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Unexpected HBsAg decrease after nucleoside analogues retreatment among HBeAg positive postpartum women: a pilot study
Virology Journal volume 22, Article number: 36 (2025)
Abstract
Background
Mother-to-child transmission (MTCT) is one of the main routes of transmission of HBV, and previous studies focused on the efficacy and safety of nucleoside analogues (NAs) in preventing MTCT. There are limited data on virologic changes of chronic hepatitis B (CHB) patients after discontinuing treatment postpartum and the efficacy of retreatment.
Methods
A retrospective-prospective real-world pilot cohort study on pregnant women with CHB was conducted. Biochemical and virological characteristics (HBsAg, HBeAg and HBV DNA) in patients received NAs treatment pre-pregnancy (n = 24), patients discontinued treatment after delivery (n = 88) and retreatment patients (n = 22) were collected during follow-up.
Results
The incidences of HBeAg clearance, half decrease of HBsAg, 0.5 lg decrease of HBsAg and HBsAg < 1000 IU/mL in patients discontinuing treatment postpartum were 5.7% (4/70), 10.0% (8/48), 6.3% (3/48) and 1.6% (1/61), respectively. More significantly decreases of HBsAg, HBeAg and HBV DNA were observed in retreatment patients compared to patients received NAs treatment pre-pregnancy. Significantly higher cumulative incidences of half decrease of HBsAg, 0.5 lg decrease of HBsAg and HBsAg < 1000 IU/mL were achieved in retreatment patients compared to patients received NAs treatment pre-pregnancy. Long-term follow-up results indicated that it is safe for HBeAg positive pregnant patients to discontinue treatment after delivery.
Conclusion
HBeAg positive patients received NAs treatment during pregnancy and discontinued it postpartum can benefit from NAs retreatment because of unexpected decrease of HBsAg, which may be helpful for achieve the goal of functional cure.
Trial registration number ClinicalTrials.gov (No.ChiCTR2100054116).
Introduction
Hepatitis B virus (HBV) infection remains a serious global public health problem, affecting approximately 257 million of patients, including 65 million women of childbearing age [1, 2]. Mother-to-child transmission (MTCT) is one of the main transmission routes of HBV, especially in Asia [2]. Current guidelines recommend that pregnant women with HBeAg positive or high viral load (HBV DNA > 200,000 IU/mL) should initiate prophylactic antiviral intervention with lamivudine, telbivudine (LdT) or tenofovir disoproxil fumarate (TDF) in third trimester to prevent MTCT [3,4,5,6,7]. Previous studies mainly focused on the efficacy and safety of nucleoside analogues (NAs) treatment in preventing MTCT, [8,9,10] and ALT flare in the short time period after delivery [11,12,13]. However, data on the long−term impact of NAs prophylactic antiviral intervention on virological dynamics in pregnant patients after delivery are limited [14].
Current guidelines recommend that patients received prophylactic antiviral intervention during pregnancy discontinue treatment after delivery or within 3 months postpartum [3,4,5,6]. However, the long−term prognosis of patients after discontinuing treatment remains unclear. Virologic rebound occurs after treatment discontinuation, and some patients experience mild ALT flare, which is generally self−limited and usually no medical intervention is required [15, 16]. But some patients required retreatment if they developed a moderate, severe or non-self-limited ALT flare and viral rebound, which indicated active hepatitis [17]. Recently, a prospective study from China showed an 11.6% retreatment rate after discontinuing treatment postpartum [18]. However, there is no data on the effectiveness of NAs retreatment in CHB patients after discontinuing treatment postpartum. In addition, long-term prognosis of patients after discontinuing treatment postpartum remains unclear.
Therefore, we conducted a pilot cohort study to first explore the virologic dynamics and liver disease progression after long−term discontinuing treatment after delivery in postpartum women who received NAs prophylactic antiviral intervention at third trimester and the effectiveness of NAs retreatment.
Patients and methods
Study design and patients
We conducted a retrospective-prospective real-world pilot cohort study of pregnant women with CHB recruited from in the Second Affiliated Hospital of Chongqing Medical University from March 2014 to December 2023 with inclusion criteria: 1) HBsAg positive for more than 6 months; 2) pregnancy; 3) initiation of antiviral treatment pre-pregnancy and continuation of treatment postpartum or initiation of antiviral treatment at 24–28 weeks of gestation and discontinuation of treatment postpartum, and exclusion criteria: 1) combination of other viral hepatitis (A, C, D, and E) or human immunodeficiency virus (HIV) infection; 2) fatty liver disease or autoimmune liver disease. The period from March 2014 to November 2022 was retrospective and the period from November 2022 to December 2023 was prospective. And the signed inform consents were obtained in November 2022.
