Serological responses to hepatitis B virus infection in multi-transfused thalassemic children.

One hundred children with beta-thalassemia major were studied prospectively. A one time analysis of serum samples was carried out for a battery of hepatitis B viral markers viz., HBsAg, anti-HBs and anti-HBc. Seven mutually different serological patterns were observed. The commonest profile seen in 49 patients was a combined seropositivity for anti-HBc and anti-HBs indicating past HBV infection with persisting immunity. Definite evidence of active HBV infection (seropositivity for HBsAg and/or HBeAg) was demonstrated in 10 cases, six of these were HBsAg positive. Anti-HBc positivity alone was detected in 17 patients. The remaining 24 children were seropositive for anti-HBs alone suggesting a possible passive transmission of anti-HBs through blood transfusion.     

Study on Efficacy of Hepatitis B Immunization in Vaccinated Beta-thalassemia Children in Tehran

Objective

In thalassemic children, HBV infection is common, thus immunization against HBV will reduce and prevent the rate of infection. The aim of this study was to evaluate the efficacy of HBV immunization and the prevalence of HBV infection in beta-thalassemic children in Tehran.

Methods

To assess the efficacy of immunization and determine the immune response of children with beta-thalassemia, sera of 99 children who had received three doses (10/20 µg) of recombinant HBV vaccine in months 0, 1, 6, were selected and tested for HBsAg, HBsAb and anti-HBc by ELISA method. Also, these sera were tested for HBV DNA using nested-PCR method.

Findings

In 99 beta-thalassemic children, 89 (89.9 %) were anti-HBs positive (responders) and 10 (10.1%) anti-HBs negative (non-responders). 3 (3.03%) were anti-HBc positive and 1(1.01%) was HBsAg positive. HBV DNA was not detected in any of them.

Conclusion

Our results have revealed that hepatitis B vaccine is highly immunogenic for thalassemic children and particularly well tolerated.     

Interferon treatment for chronic hepatitis B: enhanced response in children 5 years old or younger

OBJECTIVE: To test the hypothesis that there is an improved response to interferon in children with chronic hepatitis B (HBV) who are < or =5 years of age. STUDY DESIGN: Retrospective chart review of 22 consecutive children with chronic HBV (ages 17 months to 17 years; median, 83.9 months; 14 male, 8 female) treated with interferon-alpha2b. RESULTS: Ten patients (48%) responded to treatment [HBeAg (-), Anti-HBe (+), HBV DNA (-), HBsAg (+) and normal alanine aminotransferase/aspartate aminotransferase (ALT/AST) at 6 months after treatment], and 5 seroconverted HBsAg [above plus HBsAg negative and anti-HBs (+)]. Seven of 9 patients (78%) < or =5 years of age responded (5 cleared HBsAg). Three of 13 patients (23%) >5 years of age responded. Patient age at treatment was significantly lower in responders (63 +/- 70 months) versus nonresponders (104 +/- 55 months, P =.005). AST, ALT, and HBV DNA at the start of treatment were not different between responders and nonresponders or between patients < or =5 and >5 years old. CONCLUSIONS: Interferon treatment may be more effective in younger children with chronic hepatitis B.     

