Evolution in the hypervariable region of the hepatitis C virus in two infants infected by mother-to-infant transmission

BACKGROUND: There is little data on the evolution of hepatitis C virus (HCV) quasispecies in infants infected by mother-to-infant transmission during long-term follow up. The hypervariable region 1 (HVR1) of the HCV genome was investigated in two mother-infant pairs from birth to 7.6 and 10.2 years, respectively. METHODS: Ten cDNA clones of HVR1 generated from HCV-RNA and extracted from serum samples of both pairs were analyzed. The sequences were compared with regard to variability, identity, and hydrophobia profile, and analyzed by phylogenetic studies. RESULTS: The alanine aminotransferase (ALT) level was high with fluctuation in infant A and almost within the normal range in infant B. Sequence diversity was higher in infant A at 7.6 years than in infant B at 9.3 years (sequence identity with the mothers'; 69.3-70.7% vs 85.3-90.7% for nucleotides, and 48% vs 68-72% for amino acids, respectively). Compared to the first samples, amino acid changes greatly increased in infant A (35.2% at 4.9 years and 52% at 7.6 years), but not in infant B (4% at 5.6 years and 27.5% at 9.3 years). Phylogenetic studies revealed that quasispecies in infant A evolved to a greater extent than that in infant B. Hydrophobia profile analyses revealed that dynamic shifts between hydrophilia and hydrophobia occurred in both infants. CONCLUSIONS: As in adults, the evolution of HVR1 and variability of quasispecies increased in infants infected through mother-to-infant transmission for 10 years after birth. A large episode of ALT elevation suggested the emergence of escape mutants and the evolution of new quasispecies.     

Mother-to-infant transmission of hepatitis C virus: A prospective study

To investigate the risk of mother-to-infant transmission of hepatitis C virus (HCV) and the natural course of HCV-infected infants, we prospectively studied 31 offspring of pregnant women who were anti-HCV positive and anti-HIV negative. Sera were serially tested for anti-HCV by the second-generation ELISA-test (ELISA-2) and for HCV-RNA by the polymerase chain reaction procedure. The mean period of follow up was 19 months (range 6–41 months). The presence of HCV-RNA in the mothers was associated with a high titre of anti-HCV by ELISA-2 or a positivity of the second generation recombinant immunoblot assay. At birth, 26 babies were positive for anti-HCV. Passively transferred maternal antibodies became undetectable within 2–15 months. HCV-RNA was detected in only 3 infants (9.7%) within 1–4 weeks after birth and persisted there-after. The genotype of HCV-RNA in each of the infants was consistent with that of their mother. These 3 showed chronic transaminase elevation during the follow up that started at 1–2 months of age, although they revealed no clinical symptoms. Re-elevation of anti-HCV titre was observed in the HCV-infected infants within 10 months of age, suggesting an endogenous production of anti-HCV. The mean titre of HCV-RNA in three mothers of infected infants was higher than that in the mothers of uninfected infants (10^5.3±0.3 vs 10^4.4±0.2/ml).Conclusion Our findings indicate that HCV was most likely to have been transmitted from mothers to infants at the time of delivery and that it was capable of evoking the chronic carrier state.     

感染丙型肝炎病毒的孕妇及其新生儿随访观察

目的了解丙型肝炎病毒(HCV)母婴垂直传播情况及HCV感染后对新生儿体格发育的影响。方法用ELISA法对1023名孕妇静脉血做抗HCV检测,阳性者对其新生儿脐带血做抗HCV检测。阳性者(包括产妇及其新生儿)进一步做HCVRNA检测;对抗HCV阳性新生儿做10～12个月随访,观察HCV感染指标及新生儿喂养、患病、生长发育情况。结果产妇HCV感染率为2.74％(28/1023);抗HCV阳性产妇中HCVRNA检出率为75％(21/28);抗HCV阳性产妇的新生儿脐血中抗HCV检出率为46.43％(13/28),其中检出HCVRNA阳性5例。对抗HCV阳性新生儿1年随访,抗HCV阴转率为69.23％(9/13),实验组新生儿母乳喂养率57％明显低于对照组85％,实验组儿童人均患病1.25次,而对照组儿童为0.5次,有非常显著性差异,身长、体重指标明显落后于对照组。结论母婴间存在着HCV的垂直传播;HCVRNA的存在不但增加了母婴垂直传播的比率,而且延缓了抗HCV的阴转;HCV的感染非常明显地影响了新生儿的体格发育。     

