Effects of sex and generation on hepatitis B viral load in families with hepatocellular carcinoma

Table 1 Association between demographics and hepatitis B surface antigen status among relatives of patients with hepatocellular carcinoma n (%)

Category	HBsAg		OR (95%CI)	Adjusted OR (95%CI)1
	Positive	Negative
Total family members	314	415
Sex
Male	171 (54.46)	196 (47.23)	1.25 (0.97-1.61)
Female	143 (45.54)	219 (52.77)
Index sex
Male	229 (72.93)	302 (72.77)	1.07 (0.70-1.62)	1.25 (0.97-1.60)
Female	85 (27.07)	113 (27.23)
Age, mean ± SD	40.49 ± 10.89	37.87 ± 11.69	1.01 (1.00-1.03)	1.28 (1.00-1.64)
Relation to index
Parent	10 (3.18)	20 (4.82)	0.78 (0.37-1.64)	0.81 (0.38-1.71)
Index generation	86 (27.39)	36 (8.67)	3.89 (2.32-6.51)a	3.97 (2.38-6.63)a
Child	206 (65.61)	347 (83.61)
Grandchild	12 (3.82)	12 (2.89)	1.43 (0.66-3.13)	1.39 (0.65-3.00)
Maternal HBsAg
Negative	86 (27.38)	244 (58.80)
Positive	129 (41.08)	53 (12.77)	5.03 (3.16-8.01)a	5.00 (3.13-7.97)a
Unknown	99 (31.53)	118 (28.43)	2.01 (1.30-3.38)a	2.04 (1.33-3.13)a
Index HBsAg2
Negative	48 (15.43)	203 (49.03)
Positive	263 (84.57)	211 (50.97)	5.57 (3.56-8.71)a	5.51 (3.53-8.61)a

¹Adjusted by sex;

²Four index cases. HBsAg status unknown.

^aP < 0.0001. HBsAg: Hepatitis B surface antigen.

Table 2 Multivariate analyses using generalized estimating equation to find predictive factors for hepatitis B surface antigen status

Factor	Item	OR (95%CI)	P value
Sex	Male	1.26 (0.94-1.70)
Index sex	Male	1.28 (0.78-2.10)
Age		1.03 (1.01-1.05)	0.0037
Relation to index	Parent	0.24 (0.09-0.69)	0.0076
	Index generation	2.25 (1.29-3.94)	0.0044
	Grandchild	2.06 (0.78-5.45)
Maternal HBsAg	Positive	2.65 (1.51-4.67)	0.0007
	Unknown	1.21 (0.72-2.03)
Index HBsAg	Positive	4.19 (2.50-7.04)	5.98 × 10-8

HBsAg: Hepatitis B surface antigen.

Table 3 Association between demographics and hepatitis B virus viral load in 303 hepatitis B surface antigen-positive relatives n (%)

Factor	HBV DNA		OR (95%CI)	P value	Adjusted OR (95% CI)1	P value
	≥ 100000 cps/mL	< 100000 cps/mL
Total family members	132	171
Sex
Male	84 (63.64)	79 (46.20)	2.12 (1.34-3.39)	0.0013
Female	48 (36.36)	92 (53.80)
Index sex
Male	99 (75)	121 (70.76)	1.83 (0.69-2.04)		1.17 (0.68-2.01)
Female	33 (25)	50 (29.24)
Age, mean ± SD	40.51 ± 12.18	39.15 ± 10.55	1.01 (0.99-1.03)		1.02 (0.99-1.04)
Relation to index
Child and grandchild	83 (62.88)	128 (74.85)
Parent	7 (5.30)	2 (1.17)	4.77 (1.12-20.31)	0.0348	4.57 (1.15-18.14)	0.0307
Index generation	42 (31.82)	41 (23.98)	1.51 (0.87-2.62)		0.64 (0.36-1.14)
Maternal HBsAg
Negative	33 (25)	51 (29.82)
Positive	61 (46.21)	64 (37.43)	1.55 (0.84-2.87)		1.57 (0.84-2.92)
Unknown	38 (28.79)	56 (32.75)	1.08 (0.57-2.06)		1.20 (0.62-2.33)
Index HBsAg
Negative	12 (9.16)	32 (18.93)
Positive	119 (90.84)	137 (81.07)	2.32 (1.13-4.76)	0.0221	2.47 (1.19-5.15)	0.0158
HBV genotype2				0.0017
N3	2 (1.53)	21 (12.88)	0.11 (0.03-0.44)		0.09 (0.02-0.39)	0.0011
B	97 (74.62)	120 (73.62)
C	31 (23.85)	22 (13.50)	1.71(0.94-3.14)	0.008	1.80 (0.97-3.36)	0.0640

¹Adjusted by sex;

²There are 10 missing HBV genotypes;

³Genotyping failed due to low HBV DNA. HBV: Hepatitis B virus; HBsAg: Hepatitis B surface antigen.

Table 4 Multivariate analyses using generalized estimating equation to find predictive factors for hepatitis B virus viral load

Factor	Item	OR (95%CI)	P value
Sex	Male	2.65 (1.51-4.64)	0.0007
Index sex	Male	1.47 (0.73-2.95)
Age		1.01 (0.98-1.03)
Relation to index	Parent	6.49 (1.13-37.27)	0.0359
	Index generation	1.19 (0.60-2.37)
Maternal HBsAg	Positive	1.50 (0.71-3.17)
	Unknown	1.02 (0.49-2.15)
Index HBsAg	Positive	1.51 (0.68-3.38)
HBV genotype	N	0.12 (0.03-0.56)	0.0066
	C	1.22 (0.59-2.51)

HBV: Hepatitis B virus; HBsAg: Hepatitis B surface antigen.

Table 5 Intra-family comparison of hepatitis B virus viral load among hepatitis B surface antigen-positive siblings n (%)

HBV DNA level1	Maternal HBsAg			Total
	Positive	Unknown	Negative
Total male siblings	12	9	7	28
All high level	7 (58.33)2	2 (22.22)	2 (28.57)	11 (39.3)3
All low level	1 (8.33)2	2 (22.22)	1 (14.29)	4 (14.3)3
Older > younger	3 (25.00)	3 (33.33)	3 (42.86)	9 (32.1)
Younger > older	1 (8.33)	1 (11.11)	1 (14.29)	3 (10.7)
Other	0 (0.00)	1 (11.11)	0 (0.00)	1 (3.6)
Total female siblings	11	3	4	18
All high level	2 (18.18)2	0 (0.00)	0 (0.00)	2 (11.1)3
All low level	6 (54.55)2	1 (33.33)	3 (75.00)	10 (55.6)3
Older > younger	1 (9.09)	1 (33.33)	0 (0.00)	2 (11.1)
Younger > older	1 (9.09)	0 (0.00)	1 (25.00)	2 (11.1)
Other	1 (9.09)	1 (33.33)	0 (0.00)	2 (11.1)

¹Low HBV DNA level, < 1 × 10⁵ cps/mL; high HBV DNA level, ≥ 1 × 10⁵ cps/mL.

²OR (95%CI) = 21 (1.50-293.25), P = 0.024;

³OR (95%CI) = 29.96 (2.54-353.17), P = 0.007; logistic regression. HBV: Hepatitis B virus; HBsAg: Hepatitis B surface antigen.