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.     

Decline of maternal hepatitis A virus antibody levels in infants

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

Hepatitis 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.     

Dengue virus infection: a major cause of acute hepatic failure in Thai children

BACKGROUND: Acute hepatic failure (AHF) can be caused by a variety of viruses, drugs, toxins and metabolic disorders. AIMS: A prospective study was conducted to determine the aetiology and outcome of AHF in Thai children aged 1-15 years. METHODS: All serum samples were tested for anti-HAV IgM, HBsAg, anti-HBc IgM, anti-HCV, anti-HEV IgM and anti-dengue IgG and IgM. Further individual investigations were done according to the clinical impression. RESULTS: Forty subjects were enrolled from 14 centres during February 2000 to December 2001. Five cases were excluded owing to a lack of evidence of encephalopathy. The causes of AHF were dengue infection in 12 (34.3%), Wilson disease in 2 (5.7%), T-cell lymphoma in 2 (5.7%), ischaemic hepatitis in two (5.7%), haemophagocytic syndrome in one (2.8%), CMV in 2 (5.7%), Reye syndrome in one (2.8%) and unknown in 13 (37.1%) patients. The fatality rate was 68.6%. Eight of 24 (33.3%) deaths were caused by dengue infection. CONCLUSIONS: Improvements in sanitation and socio-economic status as well as the implementation of hepatitis B vaccine in the Extended Programme on Immunization (EPI) are likely to be the reasons for the observed absence of AHF caused by hepatitis A and B. The study showed that dengue infection, on the other hand, was a major cause of AHF in Thailand.     

Hepatitis types A,B, and non A—Non B in childhood

199 children with acute hepatitis hospitalized between 1968 and 1978 were tested for serological markers of hepatitis A and B infection. In 24 out of 28 HBsAg-positive patients, hepatitis B infection was diagnosed because of the disappearance of the antigen during convalescence. The histories of the 171 HBsAg-negative children suggested acute hepatitis A infection in 69% of the patients. This diagnosis could be confirmed in 110 of the 116 tested cases (95%) by a more than fourfold increase in the anti-HAV titer or by detection of anti-HAV of the IgM class. In the 55 HBsAg-negative patients without epidemiological clues as to the type of hepatitis, 40 children exhibited anti-HAV which could be related to acute A infection in 21 out of 22 tested cases. At least 11 patients had to be classified as having non A—non B infection.The results indicate that a combination of evaluation of the patient's history and selected serological tests will permit a fast preliminary diagnosis. This is important in the clinical management of patients and protection of contacts with immunoglobulin.     

Hepatitis A seroprevalence and demographics in Turkish children in Ankara

Background:  Hepatitis A virus (HAV) is the most common cause of hepatitis in childhood and an important public health problem. The objective of the present study was to determine the seroprevalence of hepatitis A and patient demographics in children between 1 and 15 years old who were admitted to a pediatric outpatient clinic in Ankara, Turkey.
Methods:  Hepatitis IgM and G antibodies were determined in the sera of children who attended the outpatient clinic. Informed consent was obtained from all subjects or their parents.
Results:  The mean age of the children ( n  = 335) was 7.9 ± 2.1 years; 47.5% of them were girls. The overall anti-HAV IgG prevalence in children aged 1–15 years was 47.2%. The positivity of hepatitis A IgM was highest in the 6–10 years age group (22.7%; P  < 0.001). HAV IgG was highest in the 11–15 years age group (69.4%; P  < 0.001). A total of 95.6% of the children had social insurance, 49.3% were living in poverty. The socioeconomic level of 82.4% of subjects was low. The history of hepatitis in their families was 6.9%.
Conclusions:  Hepatitis A is intermediate endemic in Ankara and children must be vaccinated before school age, in addition to health education and improved sanitation.     

