Chronic liver disease questionnaire analysis in pregnant women with hepatitis B: a prospective study

Abstract

Background

Although domestic and international guidelines increasingly emphasize preventing mother-to-child transmission (MTCT) of hepatitis B virus (HBV), the multidimensional impacts of HBV infection on pregnant women’s health-related quality of life (HRQoL) have received insufficient attention. Our previous 1:1 matched cohort study [1] identified HBV infection as an independent risk factor for impaired HRQoL in pregnant women, after adjusting for age, gestational age, and parity. Building upon this foundation, this study is a longitudinal descriptive investigation within the population of HBV-infected pregnant women, aiming to delineate HRQoL trajectories and identify stage-specific factors.

Methods

This study enrolled 126 pregnant women with hepatitis B who attended the Fifth Affiliated Hospital of Guangzhou Medical University between April 2023 and May 2024. The participants were followed up at three time points: 16–24 weeks of gestation, 32 weeks of gestation to delivery, and 5–13 weeks postpartum. The Chronic Liver Disease Questionnaire (CLDQ) was used for longitudinal assessment of changes in their HRQoL. Repeated-measures analysis of variance (RMANOVA) was applied to examine the trends of CLDQ scores, while one-way analysis of variance and multiple linear regression were used to identify influencing factors.

Results

HRQoL in HBV-infected pregnant women showed significant dynamic changes over time (total score time effect: F = 28.363, P < 0.001), with the emotional function and fatigue domains most severely impaired during late pregnancy. In mid-pregnancy, a supportive family environment was positively associated with improved systemic symptoms and emotional function (β = 0.206, P = 0.029; β = 0.366, P = 0.001), whereas out-of-pocket medical expenditures were linked to exacerbated fatigue (β =−0.444, P = 0.044). In late pregnancy, out-of-pocket payments (β =−0.680, P = 0.022) and older age (β =−0.055, P = 0.027) were associated with reduced vitality. During the postpartum period, clinical markers of HBV infection, specifically high viral load (β =−0.403, P = 0.020) and HBeAg positivity (β =−0.336, P = 0.026), correlated with worsened abdominal symptoms and fatigue, respectively. Furthermore, women receiving antiviral therapy for the prevention of mother-to-child transmission demonstrated lower scores in the vitality and emotional function domains (all P < 0.01).

Conclusions

HRQoL trajectories in HBV-infected pregnant women exhibit pronounced stage-specific variations, with notable declines in physiological and emotional function during late pregnancy. Different factors influence HRQoL at each stage, suggesting that clinical management should adopt targeted interventions tailored to each phase. Enhanced symptom monitoring and psychological support during late pregnancy and the postpartum period should be prioritized.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12884-026-09251-6.

Background

HBV infection is recognized as a major public health problem by the World Health Organization (WHO). Approximately 296 million people worldwide have chronic HBV infections, and 820,000 die from HBV-related liver disease each year [2–4]. China is a medium to high prevalence area for hepatitis B, where MTCT is the dominant mode of infection [5, 6]. WHO has proposed a priority strategy—implementing a mother-to-child “zero transmission” program in high-prevalence countries, aimed at eliminating viral hepatitis by 2030 [7]. Specifically, in 2022, China’s relevant data showed that the number of chronic hepatitis B infections reached 79.74 million [8], and the positive rate of HBsAg in women of childbearing age was still 5.76%, with approximately 800,000 to 1 million infected pregnant women facing perinatal risks each year [9]. Although domestic and international guidelines, including China’s latest 2024 hepatitis B maternal and infant transmission blocking guidelines [10–12], have increasingly focused on blocking maternal-infant transmission, the multidimensional impact of HBV infection on pregnant women remains largely overlooked. Systematic evaluations and high-quality research on the HRQoL of HBV-infected pregnant women are still scarce. Most existing studies focus on maternal-infant transmission prevention, emotional changes, and virological indicators during pregnancy, however, there is a lack of in-depth exploration into the dynamic changes in HRQoL among pregnant women with HBV infection. This research gap not only weakens the assessment of the overall disease burden but also restricts the integration of humanistic care into maternal-infant transmission prevention strategies, which may hinder the full achievement of the WHO elimination goals.

