Association of core promoter mutations of hepatitis B virus and viral load is different in HBeAg(+) and HBeAg(-) patients

doi:10.3748/wjg.v17.i6.708

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Feb 14, 2011 (publication date) through Apr 24, 2024

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Gastroenterol. Feb 14, 2011; 17(6): 708-716
Published online Feb 14, 2011. doi: 10.3748/wjg.v17.i6.708

Table 1 Demographics and characteristics of patients enrolled in this study

Characteristics	Total	CH	LC	HCC	P-value
Characteristics	Total	CH	LC	HCC	CH vs LC	CH vs HCC	LC vs HCC
n (%)	179 (100.0)	64 (35.8)	65 (36.3)	50 (27.9)	-	-	-
Gender (male/female) (% male)	129/50 (72.1)	38/26 (59.4)	47/18 (72.3)	44/6 (88.0)	0.121	< 0.001	0.040
Age (yr, mean ± SD)	45.8 ± 12.3	39.7 ± 13.3	49.9 ± 10.8	48.4 ± 9.5	< 0.001	< 0.001	0.495
AFP [ng/mL, median (min-max)]	13.2 (0.1-3 295 000.0)	3.2 (0.1-5039.0)	11.8 (1.0-444 718.0)	704.8 (1.2-3 295 000.0)	< 0.001	< 0.001	< 0.001
AST [IU/L, median (min-max)]	66.0 (7.0-3618.0)	39.5 (7.0-481.0)	66.0 (15.0-297.0)	138.0 (9.0-3618.0)	< 0.001	< 0.001	< 0.001
ALT [IU/L, median (min-max)]	50.0 (1.0-860.0)	47 (6-748)	46 (9-216)	64 (1-860)	0.480	0.481	0.123
AST/ALT	1.28 (0.1-120.6)	0.9 (0.1-2.9)	1.4 (0.2-6.0)	2.1 (0.1-120.6)	< 0.001	< 0.001	< 0.001
Serum HBV DNA (log₁₀ IU/mL, mean ± SD)	5.6 ± 2.0	6.1 ± 2.1	5.8 ± 1.4	4.6 ± 2.2	0.334	< 0.001	0.003
All HBeAg(+), (%)	71 (39.7)	36 (56.3)	19 (29.2)	16 (32.0)	0.002	0.010	0.749
All HBeAg(-), (%)	108 (60.3)	28 (43.8)	46 (70.8)	34 (68.0)
HBeAg(+); HBeAb(-), (%)	71 (39.7)	36 (56.3)	19 (29.2)	16 (32.0)	0.002	0.010	0.749
HBeAg(-); HBeAb(+), (%)	86 (48.0)	22 (34.4)	40 (61.5)	24 (48.0)	0.002	0.141	0.039
HBeAg(-); HBeAb(-), (%)	22 (12.3)	6 (9.4)	6 (9.2)	10 (20.0)	0.978	0.105	0.098
Genotype
B, n (%)	132 (73.7)	47 (73.4)	48 (73.8)	37 (74.0)	0.958	0.946	0.985
C, n (%)	47 (26.3)	17 (26.6)	17 (26.2)	13 (26.0)

CH: Chronic hepatitis; LC: Liver cirrhosis; HCC: Hepatocellular carcinoma; AFP: α-fetoprotein; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; HBV: Hepatitis B virus; HBeAg: Hepatitis B e antigen; HBeAb: Hepatitis B e antibody.

