Risks of seroconversion of hepatitis B, hepatitis C and human immunodeficiency viruses in children with multitransfused thalassaemia major

OBJECTIVES: To estimate the risks of seroconversion of hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency viruses (HIV) in children with multitransfused thalassaemia at a thalassaemic clinic in Kuala Lumpur, Malaysia. METHODS: Seventy-two children (39 males, median age 11.3 years, 2.5th-97.5th centile: 1.4-19.2 years) with thalassaemia major were studied. The risks of seroconversion of HBV, HCV and HIV were estimated by comparing the seroprevalences of hepatitis B surface antigen (HBsAg), anti-HCV and anti-HIV between a defined starting point and an end point. The end point was the point when latest serological results were available while the starting point was when regular transfusion was commenced, or approximately 5 years before the end point when the duration of transfusion was longer. RESULTS: The median duration of the study was 49 months (range 8-69 months, total 2953 patient-months). There were 2605 transfusion episodes and 4154 units of blood transfused (0.88 transfusion episode/patient per month, 1.41 units of blood transfused/patient per month). There were three new seroconversions for anti-HCV but none for HBsAg and anti-HIV. The risk of seroconversion for HCV was one in 1384 units of blood transfused (95% CI: 4000-472). The seroprevalence rates at the starting and end points were: HBsAg (1%, 1%), anti-HCV (10%, 13%) and anti-HIV (0%, 0%), respectively. CONCLUSIONS: The estimated risk of acquiring HCV infection in children receiving multiple blood transfusions in this study is surprisingly higher than the generally accepted estimated risk. Other routes of transmission may be important. A prospective, multicentre study to estimate such risks more precisely is needed.     

Hepatitis B and C virus infections in Turkish children with haemophilia

We examined 41 Turkish children with haemophilia for evidence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections using the enzyme-linked immunosorbent assay (ELISA). Hepatitis B surface antigen was found to be positive in 11 patients (26. 8%) and HCV-specific antibody (anti-HCV) was detected in 10 (24. 4%) patients. There was a close relationship of the number of transfusions of blood plasma to the presence of HCV specific antibody, but not to the serum markers of HBV infection. In countries where HBV infection is commonly seen and problems in transfusion practice continue, as in Turkey, children with haemophilia are at greater risk for HBV and HCV infections.     

Correlation of hepatitis B virus,hepatitis D virus and human immunodeficiency virus type I infection markers in hepatitis B surface antigen positive haemophiliacs and patients without haemophilia with clinical and histopathological outcome of hepatitis

The hepatitis D virus (HDV) infection plays a major role in severe liver damage caused by hepatitis. To establish the prevalence of HDV infection in haemophilic patients and patients without haemophilia, 87 patients with chronic hepatitis B virus (HBV) infection were examined for serological evidence of delta hepatitis. In addition HBV, HDV and human immunodeficiency virus type 1 (HIV) infection markers were compared to clinical and histopathological outcome of hepatitis. Out of 46 haemophiliacs 30 (65%) were anti-HD-seropositive; 10 out of 30 anti-HD-positive patients (33%) had pathological liver function tests compared to 2 out of 16 anti-HD-negative haemophiliacs (13%). The rate of HIV infection did not differ between the HDV infected and the non-HDV infected individuals with haemophilia (17/27 anti-HD-positive patients versus 12/16 anti-HD-negative patients). Two haemophilic anti-HD-positive patients underwent liver biopsy, in both cases hepatitis D antigen (HDAg) was detected in the biopsies. Only 2 out of 41 patients without haemophilia were anti-HD-positive. Both had pathological liver function tests; chronic active hepatitis and cirrhosis, respectively, were diagnosed and HDAg was found in the liver biopsies. Out of 39 anti-HD-seronegative patients without haemophilia, 26 (67%) were hepatitis B e antigen positive; in the sera of 20 patients )51%) HBV-DNA was demonstrated, but only 6 patients (15%) had pathological liver function tests. In conclusion a high seroprevalence of HDV infection was found in haemophilic patients treated with non-pasteurized commercial clotting factor concentrates. An endemic spreading of HDV infection in patients without haemophilia with chronic HBV infection could not be detected. In haemophilic patients pathological liver function tests were more frequently associated with HDV superinfection than with chronic HBV infection alone. HIV infection was diagnosed at a similar rate in anti-HD-positive and anti-HD-negative patients.     

Seroprevalence of hepatitis B, hepatitis C, and human immunodeficiency virus infections in children with cancer at diagnosis and following therapy in Turkey

BACKGROUND: Children with cancer receiving intensive chemotherapy require multiple transfusions and are at increased risk for blood transmittable diseases such as hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) infections. PROCEDURE: Sera from 50 children (24 female, 26 male) admitted between January, 1994, and December, 1995, with solid tumors receiving intensive chemotherapy and multiple transfusions were investigated for HBsAg, anti-HBs, anti-HBc, anti-HCV, and anti-HIV by ELISA at diagnosis and at the end of therapy. RESULTS: HBsAg, HBV, HCV, and HIV seropositivities were 0%, 4%, 2% and 0% at diagnosis and 10%, 20%, 14% and 0% at the end of therapy, respectively. CONCLUSIONS: The high seroprevalence of HCV may be due to the lack of anti-HCV screening of blood products in the blood banks during the study period. Although the HBV seroprevalance of 20% found in this study is much lower than the value of 56% found in a previous study conducted during 1986-1989 in a similar patient population and a similar setting, it is still high. Children infected with HBV during immunosuppressive therapy are at greater risk of becoming chronic carriers and precautions must be taken for immunization of these children.     

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。     

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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...     

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.     

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.     