Regarding assessment tools, most existing studies have employed generic instruments such as the SF-36. While such tools demonstrate reasonable reliability and validity, they lack structural validity in populations with liver disease [13]. Notably, our team along with another study focusing on social stigma, has emphasized the importance of using liver disease-specific scales to assess HRQoL of pregnant women with HBV infection [14, 15]. CLDQ [16], developed by Younossi et al. [17]via factor analysis and categorization. The CLDQ is specifically designed for patients with liver disease, covering six domains: Abdominal Symptoms (AS), Fatigue (FA), Systemic Symptoms (SS), Activity (AC), Emotional Function (EF), and Worry (WO). Comprising 29 items, it has demonstrated good reliability, validity, and responsiveness, making it an appropriate instrument for assessing quality of life in liver disease patients [17]. Our previous cross-sectional study using the CLDQ found that HBV-infected pregnant women, particularly those with high viral loads (HBV DNA ≥ 2 × 10⁵ IU/mL), exhibited significantly higher levels of anxiety compared to healthy pregnant women [14]. A subsequent prospective cohort study with healthy controls further confirmed that HBV infection is associated with an overall decline in HRQoL during pregnancy, underscoring the need to focus on influencing factors during critical periods such as late pregnancy [1].

Accordingly, the present study utilizes the CLDQ to systematically delineate the dynamic trajectories of HRQoL in HBV-infected pregnant women across three key stages—mid-pregnancy, late pregnancy, and postpartum—and to identify stage-specific influencing factors. The aim is to provide a basis for implementing phased clinical interventions for this population.

Methods

Research design

Between April 2023 and May 2024, this study recruited pregnant women with hepatitis B at the Fifth Affiliated Hospital of Guangzhou Medical University. Only those who volunteered and met the inclusion and exclusion criteria were included as research subjects. Follow-ups were conducted with the subjects at three time points: 16–24 weeks of gestation, 32 weeks of gestation until before delivery, and 5–13 weeks postpartum. Given that there is currently no internationally recognized HRQoL scale specifically developed for pregnant women with viral hepatitis, and in the absence of such a ‘gold standard’ instrument, this study utilized the CLDQ scale—which has been extensively validated and demonstrated robust reliability and validity in the international field of hepatitis B virus infection—to assess the HRQoL of this population [18–21]. RMANOVA was applied to examine changes in the total CLDQ score and each dimension score across different pregnancy stages. Furthermore, One-way ANOVA and multiple linear regression were used to identify the influencing factors.

Sample size calculation was based on the principle that, in regression analysis, the sample size should be 5–10 times the number of independent variables [22].Through literature review, a total of 22 predictive variables (including age, parity, mode of delivery, among others) were included, and the preliminary estimated required sample size was 110–220 participants. Considering research resources and feasibility comprehensively, 5 times the number of variables was taken as the basis, with a preset 10% loss-to-follow-up rate. Specifically, the final sample size was calculated as follows: 22 variables multiplied by 5, divided by 0.9 to account for a 10% loss-to-follow-up rate, resulting in a required sample size of approximately 122.

The CLDQ employed in this study covers six dimensions: Abdominal Symptoms, Fatigue, Systemic Symptoms, Activity, Emotional Function, and Worry. The Cronbach’s α coefficients for each dimension were 0.84, 0.90, 0.75, 0.76, 0.84, and 0.85, respectively, indicating that the scale possesses good internal consistency. respectively. Each item is scored on a 1–7 scale. The dimension score was calculated by dividing the total score of each dimension’s items by the number of items. The CLDQ total score was the average of all the dimension scores. A higher score means better quality of life [23].