Changing spectrum of sporadic acute viral hepatitis in Indian children

From August 1997 to January 2000, 172 children (< or = 14 years) with acute viral hepatitis were studied. Their clinical features, investigations and outcome were noted. Viral markers (IgM anti-HAV, IgM anti-HEV, HBsAg and anti-HCV) were measured by ELISA using commercial kits. The mean age of these children was 5.6 +/- 2.9 (range, 4 months to 14 years) with a male to female ratio of 120:52. Prodromal symptoms were present in 161 (94 per cent) and icteric hepatitis was diagnosed in 168 (98 per cent) cases. Splenomegaly was noted in 53 (31 per cent), ascites in 52 (30 per cent) and encephalopathy (ALF) in 56 (32.6 per cent) cases. Sixteen (31 per cent) children with ascites had spontaneous bacterial peritonitis (SBP). Fifteen (27 per cent) children with encephalopathy died. Viral markers were positive in 166 (96.5 per cent) and they were: A in 111 (64.5 per cent), E in 28 (16.3 per cent), B in 13 (7.6 per cent), A + E in 12 (7 per cent), A + E + C and A + C in one each. Mortality in acute liver failure was more when associated with SBP (100 per cent) than without (20 per cent) (p < 0.001). We conclude that HEV is the second most common cause of sporadic acute viral hepatitis in children. Atypical presentations, such as splenomegaly, ascites, and SBP were present in virtually one-third of cases. In cases of ALF, the presence of ascites and SBP depicts a worse outcome.     

Hepatitis A vaccination of infants: effect of maternal antibody status on antibody persistence and response to a booster dose

BACKGROUND: Infants with passively transferred maternal antibody (PMA) to hepatitis A virus (HAV) have lower concentrations of antibody to HAV (anti-HAV) after vaccination. We examined the effect of PMA on persistence of anti-HAV and on immune memory. METHODS: We measured anti-HAV concentrations of 6-year-old children who had responded to a three dose hepatitis A vaccine series at ages 2, 4 and 6 months. Group 1 children were born to anti-HAV-negative women; Group 2 children had anti-HAV-positive mothers and PMA at 2 months of age. Children without detectable antibody at 6-year follow-up were offered a booster dose [360 enzyme-linked immunosorbent units (ELU)]. An anamnestic response was defined as a postbooster anti-HAV concentration of > or =400 mIU/ml. RESULTS: At follow-up, before the booster dose, Group 1 subjects had a higher geometric mean concentration (50 mIU/ml vs.18 mIU/ml, P = 0.007), and a larger proportion retained seroprotective concentrations of anti-HAV [21 of 31 (68%) vs.4 of 17 (24%)] compared with Group 2 subjects. The two stage antibody decline curves for the two groups from 8 months old to follow-up testing were parallel. An anamnestic response occurred in all (5 of 5) Group 1 and 67% (4 of 6) of Group 2 children. The geometric mean antibody concentrations after the booster were 1102 and 406 mIU/ml for Groups 1 and 2, respectively (P = 0.10). CONCLUSIONS: Infants with PMA who receive hepatitis A vaccine have significantly lower concentrations of anti-HAV 6 years later than infants with no PMA who receive hepatitis A vaccine. Immune memory may remain functional despite these lower anti-HAV concentrations.     

Nationwide canadian study of hepatitis a antibody prevalence among children eight to thirteen years old

BACKGROUND: Hepatitis A vaccines provide consistent, long-lasting protection and have been available for almost 10 years in Canada, but their use remains limited. It is difficult to assess their optimal utilization given that our knowledge of hepatitis A epidemiology in Canada is fragmentary. Unlike the United States, no nationwide study of hepatitis A prevalence has ever been done in Canada. Consequently we do not know the incidence of infection in children and what would be the most appropriate age for hepatitis A vaccination. OBJECTIVE: To estimate the proportion of 8- to 13-year-old children who have been infected with hepatitis A virus (HAV) and the risk factors for this infection on a nationwide scale. METHODS: Children were sampled in 10 Canadian provinces, comprising 5 regions, using random digit dialing methodology with regional stratification. Demographic data and information about risk factors for hepatitis A were collected by the telephone interviewers. Oral fluid samples were self-collected and mailed to the laboratory, where they were tested for anti-HAV IgG. RESULTS: Of 6740 contacted families with a child of required age, 1688 (25%) agreed to participate and answered the questionnaire. From these, 1074 oral fluid samples were received, and 1057 could be analyzed. Anti-HAV IgG was detected in 2.7% of subjects, with variation by region from 0.8 to 3.4%. The parents of 54 subjects (5.1%) reported that their child had previously been vaccinated against HAV. Anti-HAV IgG was present in 2.0% of unvaccinated subjects, among whom antibody prevalence was 19.4% in children born in HAV-endemic countries, 6.1% in Native children and 4.2% in travelers to endemic countries. In multivariate analysis of all subjects, the presence of anti-HAV IgG was significantly associated with birth in an endemic country, travel to an endemic country, Native status (American Indian and Inuit population), female gender and vaccination against HAV. In nonvaccinated, non-Native children born in Canada who did not travel to endemic countries, anti-HAV prevalence was 1.1%. CONCLUSIONS: The risk for hepatitis A during childhood is low in Canada. Almost all teenagers (>97%) would be at risk for infection in case of contact with HAV. Changes in immunization policy against hepatitis A should be considered.     

