Association of vitamin D and polymorphisms of its receptor with antiviral therapy in pregnant women with hepatitis B

Table 1 Baseline characteristics, laboratory data, and single nucleotide polymorphisms of the vitamin D receptor gene of patients included in the study

	Before treatment initiation		P value	At delivery after treatment		P value
	Full responders (n = 23)	Partial responders (n = 15)		Full responders (n = 23)	Partial responders (n = 15)
Age, yr, mean ± SD	29.09 ± 3.55	28.73 ± 3.01	0.75	NA	NA
BMI, kg/m2, mean ± SD	23.15 ± 3.33	21.42 ± 3.61	0.14	NA	NA
Season of blood draw			0.552			0.311
Winter or spring	10 (43.5%)	8 (53.3%)		16 (69.6%)	8 (53.3%)
Summer or autumn	13 (56.5%)	7 (46.7%)		7 (30.4%)	7 (46.7%)
HBsAg log10 IU/mL mean (IQR)	4.33 (3.73, 4.52)	4.36 (4.1, 4.72)	0.663	4.11 (2.56, 5.44)	4.33 (3.95, 4.56)	0.256
HBeAg log10 IU/mL mean (IQR)	3.16 (2.66, 3.2)	3.16 (3.12, 3.19)	0.928	3.18 (2.85, 3.19)	6.75 (6.21, 8.49)	0.510
HBV DNA, log10 mean (IQR)	8.06 (7.61, 8.44)	8.09 (7.53, 8.16)	0.56	3.61 (2.88, 4.46)	7.41 (5.79, 7.9)	< 0.0001
Vitamin D, ng/mL, mean ± SD	25.44 ± 9.42	17.66 ± 5.34	0.006	26.76 ± 8.59	21.24 ± 6.88	0.044
≥ 30	8 (34.8%)	1 (6.7%)	0.021	10 (43.5%)	2 (13.3%)	0.127
20-30	8 (34.8%)	3 (20%)		6 (26.1%)	6 (40%)
< 20	7 (30.4%)	11 (73.3%)		7 (30.4%)	7 (46.7%)
Hemoglobin, g/dL, mean ± SD	113.78 ± 9.29	115.47 ± 8.98	0.583	114.3 ± 12.78	118 ± 10.17	0.353
WBC count, × 106/µL, mean ± SD	7.83 ± 1.54	8.61 ± 2.26	0.282	7.63 ± 1.77	7.7 ± 2.17	0.918
Platelet, × 103/µL, mean ± SD	149.52 ± 56.73	155.6 ± 53.01	0.742	137.17 ± 53.92	149.4 ± 56.21	0.506
Neutrophil, mean ± SD	5.78 ± 1.38	6.51 ± 2.0	0.289	5.33 ± 1.62	5.53 ± 1.96	0.731
Lymphocyte, mean ± SD	1.46 ± 0.4	1.49 ± 0.49	0.823	1.63 ± 1.14	1.61 ± 0.49	0.964
Total bilirubin, mg/dL, mean ± SD	14.73 ± 3.24	13.61 ± 3.09	0.299	14.97 ± 4.15	17.13 ± 4.23	0.128
Albumin, g/dL, mean ± SD	39.21 ± 2.36	39.93 ± 2.28	0.355	26.42 ± 3.19	37.33 ± 3.68	0.698
ALT, U/L, mean (IQR)	22 (19, 28)	21 (15, 32)	0.891	22 (18, 30)	21 (17, 36)	0.893
Triglyceride, mg/dL, mean (IQR)	1.74 (1.59, 2.38)	1.58 (1.34, 1.79)	0.189	3.06 (2.41, 3.67)	2.52 (2.03, 3.21)	0.131
Cholesterol, mg/dL, mean ± SD	5.33 ± 0.85	5.7 ± 1.97	0.347	4.87 ± 0.79	5.56 ± 0.96	0.001
Creatinine, mg/dL, mean (IQR)	43 (38, 49)	43 (39, 45)	0.951	44 (37, 51)	47.5 (39.8, 55)	0.397
Alkaline phosphatase, U/L, mean (IQR)	7 (5, 10)	10 (4, 23)	0.234	48 (19, 72)	52 (47, 111)	0.199
GGT, U/L, mean ± SD	12.91 ± 8.1	13.87 ± 8.4	0.675	14.48 ± 7.57	22 ± 15.19	0.115
VDR SNPs
Cdx2 TT	9 (39.1%)	2 (13.3%)	0.076	NA
TC/CC	14 (30.9%)	13 (86.7%)
Bsm1 CC	20 (87%)	13 (86.7%)	0.979	NA
CT/TT	3 (13%)	2 (13.3%)
Fokl AA/AG	18 (78.3%)	10 (66.7%)	0.431	NA
GG	5 (21.7%)	5 (33.3%)
Taq1 AA	15 (65.2%)	9 (60%)	0.744	NA
AG/GG	8 (34.8%)	6 (40%)
Apa1 CC	10 (43.5%)	7 (46.7%)	0.847	NA
CA/AA	13 (56.5%)	8 (53.3%)

VDR SNPs: Single nucleotide polymorphisms of the vitamin D receptor gene; BMI: Body mass index; HBsAg: Hepatitis B surface antigen; HBeAg: Hepatitis B e antigen; HBV: Hepatitis B virus; WBC: White blood cell; ALT: Alanine aminotransferase; GGT: Gamma-glutamyl transferase; IQR: Interquartile range; NA: Not available.

Table 2 Factors associated with hepatitis B viral deoxyribonucleic acid serum concentration (log10 IU/mL)

Variable	P value, univariate	P value, multivariate	Standard beta, multivariate
Age (yr)	0.377
BMI (kg/m2)	0.049	0.03	-0.245
25(OH)D3 (ng/mL)	0.034	< 0.0001	-0.446
HBsAg (log10 IU/mL)	0.007
HBV DNA log10	0.046
Alkaline phosphatase	0.056
HBeAg log10	0.025
WBC count	0.064
Maternal HBsAg at delivery, log10	0.003	0.05	0.285
Maternal alkaline phosphatase at delivery	0.025
Maternal cholesterol at delivery	0.001	0.015	0.341

HBV: Hepatitis B virus; BMI: Body mass index; 25(OH)D3: 25-hydroxyvitamin D3; HBsAg: Hepatitis B surface antigen; WBC: White blood cell.

Table 3 Factors associated with the targeted antiviral effects (hepatitis B viral deoxyribonucleic acid at delivery < 2 × 10⁵)

Variable	Univariate	P value	Multivariate	P value
Age (yr, continuous)	1.034 (0.85-1.26)	0.745		0.727
BMI (kg/m2, continuous)	1.18 (0.95-1.47)	0.146		0.071
25(OH) D3 (ng/mL, continuous)	1.16 (1.03-1.31)	0.014	1.23 (1.04-1.44)	0.026
VDR Cdx2 TT	0.2 (0.036-1.097)	0.064	0.09 (0.01-0.88)	0.039
Maternal GGT at delivery	0.94 (0.86-1.006)	0.075		0.05
Maternal VD at delivery (ng/mL, continuous)	1.1 (0.999-1.21)	0.053		0.385
Maternal alkaline phosphatase at delivery	0.98 (0.96-1.002)	0.081		0.64
Maternal cholesterol at delivery	0.47 (0.26-0.86)	0.015	0.39 (0.17-0.87)	0.021

BMI: Body mass index; 25(OH)D3: 25-hydroxyvitamin D3; VDR: Vitamin D receptor; GGT: Gamma-glutamyl transferase; VD: Vitamin D.