Inclusion and exclusion criteria

Inclusion criteria include individuals aged 18–45 years with a gestational age between 16 and 24 weeks. They must be capable of understanding and voluntarily signing an informed consent form. Additionally, they should be diagnosed with chronic HBV infection according to the Guidelines for the Prevention and Treatment of Chronic Hepatitis B [12]. Exclusion criteria include concurrent infectious diseases such as hepatitis A, C, D, E, or G; HIV/AIDS; or syphilis; history of miscarriage or congenital malformations in previous pregnancies; clinical symptoms of threatened miscarriage; ultrasound evidence of fetal abnormalities; severe renal, cardiovascular, pulmonary, or neurological diseases; medical or psychological comorbidities likely to significantly impact HRQoL; and unwillingness or inability to complete the entire questionnaire or non-cooperation.

Observation indicators

Standardized training was provided to all investigators to ensure consistency in data collection. Participants received comprehensive explanations regarding the study objectives prior to enrollment. They emphasized that the questionnaires would be completed anonymously and that personal information would be strictly kept confidential. Questionnaires were distributed only after obtaining informed consent. The survey was conducted through two methods: (1) For pregnant and postpartum women who visited the hospital in person, questionnaires were distributed and collected on-site; (2) For those who received medical treatment elsewhere, questionnaires were collected via telephone interviews or online surveys, based on their clinical and biochemical indicator data. During the survey, when participants had questions about the questionnaire content, researchers refrained from using leading language to ensure the authenticity and independence of the responses. All valid questionnaires were assigned serial numbers, and two researchers verified and entered the data into the database.

The participants were followed up at three time points: 16–24 weeks of gestation, from 32 weeks of gestation until delivery, and 5–13 weeks postpartum. The collected data included three categories: (1) Clinical characteristics, such as age, parity, and pregnancy complications; (2) Hepatitis B virological indicators, including HBV DNA level and the hepatitis B five-item test: ① hepatitis B surface antigen [HBsAg], ② hepatitis B surface antibody [anti-HBs], ③ hepatitis B e antigen [HBeAg], ④ hepatitis B e antibody [anti-HBe], and ⑤ hepatitis B core antibody [anti-HBc]; (3) Biochemical indicators, such as liver function tests.

Statistical analysis

The collected data were entered into an Excel table to establish a database. Subsequently, the data were processed using SPSS software version 26.0 (IBM, New York). Continuous and categorical data were summarized using the median or mean (x̄), and percentages (%), respectively. Due to the negligible missing data rate (< 5%), RMANOVA was utilized to analyze the temporal changes in HRQoL. Mauchly’s test of sphericity was performed; if violated, Greenhouse-Geisser corrections were applied. Post-hoc pairwise comparisons were conducted with Bonferroni correction to control for Type I error. Multivariable linear regression models were used as exploratory analyses to identify predictors of HRQoL. Furthermore, one-way analysis of variance and multiple linear regression models were used to identify factors influencing HRQoL. All tests were two-tailed, with a significance level set at α = 0.05. P-values less than 0.05 were considered statistically significant.

Results

This study was conducted at the Obstetrics Outpatient Department of the Fifth Affiliated Hospital of Guangzhou Medical University from April 2023 to May 2024. Initially, singleton pregnant women between 16 and 24 weeks of gestation had been recruited. After signing the informed consent form and completing the screening process, the researchers administered a total of 130 standardized questionnaires during the 16–24 weeks gestation period, covering demographic characteristics, medical history, and the CLDQ assessment. From 32 weeks of gestation until delivery, 4 participants were lost to follow-up, leaving 126 participants who continued in the study. Eventually, these 126 pregnant women completed follow-up at all three time points and were included in the final analysis.

Basic information of hepatitis B pregnant women

Among pregnant women with HBV infection, 52.4% (66 cases) had a family history of HBV infection. The HBeAg positive rate was 35.7% (45 cases), and the proportion with HBV DNA ≥ 2 × 10⁵ IU/mL was 33.1% (43 cases). Regarding antiviral treatment, 59.5% (75/126) of the women did not receive treatment, while 34.1% (43/126) were treated to prevent mother-to-child transmission. The median duration of HBV infection was 10 years (range, 3–20 years). The study population mainly consisted of young, primiparous women with HBV infection, who had strong family support and economic security through medical insurance. However, special clinical attention should be given to the high rates of pregnancy complications and elevated HBV viral load in this group.

