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.     

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.     

Chronic viral hepatitis

Among hepatitis A to E viruses, hepatitis B, C, and D viruses can cause chronic hepatitis, in both children and adults. Hepatitis B virus (HBV) infection is the most prevalent and important one. Perinatal transmission accounts for about 40–45% of chronic HBV infection in hyperendemic areas. Horizontal transmission through intramuscular injection using non-sterile needles and intrafamilial spread accounts for the other half of carriers. During the natural course of HBV infection, the host gradually clears HBV and hepatitis B e antigen (HBeAg), liver damage and elevation of aminotransferases occur during the process of HBV clearance. The most effective way to eliminate HBV infection is immunoprophylaxis starting since birth. It can prevent both HBV and hepatitis D virus (HDV) infections. Hepatitis C virus (HCV) infection in children occurs mainly in high risk children, such as those who received blood product or injection using non-sterile needles, or infants of HCV viremic mothers, etc. Screening of blood product reduced markedly the prevalence of post-transfusion HCV infection, but the prevention of sporadic cases requires HCV vaccination which is still under investigation.     

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.     

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 and C virus infection in Polish children with malignancies

Infections by hepatotropic viruses belong to the most common complications of chemotherapy in children suffering from neoplastic diseases. The rate of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection and the effectiveness of passive immunization against HBV were studied in 285 children; 148/285 with lymphoproliferative diseases and 137/285 with solid tumours. HBV infection was observed in 10.2% children receiving hepatitis B immune globulin as compared to 36.8% without passive immunization against HBV. Anti-HCV antibodies were similar in both groups amounting 38.7% and 32.6% respectively. Conclusion The results show that hepatitis B immune globulin administration is effective and that HCV might become the main cause of hepatitis among immunosuppressed patients in the future. Received: 13 December 1994 / Accepted: 18 October 1996     

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.     

Prevalence and Risk Factors for Hepatitis C Virus, Hepatitis B Virus, and Human Immunodeficiency Virus in Transfused Children in Kinshasa

Objective

To determine seroprevalence of hepatitis C virus (HCV), human immunodeficiency virus (HIV), and hepatitis B virus (HBV) and associated factors among transfused children.

Methods

A multicenter cross-sectional study of transfused children aged between 18 mo and 13 y old was conducted in 4 hospitals in Kinshasa. Blood samples were collected for the detection of Hepatitis B surface antigen (HBsAg) and antibodies to HCV, HIV 1and 2.

Results

A total of 177 (47.7 %) boys and 194 (52.3 %) girls participated in the study. The median age was 59.5 mo (Interquartile range IQR?=?60.6). The prevalence rates of HCV, HBV, and HIV infection were 13.5 %, 1.6 %, and 1.3 %, respectively. Frequency of transfusion events were significantly associated with HCV (p?<?0.001) and HIV (p?<?0.05) infections.

Conclusions

HCV infection was by far more frequently identified than HBV and HIV infections among Congolese transfused children. Frequency of transfusion events was the only significant risk factor associated with HCV and HIV infections but not for HBV.     

Management of chronic hepatitis B and C virus infections

Hepatitis B and C virus (HBV and HCV) infections present an important health problem causing significant morbidity and mortality on a worldwide scale. The younger the subjects infected, the higher the risk predisposing to progression towards chronic infection. Treatment of chronic HBV and HCV infections is aimed at reducing hepatic inflammation and thus improving the symptoms, decreasing the likelihood of long-term sequelae such as hepatocellular carcinoma, and increasing the survival rate. Interferon accelerates the spontaneous course of chronic HBV infection in children with greater disease activity and lower levels of replication. There is limited information on the use of lamivudine and its long-term benefit in children with chronic HBV infection. The response of combination therapy with IFN and ribavirin in children with chronic HCV infection is still under investigation. The long-term clinical and virological effects of various drugs used in chronic HBV and HCV infections on children remain to be evaluated.     

Delta-hepatitis

Investigations were conducted for serological evidence of hepatitis B virus (HBV) and hepatitis D virus (HDV) infections in children suffering from acute viral hepatitis. A total of 52 serum samples were analysed by enzyme immunoassay. Of these, 18 (24%) were positive for hepatitis B virus markers and 34 (65.4%) were negative. Delta virus infection was detected in 6/18 (33%) hepatitis B patients. A significant finding was, that of the 34 patients negative for hepatitis B, 4 (12%) were positive only for HDV although the latter can only occur as a coexistent infection with hepatitis B virus. From the present study it may be inferred that delta virus infection is prevalent in children and absence of HBV markers does not rule out hepatitis D.     