Table 2 Comparison of hepatitis B e antigen (+) and hepatitis B e antigen (-) patients

Characteristics	Total	HBeAg(+)	HBeAg(-)	P-value
n (%)	179 (100.0)	71 (39.7)	108 (60.3)	-
Gender (male/female) (% male)	129/50 (72.1)	47/24 (66.2)	82/26 (75.9)	0.106
Age (yr, mean ± SD)	45.8 ± 12.3	40.7 ± 11.5	49.2 ± 11.7	< 0.001
AFP [ng/mL, median (min-max)]	13.2 (0.1-3 295 000.0)	10.9 (0.2-230472.0)	19.9 (0.1-3 295 000.0)	0.008
AST [IU/L, median (min-max)]	66.0 (7.0-3618.0)	55.0 (12.0-635.0)	71.0 (7.0-3618.0)	0.028
ALT [IU/L, median (min-max)]	50.0 (1.0-860.0)	47.0 (1.0-748.0)	52.0 (6.0-860.0)	0.535
AST/ALT	1.3 (0.1-120.6)	1.1 (0.1-30.8)	1.4 (1.4-120.6)	0.022
Serum HBV DNA (log₁₀ IU/mL, mean ± SD)	5.6 ± 2.0	6.5 ± 1.8	5.0 ± 1.9	< 0.001
< 20 000 IU/mL, n (%)	40 (22.3)	6 (8.5)	34 (31.5)	< 0.001
≥ 20 000 IU/mL, n (%)	139 (77.7)	65 (91.5)	74 (68.5)
Clinical status
CH, n (%)	64 (35.8)	36 (50.7)	28 (25.9)	0.003
LC, n (%)	65 (36.3)	19 (26.8)	46 (42.6)
HCC, n (%)	50 (27.9)	16 (22.5)	34 (31.5)
Genotype
B, n (%)	132 (73.7)	50 (70.4)	82 (75.9)	0.259
C, n (%)	47 (26.3)	21 (29.6)	26 (24.1)

CH: Chronic hepatitis; LC: Liver cirrhosis; AFP: α-fetoprotein; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; HBV: Hepatitis B virus; HCC: Hepatocellular carcinoma; HBeAg: Hepatitis B e antigen.

Table 3 Comparison of patients with hepatitis B e antigen (+), before and after hepatitis B e antigen seroconversion

Characteristics	Group 1	Group 2	Group 3	P-value
Characteristics	HBeAg(+), HBeAb(-)	HBeAg(-), HBeAb(+)	HBeAg(-), HBeAb(-)	1 vs 2	1 vs 3	2 vs 3
n (%)	71 (39.7)	86 (48.0)	22 (12.3)	-	-	-
Gender (male/female) (% male)	47/24 (66.2)	71/15 (82.6)	11/11 (50.0)	0.018	0.171	0.001
Age (yr, mean ± SD)	40.7 ± 11.5	49.8 ± 11.9	46.9 ± 10.6	< 0.001	0.028	0.296
AFP [ng/mL, median (min-max)]	10.9 (0.2-230 472.0)	17.1 (0.1-3 295 000.0)	40.8 (0.4-514 412.0)	0.016	0.048	0.731
AST [IU/L, median (min-max)]	55.0 (12.0-635.0)	68.0 (7.0-3618.0)	76.5 (9.0-580.0)	0.017	0.536	0.448
ALT [IU/L, median (min-max)]	47.0 (1.0-748.0)	60.0 (9.0-860.0)	43.0 (6.0-154.0)	0.200	0.173	0.023
AST/ALT	1.1 (0.1-30.8)	1.3 (0.1-120.6)	1.7 (0.5-6.0)	0.091	0.007	0.052
Serum HBV DNA (log₁₀ IU/mL, mean ± SD)	6.5 ± 1.8	5.1 ± 1.8	4.5 ± 2.4	< 0.001	< 0.001	0.146
< 20 000 IU/mL, n (%)	6 (8.5)	25 (29.1)	9 (40.9)	0.001	< 0.001	0.286
≥ 20 000 IU/mL, n (%)	65 (91.5)	61 (70.9)	13 (59.1)
Clinical status
CH, n (%)	36 (50.7)	22 (25.6)	6 (27.3)	0.001	0.054	0.871
LC, n (%)	19 (26.8)	40 (46.5)	6 (27.3)	0.011	0.963	0.104
HCC, n (%)	16 (22.5)	24 (27.9)	10 (45.4)	0.442	0.036	0.114
Genotype
B, n (%)	50 (70.4)	66 (76.7)	16 (72.7)	0.369	0.835	0.694
C, n (%)	21 (29.6)	20 (23.3)	6 (27.3)