Health-related quality of life assessment

RMANOVA was used to compare the differences in total CLDQ scores among the three time points. The time effect was significant (F = 28.363, P < 0.001). As shown in Fig. 1, among the three time points, pregnant women with hepatitis B had the lowest CLDQ score during late pregnancy. Bonferroni post-hoc pairwise comparisons showed significant differences between mid- and late- pregnancy, as well as between late pregnancy and postpartum (both P < 0.05).

Fig. 1.

Total score time variation trend of CLDQ

Table 1 presents the mean ± standard deviation of CLDQ scores across each dimension for 126 pregnant women with hepatitis B at three stages: mid-pregnancy, late pregnancy, and postpartum. During weeks 16–24 of gestation, the FA dimension exhibited the greatest impairment (mean = 5.42, SD = 0.81). From week 32 until delivery, all dimensions showed significant declines, with the EF dimension reaching its lowest mean value (5.55 ± 0.67). In the postpartum period (weeks 5–13), the FA dimension remained the most affected (mean = 5.51, SD = 0.82).

Table 1.

Scores of CLDQ dimensions at different nodes in pregnant women with hepatitis B (n=126)

Dimension		±s
16–24 weeks of gestation	AS	6.29 ± 0.84
	FA	5.42 ± 0.81
	SS	5.99 ± 0.66
	AC	6.55 ± 0.65
	EF	5.84 ± 0.73
	WO	6.01 ± 0.79
From 32 weeks of pregnancy to delivery	AS	5.81 ± 0.99
	FA	5.16 ± 0.83
	SS	5.57 ± 0.70
	AC	5.84 ± 1.10
	EF	5.55 ± 0.67
	WO	5.98 ± 0.78
Postpartum 5–13 weeks	AS	6.44 ± 0.70
	FA	5.51 ± 0.82
	SS	6.19 ± 0.48
	AC	6.08 ± 0.89
	EF	5.76 ± 0.78
	WO	6.27 ± 0.66

CLDQ analysis at 16–24 weeks of gestation

The analysis of factors influencing the CLDQ during the 16–24 week gestation period showed no significant association between age and any demographic characteristic dimension (P > 0.05). Regarding economic factors, payment method showed significant differences across the FA, AC, and EF dimensions (P < 0.05). Notably, we observed that the public insurance payment group scored consistently higher than the medical insurance and out-of-pocket groups (Table S1). Full - time employment status and living conditions do not show statistically significant impacts. Regarding family support, participants reporting a positive family atmosphere scored significantly higher on the FA, SS, and EF dimensions (P < 0.05,Table S2). In contrast, caregiving responsibilities, perceived family support, and spouses’ attitudes showed no significant impact. Regarding health status, the severity of morning sickness was significantly associated with the SS dimension (F = 3.910, P = 0.001,Table S3). Pre-pregnancy comorbidities and pregnancy complications had no significant impact, and no differences were observed in other disease-related factors.

Multivariate regression analysis revealed that out-of-pocket payment posed a risk (β = − 0.444, P = 0.044) and was associated with lower scores on the AC dimension (β = − 0.444, P = 0.013). A positive family atmosphere correlates with higher scores on the SS dimension (β = 0.206, P = 0.029) and the EF dimension (β = 0.366, P < 0.001). Conversely, morning sickness negatively affected the SS dimension (β = − 0.141, P = 0.041). Effects of payment method and living conditions on other dimensions were not statistically significant (Table 2).

Table 2.

Multivariate linear regression analysis of factors influencing CLDQ scores at different stages in pregnant women with hepatitis B