This study is consistent with the ethical guidelines of the 1975 Declaration of Helsinki and was approved by the Ethical Committee of the Second Affiliated Hospital of Chongqing Medical University. And also, we have registered with the Chinese Clinical Trial Registry (ChiCTR2100054116).
The flowchart of participants is shown in supplementary Fig. S1. Initially, 172 pregnant women with CHB were included, finally, patients initiating NAs treatment pre-pregnancy because of ALT abnormality and continuing treatment postpartum (NAs treatment pre-pregnancy, n = 24), patients initiating NAs treatment at 24–28 weeks of gestation because of HBeAg positive and high viral load (HBV DNA > 200,000 IU/mL) and discontinuing treatment postpartum (Discontinue treatment, n = 88), and 22 patients receiving NAs retreatment were enrolled. And the criteria for NAs re−treatment are as follows: 1) persistent ALT abnormality; or 2) liver disease progression including liver fibrosis, liver cirrhosis, liver failure, or hepatocellular carcinoma [5].
Data collection and laboratory testing
Since we aimed to observe ALT and virologic changes in early discontinuation and early treatment, and pregnant women received NAs pre−pregnancy did not require so intensive follow−up, resulting in follow−up methods that differed slightly in the three groups. Clinical data were collected at time points of pre−pregnancy (within 6 months prior to pregnancy), early pregnancy, late pregnancy and routine postpartum follow−up visits (postpartum 3 months, 6 months and every 6−12 months thereafter) for patients receiving NAs treatment pre−pregnancy. Clinical data were collected at time points of 24−28 weeks of gestation, near birth, end of treatment (EOT, discontinuing treatment at delivery or within 12 weeks after delivery) and routine follow−up visits after EOT for patients discontinuing treatment. Clinical data were collected at time of retreatment, 1 month, 3 months, 6 months and every 6−12 months thereafter for retreatment patients.
Serum ALT levels were detected by Hitachi 7600–020, Tokyo, Japan with upper limit of normal (ULN) of 40 U/L. Serum HBV DNA levels were detected by Roche Amplicor/COBAS TaqMan HBV test v2.0 (Roche Molecular Diagnostics, Pleasanton, CA, USA) with lower limit of detection (LLD) of 100 IU/mL. HBsAg and HBeAg quantifications were detected by Roche COBAS HBsAgII−Q and Abbott GmbH & Co. KG, respectively. HBeAg qualitative test were also be detected by the Cobas E601 immunoassay analyzer (Roche Diagnostics GmbH, Mannheim, Germany) if the quantitative HBeAg was not available. Liver stiffness was detected by Fibroscan.
Outcome
The ALT flare is defined as > 2 ULN within 24 weeks postpartum, and the ULN is 40 U/L. To observe hepatic inflammation beyond 24 weeks of discontinuation and the indication for antiviral treatment, an ALT abnormality was defined as > 1 ULN. Outcome events were HBV DNA undetectable (undetectable with the LLOD of 100 IU/mL), HBeAg clearance (< 0.59 PEIU/mL or < 1.000 S/CO), half decrease of HBsAg from baseline, and 0.5 lg decrease of HBsAg from baseline, HBsAg < 1000 IU/mL, and HBsAg clearance (< 0.05 IU/mL).
Statistical analysis
Data were expressed as counts and percentages for categorical variables, and chi−square or Fisher exact tests were used to compare the percentages between groups. Data were expressed as mean (standard deviation) or median (range) for continuous variables. Mann–Whitney tests and paired−samples Mann–Whitney tests were used for comparison between groups and comparison of changes in parameters within groups, respectively. The cumulative incidences of outcome events were calculated by the Kaplan–Meier method and compared by the log−rank tests. Multivariate logistic regression analysis was used to identify risk factors of ALT abnormality more than 6 months after EOT. Variables with a p value < 0.1 in univariate logistic regression analysis were included in multivariate logistic regression analysis. Two−sided p values were calculated for all tests and p value < 0.05 was statistically significant. Data were analyzed via SPSS version 24.0 (IBM Corp., Armonk, NY, USA) and R4.3.1 software.