Table 4 Precore and core promoter mutations in patients with hepatitis B e antigen (+), before and after hepatitis B e antigen seroconversion n (%)

	All	Group 1	Group 2	Group 3	Group 2+3	P-value
	All	HBeAg(+), HBeAb(-)	HBeAg(-), HBeAb(+)	HBeAg(-), HBeAb(-)	HBeAg(-)	1 vs 2	1 vs 3	2 vs 3	1 vs (2+3)
T1762/A1764¹
Absent	90 (50.3)	42 (59.2)	38 (44.2)	10 (45.5)	48 (44.4)	0.062	0.258	0.915	0.054
Present	89 (49.7)	29 (40.8)	48 (55.8)	12 (54.5)	60 (55.6)
A1896²
Absent	65 (61.3)	48 (100.0)³	15 (34.9)	2 (13.3)	17 (29.3)	< 0.001	< 0.001	0.114	< 0.001
Present	41 (38.7)	0 (0.0)	28 (65.1)	13 (87.7)	41 (70.7)
A1899²
Absent	81 (76.4)	43 (89.6)	27 (62.8)	11 (73.3)	38 (65.5)	0.003	0.034	0.116	0.004
Present	25 (23.6)	5 (10.4)	16 (37.2)	4 (26.7)	20 (34.5)
T1762/A1764 and A1896²
Absent	88 (83.0)	48 (100.0)	31 (72.1)	9 (60.0)	40 (68.9)	< 0.001	< 0.001	0.383	< 0.001
Present	18 (17.0)	0 (0.0)	12 (27.9)	6 (40.0)	18 (31.0)
T1762/A1764 or A1896²
Absent	33 (31.1)	31 (64.6)	2 (4.7)	0 (0.0)	2 (1.9)⁴	< 0.001	< 0.001	0.395	< 0.001
Present	73 (68.9)	17 (35.4)	41 (95.3)	15 (100.0)	56 (98.1)

¹Total samples n = 179; Hepatitis B e antigen (HBeAg) (+) and hepatitis B e antibody (HBeAb) (-) n = 71; HBeAg(-) and HBeAb(+), n = 86; HBeAg(-) and HBeAb(-), n = 22;

²Total samples n = 106; HBeAg(+) and HBeAb(-) n = 48; HBeAg(-) and HBeAb(+), n = 43; HBeAg(-) and HBeAb(-), n = 15;

³Three samples had a mixed population of precore stop codon mutation (A1896) and its wild type (G1896);

⁴Two samples with a mixed population of basal core promoter mutation (T1762/A1764) and its wild type (A1762/G1764).

Table 5 Precore and core promoter mutations in samples with hepatitis B e antigen (-) and hepatitis B e antibody (-)

No.	Sample ID	T1762/A1764	A1896	A1899	Serum HBV DNA (log₁₀ IU/mL)
1	07.10.068	Yes	No	No	4.59
2	08.70.091	Yes	No	No	4.87
3	08.100.038	Yes	Yes	No	6.43
4	07.10.121	Yes	Yes	No	7.52
5	08.10.002	Yes	Yes	No	7.18
6	09.41.591	Yes	Yes	Yes	6.53
7	09.40.037	Yes	Yes	Yes	5.62
8	10.80.004	Yes	Yes	No	2.78
9	06.10.062	No	Yes	No	3.32
10	08.10.086	No	Yes	No	4.94
11	09.40.033	No	Yes	No	7.28
12	09.80.040	No	Yes	No	4.05
13	09.41.806	No	Yes	Yes	7.42
14	07.10.070	No	Yes	Yes	4.72
15	09.80.037	No	Yes	Yes	6.78
16	08.10.016	Yes	NA	NA	5.21
17	08.10.020	Yes	NA	NA	-0.37
18	08.10.039	Yes	NA	NA	3.10
19	P.X00.34	Yes	NA	NA	-0.54
20	07.10.117	No	NA	NA	1.73
21	07.10.026	No	NA	NA	1.27
22	07.10.173	No	NA	NA	3.48

HBV: Hepatitis B virus.