Decline in hepatitis B infection in sickle cell anaemia and beta thalassaemia major.

Seventy five Saudi children, 55 with sickle cell anaemia and 20 with beta thalassaemia major, who were negative for all hepatitis B virus (HBV) markers five years ago were recently investigated for exposure to HBV and hepatitis C virus (HCV) infection. Of the 55 patients with sickle cell anaemia and 20 with beta thalassaemia major, 20 and five patients respectively had been vaccinated against HBV earlier and all of them still had protective antibody (anti-HBs 42-96 IU) 3-5 years after vaccination and there was no vaccine failure. Among the non-vaccinated children the exposure rates to HBV were 14.3% among those with sickle cell anaemia and 26.7% among those with beta thalassaemia and this was not statistically significant when compared with the exposure rate to HBV among the general paediatric population (20.1%). Anti-HCV positivity among those with beta thalassaemia major and sickle cell anaemia was 70% and 18.2%, respectively, and this was significantly higher than anti-HCV positivity among the control group (0.8%). Anti-HCV positivity was directly related to the amount of blood transfused and to the duration of transfusion. The results of the study show that although the exposure rates to HBV among patients with sickle cell anaemia and beta thalassaemia major were not significantly different than that among the general paediatric population, infection with HBV still takes place among non-vaccinated patients despite strict precautionary measures taken. Hence early vaccination against HBV would probably be the only effective way of controlling HBV infection. For HCV infection, and because a vaccine against HCV is still not available, preventive measures such as blood screening for anti-HCV before transfusion and stringent infection control measures are crucial steps to be implemented for the control of spread of HCV among these groups of patients.     

Decline in hepatitis B infection in sickle cell anaemia and beta thalassaemia major

Seventy five Saudi children, 55 with sickle cell anaemia and 20 with beta thalassaemia major, who were negative for all hepatitis B virus (HBV) markers five years ago were recently investigated for exposure to HBV and hepatitis C virus (HCV) infection. Of the 55 patients with sickle cell anaemia and 20 with beta thalassaemia major, 20 and five patients respectively had been vaccinated against HBV earlier and all of them still had protective antibody (anti-HBs 42-96 IU) 3-5 years after vaccination and there was no vaccine failure. Among the non-vaccinated children the exposure rates to HBV were 14.3% among those with sickle cell anaemia and 26.7% among those with beta thalassaemia and this was not statistically significant when compared with the exposure rate to HBV among the general paediatric population (20.1%). Anti-HCV positivity among those with beta thalassaemia major and sickle cell anaemia was 70% and 18.2%, respectively, and this was significantly higher than anti-HCV positivity among the control group (0.8%). Anti-HCV positivity was directly related to the amount of blood transfused and to the duration of transfusion. The results of the study show that although the exposure rates to HBV among patients with sickle cell anaemia and beta thalassaemia major were not significantly different than that among the general paediatric population, infection with HBV still takes place among non-vaccinated patients despite strict precautionary measures taken. Hence early vaccination against HBV would probably be the only effective way of controlling HBV infection. For HCV infection, and because a vaccine against HCV is still not available, preventive measures such as blood screening for anti-HCV before transfusion and stringent infection control measures are crucial steps to be implemented for the control of spread of HCV among these groups of patients.     

Epidemiologic aspects and preventive strategy of hepatitis B and C viral infections in children with cancer.

AIMS: We present the efficacy of a strategy to control infections with hepatitis B (HBV) and C viruses (HCV) in children with cancer and assessment of risk for their relatives and health care personnel. A total of 1242 people entered the study, including 558 children with cancer, 193 relatives of infected children, 302 health care workers and 189 controls. METHODS: To stop dual HBV and HCV nosocomial infection in the oncology department, a preventive strategy was introduced. It involved immunoprophylaxis against HBV, screening blood donors for HCV infection, intensification of nonspecific prophylaxis, an educational program and estimation of risk for relatives of infected children and health care personnel. RESULTS: Retrospective analysis showed that the prevalence of HBV and HCV infections in children with cancer was 74 of 119 (62.2%) and 50 of 92 (54.3%), respectively, with the highest rate among patients with leukemia. Inferior anticancer therapeutic response were obtained in infected children. Specific anti-HBV immunoprophylaxis introduced simultaneously with anticancer therapy resulted in protection of 160 of 168 (95.2%) children in the first 4 years, when 62.9% of patients receiving therapy developed protective antibodies. Screening of blood donors and intensification of nonspecific prophylaxis reduced HCV prevalence to 2.8% during the most recent 1.5 years. Genotype analysis showed that the risk of HCV infection was 0.5% for relatives of infected children. The risk for health care personnel was 0 in the oncology ward and 1.9% in the other departments, and it reached 0.53% in control group. CONCLUSIONS: The preventive strategy of viral hepatitis in children with cancer, including passive-active HBV immunoprophylaxis from the beginning of chemotherapy and intensive nonspecific prophylactic measures is effective. With this strategy the risk of intrafamily and occupational infection is low.     

