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Huang XX, Lin Q, Li Y, Li L. Effects of Maternal Health During Pregnancy and Child Immunization on Mother-to-Child Transmission of Hepatitis B Virus: A Multicentre, Large-Sample Study in Southeast China. Infect Drug Resist 2024; 17:989-1001. [PMID: 38505249 PMCID: PMC10949338 DOI: 10.2147/idr.s443172] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2023] [Accepted: 02/19/2024] [Indexed: 03/21/2024] Open
Abstract
Purpose High hepatitis B infection rates in China are a major public health issue, and mother-to-child transmission (MTCT) is a significant risk factor. Patients and Methods This study was conducted with a prospective multicentre design from January 2021 to December 2022 in 245 hospitals providing midwifery services in southeastern China. The participants were pregnant women who were positive for hepatitis B surface antigen (HBs Ag) and their children. The HBs Ag concentration was tested in children aged 8-12 months. The odds ratio for each risk factor was calculated by logistic regression analysis, and the decision tree model was used. Results A total of 5369 children born to hepatitis B-infected mothers between 8 and 12 months of age were enrolled, among whom 81 (1.51%) were positive for HBsAg. The risk factors for hepatitis B infection in 5369 children under one-year-old were a high intrauterine hepatitis B exposure level, a history of hepatitis B immunoglobulin (HBIG) delay beyond 12 hours after birth, and lack of full hepatitis B vaccine (HepB), with risks of 3.356 (1.223~9.209), 5.691 (1.931~16.773), and 5.137 (2.265~11.650), respectively. The discrimination accuracy of the decision tree was 98.5%. The risk factors for hepatitis B infection in 4542 children under one year old with high exposure risk were nonstandard treatment by the mother during pregnancy, HBIG delay beyond 12 hours after birth, and no complete HepB administration, with risks of 2.925 (1.063-8.047), 5.354 (1.806-15.871) and 5.147 (2.258-11.733), respectively. The discrimination accuracy of the decision tree was 98.3%. Conclusion To prevent mother-to-child transmission of hepatitis B, it is necessary to standardize the treatment of pregnant women with a high exposure risk of hepatitis B, implement combined vaccination within 12 hours of birth, and standardise the full course of HepB.
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Affiliation(s)
- Xin-Xin Huang
- The Ministry of Health, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China
| | - Quan Lin
- Department of Obstetrics, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China
| | - Yun Li
- Department of Obstetrics, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China
| | - Li Li
- Department of Obstetrics, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian Province, People’s Republic of China
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Patra S, Chopra K. Maternal Hepatitis: Important Considerations. INFECTIONS AND PREGNANCY 2022:151-164. [DOI: 10.1007/978-981-16-7865-3_12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Wu Y, Liu J, Feng Y, Fu S, Ji F, Ge L, Yao N, Luo X, Zhao Y, Chen Y, Yang Y, Chen T. Efficacy and safety of antiviral therapy for HBV in different trimesters of pregnancy: systematic review and network meta-analysis. Hepatol Int 2020; 14:180-189. [PMID: 32193814 PMCID: PMC7136311 DOI: 10.1007/s12072-020-10026-0] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2019] [Accepted: 02/21/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Several antiviral agents licenced for blocking mother-to-child transmission (MTCT) of HBV, but their relative efficacy beginning from different trimesters has scarce been evaluated. We aimed to conduct a network meta-analysis to statistically differ the efficacy and safety of each antiviral agents initiating on different timings in preventing mother-to-infant transmission of HBV. METHODS Studies were included from PubMed, EMBASE, Web of Science, and Cochrane databases through July 1, 2019. Eligible studies recruited randomized controlled trials and nonrandomized studies reporting about infant or/and maternal efficacy and safety outcomes and were screened by two investigators independently. Extracted data were analyzed by pair-wised and network meta-analysis, respectively. RESULTS 3 Randomized and 32 nonrandomized studies enrolling 6738 pregnant female were included. Using network analysis, any antiviral agent interrupted HBV vertical transmission much more effectively than placebo. No agent showed significant efficacy different from others, but a strong trend toward significance was found in telbivudine and tenofovir, of which had the highest probability of being ranked the first- or second-best treatment for reducing MTCT of HBV. The treatment applied in the first and second trimester had a similar efficacy in preventing MTCT. Compared with the initiation during the third trimester, lower rate of MTCT was revealed when antiviral therapy was administrated before third trimester, (RR = 0.045, 95% CI 0.0053 to 0.20); a similar effect at delivery on suppressing maternal HBV DNA level and converting serum HBeAg were achieved if the timing of antiviral treatment started prior, but an obvious improvement of normalizing ALT flare was calculated out; no statistically differences among maternal and fetal safety outcomes were found if mothers received antiviral agents before pregnant 28 weeks. CONCLUSION This network meta-analysis recommended the earlier use of telbivudine or tenofovir, tends to be better to prevent MTCT of HBV in pregnancy with no increased adverse maternal or fetal outcomes.
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Affiliation(s)
- Yuchao Wu
- Department of Infection Disease and Hepatopathy, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China
| | - Jinfeng Liu
- Department of Infection Disease and Hepatopathy, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China
| | - Yali Feng
- Department of Infection Disease and Hepatopathy, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China
| | - Shan Fu
- Department of Infection Disease and Hepatopathy, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China
| | - Fanpu Ji
- Department of Infection Disease and Hepatopathy, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Long Ge
- Evidence-Based Medicine Center, Basic Medical Sciences, Lanzhou University, Lanzhou, China.,WHO Collaborating Centre for Guideline Implementation and Knowledge Translation, Lanzhou, China
| | - Naijuan Yao
- Department of Infection Disease and Hepatopathy, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China
| | - Xufei Luo
- Evidence-Based Medicine Center, Basic Medical Sciences, Lanzhou University, Lanzhou, China.,WHO Collaborating Centre for Guideline Implementation and Knowledge Translation, Lanzhou, China
| | - Yingren Zhao
- Department of Infection Disease and Hepatopathy, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China
| | - Yaolong Chen
- Evidence-Based Medicine Center, Basic Medical Sciences, Lanzhou University, Lanzhou, China. .,WHO Collaborating Centre for Guideline Implementation and Knowledge Translation, Lanzhou, China.
| | - Yuan Yang
- Department of Infection Disease and Hepatopathy, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.
| | - Tianyan Chen
- Department of Infection Disease and Hepatopathy, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.
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Deng H, Liang S, Xu M, Zhuo L, Gao H, Chen K, Shi Y, Li H, Jiao Q, Lin L, Lei Y, Liu H. Clinical efficacy and safety in telbivudine- or tenofovir-treated hepatitis B e antigen-positive pregnant women. Antivir Ther 2020; 25:33-41. [PMID: 32049069 DOI: 10.3851/imp3345] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/05/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Telbivudine (LdT) and tenofovir (TDF) are widely used in pregnant women to prevent vertical transmission; however, limited data are available on the differences in clinical efficacy and safety between the two drugs. METHODS A total of 307 hepatitis B e antigen (HBeAg)-positive pregnant women with complete follow-up data were enrolled, the patients with alanine aminotransferase (ALT) levels <1×ULN at baseline were enrolled to cohort 1 for treatment from 28 ±4 weeks gestation to delivery, while ALT levels >1×ULN at baseline were enrolled to cohort 2 for treatment from 28 ±4 weeks gestation and continued after delivery. The clinical efficacy and safety was compared in LdT- and TDF-treated patients. In addition, 32 patients in cohort 1 were analysed for nucleoside analogue (NA)-related resistance mutations at baseline and after delivery. RESULTS The results showed that HBV DNA levels were significantly lower at delivery than at baseline (P<0.001), but the decreases in HBV DNA, ALT, total bilirubin and total bile acid levels did not differ between the LdT- and TDF-treated patients at different time points (P>0.05) in the two cohorts. However, gastrointestinal adverse effects (vomiting) occurred more frequently in TDF-treated than LdT-treated patients (6.6% versus 0.0%; P=0.001). The results of NA-related resistance mutations analysis in cohort 1 revealed that short-term LdT or TDF treatment did not significantly change the NA-related resistance mutations (P>0.05). CONCLUSIONS This study revealed that the clinical efficacy in LdT- or TDF-treated HBeAg-positive Chinese pregnant women is similar, and gastrointestinal adverse effects occurred more frequently in TDF-treated patients.
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Affiliation(s)
- Haohui Deng
- Department of Infectious Diseases Center, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China
| | - Shuzhen Liang
- Community Health Service Center of Lin He Street, Guangzhou, China
| | - Min Xu
- Department of Infectious Diseases Center, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China
| | - Li Zhuo
- Department of Infectious Diseases Center, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China
| | - Hongbo Gao
- Department of Infectious Diseases Center, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China
| | - Keng Chen
- Department of Infectious Diseases Center, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China
| | - Yuming Shi
- Department of Infectious Diseases Center, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China
| | - Huihui Li
- Department of Infectious Diseases Center, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China
| | - Qian Jiao
- Department of Infectious Diseases Center, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China
| | - Liansheng Lin
- Department of Infectious Diseases Center, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China
| | - Yan Lei
- Department of Infectious Diseases Center, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China
| | - Huiyuan Liu
- Department of Infectious Diseases Center, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China
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Komatsu H, Inui A, Suzuki Y, Sugiyama M, Fujisawa T. Deep sequencing of hepatitis B surface antigen gene in the preserved umbilical cords in immunoprophylaxis failure against mother-to-child HBV transmission. BMC Infect Dis 2019; 19:985. [PMID: 31752732 PMCID: PMC6873716 DOI: 10.1186/s12879-019-4624-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2019] [Accepted: 11/08/2019] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND Vaccine escape mutants (VEMs) are one of the causes of breakthrough infections in the mother-to-child transmission of hepatitis B virus (HBV). We hypothesized that VEMs existing as minor populations in the maternal blood are associated with breakthrough infections in children. We sought to determine whether VEMs exist as minor populations in the preserved umbilical cords of children with breakthrough infections. CASE PRESENTATION Two families (Family 1: three children, Family 2: two children) were enrolled. Despite immunoprophylaxis, a breakthrough infection occurred in two Family 1 children and two Family 2 children. Preserved umbilical cords, serum, and nails were used for the HBV DNA analysis. To detect VEMs, we performed direct and deep sequencing of hepatitis B surface antigen gene. The direct sequencing showed that there were no VEMs in the serum of the children or mother of Family 1 and family 2, but it identified a G145A mutant in the nails of the mother of Family 2. In Family 1, deep sequencing detected a T143S mutant as a minor population (1.7-2.0%) in the umbilical cords and serum of all three children and in the serum of the mother. A T126A mutant was also detected in the umbilical cord (9.2%) and serum (7.0%) of the first-born child of Family 1. In Family 2, the deep sequencing showed no VEMs in the umbilical cords, but it detected D144A (2.5%) and G145A (11.2%) mutants in the serum of the 2nd-born child. CONCLUSIONS VEMs were present as minor populations in the preserved umbilical cords of children with breakthrough infections. The VEMs did not become major populations after the breakthrough infections. The evolution of VEMs from a minor form to a major form might not be a prerequisite for breakthrough infections in mother-to-child transmission.
