Clinical significance of TT virus infection in children with chronic hepatitis B

BACKGROUND: The pathogenic role of TT virus (TTV) is not clear in patients with chronic hepatitis B. The aims of the present study were to determine the frequency of TTV positivity in serum and saliva samples and the possible role of TTV in children with chronic hepatitis B. METHODS: Sera and saliva from 29 healthy children and 25 children with chronic hepatitis B were tested for TTV-DNA by means of real-time polymerase chain reaction (PCR). RESULTS: Fifty-two percent (13/25) of the serum samples and 32% (8/25) of the saliva samples were positive for TTV-DNA in children with chronic hepatitis B. In healthy non-transfused children, TTV-DNA was detected in 58% (17/29) of the serum samples and 41% (12/29) of the saliva samples. Six (46%) of 13 children with chronic hepatitis and 10 (59%) of 17 healthy children had TTV-DNA positivity both in serum and saliva samples. Two serum samples were negative for TTV-DNA while the saliva samples were positive for TTV-DNA in chronic hepatitis B and control groups. Mean age, sex, serum alanine aminotransferase levels, hepatitis B virus (HBV)-DNA values were similar in TTV-positive and -negative children with chronic hepatitis B. However, total histologic activity index (HAI), periportal necrosis and portal inflammation scores were significantly higher in children with HBV-DNA and TTV-DNA viremia (P = 0.013, P = 0.008, P = 0.015, respectively). CONCLUSIONS: Because total HAI, periportal necrosis and portal inflammation scores were higher in children with TTV coinfection, TTV infection may contribute to the progression of liver damage in children with chronic hepatitis B.     

儿童乙型肝炎病毒相关性肾炎临床病理分析

目的 探讨儿童乙型肝炎病毒相关性肾小球肾炎(HBV—GN)临床及病理特点。方法 分析35例HBV—GN的临床表现及肾活检光镜、免疫荧光和电镜特点。结果 35例HBV-GN临床表现以肾病综合征(NS)为主(32／35，91．4％)；肾小球肾炎3／35(8．6％)。病理类型以膜性肾病(MN)最多见(33／35，94．3％)；其次系膜增生性肾炎(MsPGN，2／35，5．7％)。免疫荧光检查呈多种免疫复合物沉积。电镜观察HBV—MN易见电子致密物系膜沉积，2例肾小球基底膜内观察到病毒样颗粒。结论 儿童HBV—GN临床常表现主要为NS，病理特征以Ⅲ为主，诊断不必强调HBsAg、HBcAg在肾组织上沉积，肾组织病理特点提示HBV可通过多种机制引起肾损害。     

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.     

Hepatitis B precore mutant in children with chronic hepatitis B virus infection

BACKGROUND: In adults, hepatitis B virus (HBV) with a G to A point mutation at nucleotide 83 in the precore region (mutant HBV 83), is commonly found in HB e antibody positive HBV carriers. It has been reported that this mutant is not able to produce HB e antigen. The exact prevalence of mutant HBV 83 in patients with chronic HBV infection is not fully understood, especially in children. METHODS: To investigate the role of mutant HBV 83 in children with chronic HBV infection, sera were tested for the presence of mutant HBV 83 using a mutation site-specific assay. RESULTS: Mutant HBV 83 was detected in 15 of 22 children (68%). Seven children were followed longitudinally, of which three were asymptomatic carriers and the other four had chronic hepatitis B on entry. There was no clear relationship between the disease activity and the presence of mutant HBV 83. CONCLUSIONS: It was concluded that mutant HBV 83 is commonly present in children with chronic HBV infection and this mutant is not necessarily associated with activation of hepatitis.     

