Estimate of vertical transmission of Hepatitis C virus in Pakistan in 2007 and 2012 birth cohorts

Despite a combination of high Hepatitis C virus (HCV) prevalence, a large adult population and high fertility, no published estimates of the scale and contribution of vertical transmission to HCV incidence in Pakistan exist. The objective of this study was to estimate the number of new HCV infections occurring in Pakistan as a result of vertical transmission. We adapted a published mathematical model based on HCV antibody and viraemia prevalence, fertility rates, risk of HCV vertical transmission and children mortality rates to estimate the number of infections in the 2007 and 2012 birth cohorts nationally and in four subnational regions. We estimated that 19 708 (95% uncertainty interval [UI]: 15 941‐23 819) children were vertically infected by HCV in 2007 and 21 676 (95% UI: 17 498‐26 126) in 2012. The majority of these cases (72.9% and 72.5% in 2007 and 2012, respectively) occurred in Punjab. We estimated that vertical transmission as a mode of exposure accounted for a quarter of HCV infections among children under 5 years of age (25.2% in 2007 and 24.0% in 2012). Conclusion: Our results showed that one in 260 children born in Pakistan in 2007 and 2012 acquired HCV vertically. While currently no interventions during pregnancy and childbirth are recommended to reduce this risk, prevention, testing and treatment strategies should be considered to reduce the burden of vertical HCV infections among young children. Other routes of transmission appear to contribute the majority of HCV infections among children and must also be clarified and urgently addressed.     

Vertical transmission of hepatitis B virus during pregnancy and delivery in Denmark

Objective: In Denmark, pregnant women have been screened for hepatitis B virus (HBV) since 2005, and children born to HBV-infected mothers offered hepatitis B immunoglobulin at birth, vaccination against HBV at birth and after 1, 2 and 12 months. The purpose of this study was to determine the risk of vertical HBV transmission in children born to mothers with chronic HBV infection, to investigate the antibody response in the children and to investigate possible maternal predictive risk factors for HBV transmission.

Materials and methods: Through the Danish Database for Hepatitis B and C, we identified 589 HBV-infected women who had given birth to 686 children, of whom 370 children were born to 322 women referred to hospital. 132 (36%) children, born to 109 mothers, were included in the study; 128 children had blood samples tested for HBsAg, anti-HBc (total), anti-HBs and HBV-DNA and four children had saliva samples tested for anti-HBc.

Results: We found vertical HBV transmission in Denmark to be 2.3% [95% CI: 0.5, 6.5], a high proportion of HBsAg-negative children with low levels of anti-HBs (18.4%) and a high proportion (15.2%) with resolved HBV infection. No maternal risk factor was statistically significantly associated with HBV vertical transmission.

Conclusion: In a HBV low prevalence setting as Denmark, despite a national vaccination program, vertical HBV transmission occurred in 2.3% of children born to HBV-infected mothers. In addition, a high proportion of the children had insufficient anti-HBs levels and a high proportion had serological signs of resolved HBV infection.     

The role of caesarean section and nonbreastfeeding in preventing mother‐to‐child transmission of hepatitis B virus in HBsAg‐and HBeAg‐positive mothers: results from a prospective cohort study and a meta‐analysis

The study aimed to assess whether caesarean section and nonbreastfeeding can prevent mother‐to‐child transmission (MTCT) in HBsAg‐ and HBeAg‐positive mothers via a cohort study and a meta‐analysis. (1) Pregnant women who were positive for HBsAg and HBeAg and did not receive antiviral treatment during pregnancy were recruited from the First Hospital of Jilin University, Maternal and Child Health Care Center of Jiangsu and Henan from August 2009 to June 2015. Infants received active and passive immunity. (2) In addition, a systematic literature search was performed in the PubMed, Embase, Cochrane, China National Knowledge Infrastructure and Wanfang Chinese databases. The retrieval strategy was [(“HBV” or “hepatitis b” or “hepatitis b virus”) and (“mother‐to‐infant transmission” or “vertical transmission”)]. Studies were screened, and data were extracted. The fixed‐effect model was used to analyse the studies. A total of 852 mothers and 857 newborns were enrolled. At the age of 7 months, 41 infants (4.78%) were positive for HBsAg. Multivariate analysis showed that mothers with higher HBV DNA levels (>10⁸ IU/mL; RR = 3.03, 95% CI: 1.41‐6.52) were associated with an increased risk of infection. Although there was no statistical significance, caesarean section (RR = 0.61) and nonbreastfeeding (RR = 0.88) showed a tendency to reduce the risk of infection. (2) A total of 5726 studies were identified. Together with our study, 13 were included in the analysis of delivery mode, and 12 were included in the analysis of feeding mode. The risk of infection in the caesarean section group was lower than that in the vaginal delivery group (RR = 0.58, 95% CI: 0.46‐0.74). In the analysis of feeding mode, the risk in the nonbreastfeeding group was significantly lower (RR = 0.74, 95% CI: 0.56‐0.98). In conclusion, caesarean section and nonbreastfeeding reduced the risk of MTCT in infants of HBsAg‐ and HBeAg‐positive mothers who did not receive antiviral therapy during pregnancy.     