Results
Characteristics of the enrolled patients
Table 1 shows the characteristics of the patients receiving NAs treatment pre−pregnancy, patients discontinuing treatment after delivery and retreatment patients. The three groups were comparable in terms of age and delivery history. The proportion of TDF−treatment in patients receiving treatment pre−pregnancy was comparable to that of retreatment patients, with lower proportion of HBeAg positivity, lower baseline levels and decreases in the proportion of HBsAg, HBeAg, and HBV DNA levels, and longer duration of treatment. In patients discontinuing treatment postpartum, 42 patients received TDF treatment, 41 patients received LdT treatment, 2 patients received TAF treatment, and 3 patients received LdT treatment initially then changed treatment to TDF. The median duration of TDF treatment was 4.4 months, comparable with 4.7 months of LdT treatment. 9.5% (4/42) patients received LdT treatment and 7.3% (3/41) patients received TDF treatment achieved HBV undetectable (p =1.000). Two patients received LdT treatment achieved the HBeAg clearance at the end of treatment. And after discontinuing treatment postpartum, the incidences of ALT flare (41.7% v.s. 27.0%, p = 0.223) and retreatment (42.9% v.s. 26.8%, p = 0.168) were comparable in patients received TDF and LdT treatment. At the time of retreatment, the ALT, and virologic markers (HBV DNA, HBsAg, and HBeAg) were comparable between patients received TDF and LdT treatment (all p > 0.05).
Kinetics of serum ALT and virological parameters in postpartum women discontinuing treatment
Based on the available data in the real−world study, 90.2% (74/82) of postpartum women experienced virologic rebound after discontinuing treatment postpartum. And 28.9% (22/76) of postpartum women experienced ALT flare after discontinuing treatment postpartum, significantly higher than 0% (0/24) of patients receiving NAs treatment pre-pregnancy (p = 0.001). A total of 70 patients had available HBeAg data (including HBeAg quantitative and qualitative tests), 61 patients had available quantitative HBsAg data at the last follow−up, and 48 patients had quantitative HBsAg data at both the time of retreatment and follow−up. The incidence of HBeAg clearance, half decrease of HBsAg, 0.5 lg decrease of HBsAg and HBsAg < 1000 IU/mL was 5.7% (4/70), 10.0% (8/48), 6.3% (3/48) and 1.6% (1/61), respectively, among patients discontinuing treatment postpartum.
Previous studies mainly focused on ALT flare (hepatitis within postpartum 6 months), and the attention on hepatitis after long−term follow−up is limited. In postpartum women followed up for more than 6 months after discontinuing treatment, the level of ALT significantly increased while HBeAg and HBV DNA significantly decreased at time of EOT compared to baseline. The levels of HBsAg and HBV DNA significantly increased while HBeAg significantly decreased at the last follow−up compared to the time of EOT (supplementary Fig. S2). Furthermore, 4 patients achieved spontaneously HBeAg clearance after EOT, whose kinetics of ALT and virological parameters are showed in supplementary Fig. S3.
We further analyzed the kinetics of ALT, virological parameters during pregnancy and follow−up in patients discontinuing treatment postpartum grouped by half decrease of HBsAg (Fig. 1). ALT fluctuated, more significant decrease of HBsAg in pregnancy, lower levels of HBsAg and HBeAg during follow−up, and less significant elevation of HBV DNA after EOT in patients who achieved half decrease of HBsAg compared to patients who did not.
Kinetics of serum ALT and virological parameters in patients discontinuing treatment. The red line represents population achieved half decrease of HBsAg, and the black line represents population did not. The horizontal axis represents time points (month), and the vertical axis represents levels of different variables
In total, 29 of 69 patients discontinuing treatment for more than 6 months developed ALT abnormalities and virologic rebound. Multivariable logistic regression analysis indicated that ALT flare postpartum was the strongest independent risk factor of ALT abnormality more than 6 months after EOT (odd ratio, 9.39; 95% confidence interval, 1.80–48.92; p = 0.008) (Table 2). Additionally, ALT abnormality more than 6 months after EOT was more likely to develop if patients received TDF treatment during pregnancy, compared with LDT treatment (odd ratio, 4.80; 95% confidence interval, 1.25–18.47; p = 0.023). Furthermore, we compared the kinetics of ALT and virologic parameters between patients treated with TDF and LdT. (supplementary Fig. S4.)