儿童异基因造血干细胞移植术后乙型肝炎病毒免疫标记的变化

目的 了解儿童异基因造血干细胞移植（allo-HSCT）前后乙型肝炎病毒（HBV）免疫标记的变化情况,探讨供受者allo-HSCT前不同HBV免疫状态与allo-HSCT后受者HBV免疫标记变化的关系.方法 回顾性分析2010年1月-2012年6月在我院接受allo-HSCT治疗的130例儿童血液病患儿移植前后HBV免疫标记物（HBsAg、HBsAb、HBeAg、HBeAb及HBcAb）、HBV-DNA等临床资料,移植后随访中位时间18（6 ～36）个月.结果 （1）allo-HSCT前：HBsAg阴性患儿126例,阳性4例;HBsAb阳性患儿92例;HBsAg阳性供者6例,余均为HBsAg阴性供者.（2）allo-HSCT后：16例移植前HBsAb阴性受者移植后转为HBsAb阳性：66例移植前HBsAb阳性受者接受HBsAb阳性供者移植后,47例仍为HBsAb阳性,18例为HBsAb阴性,1例发生HBV再激活;21例移植前HBsAb阳性受者接受HBsAb阴性供者移植后,13例转为HBsAb阴性.（3）移植前供者HBsAb阳性,输注CD34＋细胞＞7.24×106/kg、移植前受者HBsAb滴度高低对移植后受者HBsAb转为阴性有显著影响,P值分别为0.005、0.040和0.000.（4）2例移植前合并HBV感染患儿移植后发生HBV再激活,2例移植前无HBV感染患儿接受大三阳供者移植后继发HBV感染.结论 HBsAb阴性患儿接受HBsAb阳性供者allo-HSCT后,在造血和免疫功能重建的同时,其体内可产生针对HBV的保护性抗体;移植后受者HBsAb随时间逐渐丢失,丢失的比例与移植前受者HBsAb滴度高低、输注CD34＋细胞数高低、供者HBsAb阳性与否明显相关.因此,移植前对供受者进行针对HBV的免疫接种及移植后免疫重建后对受者再次免疫接种有利于预防移植后HBV激活及感染.     

Hepatitis A and B infections in transfusion-dependent thalassaemia from endemic areas

The aim of this study was to determine the prevalence of previous hepatitis A virus (HAV) and B virus (HBV) infection which is in 64 transfusion-dependent (TD) patients with thalassaemia including 26 patients who were transfused before blood donors were screened for HBV. Serial blood samples taken from these 64 patients and 10 non-TD beta-thalassaemia intermedia patients during a 3 year period, were tested for antibody to HAV (anti-HAV), hepatitis B surface antigen (HBsAg), antibody to HBsAg (anti-HBs), antibody to core antigen (anti-HBc) and when indicated, antibody to Delta virus (anti-Delta) and HBV DNA. Liver function tests were performed also. Similar tests were conducted on 50 donor blood units. None of the 64 TD patients had evidence of past HAV infection, but 50% of blood donors had evidence of past infection (P less than 0.001). Only 2 brothers and their mother were positive for HBsAg, and 38 patients (59.4%) had persisting HBV antibodies compared with 26% of blood donors (P less than 0.001). Our TD thalassaemic patients acquired passive immunity from donor plasma, which protected them against HAV and possibly modified the outcome of HBV infection.     

Negative serology for hepatitis A and B viruses in 18 cases of neonatal cholestasis

Serologic evidence of hepatitis A virus (HAV) or hepatitis B virus (HBV) infection was sought in 14 patients with biliary atresia and in four patients with neonatal hepatitis; maternal serum was also analyzed. Specific sensitive radioimmunoassays were used to detect HBV surface antigen (HBsAg) and antibody (anti-HBs); complement fixation was used to detect antibody to HBV core antigen (anti-HBc). Antibody to HAV (anti-HAV) was assayed by radioimmunoassay, as well as by immune adherence hemagglutination. There was no evidence of active or past HBV infection in any infant or mother studied. All three infants with detectable anti-HAV were born to mothers similarly anti-HAV positive; serial testing of sera from two of these infants documented disappearance of detectable anti-HAV by 9 months of age. It is unlikely, therefore, that either HAV or HBV had an etiologic role in neonatal cholestasis in these patients. The role of other (non-A, non-B) hepatitis viruses or nonviral etiologies must be investigated.     