Intrafamilial transmission of hepatitis C virus

Abstract The intrafamilial transmission pattern of hepatitis C virus (HCV) was examined in 118 family members of 61 index patients with type C chronic liver disease using anti-HCV antibodies and HCV RNA assay. The study subjects consisted of eight parents, 49 spouses, 50 children, eight siblings and three other relatives. The positivity rates of anti-C100, anti-JCC, second-generation anti-HCV and HCV RNA were 6.8, 12.7, 12.7 and 11.0%, respectively. Positivity in one or more anti-HCV antibody assay was detected in 3/24 (12.5%) father-child pairs, 3/17 (17.6%) mother-child pairs, 2/8 (25%) sibling pairs, 6/38 (15.8%) husband-wife pairs and 2/13 (15.4%) wife-husband pairs. In spouses, positivity for anti-HCV antibody or HCV RNA was observed after 40 years of age. None of 11 spouses married < 15 years was positive for any anti-HCV assay or HCV RNA. In spouses whose age was > 50 years and duration of marriage was > 25 years, anti-HCV or HCV RNA was frequently detected (32.0%). However, when seven pairs involving four spouses, one mother-daughter pair and two sibling pairs were subtyped, the same HCV subtypes were found in only four pairs (type II in three pairs and type III in one pair). Further, the agreement rate between anti-HCV and HCV RNA was > 90%. These results suggest that intrafamilial transmission of HCV, revealed by the subtyping method, is considered lower than the percentage of positivity for anti-HCV antibodies or HCV RNA in family members of patients with type C chronic liver disease. Thus, the intrafamilial transmission of HCV seems to be quite rare and much less common than that of HBV.     

Safety and efficacy of telbivudine in late pregnancy to prevent mother‐to‐child transmission of hepatitis B virus: A multicenter prospective cohort study

Infection of hepatitis B virus (HBV) occurs in ~10% of infants of HBV‐infected mothers with positive hepatitis B e antigen (HBeAg) after immunoprophylaxis. We aimed to evaluate the safety and efficacy of telbivudine used during late pregnancy for preventing mother‐to‐child transmission of HBV. We conducted a multicenter prospective cohort study in 5 hospitals from 2012 to 2014, which enrolled HBV‐infected singleton pregnant women with positive HBeAg. By their choice, women were divided into therapy (telbivudine 600 mg/day, from gestation 28‐32 weeks to 3‐4 weeks postpartum) and control (no antiviral agent) groups. Infants received passive‐active immunoprophylaxis and follow‐up at the age of 7‐14 months. Totally, 328 pregnant women were included: 149 in the telbivudine group and 179 in the control group. Baseline HBV DNA levels were similar in the 2 groups (7.43 vs 7.37 log₁₀ IU/mL, P = .711). At delivery, HBV DNA levels in the telbivudine and control groups were 3.80 and 7.26 log₁₀ IU/mL, respectively (P < .0001). Of the infants, 128 (85.9%) in the telbivudine group and 156 (87.2%) in the control group were followed up. No infant in the telbivudine group had chronic infection, while 2 (1.28%) infants in the control group did (P = .503). Three (2.34%) infants in the telbivudine group, but none in the control group, had severe congenital or developmental abnormalities (P = .090). The data indicate that telbivudine may block perinatal HBV transmission. However, larger studies are required to clarify whether anti‐HBV therapy in pregnancy is associated with severe adverse effects in the foetuses and infants.     