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Affiliation(s)
- Haruki Komatsu
- Department of Pediatrics, Toho University, Sakura Medical Center, 564-1 Shimoshizu Sakura, Chiba, 285-8741, Japan.
| | - Ayano Inui
- Department of Pediatric Hepatology and Gastroenterology, Eastern Yokohama Hospital, Kanagawa, Japan
| | - Yasuto Suzuki
- Department of Pediatrics, Kushiro Red Cross Hospital, Hokkaido, Japan
| | - Masaya Sugiyama
- Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Chiba, Japan
| | - Tomoo Fujisawa
- Department of Pediatric Hepatology and Gastroenterology, Eastern Yokohama Hospital, Kanagawa, Japan
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Song J, Yang F, Wang S, Tikande S, Deng Y, Tang W, Cao G. Efficacy and safety of antiviral treatment on blocking the mother-to-child transmission of hepatitis B virus: A meta-analysis. J Viral Hepat 2019; 26:397-406. [PMID: 30417469 DOI: 10.1111/jvh.13036] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2018] [Accepted: 10/25/2018] [Indexed: 02/06/2023]
Abstract
Nucleo(t)side analogues (NAs) have been administered as adjunctive therapy to interrupt the mother-to-child transmission (MTCT) of hepatitis B virus (HBV). The efficacy and safety of this method remain controversial. A meta-analysis was conducted to evaluate the efficacy and safety of NAs treatment during pregnancy. The differences among different agents and initiation trimesters were analysed. A total of 9228 mother-infant pairs in 59 studies (32 RCTs and 27 non-RCTs) were included in this meta-analysis. NAs significantly reduced the risk of MTCT, as indicated by seropositivity of hepatitis B surface antigen (HBsAg) (risk ratio (RR) = 0.51, 95% confidence interval (CI) 0.45-0.57) and HBV DNA in newborns (RR = 0.22, 95% CI 0.18-0.26). No differences in the efficacy of interrupting HBV MTCT were evident among lamivudine, telbivudine and tenofovir disoproxil fumarate. NA was more effective when administered from the second than from the third trimester as indicated by HBV DNA (RR: the second vs the third 0.08 vs 0.22, P = 0.010), but this effect was not evident as indicated by HBsAg (RR: the second vs the third 0.46 vs 0.53, P = 0.596). Antiviral treatment initiated from the second trimester did not confer a higher risk of safety problems in the newborns compared with treatment from the third trimester, as indicated by weight (P = 0.064), length (P = 0.491) and malformation rate (P = 0.635) of newborns. CONCLUSIONS: Lamivudine, telbivudine and tenofovir disoproxil fumarate are equally effective in blocking HBV MTCT. Antiviral treatment can be applied from the second trimester, without obvious safety concerns.
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Affiliation(s)
- Jiahui Song
- Department of Epidemiology, Second Military Medical University, Shanghai, China
| | - Fan Yang
- Department of Epidemiology, Second Military Medical University, Shanghai, China
| | - Shuo Wang
- Department of Epidemiology, Second Military Medical University, Shanghai, China
| | - Sakinatou Tikande
- Department of Epidemiology, Second Military Medical University, Shanghai, China
| | - Yang Deng
- Department of Epidemiology, Second Military Medical University, Shanghai, China
| | - Weina Tang
- Department of Epidemiology, Second Military Medical University, Shanghai, China
| | - Guangwen Cao
- Department of Epidemiology, Second Military Medical University, Shanghai, China
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Antiviral Therapy for AECHB and Severe Hepatitis B (Liver Failure). ACUTE EXACERBATION OF CHRONIC HEPATITIS B 2019. [PMCID: PMC7498919 DOI: 10.1007/978-94-024-1603-9_5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
This chapter describes the principles of antiviral therapy, treatment strategies, medications and recommendations for AECHB, HBV-ACLF, HBV-related liver cirrhosis, HBV-related HCC, and liver transplantation.
Severe exacerbation of chronic hepatitis B is closely related to continuous HBV replication. Therefore, inhibiting HBV replication to reduce viral load may block disease progression and improve the quality of life of these patients. ETV or TDF has been recommend first-line drug for the treatment of AECHB. A hyperactive immune response due to continuous HBV replication is the main mechanism for development of severe hepatitis B. In addition to comprehensive treatment, early administration of potent nucleoside analogs can rapidly reduce HBV DNA concentration, relieve immune injury induced by HBV, and reduce liver inflammation and patient mortality. Antiviral agents have become important in the treatment of severe exacerbation of chronic hepatitis B. Long-term antiviral treatment with nucleoside analogs can delay or reverse the progress of liver cirrhosis. Virologic response, viral resistance and adverse drug reactions should be closely monitored during treatment. The treatment should be optimized for maximum effect based on each patient’s responses. Effective antiviral therapy can suppress HBV replication and reduce the incidence of HBV-related HCC. Patients with HBV-related HCC should receive individualized and optimal multidisciplinary comprehensive treatment. Anti-viral drugs with high efficacy, low resistance and low adverse drug reactions should be selected to improve the patient’s quality of life and prolong survival time. Methods to prevent HBV reinfection after liver transplantation include passive immunization (HBIG), antiviral treatment (nucleoside analogs) and active immunization (hepatitis B vaccine). Clinical trials involving sequential combination therapy with NUC and Peg-IFN have shown statistically significant decline in HBsAg levels on treatment and high rates of sustained post-treatment serologic response. Combination therapy with novel DAA and immunotherapeutic approach may hold promise to overcome both cccDNA persistence and immune escape, representing a critical step towards HBV cure.
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Chen ZX, Zhuang X, Zhu XH, Hao YL, Gu GF, Cai MZ, Qin G. Comparative Effectiveness of Prophylactic Strategies for Perinatal Transmission of Hepatitis B Virus: A Network Meta-analysis of Randomized Controlled Trials. Open Forum Infect Dis 2017; 4:ofx225. [PMID: 29181424 PMCID: PMC5695632 DOI: 10.1093/ofid/ofx225] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2017] [Accepted: 10/10/2017] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Perinatal transmission is the main route of hepatitis B virus (HBV) transmission. While several measures have been attempted as means of preventing perinatal HBV transmission, the optimal strategy remains inconclusive. METHODS We conducted a comprehensive search, through December 2016, for randomized controlled trials (RCTs) that compared the following measures among pregnant women with HBV infection: placebo/none, active immunoprophylaxis (hepatitis B vaccine series starting at birth [HBVac]), passive-active immunoprophylaxis (hepatitis B immunoglobulin and vaccine [HBIG+HBVac]), prenatal HBIG administration (HBIG/HBIG+HBVac), and prenatal antiviral therapy (AVT/HBIG+HBVac). Direct, indirect, and network meta-analyses were performed for all treatment comparisons. RESULTS Fifteen RCTs involving 2706 infants of HBV carrier mothers were eligible for analysis. Network meta-analysis demonstrated similar results as direct and indirect comparisons. HBVac alone significantly reduced the risk of hepatitis B infection in infants of HBV carrier mothers (relative risk [RR], 0.32; 95% confidence interval [CI], 0.21-0.50). The combination of immunoglobulin with vaccine is superior to vaccine alone (RR, 0.37; 95% CI, 0.20-0.67). Prenatal HBIG administration and antiviral therapy offer further advantages over current passive-active immunoprophylaxis for infants of highly viremic (HBV DNA level higher than 2 × 105 IU/mL) mothers (RR, 0.47; 95% CI, 0.29-0.75; and RR, 0.31; 95% CI, 0.10-0.99, respectively). There was no significant publication bias. CONCLUSIONS Based on the universal infantile vaccination program, HBIG for infants born to HBV carrier mothers further reduces transmission. For highly viremic mothers whose children are still at risk for transmission under current immunoprophylaxis, prenatal HBIG administration or antiviral therapy in late pregnancy may be considered if more long-term evidence supports its efficacy and safety.