More significantly decrease of HBsAg in retreatment patients
After a median time of discontinuing treatment of 4 months (0.3−32.7 months), 22 patients received NAs re−treatment (21 patients with persistent ALT abnormality and 1 patient with liver fibrosis). The characteristics of retreatment patients are shown in Table 1. Overall, HBV DNA undetectable was achieved in 77.3% (17/22) of retreatment patients. And in patients receiving NAs treatment pre-pregnancy, 6 patients remained HBsAg lower than 1000 IU/mL, 23 patients remained HBV DNA undetectable and 1 patient achieved HBV DNA undetectable. The incidence of HBeAg clearance, half decrease of HBsAg, 0.5 lg decrease of HBsAg and HBsAg < 1000 IU/mL was achieved in 22.7% (5/22), 95.5% (21/22), 76.2% (16/21) and 40.9% (9/22) in retreatment patients, and 41.7% (5/12), 22.7% (5/22), 9.1% (2/22) and 11.8% (2/17) in patients receiving treatment pre-pregnancy, respectively. The cumulative incidence of half decrease of HBsAg, 0.5lg decrease of HBsAg and HBsAg < 1000/mL was significantly higher in retreatment patients compared to patients received treatment pre-pregnancy (p < 0.05), whereas the cumulative incidence of HBeAg clearance was comparable in both groups (p = 0.370) (Fig. 2).
Kinetics of serum ALT and virological parameters in retreatment patients and patients received NAs treatment pre-pregnancy
In patients receiving NAs treatment pre-pregnancy, the kinetics of serum ALT, HBsAg and HBeAg are described in Fig. 3A grouped by HBeAg status. Five patients presented with abnormal ALT, but not ALT flare. The trend of ALT was similar in both groups during follow-up while lower level of HBsAg was observed in HBeAg-positive patients compared to HBeAg-negative patients after 4 years of postpartum treatment.
Kinetics of ALT and virological parameters in patients received NAs treatment pre-pregnancy and retreatment patients. A: In patients received NAs treatment pre-pregnancy, red and blue lines represent individual and overall HBeAg positive patients, respectively. Black and green lines represent individual and overall HBeAg negative patients, respectively. B: In retreatment patients, red and green lines represent individuals and overall population achieved HBsAg < 1000 IU/mL, respectively. Black and green lines represent individuals and overall population who did not, respectively
In retreatment patients, the kinetics of serum ALT, HBsAg, HBeAg and HBV DNA are described in Fig. 3B grouped by whether HBsAg < 1000 IU/mL. ALT increase was found in two groups after discontinuing treatment. And after 1 month of retreatment, ALT increased and decreased in patients who achieved HBsAg < 1000 IU/mL and who did not, respectively. Both HBeAg and HBsAg showed decreasing trends in two groups after retreatment. However, more significant decrease in HBsAg at month 1 and HBeAg at month 6 were found in patients who achieved HBsAg < 1000 IU/mL compared to patients who did not. The trend of HBV DNA was similar in two groups, showing an increasing trend after discontinuing treatment and a decreasing trend after retreatment.
The kinetics of ALT and virological parameters for each individual patient with HBsAg < 1000 IU/mL were shown in supplementary Fig. S5. In addition, the proportions and numbers of retreatment patients with ALT abnormality, HBV DNA undetectable, HBeAg clearance, half decrease of HBsAg, 0.5 lg decrease of HBsAg and HBsAg < 1000 IU/mL were shown in Fig. 4. Two patients achieved HBsAg loss after NAs retreatment.
Lower level of HBV DNA at time of retreatment indicated better outcomes
Demographic data and characteristics at 24−28 weeks of gestation, at time of EOT and at retreatment were compared according to different outcome events. No significant difference in the characteristics regarding half decrease of HBsAg and 0.5 lg decrease of HBsAg. Data on supplementary Table S1 indicated younger age, lower proportion of parity, lower levels of HBsAg and HBeAg at 24–28 weeks of gestation, and lower levels of HBV DNA at time of retreatment in patients who achieved HBV DNA undetectable compared to patients who did not. Lower level of HBV DNA at the time of retreatment in patients who achieved HBeAg clearance compared to patients who did not. In addition, lower level of HBeAg at EOT and lower level of HBV DNA at the time of retreatment were found in patients who achieved HBsAg < 1000 IU/mL compared to patients who did not.
