The start codon of M0077.8%54.5%50.0%50.0%71.4%50.0%90.0%25.0%0.004
VS (aa 1-5 of pre-S2)0088.9%45.5%0.07050.0%42.9%71.4%50.0%100.0%25.0%< 0.001
pHSA (aa 3-16 of pre-S2)0100.0%88.9%36.4%0.02862.5%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.