Hepatitis A and B virus infections in children in Kuwait

In a 1-year prospective study of 1788 cases of acute viral hepatitis, 26 (1.5%) presented with evidence of simultaneous hepatitis A (HAV) and hepatitis B (HBV) virus infection. Twenty-three of 26 (88.5%) of these cases had serological evidence of a recent HAV infection in a chronic HBV carrier. The remaining 3 (11.5%) showed serological evidence of a recent concomitant HAV/HBV infection. Twenty-four of the 26 (92.3%) patients with simultaneous infection were children with a mean age of 4.6 years. Clinical and laboratory data indicated that the disease in patients with a recent concomitant HAV/HBV infection was not different from that in patients who had HAV infection superimposed on a chronic HBV carrier or that in age and sex matched patients presenting with an acute viral hepatitis A infection alone. Furthermore, the outcome of the disease was not affected by the HBeAg/anti-HBe status of the hepatitis B positive patient. All patients recovered completely and on follow-up none showed any signs of chronic liver disease. Simultaneous HAV/HBV infection, therefore, does not result in a more severe disease.     

Immunogenicity and safety of a pediatric dose of a virosome-adjuvanted hepatitis A vaccine: a controlled trial in children aged 1-16 years

BACKGROUND: The availability of pediatric formulations of hepatitis A virus (HAV) vaccines would facilitate the introduction of universal mass vaccination against HAV. The objective of this study was to compare a pediatric dose (0.25 mL) of Epaxal, a virosomal, aluminum-free HAV vaccine, to 0.5 mL standard dose, and to alum-adsorbed HAV vaccine. METHODS: Subjects aged 1-16 years, stratified for age, were randomized (2:2:1) into group A (0.25 mL Epaxal), group B (0.5 mL Epaxal), or group C (Havrix Junior). Vaccines were administered at months 0, 6. Seroprotection rates (>or=10 mIU/mL anti-HAV antibodies) were assessed for noninferiority, defined as lower limit of 1-sided 97.5% CI >-10%. Incidence of local solicited adverse events and unsolicited adverse events were recorded. RESULTS: Mean age of 308 enrolled subjects was 8.9 years (range, 1.0-17.0 years). All 3 vaccines were highly immunogenic. Noninferiority of group A versus group B and group C with regard to seroprotection was demonstrated after both vaccine doses for the entire study group and for all age subgroups (11-23 months, 2-4, 5-7, 8-10, 11-13, 14-16 years). One month after first vaccination, geometric mean antibody concentrations were 69.0, 83.5, and 50.5 mIU/mL for the 3 groups, respectively (A versus B, P = 0.0208; A versus C, P = 0.0015). Local injection site pain occurred more frequently in group C than in groups A and B. No subjects withdrew from study or reported any vaccine-related serious adverse event. CONCLUSION: In children aged 1-16 years, 0.25 mL dose of Epaxal is as immunogenic as standard 0.5 mL dose and Havrix Junior. The aluminum-free vaccine compares favorably to comparator vaccine regarding local reactogenicity.     

Disappearance of IgM antibodies to hepatitis A virus after an acute infection in children and adolescents

The kinetics of IgM antibodies to hepatitis A virus (HAV) following an acute infection, were studied in 17 children. Antibodies disappeared in two patterns, one group at 113 +/- 18 days after the acute infection in the children, and the second group at 283 +/- 90 days. The same two patterns of kinetics were seen in adults. We conclude that IgM anti-HAV antibodies can be found in the sera of children for over 6 months after the acute infection, as was observed in adults.     

Evaluation of association between hepatitis A and Helicobacter pylori infections and routes of transmission

Previous research about coexistence of Helicobacter pylori (HP) and hepatitis A virus (HAV) infections and the factors that increase their prevalence has suggested that the route of transmission of HP infection includes oral-oral and water-foods as well as the fecal-oral route. The aim of this study was to evaluate the routes of transmission of HP by comparing the seroprevalences of HP and HAV in children. One hundred and two children aged 1-18 years living in rural and urban regions of Izmir were included in this study. Anti-HP IgG and anti-HAV IgG antibodies were measured via enzyme immunoassay method. Seropositivities for HP and HAV were 56.8% and 51.9%, respectively. Seroprevalence for both infections increased with increasing age. However, a significant difference could not be detected between rural and urban areas. Sex did not have a significant effect. There was no infection in 22.1% of children, while 30.8% had both of the infections. 21.1% were positive only for HAV while 26% were positive only for HP. No significant correlation between seroprevalences of HP and HAV was detected. This study suggests the existence of various other routes of transmission of HP apart from the fecal-oral route.     