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Affiliation(s)
- Zhi-Xian Chen
- Department of Clinical Pharmacy, Nantong Health College of Jiangsu Province, Jiangsu, China
| | - Xun Zhuang
- Department of Epidemiology and Biostatistics, School of Public Health, Nantong University, Jiangsu, China
| | | | | | - Gui-Fang Gu
- Department of Obstetrics and Gynecology, Nantong Third People’s Hospital affiliated to Nantong University, Jiangsu, China
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Chen ZX, Gu GF, Bian ZL, Cai WH, Shen Y, Hao YL, Zhang S, Shao JG, Qin G. Clinical course and perinatal transmission of chronic hepatitis B during pregnancy: A real-world prospective cohort study. J Infect 2017; 75:146-154. [DOI: 10.1016/j.jinf.2017.05.012] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2016] [Revised: 03/27/2017] [Accepted: 05/11/2017] [Indexed: 01/24/2023]
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Han GR, Jiang HX, Wang CM, Ding Y, Wang GJ, Yue X, Zhou L, Zhao W. Long-term safety and efficacy of telbivudine in infants born to mothers treated during the second or third trimesters of pregnancy. J Viral Hepat 2017; 24:514-521. [PMID: 28039902 DOI: 10.1111/jvh.12670] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2016] [Accepted: 12/22/2016] [Indexed: 01/31/2023]
Abstract
Telbivudine, an FDA pregnancy category B drug, has been found to reduce hepatitis B virus (HBV) perinatal transmission with no safety concerns in infants aged up to 1 year. This study evaluated the long-term efficacy and safety of telbivudine in 214 infants born to 210 pregnant women with chronic hepatitis B infection who were treated with telbivudine during pregnancy (weeks 20-32 of gestation). The infants were followed for up to 5 years after birth. The efficacy endpoint was the rate of perinatal transmission, which was established by HBsAg and HBV DNA levels at 7 and 12 months. Safety endpoints included head circumference, weight, height, congenital abnormality and hospitalization rates. In addition, the Denver Developmental Screening Test was performed in 92 randomly selected infants. None of the 214 infants born to these women were infected with HBV, and all had effective serum hepatitis B surface antibody (HBsAb) levels. Compared with Chinese standard values, there were few differences in the infants' mean head circumference, weight, and height values. No birth defects were diagnosed, and the congenital abnormality rate was 0.934%. Serious adverse events requiring hospitalization occurred in 20 infants (9.35%). The qualified Denver Developmental Screening Test rate in 92 infants was 97.82%, which was comparable to a rate of 92% in normal Chinese children. Thus, treatment with telbivudine during the second or third trimesters of pregnancy safely blocked perinatal transmission of HBV. Infants born to telbivudine-treated mothers showed normal growth and development during long-term follow-up of up to 5 years.
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Affiliation(s)
- G-R Han
- Department of Gynecology and Obstetrics, The Second Affiliated Hospital of the Southeast University, Nanjing, China
| | - H-X Jiang
- Department of Gynecology and Obstetrics, The Second Affiliated Hospital of the Southeast University, Nanjing, China
| | - C-M Wang
- Department of Gynecology and Obstetrics, The Second Affiliated Hospital of the Southeast University, Nanjing, China
| | - Y Ding
- Department of Gynecology and Obstetrics, The Second Affiliated Hospital of the Southeast University, Nanjing, China
| | - G-J Wang
- Department of Gynecology and Obstetrics, The Second Affiliated Hospital of the Southeast University, Nanjing, China
| | - X Yue
- Department of Gynecology and Obstetrics, The Second Affiliated Hospital of the Southeast University, Nanjing, China
| | - L Zhou
- Department of Gynecology and Obstetrics, School of Medicine, Southeast University, Nanjing, China
| | - W Zhao
- Department of Infectious Diseases, The Second Affiliated Hospital of the Southeast University, Nanjing, China
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Komatsu H, Inui A, Umetsu S, Tsunoda T, Sogo T, Konishi Y, Fujisawa T. Evaluation of the G145R Mutant of the Hepatitis B Virus as a Minor Strain in Mother-to-Child Transmission. PLoS One 2016; 11:e0165674. [PMID: 27812178 PMCID: PMC5094722 DOI: 10.1371/journal.pone.0165674] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2016] [Accepted: 10/14/2016] [Indexed: 02/06/2023] Open
Abstract
The role of the hepatitis B virus (HBV) mutant G145R, with a single change in amino acid 145 of the surface protein, as a minor population remains unknown in mother-to-child transmission. The minor strain as well as the major strain of the G145R mutant were evaluated in three cohorts using a locked nucleic acid probe-based real-time PCR. The breakthrough cohort consisted of children who were born to HBV carrier mothers and became HBV carriers despite immnoprophylaxis (n = 25). The control cohort consisted of HBV carriers who had no history of receiving the hepatitis B vaccine, hepatitis B immunoglobulin or antiviral treatment (n = 126). The pregnant cohort comprised pregnant women with chronic HBV infection (n = 31). In the breakthrough cohort, 6 showed positive PCR results (major, 2; minor, 4). In the control cohort, 13 showed positive PCR results (major, 0; minor, 13). HBeAg-positive patients were prone to have the G145R mutant as a minor population. Deep sequencing was performed in a total of 32 children (PCR positive, n = 13; negative, n = 19). In the breakthrough cohort, the frequency of the G145R mutant ranged from 0.54% to 6.58%. In the control cohort, the frequency of the G145R mutant ranged from 0.42% to 4.1%. Of the 31 pregnant women, 4 showed positive PCR results (major, n = 0; minor, n = 4). All of the pregnant women were positive for HBeAg and showed a high viral load. Three babies born to 3 pregnant women with the G145R mutant were evaluated. After the completion of immunoprophylaxis, 2 infants became negative for HBsAg. The remaining infant became negative for HBsAg after the first dose of HB vaccine. G145R was detected in one-fourth of the children with immunoprophylaxis failure. However, the pre-existence of the G145R mutant as a minor population in pregnant women does not always cause breakthrough infection in infants.
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Affiliation(s)
- Haruki Komatsu
- Department of Pediatrics, Toho University, Sakura Medical Center, Chiba, Japan
- Department of Pediatric Hepatology and Gastroenterology, Eastern Yokohama Hospital, Kanagawa, Japan
- * E-mail:
| | - Ayano Inui
- Department of Pediatric Hepatology and Gastroenterology, Eastern Yokohama Hospital, Kanagawa, Japan
| | - Shuichiro Umetsu
- Department of Pediatric Hepatology and Gastroenterology, Eastern Yokohama Hospital, Kanagawa, Japan
| | - Tomoyuki Tsunoda
- Department of Pediatric Hepatology and Gastroenterology, Eastern Yokohama Hospital, Kanagawa, Japan
| | - Tsuyoshi Sogo
- Department of Pediatric Hepatology and Gastroenterology, Eastern Yokohama Hospital, Kanagawa, Japan
| | - Yasuhiro Konishi
- Department of Obstetrics & Gynecology, Eastern Yokohama Hospital, Kanagawa, Japan
| | - Tomoo Fujisawa
- Department of Pediatric Hepatology and Gastroenterology, Eastern Yokohama Hospital, Kanagawa, Japan
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Tan Z, Yin Y, Zhou J, Wu L, Xu C, Hou H. Telbivudine treatment of hepatitis B virus-infected pregnant women at different gestational stages for the prevention of mother-to-child transmission: Outcomes of telbivudine treatment during pregnancy. Medicine (Baltimore) 2016; 95:e4847. [PMID: 27749537 PMCID: PMC5059039 DOI: 10.1097/md.0000000000004847] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2015] [Revised: 07/14/2016] [Accepted: 08/17/2016] [Indexed: 12/17/2022] Open
Abstract
This prospective study evaluated the viability of telbivudine for blocking mother-to-child transmission (MTCT) of hepatitis B virus (HBV) infection.Pregnant women positive for the hepatitis B surface antigen began telbivudine treatment before 14 weeks of gestation (i.e., early), between 14 and 28 weeks of gestation (late), or not at all (control). In the late-treatment group, 55 women terminated telbivudine therapy within puerperium. All neonates underwent routine hepatitis B immunoglobulin plus vaccination. Mothers and infants were followed for 7 months after birth.Pregnancy outcomes were similar among the 3 groups. HBV MTCT rates in the early and late treatment and control groups were 0, 0, and 4.69%, respectively. The rates of infant vaccination success among the 3 groups were similar, as were neonatal outcomes including birth weights, asphyxia, hyperbilirubinemia, Apgar score, birth defects, and weight and height at 7 months. Puerperal discontinuation of telbivudine did not increase the alanine transaminase value at 7 months after birth, but increased serum HBV DNA levels, and rates of positive hepatitis Be-antigen.Telbivudine treatment in HBV-infected pregnant women was associated with lower serum HBV DNA levels and reduced rates of HBV MTCT; there were no associated changes in pregnancy or neonatal outcomes at birth or 7 months after birth, or in the rate of infant vaccination success. Puerperal drug withdrawal after short-term antiviral therapy will not influence hepatic function, but may increase virus replication.
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Affiliation(s)
| | - Yuzhu Yin
- Department of Obstetrics and Gynecology, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Correspondence: Yuzhu Yin, Department of Obstetrics and Gynecology, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China (e-mail: )
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Yi P, Chen R, Huang Y, Zhou RR, Fan XG. Management of mother-to-child transmission of hepatitis B virus: Propositions and challenges. J Clin Virol 2016; 77:32-9. [PMID: 26895227 DOI: 10.1016/j.jcv.2016.02.003] [Citation(s) in RCA: 59] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2015] [Revised: 01/26/2016] [Accepted: 02/04/2016] [Indexed: 02/07/2023]
Abstract
Chronic hepatitis B virus (HBV) infection due to mother-to-child transmission (MTCT) during perinatal period remains an important global health problem. Despite standard passive-active immunoprophylaxis with hepatitis B immunoglobulin (HBIG) and hepatitis B vaccine in neonates, up to 9% of newborns still acquire HBV infection, especially these from hepatitis B e antigen (HBeAg) positive mothers. Management of HBV infection in pregnancy still need to draw careful attention because of some controversial aspects, including the failure of passive-active immunoprophylaxis in a fraction of newborns, the effect and necessity of periodical hepatitis B immunoglobulin (HBIG) injection to the mothers, the safety of antiviral prophylaxis with nucleoside/nucleotide analogs, the benefit of different delivery ways, and the safety of breastfeeding. In this review, we highlight these unsettled issues of preventive strategies in perinatal period, and we further aim to provide an optimal approach to the management of preventing MTCT of HBV infection.
