Retrospective Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 21, 2023; 29(19): 3003-3012
Published online May 21, 2023. doi: 10.3748/wjg.v29.i19.3003
Association of vitamin D and polymorphisms of its receptor with antiviral therapy in pregnant women with hepatitis B
Rui Wang, Xia Zhu, Xuan Zhang, Huan Liu, Yu-Lin Ji, Yong-Hua Chen
Rui Wang, Yong-Hua Chen, Division of Pancreatic Surgery, Department of General Surgery, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
Xia Zhu, Huan Liu, Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
Xuan Zhang, Yu-Lin Ji, Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
Author contributions: Wang R and Zhu X contributed equally to this work; Ji YL, Zhu X and Chen YH participated in design and oversight of the study; Zhu X, Zhang X and Liu H collected and study data; Wang R, Zhu X, Zhang X, Liu H, and Chen YH analyzed the data and wrote the manuscript; Zhu X, Ji YL and Chen YH revised the manuscript for important intellectual content; all authors have read and approved the final manuscript.
Supported by the Key Research and Development Projects in Sichuan Province, No. 2021YFS0168; and the National Scientific and Technological Major Project for Infectious Diseases Control in China, No. 2018ZX10715-003.
Institutional review board statement: The study was reviewed approved by the Institutional Review Board of the West China Hospital, Sichuan University, approval No. 2019-151.
Informed consent statement: All study participants or their legal guardians provided informed written consent about personal and medical data collection prior to study enrollment.
Conflict-of-interest statement: All authors report no relevant conflict of interest for this article.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yong-Hua Chen, MD, PhD, Associate Professor, Division of Pancreatic Surgery, Department of General Surgery, West China Hospital of Sichuan University, No. 37 Guoxue Alley, Wuhou District, Chengdu 610041, Sichuan Province, China. chenyonghua2007@163.com
Received: February 17, 2023
Peer-review started: February 17, 2023
First decision: March 24, 2023
Revised: March 28, 2023
Accepted: April 24, 2023
Article in press: April 24, 2023
Published online: May 21, 2023
Processing time: 87 Days and 18.5 Hours
Abstract
BACKGROUND

The interruption of mother-to-child transmission (MTCT) is considered important to decrease the individual and population morbidity of hepatitis B virus (HBV) infection as well as the global burden of hepatitis B. Serum vitamin D (VD) is associated with hepatitis B.

AIM

To assess whether baseline VD levels and single nucleotide polymorphisms of the VD receptor gene (VDR SNPs) are associated with the efficacy of tenofovir disoproxil fumarate (TDF) in the prevention of MTCT in pregnant women with high HBV viral loads.

METHODS

Thirty-eight pregnant women who were at high risk for MTCT of HBV (those with an HBV DNA level ≥ 2 × 105 IU/mL during 12-24 wk of gestation) receiving antiviral therapy of TDF between June 1, 2019 and June 30, 2021 in Mianyang were included in this retrospective study. The women received 300 mg TDF once daily from gestational weeks 24-28 until 3 mo after delivery. To further characterize the clinical relevance of maternal serum HBV DNA levels, we stratified patients according to HBV DNA level as follows: Those with levels < 2 × 105 (full responder group) vs those levels ≥ 2 × 105 IU/mL (partial responder group) at delivery. Serum levels of 25-hydroxyvitamin D [25(OH)D], liver function markers, virological parameters, VDR SNPs and other clinical parameters were collected to analyze their association with the efficacy of TDF. The Mann-Whitney U test or t test was used to analyze the serum levels of 25(OH)D in different groups. Multiple linear regressions were utilized to analyze the determinants of the maternal HBV DNA level at delivery. Univariate and multivariate logistic regression analyses were employed to explore the association of targeted antiviral effects with various characteristics at baseline and delivery.

RESULTS

A total of 38 pregnant women in Mianyang City at high risk for MTCT of HBV were enrolled in the study. The MTCT rate was 0%. No mother achieved hepatitis B e antigen or hepatitis B surface antigen (HBsAg) clearance at delivery. Twenty-three (60.5%) participants were full responders, and 15 (39.5%) participants were partial responders according to antiviral efficacy. The present study showed that a high percentage (76.3%) of pregnant women with high HBV viral loads had deficient (< 20 ng/mL) or insufficient (≥ 20 but < 31 ng/mL) VD levels. Serum 25(OH)D levels in partial responders appeared to be significantly lower than those in full responders both at baseline (25.44 ± 9.42 vs 17.66 ± 5.34 ng/mL, P = 0.006) and delivery (26.76 ± 8.59 vs 21.24 ± 6.88 ng/mL, P = 0.044). Serum 25(OH)D levels were negatively correlated with maternal HBV DNA levels [log(10) IU/mL] at delivery after TDF therapy (r = -0.345, P = 0.034). In a multiple linear regression analysis, maternal HBV DNA levels were associated with baseline maternal serum 25(OH)D levels (P < 0.0001, β = -0.446), BMI (P = 0.03, β = -0.245), baseline maternal log10 HBsAg levels (P = 0.05, β = 0.285) and cholesterol levels at delivery (P = 0.015, β = 0.341). Multivariate logistic regression analysis showed that baseline serum 25(OH)D levels (OR = 1.23, 95%CI: 1.04-1.44), maternal VDR Cdx2 TT (OR = 0.09, 95%CI: 0.01-0.88) and cholesterol levels at delivery (OR = 0.39, 95%CI: 0.17-0.87) were associated with targeted antiviral effects (maternal HBV DNA levels < 2 × 105 at delivery).

CONCLUSION

Maternal VD levels and VDR SNPs may be associated with the efficacy of antiviral therapy in pregnant women with high HBV viral loads. Future studies to evaluate the therapeutic value of VD and its analogs in reducing the MTCT of HBV may be justified.

Keywords: Hepatitis B virus; Vitamin D; Vitamin D receptor polymorphism; Antiviral therapy; Pregnancy; Mother-to-child transmission

Core Tip: This retrospective study investigated the influence of vitamin D (VD) levels and single nucleotide polymorphisms of the VD receptor gene (VDR SNPs) on the efficacy of tenofovir disoproxil fumarate in preventing mother-to-child transmission in 38 pregnant women with high hepatitis B viral loads. We demonstrate a significant association between low serum levels of 25-hydroxyvitamin D and high levels of hepatitis B virus replication in pregnant women with high hepatitis B viral loads, and maternal VD levels as well as VDR SNPs may be associated with the efficacy of antiviral therapy.