Different outcomes of nosocomial infection with hepatitis C virus from the same origin

The outcome of infection with hepatitis C virus(HCV)varies substantially from self-limiting infection to chronichepatitis,liver cirrhosis,and hepatocellular carcinomaamong the individuals.The mechanisms that determinethe clearance or the persistence of HCV have not yetbeen clarified.Here,we experienced two cases ofhospital-related infection with HCV from the sameorigin but with quite different outcomes.One caseresolved after an episode of acute hepatitis,while theother case developed a chronic hepatitis although theywere infected with HCV of the same origin.Althoughinfected with the virus of the same origin,the clinicaland virological courses were completely different.This suggests that host factors play a major role inconditioning the outcome of acute HCV infection.     

Maternal viral load and hepatitis B virus mother‐to‐child transmission risk: A systematic review and meta‐analysis

Aim

The aim of this study was to assess the relationship between maternal viral load and mother‐to‐child transmission (MTCT) risk in hepatitis B envelope antigen (HBeAg)‐positive mothers.

Methods

PubMed and Web of Science were systematically searched. We compared MTCT incidence between maternal hepatitis B virus (HBV)‐DNA‐positive and HBV‐DNA‐negative groups. We also examined the dose–response effect of this relationship.

Results

Twenty‐one studies with 10 142 mother–child pairs were included in the studies. The mean MTCT incidence was 13.1% in the maternal HBV‐DNA‐positive group, compared with 4.2% in the negative group. The summary MTCT odds ratio of maternal HBV‐DNA positive compared with negative was 9.895 (95% confidence interval [CI], 5.333 to 18.359; Z = 7.27, P < 0.00001) by random‐effects model. In maternal HBV‐DNA <6 log10 copies/mL, 6–8 log10 copies/mL, and >8 log₁₀ copies/mL level stratifications, the pooled MTCT incidences were 2.754% (95% CI, 1.198–4.310%; Z = 3.47, P = 0.001), 9.932% (95% CI, 6.349–13.516%; Z = 5.43, P < 0.00001), and 14.445% (95% CI, 8.317–20.572%; Z = 4.62, P < 0.00001), respectively. A significant linear dose–response association was found between maternal viral load and MTCT risk, with the points estimate of increased MTCT risk 2.705 (95% CI, 1.808–4.047) at 6 log10 copies/mL compared with reference (3 log10 copies/mL), and 7.316 (95% CI, 3.268–16.378) at 9 log₁₀ copies/mL. A significant non‐linear dose–response association was also found between maternal viral load and HBV MTCT risk (model χ² = 23.43, P < 0.00001).

Conclusion

Our meta‐analysis indicated that maternal viral load was an important risk factor for MTCT in HBeAg‐positive mothers, and maternal viral load was dose‐dependent with HBV MTCT incidence.     

Efficacy of antepartum administration of hepatitis B immunoglobulin in preventing mother‐to‐child transmission of hepatitis B virus

The aim of this study was to investigate the efficacy of antepartum administration of three doses of hepatitis B immunoglobulin (HBIG) in interrupting mother‐to‐child transmission (MTCT) of hepatitis B virus (HBV). In this trial, a total of 728 HBeAg‐positive pregnant women with chronic HBV infection who had an HBV DNA level higher than 6log₁₀ copies/mL were enrolled. They were divided into three groups based on individual preference. Subjects in group A and group B received 200 IU (unit) HBIG and 400 IU (unit) HBIG intramuscularly once a month at the third, second and first month before delivery, respectively. Subjects in the control group (C) received no special treatment. All the infants received passive‐active immunoprophylaxis. The HBsAg‐positive rate of all infants at 7‐12 months of age was 5.1% (37/728). Specifically, the HBsAg‐positive rate of infants was comparable in all three groups (5.3% vs 5.1% vs 5%, P = 0.988). No significant difference was found in anti‐HBs levels between the infants aged 7‐12 months in the three groups (P = 0.469). HBV DNA levels of the umbilical cord blood in the HBV‐infected group were higher than those in the uninfected group (5.2 vs 3.4log₁₀ copies/mL, P < 0.001), and these with family history of HBV infection were also higher (45.9% vs 28.5%, P = 0.034). To conclude, administration of passive‐active immunoprophylaxis to infants contributed to effective prevention of the MTCT of HBV; extra antepartum administration of HBIG during pregnancy could not decrease the rate of MTCT or increase the anti‐HBs levels of infants born to HBsAg‐positive mothers with HBV DNA higher than 6log₁₀ copies/mL.     