丙型肝炎病毒母婴宫内传播的研究

目的为研究丙型肝炎病毒（ＨＣＶ）的母婴宫内传播，评估ＨＣＶ母婴传播的危险性。方法应用酶联免疫吸附试验（ＥＬＩＳＡ）法检测ＨＣＶ，以逆转录－聚合酶链反应（ＲＴ－ＰＣＲ）检测ＨＣＶ－ＲＮＡ。结果检测的４２７７例孕晚期孕妇血清抗－ＨＣＶ，其中６例阳性，进一步检查ＨＣＶ－ＲＮＡ，结果６例中有５例阳性，且均有受血史，５例阳性孕妇其配对婴儿脐血抗－ＨＣＶ均阳性，其中２例ＨＣＶ－ＲＮＡ阳性，肝功能异常；１例出生时ＨＣＶ－ＲＮＡ阴性，到２４个月时ＨＣＶ－ＲＮＡ阳转。ＨＣＶ母婴宫内传播率为２／５。结论表明上海地区存在ＨＣＶ母婴宫内传播，应重视有受血史的生育妇女孕期及孕前的ＨＣＶ检查及ＨＣＶ感染儿的随访。     

Post-transfusion chronic hepatitis C in children

Two hundred and twenty-six patients who received blood products for open-heart surgery in childhood were screened by a second-generation enzyme-linked immunosorbent assay and with surrogate markers for hepatitis C virus (HCV) infection, such as alanine aminotransferase (ALT). Twenty-two (14%) of the 161 recipients who received blood products before 1989 and none of the subjects who had received blood products after 1990 (the year that the blood bank began to screen for HCV antibody) were HCV seropositive. Virologic and histologic studies showed that 10 (45%) of 24 seropositive patients had persistent hepatitis C virus infection, many with ongoing hepatitis. The remaining 12 seropositive patients with absent HCV RNA had normal ALT levels, indicating resolved hepatitis C infection. Enrolment in screening is important to detect chronic hepatitis C in children who received blood products prior to screening of blood donors for HCV antibody.     

The management of infants,children, and youth at risk for hepatitis C virus infection

Hepatitis C virus (HCV) infection affects 0.5% to 1.0% of the Canadian population. Most paediatric HCV infections are a consequence of vertical transmission or, among youth and young adults, the result of engaging in high-risk behaviours, such as injection drug use and unprotected sexual activity. It is now recommended that all infants, children, and youth with one or more risk factors be screened for HCV infection. Treating chronic HCV infection with direct-acting antivirals has been shown to achieve sustained virologic suppression in 97% to 100% of children as young as 3 years old. Paediatricians and family physicians have an important role in educating youth regarding HCV infection risks and prevention, and in advocating to government and public health authorities for comprehensive harm reduction interventions targeting at-risk youth, accessible treatments, and routine prenatal screening for HCV.     

乙型肝炎病毒携带母亲母乳喂养安全性探讨

目的 观察乙型肝炎病毒携带母亲母乳喂养的安全性.方法 入选乙型肝炎病毒携带母亲的足月健康新生儿,所有婴儿均接种乙肝疫苗,或联合使用乙肝免疫球蛋白;按照母亲选择的不同喂养方式,分为母乳喂养或配方奶喂养组;婴儿出生时,3、7、12月龄,分别检测乙型肝炎抗原和抗体.结果 母乳喂养与配方奶喂养婴儿比较,HBsAg阳性率、抗-HBs阳性率以及慢性HBV感染的差异均无统计学意义(P均＞ 0.05).结论在疫苗和乙肝免疫球蛋白的联合免疫下,乙肝病毒携带母亲的母乳喂养是安全的.     

Mother-to-infant transmission of hepatitis C virus

Anti-hepatitis C virus (HCV) antibodies and HCV-RNA were measured in the sera of 22 anti-HCV positive, HIV-1 negative mothers and their infants. ELISA and RIBA II were used for anti-HCV determination. HCV-RNA was measured by a nested polymerase chain reaction. HCV-RNA was found in 12 of 22 mothers. All 22 children were followed for 12 months. All were anti-HCV positive by the fourth month; 18 became anti-HCV negative between the 8th and 12th month. HCV-RNA was detected in 5 of 22 infants in the fourth month. They remained HCV-RNA positive. All children born to HCV-RNA negative mothers were HCV-RNA negative while 5 of 12 babies born to HCV-RNA positive mothers were infected. All five infected babies were born to mothers infected through transfusions or drug use. ALT levels in mothers seemed to have no effect on mother-to-infant transmission. Hence evidence for perinatal transmission of HCV from HCV-RNA positive mothers was demonstrated in the present study.     