Dimension		Variable	β	Standard error	t	P	95%CI
16–24 weeks of gestation	FA	Payment method = public insurance	1.143	0.564	2.026	0.045	0.026,2.260
		Payment method = self pay	-0.444	0.218	-2.037	0.044	-0.875,-0.012
	AC	Payment method = public insurance	0.065	0.457	0.143	0.886	-0.831,0.962
		Payment method = self pay	-0.444	0.177	-2.516	0.013	-0.790,-0.098
	SS	Family atmosphere	0.222	0.090	2.214	0.015	0.046,0.399
		Morning sickness	-0.145	0.068	-2.131	0.035	-0.279,-0.012
	EF	Payment method = public insurance	0.860	0.484	1.776	0.078	-0.089,1.809
		Payment method = self pay	-0.268	0.191	-1.404	0.163	-0.642,0.106
	EF	Family atmosphere	0.344	0.098	3.502	0.001	0.152,0.537
From 32 weeks of gestation to delivery	AS	Work status	-0.327	0.181	-1.813	0.072	-0.685,0.030
		Liver function	0.806	0.443	1.819	0.071	-0.071,1.683
	FA	Age	0.046	0.021	2.208	0.029	0.000,0.087
		Pregnancy	-0.136	0.171	-0.799	0.426	-0.474,0.201
	SS	Payment method = public insurance	1.258	0.482	2.611	0.010	0.304,2.212
		Payment method = self pay	-0.038	0.185	-0.205	0.838	-0.405,0.329
		HBV DNA	-0.251	0.127	-1.980	0.050	-0.502,0.000
	AC	Age	-0.055	0.025	-2.233	0.027	-0.103,-0.006
		Payment method = public insurance	0.979	0.765	1.279	0.203	-0.536,2.493
		Payment method = self pay	-0.680	0.293	-0.201	0.022	-1.260,-0.010
	EF	Family atmosphere	0.196	0.090	2.177	0.031	0.018,0.375
		Payment method = public insurance	1.281	0.457	2.177	0.006	0.376,2.186
	WO	Work status	0.312	0.142	2.195	0.030	0.031,0.594
		Payment method = public insurance	1.086	0.546	1.990	0.049	0.006,2.166
Postpartum 5–13 weeks	AS	HBV DNA	-0.403	0.127	-3.177	0.020	-0.654,-0.152
	FA	HBeAg	-0.336	0.150	-2.248	0.026	-0.632,-0.040
	SS	Spousal attitude	0.156	0.215	0.724	0.471	-0.266,0.577
	AC	Treatment plan = MTCT prevention during pregnancy	-0.478	0.161	-2.960	0.004	-0.797,-0.158
	EF	family atmosphere	0.294	0.104	2.822	0.006	0.088,0.500
		Treatment plan = MTCT prevention during pregnancy	-0.391	0.139	-2.806	0.006	-0.667,-0.115

AS Abdominal Symptoms, FA Fatigue, SS Systemic Symptoms, AC Activity, EF Emotional Function, WO Worry

CLDQ analysis from 32 weeks to delivery

We analyzed the CLDQ dimensions among pregnant women with hepatitis B from 32 weeks gestation to delivery. Among demographic characteristics, age showed a positive correlation with the FA dimension (r = 0.254, P = 0.004) and a negative correlation with the AC dimension (r = -0.18, P = 0.043,Table S4).Regarding economic factors, public insurance payment was associated with higher scores across all dimensions (SS, AC, EF, and WO) compared to other payment methods (Table S5). Additionally, full-time workers exhibited lower AS scores (P = 0.048) but higher WO scores (P = 0.038;Table S6). Among family support factors, only family atmosphere was significantly associated with the EF dimension (P = 0.026), while other family-related factors showed no statistical significance (Table S7). Regarding health status, primigravidae scored lower on the FA dimension (P = 0.043, Table S8), whereas pre-pregnancy or pregnancy-related complications had no significant effect. Among HBV infection characteristics, abnormal liver function was associated with higher AS dimension scores (P = 0.048, Table S9), whereas high viral load (≥ 2 × 10⁵ IU/mL) was associated with lower SS dimension scores (P = 0.031, Table S10).

Multivariate analysis further revealed that Improved family atmosphere also contributed to the EF dimension (β = 0.196, P = 0.031). Out-of-pocket payments (β = − 0.680, P = 0.022) and increasing age (β = − 0.055, P = 0.027) had negative effects on the AC dimension. Conversely, age showed a positive association with the FA dimension (β = 0.046, P = 0.029). Furthermore, full-time employment (β = 0.312, P = 0.030) and public insurance payment (β = 1.086, P = 0.049) both increased WO dimension scores. Table 2 present variable assignment details and regression analysis results.