Efficacy and safety of telbivudine and tenofovir disoproxil fumarate in preventing hepatitis B vertical transmission: A real‐life practice

Mother‐to‐child transmission (MTCT) is a major obstacle in the elimination of hepatitis B virus (HBV) infection. Telbivudine (LdT) and tenofovir disoproxil fumarate (TDF) are the two most common antiviral medicines for preventing MTCT. However, the efficacy and safety of LdT and TDF in preventing HBV vertical transmission during the second to third trimester have not been compared rigorously. Therefore, we carried out a prospective multicentre cohort study of chronic hepatitis B in mothers with HBV DNA > 10⁶ IU/mL, receiving LdT or TDF during the second to third trimester. Among the 893 mothers enrolled, 857 (LdT/TDF/untreated group (NTx) = 396/325/136) completed consecutive follow‐up with 854 infants (LdT/TDF/NTx = 395/323/136). LdT and TDF treatment resulted in a similar decrease of HBV DNA in mothers at delivery. Multivariate analysis indicated that only HBsAg titre at the baseline correlated with viral DNA decrease (P = 0.015). With intention‐to‐treat analysis, MTCT rates in the LdT, TDF and NTx group were 4.41%, 2.42% and 22.08%, respectively. An increasing vertical transmission rate was found to be closely associated with higher HBsAg titre, 5.32% and 17.65% infection rate was estimated in infants born to mothers with HBsAg > 4 and >5 log₁₀ IU/mL, respectively. No serious side effects were reported in either mothers or infants. LdT and TDF treatments were well tolerated and showed comparable efficacy in reducing MTCT. Higher risk of MTCT was shown in pregnant women with HBsAg > 4 log₁₀IU/mL.     

A prospective study of vertical transmission of hepatitis C virus

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经母婴传播丙型肝炎病毒婴儿10年转归的研究

目的：了解丙型肝炎病毒(HCV)母婴传播的远期预后。方法：应用前瞻性研究方法，对13例母婴传播感染HCV婴儿的转归进行了10年的随访。使用聚合酶链反应(PCR)检测HCVRNA，用第二代EIA试剂检测抗HCV。结果：临床型丙型肝炎1例，血清中抗-HCV和HCV RNA分别持续7年和8年；亚临床型丙型肝炎3例，2例血清中抗-HCV于l2月龄阴转，1例于24月龄阴转，2例HCV RNA于24月龄阴转，1例于60月龄阴转；隐性感染9例，血清中抗-HCV和HCV RNA均在12月龄内阴转。随访8～10年未发现抗-HCV和HCV RNA再次转阳者。结论：提示HCV母婴传播形成HCV慢性携带和丙型肝炎慢性化的机率较低，转归较好，对婴儿生长发育影响不大。     

Influence of occult hepatitis B virus infection in chronic hepatitis C outcomes

Persistence of hepatitis B virus-DNA in the sera,peripheral blood mononuclear cells or in the liver of hepatitis B surface antigen(HBsAg) -negative patients with or without serological markers of previous exposure(antibodies to HBsAg and/or to HB-core antigen) defines the entity called occult hepatitis B infection(OBI).Co-infection with hepatitis B and hepatitis C viruses is frequent in highly endemic areas.While this co-infection increases the risk of liver disease progression,development of cirrhosis and ...     

不同方案阻断乙肝病毒母婴垂直传播的临床研究

探讨阻断乙型肝炎病毒母婴垂直传播的方法。将122例HBsAg( )孕妇分成四组,HBVac治疗组29例,HBIG组29例。左旋咪唑涂布剂与以上两者联合应用30例。未治疗组34例。均在孕26周开始干预观察,孕妇和新生儿血清HBV标志物（HBVM）检测采用ELISA法,122例孕妇按分娩方式不同分别观察对乙肝病毒母婴垂直传播影响;随访产妇及新生儿HBVM变化。脐血中HBsAg阳性率;HBVac治疗组为17.24%。HBIG治疗组为10.35%。联合治疗组为3.33%。未治疗组为23.53%。在不同的分娩方式中,急症剖宫产新生儿脐血HBsAg阳性率为13.04%,行择期剖宫产者为0,经阴道分娩者为16.67%。携带HBV孕妇于孕晚期给予HBVac,HBIG和左旋咪唑涂布剂联合以上两者治疗后,可有效阻断母婴之间传播。以联合治疗组效果最佳。不同分娩方式也影响传播,剖宫产术有助于阻断HBV母婴传播。