乙型肝炎病毒宫内感染对新生儿外周血细胞因子干扰素γ和白介素4的影响

目的 探讨乙型肝炎病毒(HBV)侵犯新生儿外周血单个核细胞(PBMC)后,对新生儿免疫功能的影响,了解其免疫失败发生的机理.方法 聚合酶链反应法(PCR)检测67对乙型肝炎表面抗原(HBsAg)、乙型肝炎e抗原(HBeAg)阳性孕妇及其新生儿血清和PBMC的HBV DNA.根据新生儿PBMC中HBV DNA分成阴性和阳性组,将新生儿的PBMC分别在植物血凝素(PHA)和纯化HBsAg刺激下进行体外细胞培养,检测培养上清液中干扰素-γ(IFN-γ)、白介素-4(IL-=4)的分泌含量.结果 (1)35例母亲PBMC HBV DNA阳性者其新生儿15例为阳性,母亲与患儿PBMC HBV DNA阳性,差异有显著统计学意义(P＜0.01).(2)新生儿PBMC内HBV DNA阳性组与阴性组比较,纯化HBsAg刺激时,阳性组IFN-γ的分泌量较阴性组低(P＜0.01),IL-4含量显示PBMC HBV DNA阳性组高于阴性组(P＜0.05),PHA刺激时,两组IFN-γ、IL-4含量差异无统计学意义(P＞0.05).结论 PBMC内的HBV DNA可能是HBV母婴垂直传播的一条重要途径;宫内新生儿PBMC感染HBV,IFN-γ特异性反应低下,而IL-4特异性反应增强,细胞调节失衡,可能是新生儿免疫失败和易于免疫耐受的一个重要原因.     

Combined lamivudine/interferon-alpha treatment in "immunotolerant" children perinatally infected with hepatitis B: a pilot study

OBJECTIVE: To investigate whether combining the antiviral effect of lamivudine with the immune-boosting action of interferon-alpha (IFN-alpha) is effective in treating hepatitis B virus (HBV) "immunotolerant" children. STUDY DESIGN: Twenty-three children (8 boys; mean age, 10 years) infected during the first year of life (17 Asian, 21 with normal aminotransferase levels, 15 with HBV-DNA >1000 pg/mL by hybridization and all with mild histologic changes) were treated with lamivudine (3 mg/kg) for 8 weeks alone and then lamivudine (3 mg/kg) and IFN-alpha (5 MU/m(2), 3 times weekly) in combination for 10 months. RESULTS: Seventy-eight percent became HBV-DNA negative at the end of treatment, 5 (22%) seroconverted to anti-HBe, 4 (17%) of whom achieved complete viral control, becoming persistently HBsAg negative and anti-HBs positive. None had YMDD mutations. The viral status of the patients has not changed after a median follow-up of 40 months (range, 36 to 48). CONCLUSIONS: This pilot study suggests that lamivudine pretreatment followed by a combination of lamivudine and IFN-alpha can induce complete viral control in HBV immunotolerant children, hitherto considered poor responders.     

Efficacy of primary hepatitis B immunization in children with acute lymphoblastic leukemia

BACKGROUND: Children with acute lymphoblastic leukemia (ALL) carry a high risk of hepatitis B virus (HIV) infection. The present study was conducted to see if prior routine hepatitis B vaccine received as a part of national immunization program could prevent HBV infection in these children. METHODOLOGY: Ninety-six children with ALL were screened for HBV. Children were divided into three groups according to their initial HBV serology; previously vaccinated children (Group I) (n=34) previously unvaccinated and seronegative children (Group II) (n=56),and unvaccinated but HBsAg negative and anti-HBs positive children (group III) (n=6). Sixty-seven of 96 (69.7%) children received vaccination. The schedule was initiated during the third month of maintenance therapy and each course consisted of three doses given at one month interval. RESULTS: Anti-HBs seroconversion following the first course of three doses of hepatitis B vaccination in group I, II and III was 57%, 33% and 100%, respectively. It increased to 97% in Group I, 62.5% in Group II, 100% in Group III. HBsAg positivity was found in 11 children (11.5%) and all of them developed chronic hepatitis B. Ten of them were in Group II whereas only one child was in Group I (P<0.04). CONCLUSION: This data reveals that routine HBV vaccination within the national immunization program plays an important role in decreasing subsequent hepatitis B infection in children with ALL.     

A study of liver HBV DNA during follow-up of acute viral hepatitis in children

Twenty-nine children with acute icteric hepatitis were classified as follows after serological tests for the agents of viral hepatitis: hepatitis B 17 patients, hepatitis A 3 patients, hepatitis A + B 1 patient, possible non-A, non-B hepatitis 8 patients. In four of these cases, hepatitis A or non-A, non-B occurred in chronic HBsAg carriers. Hepatitis B virus (HBV) DNA was present in the initial serum of 15 of the 18 patients with acute hepatitis B. About 1 year after onset, HBsAg and HBV DNA were absent in 17 of them (16 of whom developed anti-HBs) and the remaining patient became a chronic HBsAg carrier without HBV DNA in his serum. At the same time, liver biopsy samples from all 29 patients were available for HBV DNA investigation. HBV DNA sequences in the liver were never found in any patient, neither under free form nor integrated into the cellular genome. The absence of HBV DNA integration in any of the liver samples taken about 1 year after the acute phase of hepatitis B suggests that such integration is either unlikely or is transitory during the symptomatic period.     

