Hepatitis B core-related antigen serum levels may be a predictor of acute flare of chronic hepatitis B among pregnant women in the immune-tolerant phase of chronic HBV infection after short-course antiviral therapy

Figures & data

Table 1. Characteristics of chronic HBV-infected pregnant patients.

Characteristics	Baseline (24 weeks of gestation)	At delivery	Postpartum week 12	Postpartum week 16	Postpartum week 24	Postpartum week 36
Age (y, M ± SD)	26.49 ± 3.77	-	-	-	-	-
WBC count (10^9/L)	6.38 ± 1.45	8.42 ± 2.33**	6.42 ± 1.36	6.65 ± 1.55	6.26 ± 1.31	6.19 ± 1.24
RBC count (10^12/L)	4.13 ± 0.42	4.01 ± 0.36	4.64 ± 0.53**	4.75 ± 0.56**	4.91 ± 0.60**	4.73 ± 0.56**
HGB (g/L)	118.63 ± 12.3	116 ± 3.28	125.74 ± 16.47**	127.96 ± 17.31**	133.02 ± 16.02**	138.17 ± 16.93**
Platelet count (10^9/L)	208.05 ± 57.30	205 ± 55.47	225.9 ± 62.51**	229.52 ± 59.86**	237.17 ± 59.05**	241.63 ± 59.65**
ALT, U/L (median)	20.0 (15.4–29.35)	22.74(16.3–26.53)	32.4 (20.33–58.78)**	42.3 (32.4–67.9)**	33.1 (21.3–60.15)**	29.32(19.56–43.17)**
AST, U/L (median)	21.1 (17.95–25.55)	21.8(18.01–26.66)	24.65 (19.75–30.57)**	32.1 (22.18–49.2)**	25.23(19.56–33.29)**	25.05 (20.95–30.13)**
TBIL, (µmol/L, M ± SD)	9.91 ± 2.94	9.82 ± 2.58	10.44 ± 3.49	10.97 ± 3.26	10.46 ± 3.34	10.38 ± 3.69
DBIL, (µmol/L, M ± SD)	3.19 ± 1.73	3.11 ± 1.68	3.07 ± 1.75	3.62 ± 1.96	3.33 ± 2.42	3.59 ± 2.11
ALB, (g/L, M ± SD)	38.7 ± 4.45	35.49 ± 3.14	41.91 ± 4.44**	41.79 ± 2.33**	43.12 ± 3.21**	45.34 ± 3.22**
PTA (M ± SD)	113.38 ± 13.69	112.71 ± 12.98	110.81 ± 13.17	111.68 ± 12.36	113.22 ± 12.38	114.19 ± 13.46
HBsAg (log10) (median)	4.44 (3.73–4.60)	4.67(3.54–4.72)	4.35 (3.23–4.57)	4.17 (3.02–4.46)	4.51 (3.48–5.07)	4.26 (3.67–4.72)
HBeAg positive/negative	172/0	172/0	172/0	172/0	172/0	172/0
HBcrAg (M ± SD)	0.47 ± 0.19	0.31 ± 0.19	0.30 ± 0.18	0.42 ± 0.16	0.45 ± 0.15	0.46 ± 0.17
HBV-DNA (log10) (median)	8.08 (5.89–8.23)	4.71 (3.11–6.41)	3.66(2.31–4.27)	3.43 (2.14–4.05)	7.84 (7.1–8.24)	8.12(5.93–8.31)

Note: **p < 0.01.

Table 2. ALT and HBV DNA levels of acute flare of CHB patients.

Variable	Number
ALT levels (U/L)
1.1 to 2× ULN	28
2.1 to 5× ULN	49
>5× ULN	3
Acute flares of CHB
During pregnancy	21
24 weeks – delivery	21
After delivery	31
0–12 weeks after delivery	24
13–24 weeks after delivery	6
25–36 weeks after delivery	1
HBVDNA (IU/mL)
>2000	47
20–2000	5

Table 3. Dynamic changes in ALT and AST at different test points.