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.     

Hepatitis B and C viruses in infants and young children

Advances during the past 20 years have led to a better understanding of the prevention, diagnosis, and treatment of acute and chronic hepatitis B (HBV) and hepatitis C (HCV) infections in the pediatric population. Universal vaccination and prenatal testing for HBV have decreased the incidence rate of acute HBV infections from more than 3/100,000 to 0.34/100,000 in all children. Diagnosis of chronic HBV is confirmed with positive serologic testing on two occasions at least 6 months apart. Current approved therapies with interferon alpha and lamivudine for children with chronic HBV infection have shown some efficacy, but results have been variable. In contrast, the lack of an effective HCV vaccine and the risk of mother-to-child transmission may increase the number of children with vertically acquired HCV that ultimately go on to develop liver fibrosis or cirrhosis. Diagnosis of HCV in the neonate should be postponed until after the child reaches 1 year of age because infants may have transient viremia. Treatment for HCV infected children has not been studied extensively. Peginterferon alpha-2a and Ribavirin are not currently approved for pediatric use; however, recent studies in children have shown potential benefit. More effective and less toxic therapies for young patients with HBV and HCV are needed, as are methods to interrupt perinatal transmission of HBV and HCV.     

A study of hepatitis B and C prevalence and liver function in multiply transfused thalassemic and their parents.

A series of clinics were conducted in Delhi, India, in January, 1990. Of 54 patients with beta thalassemia major (mean age 7.6 years), 11.1% (6 out of 54) tested positive for antibodies to hepatitis C virus (anti HCV antibodies) and 66.6% (36 out of 54) showed evidence of hepatitis B virus (HBV) infection. Only 7.4% (4 out of 54) were hepatitis B surface antigen (HBsAg) positive. Of their parents, 2.2% (2 out of 90) tested positive for anti HCV antibodies, 28.9% (26 out of 90) showed evidence of previous HBV infection and 11.1% (10 out of 90) were HBsAg positive. We argue that HCV constitutes a greater long term threat than HBV in these patients due to the higher incidence of chronic liver disease. We would advocate the introduction of HCV screening of donated blood as well as reinforcing the importance of HBV screening and immunization.     

Importance of recall and follow-up screening for chronic hepatitis C in children receiving blood products prior to 1990 in Japan

The objective was to detect chronic hepatitis C virus infection in recipients of blood products using retrospective analysis by recall and enrollment of recipients. 226 patients who received blood products for open heart surgery from January 1983 to June 1992 were examined for HCV antibody by using a second generation assay and liver function test. 22 (14%) of the 161 patients who received blood products before November 1989 had detectable HCV antibody, but none of the 65 recipients receiving blood products after 1990, the year the Japanese blood bank began to screen for HCV-antibody. Abnormal alanine aminotransferase (ALT) levels, more than 25 iu/L, during the chronic phase of HCV infection was recognized in nine of 22 (41%) seropositive patients. The liver function test and second generation HCV antibody in the serum are effective markers to screen for chronic hepatitis C in blood product recipients transfused before 1990.     

Hepatic dysfunction in children with acute lymphoblastic leukemia in remission: relation to hepatitis infection