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.     

Hepatitis D virus infection in children with acute or chronic hepatitis B virus infection in Taiwan

To investigate the prevalence and clinical features of hepatitis D virus infection (HDV) in childhood, total antibody to hepatitis D antigen (anti-HD) in serum samples from 247 children (29 with acute hepatitis B, 68 with chronic hepatitis B, and 150 with asymptomatic hepatitis B surface antigen (HBsAg) carriers with normal liver function profiles) were studied using solid-phase competitive radioimmunoassay. Anti-HD was detected in three of the 29 children with acute hepatitis B and in only one of the 68 with chronic hepatitis B; none of the serum specimens from 150 asymptomatic carriers with normal liver function profile showed detectable anti-HD. All three children with HDV coinfection cleared HBsAg and seroconverted to anti-HBs, whereas one with superinfection finally had normal liver function without clearance of HBsAg. To identify possible sources of HDV infection, HBV markers and anti-HD in family members were also examined. One 4-month-old infant boy became infected through a blood transfusion from his hepatitis B e antigen (HBeAg)-positive carrier father, who had anti-HD. A 4-month-old infant girl was infected through close contact with her HBeAg-negative carrier father, who had HDV superinfection. The infection sources remained undefined in another two patients. The mothers of these four children were seronegative for anti-HD, indicating that perinatal transmission is not the usual mode of HDV infection in Taiwan. The natural course of either acute or chronic HBV infections in childhood in Taiwan may be more closely related to HBV itself, or to some other yet unrecognized factor, rather than to HDV infection.     

Acute and chronic hepatitis in childhood leukemia: a multicentric study from the Italian Pediatric Cooperative Group for Therapy of Acute Leukemia (AIL-AIEOP)

The incidence of acute and chronic liver damage and its relation to hepatitis B virus (HBV) infection was evaluated in 164 consecutive children with acute leukemia seen in ten Italian hemato-pediatric units. Thirteen out of 164 children (7.9%) had acute hepatitis (AH) during treatment, while 8/90 (8.8%) showed an acute exacerbation of liver damage within 6 months after therapy withdrawal. Seven of the 13 children with AH while on therapy were HBsAg positive. In 12/13 cases, liver disease progressed to chronicity. Five of eight children who developed AH after completion of treatment were HBsAg positive. Eighty-nine patients (54.2%) developed biochemical evidence of chronic hepatitis during therapy; 48/89 were followed after cessation of treatment and 33 of them showed persisting evidence of liver cell necrosis. Thirty-three out of 133 children (24.8%) tested for serum HBsAg were found positive: 26 (78.7%) of them developed chronic hepatitis. Sixty-four out of 133 patients were evaluated after cessation of treatment: Chronic hepatitis persisted in 16/22 HBsAg-positive (72.7%) and in 17/42 HBsAg-negative (40.4%) children during follow-up. The outcome of these liver diseases after treatment withdrawal did not differ significantly in relation to HBV serology, suggesting that viral rather than toxic agents were responsible for liver damage also in most HBsAg-negative patients. The high incidence of chronic HBV infection in children with leukemia found in this multicentric study could suggest a need for active immunization with HBV vaccine, but the efficacy of such approach in this clinical setting is still to be validated.     