High rate of maternal-infant transmission of hepatitis G virus in HIV-1 and hepatitis C virus-infected women

The prevalence of hepatitis G virus (HGV) infection was investigated in 56 mothers with both human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) infection. Thirty-three (58.8%) women had markers of HGV infection, including 7/15 (46.6%) with no history of parenteral exposure to blood. Sixteen (48%) had HGV RNA in serum by a polymerase chain reaction assay, and 17 (52%) had antibody to E2 viral protein. No woman was positive for both markers. Of 20 infants born to the 16 mothers with HGV viremia, 9 (45%, 95% CI 34-56%) acquired the infection. No infected child seroconverted to HGV during the first year of life. At the latest visit (mean: 37.1 mo, range: 9-89 mo) 7 children were still seronegative HGV RNA carriers, 1 was both RNA- and antibody-negative, while 1 RNA-negative child had developed the E2 antibody. Of the 20 HGV-exposed infants, 2 contracted HCV and 1 HIV-1 (all 3 with HGV coinfection). No abnormalities in clinical findings and ALT levels were observed throughout the follow-up period in the six children with HGV infection alone. Our findings show that HGV infection is widespread among HIV-1- and HCV-infected women. Maternal-infant transmission of HGV is common and occurs independently from that of HIV-1 and HCV in women with triple infection. Most perinatally HGV-infected children develop persistent infection with no clinical or biological signs of liver damage, at least in the first years of life.     

乙型肝炎病毒DNA定量在母婴传播中的意义

目的　探讨孕妇不同血清HBV DNA含量对HBV母婴传播的影响。方法　应用荧光定量PCR技术检测 6 9对母婴血清HBV DNA含量 (所测数据经对数转换 ) ,对孕妇不同血清HBV DNA含量进行分组。结果　孕妇HBV DNA含量为 (6 3± 1 9)拷贝 /ml,婴儿为 (4 8± 2 0 )拷贝 /ml,两者之间呈正相关 (r=0 310 ,P <0 0 1)。 6 9例婴儿中 ,45例HBV DNA定性和 (或 )HBV血清学检查异常 ,提示HBV母婴垂直传播 ,传播率为 6 5 %;HBV母婴传播率随孕妇血清HBV DNA浓度增高而增高 ;根据孕妇血清HBV DNA含量分别向下和向上累计分析 ,显示孕妇HBV DNA含量在 5 0、6 0和 7 0拷贝 /ml三个界面的上下浓度区域 ,HBV母婴传播率差异有显著性 ,其差值分别为 32 %、34 %和 2 8%。本组资料中 ,孕妇HBeAg阳性 19例 ,HBsAb阳性 17例 ,HBeAg阳性组HBV DNA[(7 6± 1 3)拷贝 /ml]明显高于阴性组 [(5 8± 1 9)拷贝 /ml],其HBV母婴传播率 (90 %)明显高于阴性组 (5 6 %) ;HBsAb阳性组HBV DNA含量 [(5 3± 1 6 )拷贝 /ml]明显低于阴性组 [(6 6± 1 9)拷贝 /ml],HBV母婴传播率 (2 9%)也明显低于阴性组 (77%)。同时 ,HBeAg阳性主要分布在HBV DNA测定值较高的孕妇中 ,HbsAb阳性主要分布在HBV DNA测定值较低的孕妇组。结论　HBV母婴传播率受孕妇血清H     

A case of vertical transmission of hepatitis A virus infection

We present a case of hepatitis A infection in a 2.5-month-old male who became icteric after 18 d of birth. The diagnosis of hepatitis A was made by compatible clinical symptoms, laboratory results and liver biopsy showing evidence of hepatitis, and confirmed by detection of anti-HAV IgM antibodies. Because the mother had an acute icteric hepatitis A 1 week before delivery, and the viraemic phase of hepatitis A infection is very short, approximately 7 d, we suggest that the infant was infected by his mother, before birth.     

Diagnosis and management of paediatric hepatitis C virus infection

Hepatitis C virus (HCV) infection in children is uncommon and there are few guidelines indicating optimal management. It is estimated that 125-250 children are infected vertically with HCV in Australia each year and very few of these children are diagnosed and followed medically. Without accurate diagnosis and follow up, these children cannot be offered optimal care, and are at risk of presenting in adult life with significant liver pathology and long-term sequelae.     

Decline of maternal hepatitis A virus antibody levels in infants

Hepatitis A is a common viral infection causing substantial morbidity and mortality. The anti-hepatitis A virus (HAV) vaccination in infants would guarantee control of the infection. However, the immunogenicity of the HAV vaccine in infants could be impaired by the presence of passively acquired maternal HAV antibodies. This study evaluated the prevalence of HAV antibodies in 103 women at delivery and in their babies in the first year of life. Eighteen mothers (17.5%) had anti-HAV serum level >10 mIU ml(-1). In their infants the anti-HAV level was still positive in 11 out of 18 (61.1%) at 12 mo. Two out of 85 infants born to anti-HAV-negative mothers and anti-HAV negative at birth were found to be positive at 5 mo of age. Conclusion: It is proposed that all women be screened at delivery for anti-HAV antibodies. Children born to anti-HAV-negative mothers could be vaccinated early during the first year of life, whereas vaccination could be postponed in children born to anti-HAV-positive mothers, if necessary.     