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Affiliation(s)
- Panpan Yi
- Department of Infectious Diseases, Key Laboratory of Viral Hepatitis of Hunan, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Ruochan Chen
- Department of Infectious Diseases, Key Laboratory of Viral Hepatitis of Hunan, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Yan Huang
- Department of Infectious Diseases, Key Laboratory of Viral Hepatitis of Hunan, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Rong-Rong Zhou
- Department of Infectious Diseases, Key Laboratory of Viral Hepatitis of Hunan, Xiangya Hospital, Central South University, Changsha 410008, China.
| | - Xue-Gong Fan
- Department of Infectious Diseases, Key Laboratory of Viral Hepatitis of Hunan, Xiangya Hospital, Central South University, Changsha 410008, China.
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Wu Q, Xu C, Li J, Li L, Yan G, Yue L, Zeng Y, Huang H, Deng G, Wang Y. Evolution and mutations of hepatitis B virus quasispecies in genotype B and C during vertical transmission. J Med Virol 2015; 88:1018-26. [PMID: 26531675 DOI: 10.1002/jmv.24424] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/02/2015] [Indexed: 12/15/2022]
Abstract
Evolution patterns of HBV QS between genotype B and C during vertical transmission are not well understood. In this study, we enrolled 10 HBV infected mother-infant pairs (four pairs with genotype B, four pairs with genotype C, and two with co-infection) without anti-viral therapy. Serum HBV DNA of mothers and infants were sequenced, HBV QS complexity and diversity were analyzed, polymorphisms and mutation sites were recorded, and phylogenetic trees were performed. Our result showed that the QS complexities in P (amino acid), C/PreC (amino acid), and PreS1 (nucleotide) gene were significantly higher in mothers than in infants in pairs with genotype C (P < 0.05), however, full-length and other genes showed non-significant differences (P > 0.05). Unlike genotype C, QS complexity of P gene (nucleotide) was significantly higher in infants than in mothers (P < 0.05) in pairs with genotype B, similarly, QS complexities of full-length and other genes (except Pre S2) were also higher in infants than in mothers but without significant differences (P > 0.05). QS diversities of full-length and most genes in genotype B were comparable between mothers and their infants (P > 0.05), in pairs with genotype C, dS of P, X, RT genes, genetic distance of Pre S1 gene (amino acid) and dN of Pre S1 gene were significant higher in mothers than in infants (P < 0.05). Several HBV mutations correlated with immune escape, e antigen loss and drug resistance were observed in infants. The results indicated that differences of HBV QS evolution patterns between genotype B and C during vertical transmission might contribute to distinct prognosis.
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Affiliation(s)
- Quanxin Wu
- Department of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing, China.,The Chongqing Key Laboratory for Research of Infectious Diseases, Chongqing, China.,Cadre Ward Two, Wuhan General Hospital of Guangzhou Military Command, Wuhan, China
| | - Cheng Xu
- Department of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing, China.,The Chongqing Key Laboratory for Research of Infectious Diseases, Chongqing, China
| | - Junnan Li
- Department of Gynecology and Obstetrics, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Li Li
- Department of Gynecology and Obstetrics, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Guohua Yan
- Department of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing, China.,The Chongqing Key Laboratory for Research of Infectious Diseases, Chongqing, China
| | - Liangliang Yue
- National Plateau Wetland Research Center, Southwest Forest University, Kunming, China
| | - Yi Zeng
- Department of Gynecology and Obstetrics, The First People's Hospital, Zigong, Sichuan, China
| | - Hongfei Huang
- Department of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing, China.,The Chongqing Key Laboratory for Research of Infectious Diseases, Chongqing, China
| | - Guohong Deng
- Department of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing, China.,The Chongqing Key Laboratory for Research of Infectious Diseases, Chongqing, China
| | - Yuming Wang
- Department of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing, China.,The Chongqing Key Laboratory for Research of Infectious Diseases, Chongqing, China
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Wu Q, Huang H, Sun X, Pan M, He Y, Tan S, Zeng Y, Li L, Deng G, Yan Z, He D, Li J, Wang Y. Telbivudine prevents vertical transmission of hepatitis B virus from women with high viral loads: a prospective long-term study. Clin Gastroenterol Hepatol 2015; 13:1170-6. [PMID: 25251571 DOI: 10.1016/j.cgh.2014.08.043] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2014] [Revised: 08/28/2014] [Accepted: 08/30/2014] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Hepatitis B virus (HBV) infection is a leading cause of liver diseases. We investigated the efficacy and safety of telbivudine in preventing transmission of HBV from hepatitis B e antigen-positive pregnant women with high viral loads to their infants in an open-label study. METHODS We performed a prospective study of 450 hepatitis B e antigen-positive pregnant women with HBV DNA levels greater than 10(6) IU/mL; 279 women received telbivudine (600 mg/d) during weeks 24 to 32 of gestation, and 171 women who were unwilling to take antiviral drugs participated as controls. All newborns were vaccinated with a recombinant HBV vaccine and hepatitis B immune globulin, according to a standard immunoprophylaxis procedure. Mother-to-child transmission of HBV was determined by detection of hepatitis B surface antigen and HBV DNA in the infant 6 months after birth. RESULTS None of the infants whose mothers were given telbivudine tested positive for of hepatitis B surface antigen at 6 months, compared with 14.7% of infants in the control group (P = 5.317 × 10(-8)). Levels of HBV DNA also decreased among women given telbivudine; 40 of 172 (23.2%) women given telbivudine had undetectable HBV DNA levels before delivery, compared with none of the controls. A significantly higher proportion of women given telbivudine had undetectable levels of HBV DNA in cord blood (99.1%) than controls (61.5%; P = 1.195 × 10(-22)). No severe adverse events or complications were observed in women or infants. CONCLUSIONS Telbivudine significantly reduces vertical transmission of HBV from pregnant women to their infants; it is safe and well tolerated by women and infants. Antiretroviral Pregnancy Registry Health Care Providers ID: 26592; Government number: Natural Science Foundation of China (NSFC) 30830090, 30972598; and Third Military Medical University Key Project for Clinical Research: 2012XLC05).
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Affiliation(s)
- Quanxin Wu
- Department of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing, China; The Chongqing Key Laboratory for Research of Infectious Diseases, China
| | - Hongfei Huang
- Department of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing, China; The Chongqing Key Laboratory for Research of Infectious Diseases, China
| | - Xiaowen Sun
- Department of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing, China; The Chongqing Key Laboratory for Research of Infectious Diseases, China
| | - Meimin Pan
- Department of Infectious Diseases, The First Hospital of Changsha, Hunan, China
| | - Yun He
- The 309th Hospital of Chinese People's Liberation Army, Beijing, China
| | - Shun Tan
- Department of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing, China; The Chongqing Key Laboratory for Research of Infectious Diseases, China
| | - Yi Zeng
- Department of Gynecology and Obstetrics, the First People's Hospital, Zigong, Sichuan, China
| | - Li Li
- Department of Gynecology and Obstetrics, Southwest Hospital, Third Military Medical University, China
| | - Guohong Deng
- Department of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing, China; The Chongqing Key Laboratory for Research of Infectious Diseases, China
| | - Zehui Yan
- Department of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing, China; The Chongqing Key Laboratory for Research of Infectious Diseases, China
| | - Dengming He
- Department of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing, China; Liver Disease Diagnoses and Treatment Center, the 88th Hospital of Chinese People's Liberation Army, Taian, Shandong, China
| | - Junnan Li
- Department of Gynecology and Obstetrics, Southwest Hospital, Third Military Medical University, China.
| | - Yuming Wang
- Department of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing, China; The Chongqing Key Laboratory for Research of Infectious Diseases, China.
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16
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Foaud H, Maklad S, Mahmoud F, El-Karaksy H. Occult hepatitis B virus infection in children born to HBsAg-positive mothers after neonatal passive-active immunoprophylaxis. Infection 2015; 43:307-314. [PMID: 25665956 DOI: 10.1007/s15010-015-0733-6] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2014] [Accepted: 01/19/2015] [Indexed: 01/04/2023]
Abstract
BACKGROUND Occult hepatitis B virus infection (OBI) is a well-recognized clinical entity characterized by the detection of HBV DNA in serum and/or liver in the absence of detectable HBsAg. Diagnosis of OBI requires a sensitive HBV DNA assay. AIM We aimed at determining the frequency of OBI in infants, born to HBsAg-positive mothers, who received immunoprophylaxis at birth. METHODS Sixty-four infants and children, born to HBsAg-positive mothers, who received hepatitis B immunoglobulin and HBV vaccine within 48 h after birth, were tested for HBV serological profile and HBV DNA by real-time PCR at least 1 month after last dose of HBV vaccine and not before 6 months of age. RESULTS The median age of the studied infants and children was 8 months, ranging from 6 to 132 months; 54.7 % were females. HBV DNA was detected in 2 infants. One case had OBI; she was negative for HBsAg, anti-HBc total, HBeAg and was positive for anti-HBs (titer 267 mIU/mL) with low level of viremia (HBV DNA 1.13 x 10(3) IU/mL). Another infant showed immunoprophylaxis failure with positive HBsAg, anti-HBc total, HBeAg, negative anti-HBe and anti-HBs; HBV viral load was 1.7 × 10(8) IU/mL. Both mothers were HBsAg and HBeAg-positive. CONCLUSION OBI may occur in infants born to HBsAg-positive mothers despite the receipt of immunoprophylaxis. OBI was detected in a low frequency in the present study. Anti-HBs positivity does not exclude OBI.