Evaluation of screening for hepatitis B surface antigen during pregnancy in a population with a high prevalence of hepatitis B surface antigen-positive/hepatitis B e antigen-negative carriers

BACKGROUND: Universal hepatitis B vaccination in infancy was implemented in Israel in 1992. The program consists of active vaccination at birth and at 1 and 6 months of age, without hepatitis B surface antigen (HBsAg) screening during pregnancy. Infants of HBsAg carrier mothers do not receive specific hepatitis B immunoglobulin in addition to vaccine at birth. The recently arrived Jewish immigrants from Ethiopia are the group with the highest rate of HBsAg carriage (approximately 10%) in Israel. AIM: The objective of this study was to evaluate whether the present policy is effective against perinatal HBV transmission from mothers of Ethiopian origin to their infants. METHODS: The study group included 411 Israeli born children, offspring of mothers of Ethiopian origin. All infants were fully vaccinated starting at birth. Sera were collected from the children at the age of 9 to 36 months and from their mothers. Tests for HBsAg, antibodies to HBsAg (anti-HBs) and antibodies to hepatitis B core antigen (anti-HBc) were performed. RESULTS: Eighty-nine percent of the children had detectable anti-HBs, including 82.2% with protective anti-HBs concentrations (> or =10 mIU/ ml). Although 24 mothers (6.2%) were HBsAg carriers, none of the children was HBsAg-positive. Seven of 394 infants (1.7%) tested positive for anti-HBc. This test became negative in 5 of 6 who were followed for 12 months. The percentage of infants with protective anti-HBs concentrations decreased significantly from 91.4% at 9 to 12 months to 70.1% at 31 to 36 months of age. The mother's infection status was not associated with the infant's response to vaccine. Calculation based on the above data suggests that screening for HBsAg in pregnancy in that group is not cost-effective. CONCLUSIONS: Our results suggest that the Israeli vaccination program against HBV infection is effective, even in a high risk population, and additional measures are not cost-effective.     

Efficacy of immunization against hepatitis B virus infection in children with cancer

BACKGROUND: The purpose of this study was to evaluate the impact of hepatitis B prophylaxis in preventing hepatitis B infection in children with malignancy. PROCEDURE: Between May, 1993, and September, 1998, a total of 151 children (95 boys, 56 girls), 29 (19%) with lymphoma, 58 (39%) with leukemia, and 64 (42%) with solid tumor, were screened for hepatitis B virus (HBV). The mean age was 7. 5 +/- 2.5 years. Children with negative serology received active and/or passive immunization. HBsAg and anti-HBs were positive prior to vaccination in 16 (10%) and 17 (11%) children, respectively. One hundred eighteen children (78%) of one hundred fifty-one with negative serology were included in the vaccination program. The vaccine dose was 40 microg. Children with solid tumor and lymphoma received recombinant hepatitis B vaccine at diagnosis, repeated at months 1, 2, and 12. Hyperimmunglobulin was administered monthly in children with leukemia during the intensive chemotherapy period. They were then vaccinated following the third month of maintenance therapy with the schedule described above. Anti-HBs titers were measured every 3 months, and titers above 10 mlU/ml were accepted as protective. RESULTS: Anti-HBs positivity after the first three doses was 77% in solid tumors, 88% in acute leukemia, and 48% in lymphomas. Anti-HBs positivity with respect to diagnosis in children completing the vaccination schedule was 94% in solid tumor, 90% in leukemia, and 74% in lymphoma (P > 0.05). Thirty-three percent of children have not received the fourth dose as yet. In total 78% of the children developed protective antibody titers with or without the fourth dose, and none was infected with HBV during 3 years of follow-up. Ten (39%) of twenty-six children who remained unresponsive to immunization were infected with HBV. CONCLUSIONS: These data reveal that HBV prophylaxis is necessary and that our vaccination schedule is effective in preventing HBV infection in these children.     

Lack of perinatal transmission of hepatitis B virus infection in Senegal, West Africa