We found the lower level of HBV DNA at time of retreatment may be associated with virological response. Therefore, we further performed subgroup analysis, showing significantly higher cumulative incidence of HBV DNA undetectable, HBeAg clearance and HBsAg < 1000 IU/mL in patients with HBV DNA level not higher than 7 log compared to patients with HBV DNA level higher than 7 log. (Fig. 5).
Effectiveness of MTCT and safety after treatment discontinuation
In terms of effectiveness of MTCT, no infant born to pregnant women enrolled in this study were infected with HBV following standard hepatitis B vaccination and hepatitis B immunoglobulin administration. And in terms of safety after treatment discontinuation, no patient developed jaundice or liver failure during follow-up after discontinuing treatment. And no patient developed to liver cirrhosis and only 1 patient developed to liver fibrosis which was regressed after retreatment. The median liver stiffness was 4.8 kPa (2.8–13.9 kPa) in patients discontinuing treatment more than 6 months, comparable with 4.6 kPa (3.2–9.4 kPa) in patients receiving NAs treatment pre-pregnancy (p = 0.381). Therefore, it is safe for HBeAg positive pregnant patients to discontinue treatment postpartum.
Discussion
Our retrospective−prospective real−world cohort study first explored the long−term virological kinetics and liver disease progression of postpartum women receiving NAs treatment at 24–28 weeks of gestation and discontinuing treatment postpartum. We found that TDF treatment during pregnancy and ALT flare postpartum increased the risk of ALT abnormality after more than 6 months of treatment discontinuation. Our data showed that treatment discontinuation after delivery is relatively safe. Moreover, despite shorter treatment duration and higher HBsAg levels in retreatment patients compared to patients received NAs pre−pregnancy, there was a more significant decrease in HBsAg. Our study provided complementary evidence on effectiveness of NAs retreatment and safety of discontinuing treatment postpartum, filling the gap in postpartum management of pregnant women with CHB.
It remains controversial for pregnant CHB patients over whether discontinuing treatment after delivery, and data on liver disease progression and changes in virologic markers after long−term postpartum discontinuation of treatment are still lacking. Our data indicated few patients progressed to liver fibrosis and cirrhosis after long−term discontinuation of treatment, except for one patient with normal ALT progressed to liver fibrosis 12 months after discontinuing treatment. In addition, no patient developed jaundice or liver failure after discontinuing treatment. HBeAg declined after discontinuing treatment, with some patients achieving spontaneous HBeAg clearance as well as HBsAg decline. Therefore, our results provided complementary evidence for prognosis of pregnant CHB women after discontinuing treatment postpartum, thus contributing to postpartum management.
Data on the efficacy of postpartum retreatment in patients received a short period of NAs treatment during pregnancy are limited. Lu et al. explored the efficacy of combining Peg IFN α−2a with Adefovir in pregnant women received LdT treatment during pregnancy and with normal ALTs and high viral loads after delivery, showing higher rates of viral response compared to patients discontinuing treatment after delivery, suggesting that postpartum may be an opportunity to achieve a clinical cure [19]. However, ALT flare after postpartum treatment discontinuation is common and may require initiation of antiviral therapy, but there are no data to clarify the effectiveness of NAs retreatment. Here, we first explored the effectiveness of NAs retreatment in postpartum women discontinuing treatment, showing more significantly decrease of HBsAg and higher proportion of HBsAg < 1000 IU/mL in retreatment patients compared to patients received treatment pre-pregnancy. And over 40% of retreatment patients achieved HBsAg < 1000 IU/mL, even with higher levels of HBsAg and shorter treatment duration (Median time: 25 months) compared to patients received NAs treatment pre−pregnancy. And previous studies have indicated that patients with HBsAg <1000 IU/mL may gain a relatively high probability of HBsAg clearance [20, 21]. In the present study, almost all retreatment patients had ALT abnormalities, and many previous studies have shown more pronounced immune activation in patients with postpartum ALT abnormality, [22, 23] suggesting postpartum immune reconstitution may be an opportunity to achieve functional cure. And future studies are required to explore the immune response during retreatment to explain our results.