CLDQ analysis was performed at 5 to 13 weeks postpartum

We analyzed the CLDQ dimensions among pregnant women with hepatitis B infection at 5 to 13 weeks postpartum. The results showed no significant influence from demographic characteristics or economic factors (all P > 0.05). Regarding family support, a positive family atmosphere correlated with higher EF dimension scores (P = 0.007, Table S11), while spousal supportive attitudes also contribute to higher SS dimension scores (P = 0.038,Table S12). The analysis showed that no statistically significant differences were observed in health status, pregnancy conditions, or postpartum behaviors. Moreover, further analysis revealed that specific HBV infection indicators and treatment modalities significantly influenced quality of life. HBeAg-positive individuals were associated with lower AS, FA, AC, and EF dimension scores (P < 0.05, Table S13). High viral load (≥ 2 × 10⁵ IU/mL) was linked to reduced scores in AS, FA, AC, EF, and WO dimensions (P < 0.05,Table S14). Additionally, pregnant women receiving prevention therapy for MTCT were associated with lower AS, AC, and EF scores (P < 0.05, Table S15).

Multivariate analysis further clarified that high viral load (DNA ≥ 2 × 10⁵ IU/mL) was associated with reduced AS dimension scores (β = -0.403, P = 0.020); HBeAg-positive status was associated with lower FA dimension scores (β = -0.336, P = 0.026); while mother-to-child transmission prevention therapy exerted negative effects on AC and EF dimensions (β = -0.478, P = 0.004; β = -0.391, P = 0.006). A positive family atmosphere emerged as a protective factor for the EF dimension (β = 0.294, P = 0.006), whereas spousal attitude showed no significant impact on the SS dimension (P > 0.05). Details on the variable coding system and complete regression results are provided in Table 2.

Discussion

HBV infection is a major global public health issue. When complicated by pregnancy, it often poses multidimensional challenges to the health of pregnant and postpartum women. However, previous research has paid insufficient attention to the HRQoL of pregnant women with hepatitis B. Most studies have employed generic instruments such as the SF-36, which may not adequately capture liver disease-specific symptomatology. The CLDQ, as a disease-specific HRQoL measure for patients with HBV infection [24], has been underutilized in pregnant women with hepatitis B infection.Notably, our team has previously applied the CLDQ in a cross-sectional study, revealing a negative impact of HBV infection on Worry domain scores in pregnant women [14].Furthermore, our subsequent 1:1 matched-cohort study confirmed that HBV infection independently exacerbates HRQoL decline during pregnancy beyond normal physiological changes [1].Building upon the aforementioned research, this prospective longitudinal study employed the CLDQ to systematically analyze the dynamic changes in HRQoL among pregnant women with HBV infection during three critical stages: mid-pregnancy, late pregnancy, and the postpartum period. It further identified specific influencing factors at each stage, aiming to provide more refined longitudinal evidence regarding the phased evolution of perinatal HRQoL in this population.

The analysis revealed significant differences in total CLDQ scores across these time points (F = 28.363, P < 0.001), with the lowest scores observed in the third trimester. Statistically significant changes were noted during both the mid-trimester to late-trimester transition and the late-trimester to postpartum period (P < 0.05). This trend is highly correlated with the phase characteristics of physiological load during pregnancy; in the third trimester, rapid fetal development, increased metabolic demands, and heightened liver burden can exacerbate hepatitis B-related clinical symptoms [25], and even trigger complications like hyperemesis gravidarum, cholestasis, or preeclampsia. Although the total postpartum CLDQ score shows improvement, it remains below mid-pregnancy levels, indicating a lag in postpartum recovery. This may be related to delivery stress, lactation [26], and the persistent pressure of disease management.

Among the multidimensional assessments, the EF and FA dimensions showed the most significant impairment. The EF dimension drops to its lowest level in the third trimester of pregnancy, suggesting that pregnant women may face significant psychological pressure due to physical discomfort and restricted social activities during this stage. Although this decline in emotional functioning is common among patients with chronic diseases, the particularity of pregnancy may further amplify its impact [27]. Lower FA scores further confirm that HBV infection combined with pregnancy-related factors highly likely restricts physical activity [28], particularly during the fetal growth acceleration phase in late pregnancy. The SS and AS dimensions of the CLDQ showed that physical symptoms and fatigue increased in pregnant women with hepatitis B, suggesting HBV infection may impair physiological function.