Between 1977 and 1980, 1442 pregnant women in Thies, Senegal, were tested for serologic markers of hepatitis B virus (HBV) infection. Of these, 9.8% were HBsAg(+), 59.9% were anti-HBs(+), and 15.6% had anti-HBc alone. Of 116 HBsAg(+) pregnant women, only 19.8% were HBeAg(+), a much lower proportion of infectious carriers than seen in Asian populations. Cord blood from 1353 babies was HBsAg(-), implying that the babies were not infected prior to birth. Four hundred sixty-two babies, including 88 born to HBsAg(+) mothers, were observed for 2 weeks to 38 months after birth. In contrast to observations in Asia, none of the babies became HBsAg(+) before 5 months of age, and only three of the 16 born to HBeAg(+) mothers became HBsAg(+) within the first year of life; all three developed chronic infections (i.e., HBsAg(+) for greater than or equal to 6 months. In the second year of life, six of 34 babies born to HBsAg(+), HBeAg(-)/anti-HBe(-) mothers became infected with HBV, and four of the six developed chronic infections. During the first 3 years of life, infections occurred at a higher rate in infants born to HBsAg(+) (17%) than to HBsAg(-) (4%) women. The latter group of infants included 4.0% of those born to anti-HBs(+) mothers, 4.6% born to anti-HBcAg(+), and 3.2% born to uninfected women. These observations indicate that HBV infections in Senegal usually do not occur perinatally, but do occur at high incidence later in infancy and childhood. Such infections can be prevented by the use of hepatitis B vaccine alone; administration of hepatitis B immune globulin should not be needed.     

Clinical importance of hepatitis B virus DNA detection in serum of children with chronic hepatitis B]

206 sera from 172 children with chronic hepatitis B infection were tested for HBV DNA by dot blot hybridization. 111 were positive and 95 negative for HBV DNA. 103 (78.6%) of the positive patients had HBeAg and 5 (7.7%) anti-HBe. In 60 (92.3%) of the anti-HBe positive sera no HBV DNA could be detected. Children with elevated liver enzymes had HBV DNA in 80.1%, whereas in 71.6% of the chronic HBsAg carriers with normal liver enzymes no HBV DNA was found. In 87 of the 95 dot blot negative patients polymerase chain reaction was performed. 73 (83.9%) children of this group were HBV DNA positive. All HBeAg positive patients and those with elevated aminotransferases had HBV DNA in their serum. 56 anti-HBe-positive HBsAg carriers were also positive; 14 were negative for HBV DNA. Our results demonstrate that viral sequences can be found in all HBeAg positive and in most of the anti-HBe positive children. Patients with ongoing virus replication have to be considered infectious and recommendation for vaccination of close relatives of these patients must be stressed.     

Increased risk of chronic hepatitis in children with cancer

BACKGROUND: There is a risk of viral hepatitis for children with cancer. Both hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in countries with high prevalence cause major problems in the management of cancer patients. In this study, we evaluated the incidence and chronicity of HBV and HCV infections in children with malignant diseases receiving chemotherapy. PROCEDURE: One hundred ninety-eight children with cancer (mean age = 7.5 +/- 2.5 years) and 100 healthy children as a control group were screened for HBV and HCV. Liver function tests, the number of transfusions, HBV and HCV serology were regularly monitored. In seropositive children, HBV-DNA and HCV-RNA were measured. Chronic hepatitis was defined as having an alanine aminotransferase (ALT) level three times of upper normal limit, positive HBV and HCV antigenemia for longer than 6 months. Liver biopsies were performed in all children with chronic hepatitis. The relationship between the chronic hepatitis and study parameters was statistically analyzed. RESULTS: HBsAg positivity, anti-HCV, and mixed (HBV and HCV) infection were found in 11.6, 5.5, 2% of children, respectively. Most HBV infected children developed chronic hepatitis (48%) while 26 and 21.7% became carriers and immune, respectively. One died of acute fulminant HBV hepatitis. Of HCV infected children, 63.6% also had positive HCV-RNA. Four children with mixed infection (100%) all progressed to chronic hepatitis. In this setting, chronic hepatitis was observed in 22 of 38 infected children (57.8%). The majority had leukemia and lymphoma. Children with HBsAg antigenemia developed chronic hepatitis in shorter time than HCV positive children (median 13 months vs. 51 months, P < 0.001). CONCLUSION: We observed an increased incidence of chronic hepatitis and even mortality due to HBV infection. This suggests that HBV and HCV infections are serious causes of morbidity and mortality in children with cancer.     