Changes in hepatitis B virus serology in bone marrow transplanted children

Suppression of the immune system and reconstitution of the donor's immune system may affect the course of a chronic viral infection in the recipients. The aim of this study is to evaluate changes in hepatitis B virus (HBV) serology after bone marrow transplantation (BMT). HBV serology and hepatic function tests were examined in 45 children before and after BMT. Before BMT, 40 patients were HBsAg negative and 5 positive. There were no HBsAg positive donors. HBsAg disappeared in two patients and anti-HBs became positive in one. Donors of these patients were anti-HBs positive. In a third patient, acute HBV infection developed and lasted without complication. This patient also seroconverted to anti-HBs. Anti-HBs disappeared in 7 of 21 anti-HBs positive patients. Among 18 patients who were HBsAg and anti-HBs negative, 11 seroconverted to anti-HBs positivity. Our findings support the notion that having an anti-HBs positive donor is important for adoptive immunity transfer and for preventing HBV replication.     

粒细胞-巨噬细胞集落刺激因子联合乙肝疫苗对宫内感染HBV携带儿童治疗机制初探

目的从细胞因子水平初步探讨粒细胞一巨噬细胞集落刺激因子(GM—CSF)联合乙肝疫苗对宫内HBV感染携带儿童的疗效机制。方法采用ELISA和半定量逆转录-聚合酶链反应(RT—PCR)，对12例GM—CSF联合乙肝疫苗治疗后儿童、6例乙肝免疫球蛋白(HBIG)联合乙肝疫苗治疗后儿童及9例未治疗的宫内感染儿童外周血单个核细胞在PHA LPS、HBsAg及无刺激物时γ-干扰素、白细胞介素(IL)-4分泌及mRNA表达水平进行检测。结果与对照组比较，GM-CSF联合乙肝疫苗治疗儿童γ-干扰素自发分泌显著增加(P=0．017)，HBIG联合乙肝疫苗治疗儿童IL-4 mRNA转录显著降低(P=0．002)。结论GM—CSF联合乙肝疫苗治疗宫内感染HBV慢性携带儿童时HBV受抑制可能与γ-干扰素产生增多有关，HBIG联合乙肝疫苗治疗时IL-4转录受抑不影响HBV复制，提示慢性HBV感染治疗应以增强Th1应答为主。     

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.     

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.     

Seroprevalence of Helicobacter pylori infection among children and their parents in eastern Turkey

OBJECTIVES: To determine the seroprevalence of Helicobacter pylori infection among healthy children in eastern Turkey, to assess risk factors for seroconversion, and to assess the role of parental infection status in the transmission of H. pylori. METHODS: A commercial enzyme immunoassay test for IgG to H. pylori was used. Demographic information obtained included age, gender, socio-economic status and living conditions. RESULTS: One hundred and fifty-two (43.9%) of 346 children were seropositive. There was no significant difference in rates of seroprevalence between boys and girls (P > 0.05), but a significant rise was noted with increasing age (P < 0.001). We found a strong inverse correlation between family income and seropositivity (P < 0.001). Seroprevalence also varied significantly with the educational level of the mother (P < 0.001). There were no significant differences in seroprevalence associated with place of residence, water supply and the number of persons per room (P > 0.05). The prevalence of infection in the corresponding parents was 85.4% for mothers and 76.3% for fathers. Seroprevalence was higher in children whose mother was infected (P < 0.001). CONCLUSIONS: In eastern Turkey, as in other developing countries, H. pylori infection occurs early and increases with age. Infected parents, especially infected mothers, may have a important role in the transmission of H. pylori within families.     

小儿乙型肝炎超微结构与临床

研究小儿乙型病毒性肝炎超微结构和临床特点。方法应用光镜、电镜、免疫组化多克隆HBV（PAP）法，血乙肝标志物用ELISA法，HBV-IgM斑点杂交法结合临床对27例住院患儿肝穿刺活组织标本进行对比观察，并结合临床进行分析。结果在各型乙肝过程中，肝细胞核与细胞器病变均较广泛，且病理诊断常重于临床诊断。结论光镜结合电镜是明确肝炎型别和寻找病因的一种重要方法，能使诊断更趋完善和准确。     

妊娠晚期乙肝孕妇注射乙肝免疫球蛋白对阻断乙肝病毒母婴传播的作用

目的 探讨慢性乙肝病毒感染的孕妇于妊娠晚期注射乙肝免疫球蛋白(HBIG)对阻断乙肝病毒母婴传播的效果.方法 将慢性乙肝病毒携带者或慢性乙肝孕妇及其所生新生儿分为2组,A组孕妇于孕期第28、32及36周时分别肌肉注射HBIG 200 IU;B组孕妇未注射HBIG.分别检测两组孕妇及其所生新生儿血清乙肝病毒标志物(HBVM)及乙肝病毒DNA(HBV DNA).结果 A组孕妇378例,共分娩新生儿378例,其中新生儿血HBV DNA>500 copies/ml 17例,新生儿宫内感染发生率为4.497%;B组孕妇391例,共分娩新生儿391例,新生儿血HBVDNA>500 copies/ml 17例,新生儿宫内感染发生率为4.348%(X<'2>=0.005 6,P>0.05).血清抗-HBs阴性的孕妇所生新生儿中,A组有9例血清抗-HBs阳性,B组未见血清抗-HBs阳性(X<'2>=7.474,P<0.05).结论 给慢性乙肝病毒感染的孕妇于妊娠晚期注射HBIG 3次,每次200 IU不能明显降低新生儿发生乙肝病毒宫内感染的机会,但部分新生儿可获得血清抗-HBs.HBIG在慢性乙肝病毒感染妊娠妇女中的应用尚待进一步探讨.