Hepatitis B virus pre-S2 start codon mutations in Indonesian liver disease patients

Table 1 Demographic data and the prevalence of pre-S mutations associated with progressive liver disease

	AC	CH	LC	HCC	All	P value (all)	P value (AC-CH vs LC)	P value (AC-CH vs HCC)
n (%)	73 (27.2)	66 (24.6)	66 (24.6)	63 (23.5)	268 (100.0)	-	-	-
Gender, n (%)
Male	69 (94.5)	49 (74.2)	46 (69.7)	49 (77.7)	213 (79.5)	0.002	0.027	0.314
Female	4 (5.5)	17 (25.8)	20 (30.3)	14 (22.2)	55 (20.5)
Age (yr, mean ± SD)	32.3 ± 9.1	41.9 ± 13.3	50.1 ± 10.9	48.6 ± 11.6	42.9 ± 13.3	< 0.001	< 0.001	< 0.001
Genotype, n (%)
B	56 (76.7)	46 (69.7)	46 (69.7)	52 (82.5)	200 (74.6)	0.267	0.453	0.393
C	17 (23.3)	20 (30.3)	20 (30.3)	11 (17.5)	68 (25.4)
HBeAg1
HBeAg(+)	13 (22.0)	36 (56.3)	18 (30.5)	15 (28.3)	82 (34.9)	< 0.001	0.222	0.144
HBeAg(-)	46 (78.0)	28 (43.8)	41 (69.5)	38 (71.7)	153 (65.1)
Mutation
M120	2 (2.7)	12 (18.2)	27 (40.9)	18 (28.6)	59 (22.0)	< 0.001	< 0.001	0.002
T130	8 (11.0)	19 (28.8)	18 (27.3)	25 (39.7)	70 (26.1)	0.0018	0.311	0.054
Q132	11 (15.1)	19 (28.8)	21 (31.8)	26 (41.3)	77 (28.7)	0.008	0.111	0.04
A138	10 (13.7)	21 (31.8)	22 (33.3)	26 (41.3)	79 (29.5)	0.003	0.089	0.094

¹Number of samples for HBeAg. n (all) = 235, n (AC:CH:LC:HCC) = 59:64:59:53. AC: Asymptomatic carrier; CH: Chronic hepatitis; LC: Liver cirrhosis; HCC: Hepatocellular carcinoma; HBeAg: Hepatitis B e antigen.

Table 2 Pre-S mutation as risk factor for progressive liver disease adjusted with age, sex, and hepatitis B e antigen (n = 235)

	P-value	OR (95% CI)	P-value	OR adjusted (95% CI)
AC-CH vs LC-HCC
Age, mean ± SD	1.99E-11	1.099 (1.069-1.130)
Gender (male)	0.049	0.531 (0.281-1.002)
HBeAg(-)	0.096	1.585 (0.921-2.730)
Mutation
M120	3.23E-06	4.942 (2.427-10.064)	0.0005	3.996 (1.830-8.729)
T130	0.078	1.684 (0.940-3.016)	0.531	1.246 (0.626-2.483)
Q132	0.029	1.885 (1.064-3.339)	0.352	1.379 (0.701-2.712)
A138	0.041	1.801 (1.020-3.178)	0.580	1.209 (0.617-2.370)
AC-CH vs LC
Age, mean ± SD	8.86E-09	1.096 (1.063-1.131)
Gender (male)	0.027	0.442 (0.213-0.920)
HBeAg(-)	0.222	1.508 (0.778-2.922)
Mutation
M120	9.50E-07	6.343 (2.878-13.980)	4.00E-05	6.406 (2.640-15.540)
T130	0.311	1.440 (0.710-2.918)	0.672	1.198 (0.518-2.770)
Q132	0.111	1.740 (0.878-3.449)	0.364	1.457 (0.646-3.287)
A138	0.089	1.791 (0.911-3.523)	0.485	1.330 (0.597-2.964)
AC-CH vs HCC
Age, mean ± SD	2.13E-07	1.084 (1.052-1.118)
Gender (male)	0.314	0.663 (0.298-1.479)
HBeAg(-)	0.144	1.677 (0.835-3.372)
Mutation
M120	0.002	3.651 (1.570-8.490)	0.052	2.538 (0.992-6.494)
T130	0.054	1.987 (0.981-4.022)	0.402	1.413 (0.629-3.174)
Q132	0.041	2.056 (1.024-4.129)	0.498	1.321 (0.590-2.953)
A138	0.094	1.811 (0.900-3.644)	0.744	1.144 (0.509-2.571)

AC: Asymptomatic carrier; CH: Chronic hepatitis; LC: Liver cirrhosis; HCC: Hepatocellular carcinoma; CI: Confidence interval; OR: Odds ratio; HBeAg: Hepatitis B e antigen.