It remains controversial whether to initiate antiviral treatment for CHB patients in immune−tolerant phase. Previous studies indicated that antiviral treatment should not be recommended because of the low incidences of HBeAg seroconversion, HBsAg loss and other reasons [3, 5, 24, 25]. However, increasing evidence indicated persistent high viremia and persistent HBeAg increased the risk of cirrhosis, hepatocellular carcinoma, and liver−related death [26, 27]. Most pregnant women are in the immune-tolerance phase, and the immune system changed during pregnancy and postpartum may result the change of natural history [17, 28, 29]. The ALT flare postpartum may indicate the reactivation of HBV. Previous study indicated that ALT flare was self−limited and retreatment was not required [30]. However, if the patient developed a moderate, severe or non-self-limited ALT flare and viral rebound, indicating active hepatitis and retreatment was required, [17] thus the postpartum hepatitis and retreatment maybe an opportunity for functional cure for HBeAg positive women of childbearing age immune-tolerance phase.
This real−world pilot cohort study first investigated the effectiveness of NAs retreatment in postpartum women and provided evidence for prognosis after long−term postpartum treatment discontinuation. There are several limitations. First, patients receiving NAs treatment at 24–28 weeks of gestation showed remarkable decline in HBsAg and HBV DNA during pregnancy and therefore chose to continuing treatment postpartum. Therefore, these patients were not enrolled in our study. Second, the number of retreatment patients is relatively small in this retrospective−prospective study, which may affect the reliability of the results. However, patients enrolled in our study had a regular follow−up, which increased the reliability of results. Third, an HBV DNA assay with a lower limit of detection of 100 IU/mL was not the most sensitive. Fourth, we just evaluated the virologic kinetics in patients discontinuing treatment and after retreatment, the immunologic kinetics, the relationship between immunologic and virologic kinetics, and the suitable criteria for the patients who will be benefit from NAs retreatment need to be further explored in well-designed, multi-center, and prospective cohort studies with large samples.
Conclusions
In conclusion, this study provided a first clinical demonstration that HBeAg positive patients received NAs during pregnancy and discontinued it postpartum can benefit from NAs retreatment because of unexpected decrease of HBsAg, which may be helpful for CHB women of childbearing age to achieve functional cure.
Availability of data and materials
The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.
Abbreviations
- ALT:
-
Alanine aminotransaminase
- CHB:
-
Chronic hepatitis B
- CI:
-
Confidence interval
- DNA:
-
Deoxyribonucleic acid
- EOT:
-
End of treatment
- HBV:
-
Hepatitis B virus
- HBeAg:
-
Hepatitis B e antigen
- HBsAg:
-
Hepatitis B surface antigen
- LdT:
-
Telbivudine
- LLD:
-
Lower limit of detection
- MTCT:
-
Mother-to-child transmission
- NAs:
-
Nucleoside analogues
- Peg IFN a−2a:
-
Pegylated interferon α-2a
- TDF:
-
Tenofovir disoproxil fumarate
- ULN:
-
Upper limit of normal
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Acknowledgements
The authors are grateful to all research and clinic staff contributing to our work.
Funding
This work was funded in part by grants from the National Science and Technology Major Project of China (2017ZX10202203008), the National Natural Science Foundation of China (81772171), the Chongqing Talents Project (cstc2021ycjh−bgzxm0150), the First batch of key Disciplines on Public Health in Chongqing, Health Commission of Chongqing, China, the Remarkable Innovation–Clinical Research Project, The Second Affiliated Hospital of Chongqing Medical University and Scientific and the Technological Research Program of Chongqing Municipal Education Commission, The Second Affiliated Hospital of Chongqing Medical University (KJZD−K202300404). 3
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Qiao Tang contributed to writing the manuscript, data analysis and interpretation of the data. Peng Hu conceived the study, Chunrui Wang, Hu Li, Zhiwei Chen, Li Zhang, Xiaoqing Liu, Jing Zhang, Yunling Xue, Yue Qiu, Mingli Peng and Yi Zeng were involved in the study supervision and interpretation of the data. All authors have read and approved the final manuscript.
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This study was approved by the Institutional Review 2 Board of the Second Affiliated Hospital of Chongqing Medical University and was registered with the Chinese Clinical Trial Registry (ChiCTR2100054116). The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki. Obtained informed consent forms signed by all participants.
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Tang, Q., Wang, C., Li, H. et al. Unexpected HBsAg decrease after nucleoside analogues retreatment among HBeAg positive postpartum women: a pilot study. Virol J 22, 36 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12985-025-02632-x
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DOI: https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12985-025-02632-x