Next, this study systematically identified multidimensional factors influencing HRQoL in pregnant women with HBV infection through univariate and multivariate regression analyses. The factors covered dimensions such as family support, economic security, virological characteristics, and clinical interventions. In terms of family support, a positive family atmosphere significantly improved the mental health and emotional function of these women throughout the perinatal period. This result is consistent with previous studies [29], further confirming the critical role of family support in alleviating negative emotions among HBV-infected individuals. Regarding social support, economic security helped reduce the pregnancy-related anxiety of HBV-infected women. Specifically, women with public health insurance demonstrated higher scores in AC and EF during weeks 16–24 and 32 through delivery compared to those using other payment methods. This phenomenon likely stems from improved healthcare accessibility and enhanced psychological security provided by health insurance. However, due to inherent limitations from insufficient sample size in the public medical insurance group, we present only descriptive analysis here, requiring large-scale validation. It should be noted that the positive impact of economic security has been previously reported in other studies. As noted in the social support theory [30], economic security, a key dimension of instrumental support, can regulate stress responses by reducing uncertainty in medical decision-making. For pregnancy-related factors, morning sickness had a negative impact on the score of the SS dimension (β = -0.141, P = 0.041), suggesting that symptoms like nausea and vomiting increase the burden of physical discomfort and related systemic symptoms in HBV-infected pregnant women.

Additionally, this study found that pregnant women with HBV infection not only experienced impaired mental health during late pregnancy but may also face postpartum physical recovery difficulties. Pregnant women with a high hepatitis B viral load may experience heightened hepatitis activity and related symptoms during the third trimester. Postpartum breastfeeding fatigue may further exacerbate these symptoms [31], especially abdominal discomfort (β=-0.403, P = 0.020). This finding aligned with the conclusions from our team’s previous cross-sectional study [14]. Meanwhile, HBV-infected women positive for HBeAg reported higher levels of fatigue postpartum (β = -0.336, P = 0.026). This fatigue is usually associated with active viral replication and may exacerbate feelings of fatigue by inducing persistent low-grade inflammation. Furthermore, this study found that MTCT prevention treatment during pregnancy was associated with decreased scores in postpartum activity (β = -0.478, P = 0.004) and emotional function (β = -0.391, P = 0.006) among HBV-infected pregnant women. Naturally, this phenomenon may be influenced by several factors. Firstly, regarding drug side effects, antiviral medications may lead to adverse reactions such as fatigue and muscle soreness, which in turn affect postpartum physical activity [24]. Secondly, the risk of postpartum hepatitis flares cannot be overlooked, as some women discontinue antiviral therapy after delivery; this may trigger HBV reactivation, leading to liver inflammation and subsequently impacting both physical and mental status [25]. Thirdly, the psychological burden plays a significant role, as pregnant women may experience substantial pressure due to concerns about the potential effects of antiviral drugs on the fetus and the overall efficacy of MTCT blockade. Finally, certain confounding factors must be considered, given that patients receiving MTCT prevention treatment are predominantly individuals with high baseline viral loads, and the liver damage inherent to the virus itself may further exacerbate postpartum discomfort [32, 33]. Given the observational nature of this study, these associations cannot yet be equated with causal relationships. Future large-sample prospective interventional studies are therefore required to exclude residual confounding and further elucidate the definitive effect of MTCT prevention treatment on HRQoL.

Our findings preliminary suggest that incorporating HRQoL assessment into the routine prenatal care of HBV-infected pregnant women could be beneficial, with a particular focus on psychological screening during late pregnancy and symptom management postpartum. Furthermore, developing a multi-dimensional support system—including enhanced family involvement and optimized medical insurance policies—alongside tailored health counseling for high-risk individuals (e.g., those with high viral loads or HBeAg positivity) may improve overall well-being. However, considering the observational nature of this study, these proposed management strategies require further validation through large-scale, multicenter interventional research to confirm their clinical efficacy and long-term impact.