Natural History of Hepatitis B Virus Carriers Born to Hepatitis B Virus Carrier Mothers

Ninety-five infants born to hepatitis B virus (HBV) carrier women were followed without hepatitis B immune globulin injections over five months. Twenty-one infants (22%) became HBV carriers. These 21 HBV carrier children were followed and the mean follow-up period is six years and nine months. Eighteen mothers (85.7%) of these HBV carrier children were HBeAg positive in perinatal period. One was both HBeAg and anti-HBe negative and the status of the other two was unknown. The mean appearance time of HBsAg is 2.0 ± 1.2 months. Nine carrier children (42.9%) became HBeAg negative in the observation period. In seven cases (33.3%), seroconversion from HBeAg to anti-HBe was observed. In six of seven seroconverted cases, liver dysfunction was observed from the HBeAg positive phase and the liver function normalized within one year after the appearance of anti-HBe except in one case. The mean values of AST (Aspartate aminotransferase or SGOT) and ALT (Alanine aminotransferase or SGPT) of the seroconverted group during the whole observation period were significantly higher than those of the persistent HBeAg positive group. The HBeAg positive rate decreases year by year and inversely the anti-HBe positive rate increases. At 8 years old, the former rate is 55.6%, and the latter rate is 33.3%. The mean annual disappearance rate of HBeAg under eight years is 10.1 ± 5.8% and the mean annual appearance rate of anti-HBe under eight years is 6.1 ± 5.8%. The higher the mean annual disappearance rate of HBeAg, the lower the positive rate of HBeAg in pregnant women. This may contribute to the decrease in the appearance of new HBV carriers.     

ANTIBODY TITRATION AND IMMUNE RESPONSE OF IRANIAN β-THALASSEMIC PATIENTS TO HEPATITIS B VIRUSE VACCINE (BOOSTER EFFECT)

Background: Thalassemia is hereditary anemia with lifelong transfusion as treatment and hepatitis B virus (HBV) infection is one of the transfusion transmitted infections (TTI). HBV vaccinination is obligatory for these patients by 3 double-dose injections. The authors studied the HBV status and immune response to vaccination by hepatitis B surface antibody (HBsAb) titration in their thalassemic patients. They also compared these results with their previous study to find out the effectiveness of a booster dose in the immunity of patients against HBV. Materials and Methods: Hepatitis B surface antigen (HBsAg), HBsAb, and hepatitis B core antibody (HBcAb) were detected in sera of 416 patients at the Tehran Adult Thalassemia Clinic. The immune status was classified into 4 categories: (1) immune to HBV via the vaccination (positive vaccinal)—if HBs Ag: negative, HBsAb: positive, HBcAb: negative; (2) immune to HBV via the natural disease (past infection)—if HBs: negative, HBsAb and HBcAb: both positive; (3) nonimmune to HBV (negative)—if all three parameters were negative; (4) carrier of HBV (carrier state)—if HBs Ag was positive and HBsAb and HBc Ab: both negative. Also grading of immunity done by HBsAb titration as positive if HBsAb titer was more than 100 IU/mL, negative if HBsAb titer was less than 10 IU/mL, and weakly positive if antibody level was 10–100 IU/mL. Results: There were 416 patients: 302 (72.5%) with thalassemia major (TM), 104 (25%) thalssemia intermedia (TI), 7 (1.6%) sickle thalassemia (ST), and 3(0.7%) α-thalassemia (HbH disease). The mean age was 25.6 ± 8.3 yr and median age was 24 yr; there were 247 (59.4%) males and 169 (40.6%) females. A total of 257 patients (61.7%) were splenectomized. According to our classification 289 (69.4%) were immunized by vaccination; 80 (19.2%) were immunuzed by past infection; 44 (10.5%) were negative, and 3 (0.7%) were in carrier state of HBV. In grading of immunity to HBV vaccination, 319 (76.6%) patients had HBsAb > 100 IU/mL (positive), 77 (18.5%) between 10 and 100 IU/mL (weakly positive), and 20 (4.8%) less than 10 IU/mL (negative). There was no significant correlation between the level of HBsAb and spelenectomy or type of thalassemia. Conclusion: Response rate to vaccination is more than 95% after complete course (3 doses) in healthy individuals but failure to fulfill vaccination seems a problem in chronic transfused patients. These results reflect advantages of a booster dose of vaccine, which increased the protection level among these high-risk patients from 46.9% (in the authors’ previous data) up to 69.4% in this study.