Table 3 Prevalence of pre-S mutations in hepatitis B virus genotype B and C associated with progressive liver disease

Mutations	Genotype B						Genotype C
	AC	CH	LC	HCC	All	P-value	AC	CH	LC	HCC	All	P-value
	n = 56	n = 46	n = 46	n = 52	n = 200		n = 17	n = 20	n = 20	n = 12	n = 68
M120	1 (1.8)	8 (17.4)	21 (45.7)	16 (30.8)	46 (23.0)	< 0.001	1 (5.9)	4 (20.0)	6 (30.0)	2 (16.7)	13 (19.1)	0.324
T130	6 (10.7)	11 (23.9)	10 (21.7)	19 (36.5)	46 (23.0)	0.017	2 (11.8)	8 (40.0)	8 (40.0)	6 (50.0)	24 (35.3)	0.098
Q132	9 (16.1)	11 (23.9)	12 (26.1)	20 (38.5)	52 (26.0)	0.067	2 (11.8)	8 (40.0)	9 (45.0)	6 (50.0)	25 (36.8)	0.081
A138	8 (14.3)	12 (26.1)	13 (28.3)	20 (38.5)	53 (26.5)	0.042	2 (11.8)	9 (45.0)	9 (45.0)	6 (50.0)	26 (38.2)	0.070

AC: Asymptomatic carrier; CH: Chronic hepatitis; LC: Liver cirrhosis; HCC: Hepatocellular carcinoma.

Table 4 Demographic data of samples with hepatitis B e antigen (+) and hepatitis B e antigen (-) n (%)

	HBeAg(+)	HBeAg(-)	P-value
	82 (34.9)	153 (65.1)
Gender,
Male	58 (70.7)	127 (83.0)	0.028
Female	24 (29.3)	26 (17.0)
Age, mean ± SD	39.2 ± 11.9	44.7 ± 13.9	0.003
Genotype,
B	56 (68.3)	116 (75.8)	0.215
C	26 (31.7)	37 (24.2)
Clinical diagnosis,
AC	13 (15.9)	46 (30.1)	< 0.001
CH	36 (43.9)	28 (18.3)
LC	18 (22.0)	41 (26.8)
HCC	15 (18.3)	38 (24.8)

AC: Asymptomatic carrier; CH: Chronic hepatitis; LC: Liver cirrhosis; HCC: Hepatocellular carcinoma; HBeAg: Hepatitis B e antigen.

Table 5 Prevalence of pre-S mutations in hepatitis B e antigen (-) and hepatitis B e antigen (+) associated with progressive liver disease

Mutation	HBeAg(-)						HBeAg(+)
	AC	CH	LC	HCC	All	P-value	AC	CH	LC	HCC	All	P-value
	n = 46	n = 28	n = 41	n = 38	n = 155		n = 13	n = 36	n = 18	n = 15	n = 82
M12	0 (0.0)	10 (35.7)	17 (41.5)	9 (23.7)	36 (23.5)	< 0.001	0 (0.0)	2 (5.6)	7 (38.9)	6 (40.0)	15 (18.3)	< 0.001
T130	6 (13.0)	10 (35.7)	11 (26.8)	13 (34.2)	40 (26.1)	0.082	2 (15.4)	9 (25.0)	6 (33.3)	6 (40.0)	23 (28.0)	0.474
Q13	6 (13.0)	10 (35.7)	12 (29.3)	14 (36.8)	42 (27.5)	0.057	3 (23.1)	9 (25.0)	8 (44.4)	6 (40.0)	26 (31.7)	0.389
A13	6 (13.0)	10 (35.7)	13 (31.7)	13 (34.2)	42 (27.5)	0.072	2 (15.4)	11 (30.6)	8 (44.4)	6 (40.0)	27 (32.9)	0.344

AC: Asymptomatic carrier; CH: Chronic hepatitis; LC: Liver cirrhosis; HCC: Hepatocellular carcinoma; HBeAg: Hepatitis B e antigen.