Characteristics		Baseline	At delivery	Postpartum week 12	Postpartum week 16	Postpartum week 24	Postpartum week 36
ALT, U/L (median)	Acute flare of CHB patients	20.3 (13.52–32.45)	54.6(38.35–73.9)	60.2(52.05–85.2)	70.1(53.1–95.65)	48.6(43.9–67.4)	42.5(28.53–55.53)
	No acute flare of CHB patients	20.0 (16.55–26.55)	19.3(14.65–25.25)	21.5(14.85–26.1)	19.9(12.5–26.65)	21.2(16.05–26.9)	19.6(14.1–26.0)
AST, U/L (median)	Acute flare of CHB patients	21.25 (18.2–27.38)	52.4(20.8–92.35)	59.1(52.05–76.5)	64(51.53–82.03)	38.9(27.4–54.1)	34.7(27–42.5)
	No acute flare of CHB patients	20.6(18.05–23.7)	20.3(17.7–26.1)	21.4(17.23–26.88)	20.55(16.45–25.28)	22.3(19.48–28.55)	19.9(18–24.1)

Figure 1. Characteristics of newborn infants of chronic HBV-infected mothers.

A total of 171 of 172 infants were HBsAb positive, and 1 infant was HBsAb negative at week 28. Among the 171 infants, 12 in the 10–99 IU/ml group, 52 in the 100–999 IU/ml group, and 107 in the ≥1000 IU/ml group.

Figure 2. Dynamic changes in HBcrAg at different test points.

Compared with baseline, HBcrAg levels significantly decreased at delivery and postpartum week 12 (TDF cessation) after TDF antiviral treatment (**p < 0.01). After TDF discontinuance, HBcrAg increased significantly at postpartum week 16, postpartum week 24, and postpartum week 36. Compared with delivery, HBcrAg levels significantly increased at postpartum week 16, postpartum week 24, and postpartum week 36 (**p < 0.01).

Figure 3. HBcrAg levels of acute flare of CHB patients and no acute flare of CHB patients at postpartum week 12.

Compared with no acute flare of CHB patients, HBcrAg levels significantly increased in the acute flare of CHB patients at postpartum week 12 (**p < 0.01).

Figure 4. ROC curve analysis of serum HBcrAg in identifying patients with acute flares of CHB.

The HBcrAg serum value can effectively identify patients with acute flares of CHB, with an AUROC of 0.84 (95% CI, 0.78–0.91).

Table 4. Negative predictive value of serum HBcrAg in predicting acute flares of CHB.

	Hepatitis B
HBcrAg	No acute flare of CHB	Acute flare of CHB	Total
<0.275	85.7% (n = 81)	14.3% (n = 7)	88
≥0.275	28.3% (n = 39)	71.7% (n = 45)	84
Total	120	52	172

Table 5. HBcrAg and HBsAg are associated with acute flare of CHB.

Factors	OR	95% CI	P value
ALT	1.41	0.80–2.47	0.234
AST	1.49	0.85–2.60	0.163
TBIL	1.09	0.70–1.68	0.712
ALB	0.82	0.53–1.26	0.367
PTA	0.79	0.52–1.19	0.255
HBsAg	2.52	1.13–5.65	0.025*
HBV DNA	1.22	0.72–2.06	0.457
HBcrAg	4.52	2.58–7.92	<0.001**
WBC	1.14	0.76–1.79	0.536
RBC	1.55	0.91–2.63	0.109
HGB	0.69	0.41–1.16	0.164
PLT	1.01	0.65–1.59	0.962

Note: *p < 0.01, **p < 0.01.

Data availability statement

The datasets used and/or analysed during the current study are available from the corresponding author upon reasonable request. If you need supporting data, you can contact us at any time. Email: [email protected].