Several limitations of this study warrant consideration. First, the absence of an internal healthy control group makes it challenging to fully isolate the specific impact of HBV infection from the normal physiological and psychological changes associated with pregnancy, although our team’s prior matched-cohort research provided preliminary foundational evidence. Second, the single-center design resulted in a relatively homogeneous study population (characterized by younger age, strong family support, and high insurance coverage); consequently, patients with more severe disease or lower socioeconomic status may be underrepresented, which limits the generalizability of our findings. Third, the use of self-reported questionnaires may have introduced recall bias or subjective cognitive discrepancies. Fourth, certain subgroup analyses (e.g., participants with public insurance) were limited by small sample sizes, potentially leading to insufficient statistical power and less reliable estimates; thus, these results should be interpreted with caution. Fifth, as an observational study, this research has inherent limitations in establishing causal relationships compared to interventional designs. Finally, despite our efforts to control for major covariates, potential residual confounding from unmeasured factors—such as educational level, occupational stress, and postpartum parenting styles—cannot be entirely ruled out.

Conclusions

In conclusion, this longitudinal study systematically depicts the dynamic trajectory of HRQoL among HBV-infected pregnant women across different perinatal stages. It also reveals potential associations between HRQoL and factors such as physiological burden, viral characteristics, and social support. Future research should involve multicenter cohort studies with larger sample sizes and more diverse participants, including those from varying socioeconomic backgrounds and with different levels of disease severity. Furthermore, subsequent studies may incorporate robust estimation models (such as linear mixed-effects models) to reduce confounding factors.

Abbreviations

HBV

Hepatitis B virus

WHO

World Health Organization

MTCT

Mother to child transmission

CHB

Chronic hepatitis B

HBsAg

Hepatitis B surface antigen

HRQoL

Health-related quality of life

QoL

Quality of Life

SF-36

36-item Short Form Survey

HBV DNA

Hepatitis B virus deoxyribonucleic acid

CLDQ

Chronic Liver Disease Questionnaire

AS

Abdominal Symptoms

FA

Fatigue

SS

Systemic Symptoms

AC

Activity

EF

Emotional Function

CI

Confidence interval

HBeAg

Hepatitis B e antigen

HBsAg

Hepatitis B surface antigen

HBcAg

Hepatitis B core antigen

PROs

Patient-Reported Outcomes

Authors’ contributions

TP and SO were responsible for the original conception and design of the study, data analysis and interpretation, critical revision of the manuscript, and final approval of the manuscript. YD, WC and YL were responsible for drafting the article, data interpretation, revising the manuscript, and final approval of the manuscript. DX and ZC were responsible for data collection and statistical analysis.

Funding

This study was supported by the ‘Plan on enhancing scientific research in GMU’ (02-410-2302092XM), the ‘2022 Guangzhou Medical University discipline construction projects’ (02-410-2206013), the ‘2022 Student Innovation Capacity Enhancement Program Project of Guangzhou Medical University’ (02-408-2304-19064XM), the ‘2023 City school (college) enterprise joint funding projects’ (2023A03J0421),the ‘Key Laboratory of Guangdong Higher Education Institutes’ (2021KSYS009), the ‘Guangzhou Medical University First-Class Discipline Construction Project − 2025 College Student Innovation Training Program’ (02-408-2501-2214), the ‘Construction and Application Research of a Clinical Monitoring and Early Warning System for the COVID-19 Pandemic’ (2023YFC3043500), the ‘Guangdong Basic and Applied Research Foundation’ (2023A1515220242), the ‘2024 Tertiary Education Scientific research project of Guangzhou Municipal Education Bureau’ (2024312257).

Data availability

All data generated or analyzed during this study are included in this published article.

Declarations

Ethics approval and consent to participate

All general and laboratory data were exclusively used in this study. The study protocol was reviewed and approved by the Ethics Committee of the Fifth Affiliated Hospital of Guangzhou Medical University (Ethics Approval Number: GYWY-L2023-36).

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.