HBsAg阳性母亲的婴儿接种乙肝疫苗后慢性HBV感染相关因素探讨

为探讨HBsAg阳性母亲的婴儿接种乙肝疫苗后慢性HBV感染相关因素及机制,对624名儿童随访了(6.34±1.71)年。结果发现慢性HBV感染89例,其中82.0％始于6月龄前。HBeAg同时阳性母亲的婴儿慢性HBV感染率高于单阳性母亲的婴儿(单用疫苗,P<0.005;HBIG+疫苗,P<0.05),且在6月龄内出现HBsAg阳性时,慢性化率也高(单用疫苗,P<0.025)。联合使用HBIG和疫苗可进一步减少慢性HBV感染率(单阳性组,P<0.025,双阳性组,P<0.005)及在1月～6月HBsAg阳性婴儿慢性化率(双阳性组,P<0.025)。提示HBsAg阳性母亲的婴儿接种乙肝疫苗后慢性HBV感染主要发生于宫内或产程中。双阳性母亲的婴儿更易形成慢性HBV感染,HBIG联合疫苗的预防效果优于单用疫苗。     

苏州市1500名5岁～10岁儿童乙肝病毒感染的调查研究

为了解乙肝疫苗接种预防儿童乙肝病毒（HBV）感染的效果，根据随机分层抽样原则，于1997年5月－10月对市区1500名5－10岁儿童进行乙肝病毒血清学检测和乙肝疫苗接种情况调查。结果表明，儿童HBV总感染率为3．60％（54／1500名），随年龄增大有上升趋势，接种组HBV感染率为1．65％，未接种组为19．63％（P＜0．001）；加强免疫的儿童抗HBs阳性率85．78％，HBV感染率0．73％；未进行加强免疫的儿童抗HBs阳性率为43．21％，HBV感染率为2．60％（P＜0．01）。提示儿童乙肝疫苗接种显著降低了儿童HBV感染率，但随年龄增长，50％以上儿童抗HBs滴度低于保护阈值，HBV感染率上升，加强免疫接种打破了这种趋势，值得提倡。     

Seroepidemiology of hepatitis B virus infection among children in Mongolia: Results of a nationwide survey

BACKGROUND: Because Mongolia is one of the highly endemic countries for hepatitis B virus (HBV) infection in the world, hepatitis B (HB) vaccine was introduced into the National Expanded Program on Immunization in 1991. However, relatively few data are available concerning HBV infection among children born after the start of the program, so far. The aim of the present paper was to describe the seroepidemiology of HBV infection among primary school children using representative national data. METHODS: In 2004, a nationwide school-based cross-sectional serosurvey was carried out throughout Mongolia, covering both urban and rural areas. Serum samples were tested for hepatitis B surface antigen (HBsAg), antibody to hepatitis B core antigen (anti-HBc) and hepatitis B e antigen (HBeAg) as well as for liver enzymes. RESULTS: A total of 1145 children aged 7-12 years were studied, which represents nearly 2% of the second grade population of elementary schools in Mongolia. The overall prevalence of HBsAg and anti-HBc was 5.2% (95% confidence interval [CI]: 3.9-6.5%) and 15.6% (95%CI: 13.5-17.7%), respectively. Among HBsAg-positive children 67.8% (95%CI: 55.9-79.7%) were also positive for HBeAg. The prevalence of chronic HBV infection increased by age and was significantly higher among children from rural areas compared to those from urban areas (7.7% vs 3.0%; P < 0.001). In the multivariate logistic regression analysis, rural residence (odds ratio [OR]: 2.57; 95%CI: 1.45-4.58), male sex (OR: 1.9; 95%CI: 1.08-3.26) and age (OR: 1.5; 95%CI: 1.10-2.05) were independent demographic predictors for chronic HBV infection. CONCLUSIONS: The prevalence of chronic HBV infection has been decreasing in the Mongolian young generation, most likely due to infant HB vaccination. However, significant rural-urban differences in the prevalence of HBV infection were found that demand further investigation to estimate the potential causes.     