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Affiliation(s)
- Hanan Foaud
- Department of Pediatrics, National Hepatology and Tropical Medicine Research Institute, 7101 El-Kahera Buildings, El-Mokattam, Cairo, 11415, Egypt,
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Lamberth JR, Reddy SC, Pan JJ, Dasher KJ. Chronic hepatitis B infection in pregnancy. World J Hepatol 2015; 7:1233-7. [PMID: 26019737 PMCID: PMC4438496 DOI: 10.4254/wjh.v7.i9.1233] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2014] [Revised: 01/26/2015] [Accepted: 02/10/2015] [Indexed: 02/06/2023] Open
Abstract
There are no standard guidelines to follow when a patient with chronic hepatitis B infection becomes pregnant or desires pregnancy. Topics to consider include which patients to treat, when to start treatment, what treatment to use and when to stop treatment. Without any prophylaxis or antiviral therapy, a hepatitis B surface antigen and E antigen positive mother has up to a 90% likelihood of vertical transmission of hepatitis B virus (HBV) to child. Standard of care in the United States to prevent perinatal transmission consists of administration of hepatitis B immune globulin and HBV vaccination to the infant. The two strongest risk factors of mother to child transmission (MTCT) of HBV infection despite immunoprophylaxis are high maternal HBV viral load and high activity of viral replication. The goal is to prevent transmission of HBV at birth by decreasing viral load and/or decreasing activity of the virus. Although it is still somewhat controversial, most evidence shows that starting antivirals in the third trimester is effective in decreasing MTCT without affecting fetal development. There is a growing body of literature supporting the safety and efficacy of antiviral therapies to reduce MTCT of hepatitis B. There are no formal recommendations regarding which agent to choose. Tenofovir, lamivudine and telbivudine have all been proven efficacious in decreasing viral load at birth without known birth defects, but final decision of which antiviral medication to use will have to be determined by physician and patient. The antivirals may be discontinued immediately if patient is breastfeeding, or within first four weeks if infant is being formula fed.
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Affiliation(s)
- Jennifer R Lamberth
- Jennifer R Lamberth, Sheila C Reddy, Jen-Jung Pan, Kevin J Dasher, Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, the University of Texas Health Science Center at Houston, Houston, TX 77030, United States
| | - Sheila C Reddy
- Jennifer R Lamberth, Sheila C Reddy, Jen-Jung Pan, Kevin J Dasher, Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, the University of Texas Health Science Center at Houston, Houston, TX 77030, United States
| | - Jen-Jung Pan
- Jennifer R Lamberth, Sheila C Reddy, Jen-Jung Pan, Kevin J Dasher, Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, the University of Texas Health Science Center at Houston, Houston, TX 77030, United States
| | - Kevin J Dasher
- Jennifer R Lamberth, Sheila C Reddy, Jen-Jung Pan, Kevin J Dasher, Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, the University of Texas Health Science Center at Houston, Houston, TX 77030, United States
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18
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Li Z, Hou X, Cao G. Is mother-to-infant transmission the most important factor for persistent HBV infection? Emerg Microbes Infect 2015; 4:e30. [PMID: 26060603 PMCID: PMC4451268 DOI: 10.1038/emi.2015.30] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2015] [Revised: 03/24/2015] [Accepted: 04/06/2015] [Indexed: 02/06/2023]
Abstract
Of the infants born to hepatitis B surface antigen (HBsAg)-positive mothers globally, 42.1% who did not receive hepatitis B virus (HBV) passive-active immunoprophylaxis and 2.9% of infants who received the immunoprophylaxis acquired HBV infection perinatally. Moreover, perinatal infection occurred in 84.2% (18.8%-100%) and 8.7% (0.0-21.0%) of infants born to hepatitis B e-antigen (HBeAg)-positive mothers who did not and did receive immunoprophylaxis, respectively; by contrast, the infection rates were 6.7% (0.0-15.4%) and 0.4% (0.0-2.5%) for infants born to HBeAg-negative-carrier mothers, respectively. The chronicity rates of HBV infection acquired perinatally were 28.2% (17.4%-33.9%) in infants born to HBeAg-negative mothers and 64.5% (53.5%-100%) in infants born to HBeAg-positive mothers. HBV mother-to-child transmission was more frequent in East Asia relative to other areas. In addition to differences in the endemic HBV genotype, the interchange of allelic dominance in genetic polymorphisms in HLA class II and NF-κB between the Chinese and European populations may explain why chronic HBV infection frequently affects the Chinese. The risk of progressing into chronic infection was inversely related to the age of children at the time of horizontal transmission. To further diminish HBV chronic infection, it is necessary to enforce antiviral treatment after the 28th week of gestation for HBeAg-positive mothers and to improve the health habits of carrier mothers and household sanitary conditions.
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Affiliation(s)
- Zixiong Li
- Department of Epidemiology, Second Military Medical University , Shanghai 200433, China
| | - Xiaomei Hou
- Department of Epidemiology, Second Military Medical University , Shanghai 200433, China
| | - Guangwen Cao
- Department of Epidemiology, Second Military Medical University , Shanghai 200433, China
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Abstract
For two decades, hepatitis B vaccine has been integrated into national routine childhood vaccination programs in almost all countries. The prevalence of HBsAg has decreased in children worldwide. However, there are children who miss the benefit of hepatitis B vaccine in some regions and countries. Long-term follow-up studies have revealed the clinical outcomes of chronic hepatitis B virus infection in children. A small percentage of chronically infected children develop liver cirrhosis and hepatocellular carcinoma. However, it is controversial who should be treated and when antiviral treatment should be initiated in children. Compared with adult studies, the data are insufficient to evaluate the pathogenesis of hepatitis B infection and the efficacy of antiviral treatment in childhood. New antiviral drugs have been approved for children and adults. Also, oral antiviral drugs are administered to pregnant women to reduce the hepatitis B virus mother-to-child transmission rate.
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Affiliation(s)
- Haruki Komatsu
- Department of Pediatrics, Toho University, Sakura Medical Center, 564-1 Shimoshizu Sakura, Chiba, 285-8741, Japan
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Abdi F, Novin MG, Afrakhteh M, Khorvash F. Hepatitis B and pregnancy: An update review article. World J Obstet Gynecol 2015; 4:1-8. [DOI: 10.5317/wjog.v4.i1.1] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2014] [Revised: 03/24/2014] [Accepted: 11/03/2014] [Indexed: 02/05/2023] Open
Abstract
Chronic hepatitis B, as a global health problem, is a disease that begins in the prenatal period and its complications gradually become clear later in life. About 5% of women worldwide are carriers of chronic hepatitis B virus (HBV). The most common method of transmission of HBV around the world is from mother to infant. This article aims to review the unique challenges of hepatitis B in pregnancy. Data for this review were collected from our previous studies and experiences plus various data banks, such as PubMed, EMBASE, ISI Web of science, Scopus, Google Scholar and Iranian databases. A comprehensive search was performed using the combinations of the keywords to review relevant literature and higher education journals. All published data up to February 2014 have been included in this review. This article addresses several interesting aspects. First, hepatitis B in pregnancy can vary regarding prevalence, virus behavior, prenatal transmission and outcome of the pregnancy. Second, the women of reproductive age with chronic HBV remain a major source for continued spread of the virus. Finally, pregnant women need screening in prenatal care to enable early intervention when necessary.
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Elefsiniotis I, Vezali E, Vrachatis D, Hatzianastasiou S, Pappas S, Farmakidis G, Vrioni G, Tsakris A. Post-partum reactivation of chronic hepatitis B virus infection among hepatitis B e-antigen-negative women. World J Gastroenterol 2015; 21:1261-1267. [PMID: 25632200 PMCID: PMC4306171 DOI: 10.3748/wjg.v21.i4.1261] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2014] [Revised: 08/20/2014] [Accepted: 10/15/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the frequency and timing of post-partum chronic hepatitis B virus (HBV) reactivation and identify its pre-partum predictors.
METHODS: Forty-one hepatitis B e antigen (HBeAg)-negative chronic HBV infected pregnant women were prospectively evaluated between the 28th and the 32nd week of gestation. Subjects were re-evaluated at 3-mo intervals during the first post-partum year and every 6 mo during the following years. HBV DNA was determined using real-time reverse transcription polymerase chain reaction (Cobas TaqMan HBV Test) with a lower detection limit of 8 IU/mL. Post-partum reactivation (PPR) was defined as abnormal alanine aminotransaminase (ALT) levels and HBV DNA above 2000 IU/mL.
RESULTS: Fourteen out of 41 women (34.1%) had pre-partum HBV DNA levels > 2000 IU/mL, 18 (43.9%) had levels < 2000 IU/mL and 9 (21.9%) had undetectable levels. Fourteen women were lost to follow-up (failure to return). PPR occurred in 8 of the 27 (29.6%) women evaluated, all within the first 6 mo after delivery (5 at month 3; 3 at month 6). Five of the 6 (83.3%) women with pre-partum HBV DNA > 10000 IU/mL exhibited PPR compared with 3 of the 21 (14.3%) women with HBV DNA < 10000 IU/mL (two with HBV DNA > 2000 and the third with HBV DNA of 1850 IU/mL), P = 0.004. An HBV DNA level ≥ 10000 IU/mL independently predicted post-partum HBV infection reactivation (OR = 57.02, P = 0.033). Mean pre-partum ALT levels presented a non-significant increase in PPR cases (47.3 IU/L vs 22.2 IU/L, respectively, P = 0.094).
CONCLUSION: In the present study, PPR occurred in approximately 30% of HBeAg-negative pregnant women; all events were observed during the first semester after delivery. Pre-partum HBV DNA level > 10000 IU/mL predicted PPR.