BACKGROUND: Viral hepatitis is a cause of hepatic dysfunction in children with ALL in remission during maintenance therapy is debated. The aims of the current study were (1) to explore the incidence of hepatic dysfunction in a group of children (Egyptian and Saudi) with ALL under maintenance therapy, (2) to study the prevalence of hepatitis B (HBV) and/or C (HCV) infection and their contributions to chronic liver disease that might be induced by maintenance therapy. PROCEDURE: The current study included 105 children with ALL (54 Egyptian and 51 Saudi). All eligible patients had been on maintenance therapy for at least 12 months and all had serial assessments of liver function. These included determination of total bilirubin, AST, ALT, and alkaline phosphatase. Markers for HBV and HCV including HBsAg, anti-HBC, and anti-HCV and for some patients HCV RNA by PCR were studied. Percutaneous liver biopsy was performed for a group of children. RESULTS: The prevalence of hepatitis infection (HBV and/or HCV) among Egyptian children was found to be high (43/54-80%). Only five Saudi children had evidence of exposure to HBV (5/51-9.8%), P<0.0001. During the period of study, 22 Egyptian patients vs. four Saudi patients (41 vs. 7.8%, P<0.0001) experienced at least one episode of elevation of liver enzymes, three times the upper limit of normal or more. Twenty-six of the 48 patients (54%) with HBV and/or HCV infection had episodes of elevated liver enzymes, while there was no occurrence among the patients negative for HBV and HCV. In patients with HBV infection, the presence of HBsAg was strongly associated (100%) with elevated liver enzymes. Histopathologic examination of liver biopsies obtained from 35 patients revealed that all five patients negative for HBV and HCV had normal liver biopsies in spite of being under maintenance therapy. CONCLUSION: In children undergoing treatment for ALL, elevations in liver enzymes may be primarily due to hepatitis viruses. However, maintenance therapy using known hepatotoxic drugs, may have additive deleterious effects. Liver enzymes are normalized in affected patients when maintenance therapy is temporarily suspended.     

儿童病毒性肝炎感染模式的临床研究

目的　探讨儿童病毒性肝炎临床感染模式及其对肝功能的影响。方法　对 15 0例儿童病毒性肝炎临床资料进行分析并采用 χ2 检查和t检查对其进行统计学处理。结果　 15 0例儿童病毒性肝炎 ,单一肝炎病毒感染占 77.3% ,病原有HAV ,HBV ,HCV及HEV ,其构成分别为 5 4.7% ,18.0 % ,2 .7%和 2 .0 %。甲型肝炎 (TAH)好发于 7～ 12岁儿童 ,女性比率高于男性。乙型肝炎 (TBH)好发于 7～ 9岁年龄组 ,男性为主。二重感染占总数的10 .7% ,有HAV -HBV ,HBV -HCV ,HBV -HDV和HBV -HEV等模式 ,感染率分别为 8.0 % ,0 .7% ,1.3%和0 .7%。三重感染 5例 ,为总数的 3.3% ;有HAV -HBV -HDV和HAV -HCV -HEV模式 ,前者 3例 ,感染率为2 % ,后者 2例为 1.3%。重叠感染好发于 7～ 9和 10～ 12岁年龄段儿童 ,且男性多见。此外有 8例各项病原学检测均为阴性 ,占 5 .3%。结论　儿童病毒性肝炎有单一和重叠感染模式 ,并有明显年龄与性别差异 ,肝功能改变与感染模式关系不大。     

Persistence of antibody to hepatitis B and protection from disease among Alaska natives immunized at birth

BACKGROUND: Alaska Native (AN) children were at high risk of acquiring hepatitis B virus (HBV) infection before vaccination began in 1983. We evaluated the long-term protection from hepatitis B (HB) vaccination among AN children immunized when infants. METHODS: During 1984-1995, we recruited a convenience sample of AN children who had received a three dose series of HB vaccine starting at birth and had serum antibody to hepatitis B (anti-HBs) concentrations of >/= 10 mIU/mL at 7-26 months of age. We evaluated anti-HBs concentrations and the presence of anti-HBc in participants' sera every other year up to age 16 years. Anti-HB core antigen (anti-HBc)-positive specimens were tested for hepatitis B surface antigen and for HBV DNA. RESULTS: We followed 334 children for 3151 person-years (median, 10 years per child) with 1610 specimens collected. Anti-HBs concentrations dropped rapidly among all participants. Among children 2, 5 and 10 years of age, 37 of 79 (47%), 33 of 176 (19%) and 8 of 95 (8%), respectively, had anti-HBs concentrations of >/= 10 mIU/mL. Receipt of recombinant vaccine was significantly associated with a more rapid antibody decline (P < 0.001). Six (1.8%) children acquired anti-HBc, 3 of whom had definite breakthrough infections (at least 2 consecutive anti-HBc-positive specimens or at least 1 anti-HBc-positive specimen and HBV DNA detection by PCR). None of these children had detectable hepatitis B surface antigen, and none had symptoms of hepatitis. CONCLUSIONS: Anti-HBs concentrations declined over time among AN infants successfully immunized with HB vaccine starting at birth. Transient anti-HBc appeared in a small percentage of children; however, none developed clinical signs of hepatitis or chronic HBV infection.