Changing patterns of hepatitis A and E sero-prevalences in children after the 1999 earthquakes in Duzce, Turkey

Aim:   Hepatitis A and E are enteric viral diseases that are characteristically found in developing countries. Sero-epidemiological data about both infections showed higher prevalence rates soon after the 1999 earthquakes in Duzce, Turkey. The aim of the present study was to evaluate the data 4 years after the earthquakes.
Methods:   The study group included 589 children (72.3% boys) who were between the ages of 6 months and 17 years (mean age 11.5 years). The children were separated into three groups: Group 1 (ages 6 months to 5.9 years), Group 2 (ages 6.0–12.9 years) and Group 3 (ages 13.0–17.0 years). Serum anti-hepatitis A virus IgG and anti-hepatitis E virus IgG were determined using commercial enzyme-linked immunosorbent assay kits. The data were tested for statistical significance with the χ²-test.
Results:   The sero-prevalence rates of hepatitis A and E were 63.8% and 0.3%, respectively. The sero-prevalence rates of both hepatitis A and E increased with age, and there was no significant difference between the genders. Hepatitis A infection was associated with socio-economic condition, crowded living environment, and education level of the family ( P  < 0.01).
Conclusions:   Hepatitis A infection is still common, whereas hepatitis E infection appears to be relatively rare in paediatric age groups in Duzce, Turkey.     

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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...     

Tolerance of interferon-alpha therapy in children with chronic hepatitis B

OBJECTIVE: To assess the side-effects of interferon-alpha (IFN-alpha) therapy in children with chronic hepatitis B. METHODS: This prospective study was performed on one hundred children by interviewing the patients and their parents; clinical examinations and laboratory investigations were performed during and after therapy. RESULTS: The most frequent side-effects of IFN-alpha therapy were fever, flu-like symptoms, and headaches. Lowering of the mean haemoglobin level, leukocyte and platelet count was significant, but transient during INF-alpha treatment. No increase in autoantibody titres or significant alterations in thyroid function was observed. Twelve months after treatment, hepatitis Be antigen (HBeAg) elimination and alanine aminotransferase (ALT) normalization was achieved in 46% of the children; HBeAg and hepatatis B surface antigen (HBsAg) elimination, together with ALT normalization, was achieved in 14% of the cases. CONCLUSION: The side-effects of the IFN-alpha therapy in children such as fever, flu-like symptoms and bone marrow suppression are common, but transient and mild.     

Viral hepatitis

Hepatitis viruses A to E can cause abnormal liver function tests in children. Although, overall, they are relatively uncommon in children in Australia, epidemiology diagnosis and treatment modalities for these viruses have evolved over the last decade. This review provides an update on the diagnosis and treatment of viral hepatitis in children.     

Alpha interferon and lamivudine combination therapy for chronic hepatitis B in children

BACKGROUND: Lamivudine is a new alternative therapeutic agent for chronic hepatitis B, in which alpha interferon (IFN-alpha) monotherapy is not successful enough. Published reports have revealed no satisfactory data on IFN-alpha and lamivudine combination therapy in children. The aim of this study is to investigate the efficacy and safety of this combination therapy in children with chronic hepatitis B. METHODS: Children with chronic hepatitis B were given either IFN-alpha and lamuvidine (group 1, n = 47) or IFN-alpha alone (group 2, n = 30). Alpha interferon was administered as 5 million U/m2 s.c., thrice a week for 6 months and lamivudine 4 mg/kg per day p.o., maximum 100 mg, for 1 year. Clinical examination was performed; blood cell counts and serum alanine aminotransferase (ALT) and amylase were studied at each visit. At the third, sixth and twelfth month, serological markers were determined. RESULTS: End of therapy response was achieved in 19 (40.4%) patients in group 1 and in 14 (46.7%) children in group 2 (P > 0.05). In group 1, pretreatment serum ALT and hepatic activity index (HAI) were statistically higher in children who responded to therapy (P < 0.005). In group 2, mean serum ALT was higher and hepatitis B virus (HBV) DNA was lower in responders. Sustained response rate was 40.4 versus 43.3% in two groups. CONCLUSION: The response rate of IFN-alpha and lamivudine combination therapy in children with chronic hepatitis B was similar to that of IFN-alpha monotherapy. High ALT level and HAI, rather than low HBV-DNA level were found to be important predictors of response.     