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Zhou F, Li J, Lin K, Ji P, Sun Y. Across-sectional study on anxiety and stress in pregnant women with chronic HBV infection in the People's Republic of China. Neuropsychiatr Dis Treat 2015; 11:2225-32. [PMID: 26346004 PMCID: PMC4556245 DOI: 10.2147/ndt.s88602] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
PURPOSE To investigate the anxiety and pregnancy-associated stress of pregnant women with chronic hepatitis B virus (HBV) infection in the People's Republic of China and analyze the relationship between anxiety and pregnancy-associated stress in the hope of finding ways to reduce the stress or improve the coping skills for these mothers-to-be during pregnancy. METHODS A cross-sectional study was conducted. One hundred and sixty chronic HBV-infected pregnant women (HBV group) and 160 healthy pregnant women (control group) selected from three Peking University-affiliated hospitals participated in the study, and completed the State-Trait Anxiety Inventory (STAI) and Pregnancy Stress Rating Scale (PSRS) survey. RESULTS The mean scores of STAI and PSRS for the HBV group were higher than for the control group. Factor 2 of PSRS (stress caused by worrying about mother and child's health and safety) was the highest, and was significantly higher in the HBV group than in the control group. Correlation analysis showed STAI scores were significantly correlated with economic status and diagnosis, as well as the total score, factor 1 (stress about identifying with the role of mother), and factor 2 of PSRS, but not significantly correlated with factor 3 of PSRS (stress caused by the changes of body shape and physical activity). CONCLUSION Pregnant women with chronic HBV infection experienced higher levels of anxiety and stress than healthy pregnant women. Their major stress came from concerns for the health and safety of the mother and the child.
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Affiliation(s)
- Fen Zhou
- School of Nursing, Peking University, Beijing, People's Republic of China
| | - Jianju Li
- Infection Control Department, Beijing Ditan Hospital, Capital Medical University, Beijing, People's Republic of China
| | - Keke Lin
- School of Nursing, Peking University, Beijing, People's Republic of China
| | - Ping Ji
- School of Nursing, Peking University, Beijing, People's Republic of China
| | - Yumei Sun
- School of Nursing, Peking University, Beijing, People's Republic of China
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23
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Antiviral treatment among pregnant women with chronic hepatitis B. Infect Dis Obstet Gynecol 2014; 2014:546165. [PMID: 25548510 PMCID: PMC4274824 DOI: 10.1155/2014/546165] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2014] [Revised: 10/23/2014] [Accepted: 10/23/2014] [Indexed: 12/15/2022] Open
Abstract
Objective. To describe the antiviral treatment patterns for chronic hepatitis B (CHB) among pregnant and nonpregnant women. Methods. Using 2011 MarketScan claims, we calculated the rates of antiviral treatment among women (aged 10–50 years) with CHB. We described the pattern of antiviral treatment during pregnancy and ≥1 month after delivery. Results. We identified 6274 women with CHB during 2011. Among these, 64 of 507 (12.6%) pregnant women and 1151 of 5767 (20.0%) nonpregnant women received antiviral treatment (P < 0.01). Pregnant women were most commonly prescribed tenofovir (73.4%) and lamivudine (21.9%); nonpregnant women were most commonly prescribed tenofovir (50.2%) and entecavir (41.3%) (P < 0.01). Among 48 treated pregnant women with an identifiable delivery date, 16 (33.3%) were prescribed an antiviral before pregnancy and continued treatment for at least one month after delivery; 14 (29.2%) started treatment during the third trimester and continued at least one month after delivery. Conclusion. Among this insured population, pregnant women with CHB received an antiviral significantly less often than nonpregnant women. The most common antiviral prescribed for pregnant women was tenofovir. These data provide a baseline for assessing changes in treatment patterns with anticipated increased use of antivirals to prevent breakthrough perinatal hepatitis B virus infection.
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Zhang Z, Chen C, Li Z, Wu YH, Xiao XM. Individualized management of pregnant women with high hepatitis B virus DNA levels. World J Gastroenterol 2014; 20:12056-12061. [PMID: 25232243 PMCID: PMC4161794 DOI: 10.3748/wjg.v20.i34.12056] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2013] [Revised: 01/09/2014] [Accepted: 04/03/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B is a major health concern in the Asia-Pacific region, and is endemic in China, Southeast Asia, and Africa. Chronic hepatitis B virus (HBV) infection may cause hepatic cirrhosis and liver cancer. It is estimated that there are more than 350 million chronic HBV carriers worldwide, of whom approximately one quarter will die of chronic hepatitis B-related liver diseases. HBV is transmitted horizontally through blood and blood products or by sexual transmission, and vertically from mother to infant. Perinatal infection is the predominant mode of transmission in countries with a high prevalence of hepatitis B surface antigen (HBsAg) carriage, and perinatal transmission leads to high rates of chronic infection. Therefore, it is important to prevent the mother-to-child transmission (MTCT) of HBV. Research has shown that pregnant women with high HBV DNA levels have an increased risk of MTCT. However, most of the obstetrics guidelines do not make a distinction between pregnant women with high HBV DNA levels and those who are HBsAg positive only. This review addresses the management of pregnant women with high levels of HBV viremia, in terms of antiviral therapy, use of hepatitis B immunoglobulin (HBIG), the combined application of hepatitis B vaccine and HBIG, choice of delivery mode and feeding practices.
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Li Z, Xie Z, Ni H, Zhang Q, Lu W, Yin J, Liu W, Ding Y, Zhao Y, Zhu Y, Pu R, Zhang H, Dong H, Fu Y, Sun Q, Xu G, Cao G. Mother-to-child transmission of hepatitis B virus: Evolution of hepatocellular carcinoma-related viral mutations in the post-immunization era. J Clin Virol 2014; 61:47-54. [DOI: 10.1016/j.jcv.2014.06.010] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2014] [Revised: 05/29/2014] [Accepted: 06/10/2014] [Indexed: 12/13/2022]
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Fan L, Owusu-Edusei K, Schillie SF, Murphy TV. Cost-effectiveness of testing hepatitis B-positive pregnant women for hepatitis B e antigen or viral load. Obstet Gynecol 2014; 123:929-937. [PMID: 24785842 PMCID: PMC4682356 DOI: 10.1097/aog.0000000000000124] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
OBJECTIVE To estimate the cost-effectiveness of testing pregnant women with hepatitis B (hepatitis B surface antigen [HBsAg]-positive) for hepatitis B e antigen (HBeAg) or hepatitis B virus (HBV) DNA, and administering maternal antiviral prophylaxis if indicated, to decrease breakthrough perinatal HBV transmission from the U.S. health care perspective. METHODS A Markov decision model was constructed for a 2010 birth cohort of 4 million neonates to estimate the cost-effectiveness of two strategies: testing HBsAg-positive pregnant women for 1) HBeAg or 2) HBV load. Maternal antiviral prophylaxis is given from 28 weeks of gestation through 4 weeks postpartum when HBeAg is positive or HBV load is high (10 copies/mL or greater). These strategies were compared with the current recommendation. All neonates born to HBsAg-positive women received recommended active-passive immunoprophylaxis. Effects were measured in quality-adjusted life-years (QALYs) and all costs were in 2010 U.S. dollars. RESULTS The HBeAg testing strategy saved $3.3 million and 3,080 QALYs and prevented 486 chronic HBV infections compared with the current recommendation. The HBV load testing strategy cost $3 million more than current recommendation, saved 2,080 QALYs, and prevented 324 chronic infections with an incremental cost-effectiveness ratio of $1,583 per QALY saved compared with the current recommendations. The results remained robust over a wide range of assumptions. CONCLUSION Testing HBsAg-positive pregnant women for HBeAg or HBV load followed by maternal antiviral prophylaxis if HBeAg-positive or high viral load to reduce perinatal hepatitis B transmission in the United States is cost-effective.
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MESH Headings
- Antibiotic Prophylaxis/economics
- Antiviral Agents/economics
- Antiviral Agents/therapeutic use
- Cost-Benefit Analysis
- DNA, Viral/blood
- DNA, Viral/economics
- Female
- Hepatitis B Surface Antigens/blood
- Hepatitis B e Antigens/blood
- Hepatitis B e Antigens/economics
- Hepatitis B virus/genetics
- Hepatitis B virus/immunology
- Hepatitis B, Chronic/blood
- Hepatitis B, Chronic/drug therapy
- Hepatitis B, Chronic/economics
- Hepatitis B, Chronic/transmission
- Humans
- Immunization, Passive/economics
- Infant, Newborn
- Infectious Disease Transmission, Vertical/economics
- Infectious Disease Transmission, Vertical/prevention & control
- Pregnancy
- Quality-Adjusted Life Years
- Serologic Tests/economics
- Vaccination/economics
- Viral Load/economics
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Affiliation(s)
- Lin Fan
- National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia
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Zhang Z, Li A, Xiao X. Risk factors for intrauterine infection with hepatitis B virus. Int J Gynaecol Obstet 2014; 125:158-61. [PMID: 24598349 DOI: 10.1016/j.ijgo.2013.10.028] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2013] [Revised: 10/31/2013] [Accepted: 01/29/2014] [Indexed: 12/20/2022]
Abstract
OBJECTIVE To investigate risk factors for hepatitis B virus (HBV) intrauterine infection. METHODS Peripheral blood samples and clinical data were collected from 174 pregnant women who were positive for hepatitis B surface antigen (HBsAg). Their 176 neonates received an active-passive immunization schedule at 0, 1, and 6 months. Blood samples from the infants, collected before immune prophylaxis administration, were tested for HBV markers and HBV DNA. RESULTS The intrauterine infection rate at 6 months after birth was 5.1%. Maternal HBV DNA positivity (OR 11.362; 95% CI, 1.389-92.931), hepatitis B e antigen (HBeAg) positivity (OR 7.278; 95% CI, 1.734-30.538), and thalassemia minor (OR 15.619; 95% CI, 2.239-108.964) were associated with intrauterine infection. The intrauterine infection rate for mothers with 10(5) copies/mL of serum HBV DNA or more was 18.2%, compared with 0.8% for mothers with less than 10(5) copies/mL. CONCLUSION A positive HBsAg test at 24 hours and/or 1 month of age followed by a positive test at 6 months is an objective and comprehensive criterion for the diagnosis of HBV intrauterine infection. Maternal HBV DNA positivity (especially 10(5) copies/mL of HBV DNA or more), HBeAg positivity, and thalassemia minor are risk factors for HBV intrauterine infection.