Table 6 Precore and core promoter mutations related to serum hepatitis B virus DNA and alanine aminotransferase in hepatitis B e antigen (+) patients

	Serum HBV DNA (log₁₀ IU/mL) (mean ± SD) (n)		P-value	ALT (IU/L) [median (min-max)] (n)		P-value
	Absent	Present	P-value	Absent	Present	P-value
T1762/A1764¹	7.14 ± 1.46 (42)	5.60 ± 1.99 (29)	< 0.001	43.5 (13.0-748.0) (42)	48.5 (1.0-215.0) (29)	0.806
A1896²	6.98 ± 1.27 (48)	-	-	47.0 (1.0-748.0) (48)	-	-
A1899²	7.01 ± 1.25 (43)	6.68 ± 1.53 (5)	0.609	45.5 (1.0-748.0) (43)	55.0 (36.0-92.0) (5)	0.627
T1762/A1764 and A1896²	6.98 ± 1.27 (48)	-	-	47.0 (1.0-748.0) (48)	-	-
T1762/A1764 or A1896²	7.33 ± 1.23 (31)	6.33 ± 1.08 (17)	0.011	50.0 (15.0-748.0) (31)	41.5 (1.0-117.0) (17)	0.459

¹Total samples hepatitis B e antigen (HBeAg) (+) n = 71;

²Total samples HBeAg(+) n = 48. HBV: Hepatitis B virus; ALT: Alanine aminotransferase.

Table 7 Precore and core promoter mutations related to serum hepatitis B virus DNA and alanine aminotransferase in hepatitis B e antigen (-) patients

	Serum HBV DNA (log₁₀ IU/mL) (mean ± SD) (n)		P-value	ALT (IU/L) [median (min-max)] (n)		P-value
	Absent	Present	P-value	Absent	Present	P-value
T1762/A1764¹	4.64 ± 2.00 (48)	5.23 ± 1.79 (60)	0.095	57.0 (6.0-302) (48)	51.5 (6.0-860.0) (60)	0.885
A1896²	5.44 ± 1.66 (17)	5.91 ± 1.35 (41)	0.231	46.0 (15.0-860.0) (17)	63.5 (14.0-302.0) (41)	0.321
A1899²	5.80 ± 1.29 (38)	5.72 ± 1.76 (20)	0.382	52.0 (14.0-860.0) (38)	58.5 (17.0-302.0) (20)	0.693
T1762/A1764 and A1896²	5.59 ± 1.51 (40)	6.17 ± 1.27 (18)	0.138	65.0 (14.0-860.0) (40)	51.0 (17.0-174.0) (18)	0.543
T1762/A1764 or A1896²	2.77 ± 4.31 (2)	5.88 ± 1.23 (56)	< 0.001	59.5 (23.0-96.0) (2)	52.0 (42.0-860.0) (56)	0.847

¹Total samples hepatitis B e antigen (HBeAg) (-) n = 108;

²Total samples HBeAg(-) n = 58. HBV: Hepatitis B virus; ALT: Alanine aminotransferase.

Citation: Utama A, Siburian MD, Purwantomo S, Intan MDB, Kurniasih TS, Gani RA, Achwan WA, Arnelis, Lelosutan SA, Lukito B, Harmono T, Zubir N, Julius, Soemohardjo S, Lesmana LA, Sulaiman A, Tai S. Association of core promoter mutations of hepatitis B virus and viral load is different in HBeAg(+) and HBeAg(-) patients. World J Gastroenterol 2011; 17(6): 708-716
URL: https://www.wjgnet.com/1007-9327/full/v17/i6/708.htm
DOI: https://dx.doi.org/10.3748/wjg.v17.i6.708