Hepatitis C virus antibodies in a long-term follow-up of beta-thalassaemic children with acute and chronic non-A non-B hepatitis

The presence of antibodies toward hepatitis C virus (HCV) was examined in 78 polytransfused betathalassaemic children. The anti-HCV status was correlated with acute and chronic non-A non-B (NANB) hepatitis that developed during a follow up of about 13 years. Anti-HCV was present in 83.3% of children with acute NANB hepatitis and in 82.9% of those with chronic NANB hepatitis. The percentage of chronic evolution was 56.7% for acute anti-HCV positive NANB hepatitis and 50.0% for anti-HCV negative NANB hepatitis. The long-term persistence of anti-HCV antibodies did not correlate with chronic evolution of liver infection in thalassaemic patients. Histological features of chronic hepatitis showed little or no difference between HCV associated or non-associated liver disease. The multifactorial liver injury in beta-thalassaemic children explains the high prevalence of cirrhosis (about 30%) observed in these patients with NANB hepatitis. On the other hand, independent of liver disease, some patients never seroconverted during the follow up in spite of the high number of transfusions suggesting the existence of non-responders.     

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目的了解儿童乙型肝炎病毒(HBV)基因型与临床分度的关系。方法选择甘肃省人民医院儿科和兰州大学第一医院感染科2008年4月至2010年4月门诊和住院患儿中HBV-DNA阳性的124例乙型肝炎患儿,其中男84例,女40例。HBV携带者65例,慢性乙型肝炎59例(轻度31例、中度18例、重度10例),对以上患儿进行基因分型、同时检测肝功、术前出凝血、HBV-DNA载量。结果 124例肝病患儿中,C基因型62例(50.0%),B基因型48例(38.7%),B/C混合型9例(7.3%),非B/C型5例(4.0%);HBV携带者和轻度组中,以B基因型为主,分别为47.7%和45.2%;中度和重度组中,以C基因型为主,分别为72.2%和80%;在C、B基因型分布方面,HBV携带者和轻度组与中度和重度组比较差异有统计学意义;C基因型患者的HBV-DNA载量、丙氨酸转氨酶(ALT)、天冬氨酸转移酶(AST)、总胆红素(TBIL)均高于B基因型;C基因型患者与B基因型比较,凝血酶原时间(PT)延长、凝血酶原活动度(PTA)下降、纤维蛋白原(FIB)减少。B、C型通过母婴传播的比例差异无统计学意义。结论甘肃省儿童乙型肝炎病毒基因...     

乙型肝炎病毒母婴传播影响因素探讨

目的：探讨乙型肝炎病毒(HBV)母婴传播的影响因素,寻求降低婴儿HBV感染率的方法。方法：HBV携带及慢性乙型肝炎孕妇共635例,分别比较不同血HBV DNA滴度,不同分娩方式（剖宫产或自然分娩）,以及不同肝功能状态孕妇所生婴儿出生时及3月龄时HBV的感染率。新生儿生后12 h内肌注乙肝免疫球蛋白200 U 及重组酵母乙肝疫苗10 μg;生后即刻显示血清HBV感染存在者,14 d时再肌注乙肝免疫球蛋白200 U。结果：孕妇高滴度组（HBV DNA>105拷贝/mL）所生新生儿出生时（14.4% vs 4.1%,P<0.01）与3月龄时（4.7% vs 0,P<0.01）HBV感染率均高于低滴度组（HBV DNA ≤105拷贝/mL）。两组新生儿3月龄时HBV感染率均低于出生时（P<0.05）。自然分娩的孕妇其婴儿出生时HBV感染率明显高于剖宫产组（P<0.01）,但3月龄时,两组感染率接近。HBV携带孕妇所生婴儿出生时HBV感染率明显高于慢性乙型肝炎孕妇所生婴儿（P<0.01）,但3月龄时两组婴儿HBV感染率亦接近。结论：孕妇血清HBV DNA水平与新生儿HBV宫内感染密切相关,故降低孕妇血清HBV DNA水平可能成为减少新生儿HBV感染的一种有效途径。在乙肝免疫球蛋白及重组酵母乙肝疫苗的双重保护下,孕妇的分娩方式与肝功能状态对HBV母婴传播无影响。