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Affiliation(s)
- Zhao Zhang
- Department of Obstetrics and Gynecology, First Affiliated Hospital of Jinan University, Guangzhou, China
| | - Aizhen Li
- Department of Obstetrics and Gynecology, First Affiliated Hospital of Jinan University, Guangzhou, China; Department of Obstetrics, Obstetrics and Gynecology Affiliated Hospital of Fudan University, Shanghai, China
| | - Xiaomin Xiao
- Department of Obstetrics and Gynecology, First Affiliated Hospital of Jinan University, Guangzhou, China.
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Elefsiniotis IS, Tsoumakas K, Kapritsou M, Magaziotou I, Derdemezi A, T MS, Katsoulas T, Konstantinou EA. Liver function tests in viremic and nonviremic chronic hepatitis B virus-infected pregnant women: importance of alanine aminotransferase/sodium ratio. Gastroenterol Nurs 2013; 36:422-428. [PMID: 24304526 DOI: 10.1097/sga.0000000000000004] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
The major risk factor of perinatal transmission of Hepatitis B virus (HBV) infection is the level of maternal HBV-deoxyribonucleic acid (DNA) during the third trimester of pregnancy. The primary aim of this study was to evaluate the hematological and biochemical status in Hepatitis B e-antigen (HBeAg)-negative chronic HBV-infected pregnant women and to correlate the findings with the presence or absence of viremia. Ninety-five consecutive chronic HBV-infected pregnant women were evaluated between the 28th and 32nd week of gestation. Viral load was determined by using the COBAS TaqMan HBV test. Sixty-nine women were evaluated and 14 of them exhibited HBV-DNA levels higher than 2000 IU·ml. In this study, viremic women exhibited significantly higher alanine aminotransferase (ALT), creatinine, and uric acid values as well as significantly lower white blood cell count compared with nonviremic women. There was also a significant statistical difference concerning ALT/sodium ratio between viremic and nonviremic women (0.20 ± 0.22 vs. 0.10 ± 0.09, respectively, p= .024). The optimal cutoff points discriminating those women with a high probability to have detectable serum HBV-DNA were 0.092 for ALT/sodium ratio (sensitivity = 73.0%, specificity = 61.5%, area under the receiver operating characteristic curve [AUC] = 71.05%) and 12.8 IU/L for ALT (sensitivity = 73.0%, specificity = 63.0%, AUC = 72.2%). Chronic HBV-infected pregnant women with ALT/sodium ratio ≥ 0.11 had the higher probability of having serum HBV-DNA levels higher than 2000 IU/ml (sensitivity = 76.92%, specificity = 58%, AUC = 62.38%). Presence of HBV-DNA in maternal blood during the third trimester of pregnancy is significantly associated with maternal serum ALT levels in HBeAg-negative chronic HBV-infected pregnant women. Women with an ALT/sodium ratio greater than 0.092 have the higher probability of HBV-DNA presence in maternal blood whereas an ALT/sodium ratio greater than 0.11 could discriminate those women with HBV-DNA levels higher than 2000 IU/ml.
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Affiliation(s)
- Ioannis S Elefsiniotis
- Ioannis S. Elefsiniotis, PhD, MD, is Assistant Professor, University Department of Internal Medicine-Hepatology Unit, Elena Venizelou Hospital, Athens, Greece. Konstantinos Tsoumakas, PhD, MD, is Associate Professor, University Department of Pediatrics, Faculty of Nursing, Athens, Greece. Maria Kapritsou, PhD, MSc, BSN, RN, is Registered Nurse, Hellenic Anticancer Institute, Saint Savvas Hospital, Athens, Greece. Ioanna Magaziotou, PhD(c), RN, is Pediatrician, Faculty of Nursing, National and Kapodistrian University of Athens, Athens, Greece. Angeliki Derdemezi, PhD, MSc, RN, is Registered Nurse, University Department of Pediatrics, Faculty of Nursing, Athens, Greece. Mariolis-Sapsakos T. PhD, MD, is Lecturer in Anatomy, Faculty of Nursing, National and Kapodistrian University of Athens, Athens, Greece. Evangelos A. Konstantinou, PhD, MSc, RN, is Associate Professor of Nursing Anaesthesiology, National and Kapodistrian University of Athens, Athens, Greece
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Giles ML, Grace R, Tai A, Michalak K, Walker SP. Prevention of mother-to-child transmission of hepatitis B virus (HBV) during pregnancy and the puerperium: current standards of care. Aust N Z J Obstet Gynaecol 2013; 53:231-5. [PMID: 23452292 DOI: 10.1111/ajo.12061] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2012] [Accepted: 01/10/2013] [Indexed: 11/28/2022]
Abstract
BACKGROUND Mother-to-child transmission (MTCT) of hepatitis B virus continues to occur despite the interventions of hepatitis B vaccination and immunoglobulin. The most significant risk factor in transmission is high maternal viral load. Being aware of viral replicative activity permits risk stratification and allows the opportunity for additional preventative measures such as antiviral therapy. METHODS Retrospective audit of investigations and clinical management among hepatitis B surface antigen-positive pregnant women from three maternity services across Victoria over a five-year period from 2006 to 2011. RESULTS Over the study period at the three institutions, there were 46,855 births, and 398 hepatitis B-positive pregnant women. 87% of the women were non-Australian-born. Viral load testing was performed in <20% of all pregnancies, and hepatitis B e antigen status assessed in 33%. Only 18% of the women with hepatitis B were referred for specialist care, but if referred, they were more likely to have an assessment of viral replicative status performed. Compliance with administration of neonatal hepatitis B immunoglobulin and birth-dose vaccination was high (>90%). CONCLUSION There is scope for considerable improvement in referral and assessment of pregnant women with hepatitis B infection. Guidelines addressing the issue of maternal viral replicative status and the need for antiviral therapy may assist in guiding clinical management.
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Affiliation(s)
- Michelle L Giles
- The Alfred Hospital, Monash Medical Centre and the Royal Women's Hospital, Melbourne, Victoria 3004, Australia.
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Liu MH, Sheng YJ, Liu JY, Hu HD, Zhang QF, Ren H. Efficacy of telbivudine on interruption of hepatitis B virus vertical transmission: a meta-analysis. Ann Saudi Med 2013; 33:169-76. [PMID: 23563007 PMCID: PMC6078630 DOI: 10.5144/0256-4947.2013.169] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND AND OBJECTIVES Hepatitis B virus (HBV) infection is one of the most common infections in the world. Vertical transmission is the main reason for the continued endemic infection rates, at least in Asia. This study aimed to investigate the efficacy of telbivudine on mother-to-child transmission (MTCT) interruption. METHODS Studies up to April 2012 were collected by searching Pubmed, EMBASE, the Cochrane Library, EBM Review, WangFang Database and China National Knowledge Infrastructure. Serum hepatitis B surface antigen (HBsAg) and HBV DNA in newborns and infants, maternal HBV DNA negative conversion and alanine trans.aminase (ALT) normalization and adverse events were analyzed. RESULTS Seven clinical trials involving 644 pregnant women were included in this meta-analysis. Telbivudine resulted in lower HBsAg and HBV DNA seroprevalence in newborns and infants. When maternal viral load prior to delivery was higher than 103copies/mL, HBsAg or HBV DNA positivity had no statistical difference. CONCLUSIONS Telbivudine treatment has efficacy and safety on MTCT interruption during late pregnancy. In addition, we demonstrated benefit of telbivudine for mothers in terms of HBV DNA negative conversion and ALT normalization. Telbivudine treatment at the end of pregnancy should be considered in women with high viral load.
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Affiliation(s)
- Min-Hui Liu
- Department of Infectious Diseases, Institute of Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China
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Sa-Nguanmoo P, Tangkijvanich P, Tharmaphornpilas P, Rasdjarmrearnsook AO, Plianpanich S, Thawornsuk N, Theamboonlers A, Poovorawan Y. Molecular analysis of hepatitis B virus associated with vaccine failure in infants and mothers: a case-control study in Thailand. J Med Virol 2012; 84:1177-85. [PMID: 22711345 DOI: 10.1002/jmv.23260] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Perinatal transmission of hepatitis B virus (HBV) has been controlled incompletely despite adequate immunoprophylaxis in infants. The aim of this study was to characterize virological factors of HBV associated with vaccine failure in Thailand. Sera of 14 infected infants (13 HBeAg-positive and one HBeAg-negative) with vaccine failure and their respective mothers (group M1) were tested quantitatively for HBV DNA by real-time PCR, HBV genotypes and mutations were characterized by direct sequencing. Sera collected from 15 HBeAg-positive (group M2) and 15 HBeAg-negative (group M3) mothers whose infants had been vaccinated successfully served as controls. The results showed that group M1 and group M2 mothers had equal titers of HBV DNA but higher titers than group M3. All infected infants and their respective mothers had the same HBeAg status and HBV genotypes. DNA analysis in a pair of HBeAg-negative infant and mother revealed that both were infected with an HBV precore mutant (G1896A). Escape mutants in the "a" determinant region (residues 144 and 145) were detected in two (14%) infected infants. The prevalence of BCP mutations/deletions in groups M2 and M3 was higher significantly than in group M1 (P = 0.022 and P < 0.001, respectively). In conclusion, instead of the HBeAg status, a high titer of HBV DNA in mothers was the major contributor to perinatal transmission of HBV. Escape mutants might be associated with vaccine failure in some infants. BCP mutations/deletions in mothers might contribute to the prevention of mother-to-infant transmission of HBV.