Enteroviral myocarditis in neonates

Enteroviruses are a leading cause of viral infections in children. While most enteroviral infections are mild and self‐limiting, severe disease such as a viral sepsis syndrome, myocarditis, hepatitis and meningoencephalitis may occur. We present two cases of neonatal enteroviral myocarditis. Cardiorespiratory failure occurred in both cases, and severe shock refractory to conventional treatment required support with extracorporeal membrane oxygenation (ECMO). One child with coxsackievirus B3 myocarditis failed to recover and died after 3 weeks on ECMO, while one child could be decannulated successfully after 9 days of ECMO and recovered completely subsequently. In conclusion, neonatal myocarditis has a very high mortality, and ECMO should be considered early in neonates with rapid clinical and echocardiographic deterioration despite adequate inotropic support.     

Hepatitis B immunoglobulin in combination with lamivudine for prevention of hepatitis B virus reactivation in children undergoing bone marrow transplantation

There is little information in literature about the use of hepatitis B immunoglobulin (HBIg) in recipients of bone marrow transplantation (BMT). Here, we report two children who received IV HBIg (Hepatect-CP) and lamivudine treatment during BMT course for either patient or donor hepatitis B virus (HBV) viremia. A four-year-old girl underwent a fully human leukocyte antigen-matched allogeneic BMT for thalassemia major from her mother positive for hepatitis B surface antigen (HBsAg). A 12-yr-old boy with chronic myeloid leukemia, positive for HBsAg and HBV-DNA received a fully HLA-matched allogeneic BMT from his sister in the first chronic phase of the disease. HBIg was successfully used in both cases to prevent HBV reactivation of the recipients. The results of our observations are encouraging and we suggest that HBIg in combination with lamivudine may be used in such cases especially in post-transplant early period to prevent HBV reactivation.     

Efficacy of vitamin E in children with immunotolerant-phase chronic hepatitis B infection

BACKGROUND: The purpose of the present paper was to investigate the efficacy of vitamin E in children with immunotolerant-phase chronic hepatitis B virus (CHB) infection. METHODS: Fifty-eight immunotolerant children were prospectively and randomly recruited into two groups. Group 1 (study group) included 30 patients who received vitamin E at a dose of 100 mg/day throughout 3 months; group 2 (control group) contained 28 patients who did not receive any medication. Comparison of serological, virologic, and biochemical response ratios were done at the end of the therapy and after 6 months of vitamin E discontinuation. RESULTS: Mean alanine transaminase (ALT) values in group 1 at the beginning of the therapy, 3 months after the therapy initiation and 6 months after discontinuation were 30.4 +/- 7.3 IU/L, 31.3 +/- 7.8 IU/L and 32.1 +/- 8.5 IU/L, respectively. The mean hepatitis B virus (HBV)-DNA load of group 1 at onset, and at the third and ninth months of the treatment were 3106 +/- 718 pg/mL, 3530 +/- 137 pg/mL and 3364 +/- 1246 pg/mL, respectively. These changes in both ALT and HBV-DNA values did not reach significant levels (P > 0.05). In group 2, mean ALT values at the beginning of therapy, and at the third and ninth months were 28.0 +/- 1.8 IU/L, 34.6 +/- 8.1 IU/L, and 34.1 +/- 7.0 IU/L, respectively (P > 0.05), and mean viral load of HBV-DNA was 4227 +/- 1435 pg/mL, 3368 +/- 2673 pg/mL, and 3018 +/- 2814 pg/mL, respectively (P > 0.05). There was no statistically significant difference between group 1 and group 2 at the third and ninth months in the mean ALT values and viral load of HBV-DNA (P > 0.05). Hepatitis B s antigen and hepatitis B e antigen clearance or hepatitis B s antibody and hepatitis B e antibody seroconversion were not observed in either group. CONCLUSION: As a first study investigating the effect of vitamin E in children with immunotolerant CHB infection, no beneficial effect could be demonstrated. Different immunomodulator protocols should be considered for future investigations.