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Affiliation(s)
- Pattaratida Sa-Nguanmoo
- Center of Excellence in Clinical Virology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
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Han GR, Xu CL, Zhao W, Yang YF. Management of chronic hepatitis B in pregnancy. World J Gastroenterol 2012; 18:4517-21. [PMID: 22969224 PMCID: PMC3435776 DOI: 10.3748/wjg.v18.i33.4517] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2011] [Revised: 03/15/2012] [Accepted: 03/29/2012] [Indexed: 02/06/2023] Open
Abstract
Pregnancy associated with chronic hepatitis B (CHB) is a common and important problem with unique challenges. Pregnant women infected with CHB are different from the general population, and their special problems need to be considered: such as the effect of hepatitis B virus (HBV) infection on the mother and fetus, the effect of pregnancy on replication of the HBV, whether mothers should take HBV antiviral therapy during pregnancy, the effect of these treatments on the mother and fetus, how to carry out immunization of neonates, whether it can induce hepatitis activity after delivery and other serious issues. At present, there are about 350 million individuals with HBV infection worldwide, of which 50% were infected during the perinatal or neonatal period, especially in HBV-endemic countries. Currently, the rate of HBV infection in the child-bearing age group is still at a high level, and the infection rate is as high as 8.16%. Effective prevention of mother-to-child transmission is an important means of reducing the global burden of chronic HBV infection. Even after adopting the combined immunization measures, there are still 5%-10% of babies born with HBV infection in hepatitis B e antigen positive pregnant women. As HBV perinatal transmission is the main cause of chronic HBV infection, we must consider how to prevent this transmission to reduce the burden of HBV infection. In this population of chronic HBV infected women of childbearing age, specific detection, intervention and follow-up measures are particularly worthy of attention and discussion.
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Zou H, Chen Y, Duan Z, Zhang H, Pan C. Virologic factors associated with failure to passive-active immunoprophylaxis in infants born to HBsAg-positive mothers. J Viral Hepat 2012; 19:e18-25. [PMID: 22239517 DOI: 10.1111/j.1365-2893.2011.01492.x] [Citation(s) in RCA: 275] [Impact Index Per Article: 21.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
In infants born to hepatitis B surface antigen (HBsAg)-positive mothers, failure after passive-active immunization still occurs. The role of maternal hepatitis B DNA level and other risk factors in this setting remains unclear. This study retrospectively evaluated virologic and other risk factors associated with immunoprophylaxis failure in infants born to HBsAg-positive mothers. Between January 2007 and March 2010, we reviewed the clinical and virologic tests in 869 mother-infant pairs. All infants received the identical passive-active immunization schedule after birth. The failure infants (HBsAg positive at 7-12 months of age) were compared to infants who were HBsAg negative when tested during this time period. Among 869 infants, 27 (3.1%) infants were immunoprophylaxis failures and the other 842 (96.9%) infants remained HBsAg negative. When mothers' pre-delivery HBV DNA levels were stratified to <6, 6-6.99, 7-7.99 and ≥ 8 log(10) copies/mL, the corresponding rates of immunoprophylaxis failure were 0%, 3.2% (3/95), 6.7% (19/282) and 7.6% (5/66), respectively (P < 0.001 for the trend). All failure infants were born to hepatitis B e antigen (HBeAg)-positive mothers. Multivariate logistic regression analysis identified maternal HBV DNA levels [odds ratio (OR) = 1.88, 95% confidence interval (CI): 1.07-3.30] and detectable HBV DNA in the cord blood (OR = 39.67, 95% CI: 14.22-110.64) as independent risk factors for immunoprophylaxis failure. All failure infants were born to HBeAg-positive mothers with HBV DNA levels ≥ 6 log(10) copies/mL. The presence of HBV DNA in cord blood predicted failure to passive-active immunization.
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Affiliation(s)
- H Zou
- Artificial Liver Center, Beijing Youan Hospital, Capital Medical University, Beijing, China
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Komatsu H, Inui A, Sogo T, Konishi Y, Tateno A, Fujisawa T. Hepatitis B surface gene 145 mutant as a minor population in hepatitis B virus carriers. BMC Res Notes 2012; 5:22. [PMID: 22233650 PMCID: PMC3283482 DOI: 10.1186/1756-0500-5-22] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2011] [Accepted: 01/10/2012] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Hepatitis B virus (HBV) can have mutations that include the a determinant, which causes breakthrough infection. In particular, a single mutation at amino acid 145 of the surface protein (G145) is frequently reported in the failure of prophylactic treatment. The aim of this study was to evaluate the frequency of the a determinant mutants, especially the G145 variant, in Japan, where universal vaccination has not been adopted. METHODS The present study was a retrospective study. The study cohorts were defined as follows: group 1, children with failure to prevent mother-to-child transmission despite immunoprophylaxis (n = 18, male/female = 8/10, age 1-14 years; median 6 years); group 2, HBV carriers who had not received vaccination or hepatitis B immunoglobulin (n = 107, male/female = 107, age 1-52 years; median 16 years). To detect the G145R and G145A mutants in patients, we designed 3 probes for real-time PCR. We also performed direct sequencing and cloning of PCR products. RESULTS By mutant-specific real-time PCR, one subject (5.6%) was positive for the G145R mutant in group 1, while the G145 mutant was undetectable in group 2. The a determinant mutants were detected in one (5.6%) of the group 1 subjects and 10 (9.3%) of the group 2 subjects using direct sequencing, but direct sequencing did not reveal the G145 mutant as a predominant strain in the two groups. However, the subject who was positive according to the mutant-specific real-time PCR in group 1 had overlapped peaks at nt 587 in the electropherogram. In group 2, 11 patients had overlapped peaks at nt 587 in the electropherogram. Cloning of PCR products allowed detection of the G145R mutant as a minor strain in 7 (group 1: 1 subject, group 2: 6 subjects) of 12 subjects who had overlapped peaks at nt 587 in the electropherogram. CONCLUSIONS The frequency of the a determinant mutants was not high in Japan. However, the G145R mutant was often present as a minor population in children and adults. HBV carriers might have the a determinant mutants as a minor form.
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Affiliation(s)
- Haruki Komatsu
- Division of Hepatology and Gastroenterology, Department of Pediatrics, Eastern Yokohama Hospital, 3-6-1 Simosueyoshi Tsurumi, Yokohama, Kanagawa, Japan.
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35
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Carosi G, Rizzetto M, Alberti A, Cariti G, Colombo M, Craxì A, Filice G, Levrero M, Mazzotta F, Pastore G, Piccinino F, Prati D, Raimondo G, Sagnelli E, Toti M, Brunetto M, Bruno R, Di Marco V, Ferrari C, Gaeta GB, Lampertico P, Marzano A, Pollicino T, Puoti M, Santantonio T, Smedile A. Treatment of chronic hepatitis B: update of the recommendations from the 2007 Italian Workshop. Dig Liver Dis 2011; 43:259-65. [PMID: 21276760 DOI: 10.1016/j.dld.2010.10.014] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2010] [Accepted: 10/21/2010] [Indexed: 12/11/2022]
Abstract
The Italian recommendations for the therapy of hepatitis B virus (HBV)-related disease were issued in 2008. Subsequently in 2008 the nucleotide analogue (NA) Tenofovir was approved for antiviral treatment. The introduction of this important new drug has called for the current guidelines update, which includes some additional revisions: (a) the indication for therapy is extended to mild liver fibrosis and the indication for treatment is graded as "possible", "optional" or "mandatory" according to the fibrosis stage; (b) two different treatment strategies are described: first line definite duration treatment with interferon, long-term treatment of indefinite duration with NA; (c) the indication to follow either strategy is also based on the stage of liver fibrosis; (d) virological monitoring is modified to include the definitions of failure and of sustained virological response to interferon therapy; (e) the recommendation to use HBV DNA assays with high sensitivity and wide linear ranges is underlined (f) guidelines on post-treatment follow-up after finite treatment with NA, potential side effects of therapy and non-virological monitoring are defined; (g) definitions and treatment of patients without optimal response to NA are reported; (f) treatment and monitoring of compensated or decompensated cirrhosis and hepatocellular carcinoma are updated.
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Affiliation(s)
- Giampiero Carosi
- Department of Infectious and Tropical Diseases, University of Brescia, Brescia, Italy.
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Shao ZJ, Zhang L, Xu JQ, Xu DZ, Men K, Zhang JX, Cui HC, Yan YP. Mother-to-infant transmission of hepatitis B virus: a Chinese experience. J Med Virol 2011; 83:791-5. [PMID: 21360547 DOI: 10.1002/jmv.22043] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/23/2010] [Indexed: 01/05/2023]
Abstract
Over 90% of infants infected with hepatitis B virus (HBV) caused by mother-to-infant transmission will evolve to carrier status, and this cannot be prevented until widespread administration of the HB vaccine and hepatitis B immune globulin (HBIG) is implemented. This prospective study of 214 infants born to HBsAg-positive mothers was carried out to determine if either perinatal or intrauterine HBV transmission could be effectively prevented with HBIG and the HB vaccine. Peripheral blood was collected from mothers and from newborns before they received HBIG and the HB vaccine, as well as at 0, 1, 7, 24, and 36 months after birth. Infants born with an ratio of signal to noise(S/N) value of >5 for HBsAg (ABBOTT Diagnostic Kit) were defined as mother-to-infant transmission cases, those with an S/N between 5 and 50 were classified as perinatal transmission cases, and those with an S/N >50 were considered intrauterine transmission cases. Mother-to-infant transmission occurred in approximately 4.7% (10/214) of the infants; the perinatal transmission and intrauterine transmission rates were 3.7% (8/214) and 0.9% (2/214), respectively. The risk of mother-to-infant transmission increased along with maternal HBeAg or HBVDNA levels. After 36 months of follow-up, all perinatal cases became HBsAg-negative, whereas all intrauterine transmission cases evolved into carrier status. These results indicate that infants infected via intrauterine transmission cannot be effectively protected by HBIG and HB vaccine.
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Affiliation(s)
- Zhong-Jun Shao
- Department of Epidemiology, School of Public Health, The Fourth Military Medical University, Xi'an, China
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