Immunogenicity and safety of hepatitis A vaccine in children with chronic liver disease

BACKGROUND: Acute hepatitis A superimposed on chronic liver disease has been associated with a more severe course of disease and development of fulminant hepatitis. The aim of this study was to evaluate the immunogenicity and safety of an inactivated hepatitis A virus vaccine in children with chronic liver disease. PATIENTS AND METHODS: This was an open, prospective, and controlled trial with 89 anti-HAV negative children between 1 and 16 years of age studied at a pediatric liver disease and transplantation referral center. Inactivated HAV vaccine (Havrix), from GlaxoSmithKline Biologicals containing 720 Elisa units of alum-adsorbed hepatitis A antigen per 0.5 ml dose was used. Thirty-four pediatric patients with chronic liver disease (mean age: 7.0 +/- 4.86 years) and 55 healthy controls (mean age: 4.8 +/- 2.7 years) received two doses of Havrix vaccine in months zero and six. Seroconversion and anti-HAV titers expressed as geometric mean titers (GMT) in mIU/ml were measured at months one and seven, by a modified Hepatitis A virus antibodies (HAVAB) assay. RESULTS: Seroconversion rates at four weeks after primary immunization were 76% and 94% and the GMT 107.77 and 160.77 mIU/ml in the patient and control groups, respectively. One month after second dose the seroconversion rates were 97% and 100% in the groups with GMT of 812.40 and 2,344.90 mIU/ml. Both doses were well tolerated with no significant adverse events observed. Local injection-site symptoms were the most common reactions reported in both groups. CONCLUSION: Although GMTs were significantly lower in children with chronic liver disease compared to healthy controls, the overall seroconversion rates were not different. Hepatitis A virus vaccine was safe, well-tolerated, and immunogenic in children with chronic liver disease.     

Clinical trial to evaluate immunogenicity and safety of inactivated hepatitis A vaccination starting at 2-month-old children

Active immunization with hepatitis A vaccine has been shown to provide long-term protection against hepatitis A virus (HAV) infection. However, few data are available regarding use of the hepatitis A vaccine in children under two years of age. The present study was conducted to test the safety and immunogenicity of inactivated hepatitis A vaccine administered to infants, and to evaluate the correlation between mother and infant anti-HAV antibodies. A total of sixty healthy children, two months of age, were enrolled in this study and immunized with 360 EU of inactivated hepatitis A vaccine (Havrix) according to the two, four and six months of age schedule. Blood sampling was performed prior to the first vaccination and one month after the third vaccination at seven months. Venipuncture was also done on mother on admission. The reactogenicity was expressed as the percentage of reported local and systemic reactions. The most common side effects were erythema on the injection site and fever. Infants with passively transferred maternal anti-HAV antibodies had a reduced anti-HAV GMT after vaccination. On admission, only one infant and his mother were seronegative and seroconversion was only detected in this infant. One month after the third dose seven infants (12.3%) were found to be seronegative. The infant without passively acquired maternal anti-HAV had the protective levels with a GMT of 3176 mIU/ml one month following the third dose. There was a significant positive correlation between the titers of mother and infant anti-HAV antibodies (n = 0.96, p < 0.001) on admission. Hepatitis A vaccine showed no immunogenicity in infants with presence of maternal antibodies. Hepatitis A vaccine is safe but it should be used after the disappearance of maternal antibodies.     

IgM antibody to hepatitis B core antigen in children with chronic type B hepatitis

IgM antibody to hepatitis B core antigen (anti-HBc IgM) was investigated by an antibody-capture radioimmunoassay (serum dilution 14000) in serum samples from 31 untreated children with chronic hepatitis B who were followed prospectively for 1–7 years. At the start, all patients were positive for hepatitis B e antigen (HBeAg), and anti-HBc IgM was detected in 23 cases, including 15 out of 16 with chronic active hepatitis and 7 out of 14 with chronic persistent hepatitis. A significant positive correlation was found between anti-HBc IgM levels and severity of liver damage (P<0.05), while an inverse relationship was found between anti-HBc IgM levels and distribution of hepatitis B core (HBcAg) antigen in the liver as detected by immunofluorescence. In fact 75% of anti-HBc IgM positive patients showed a focal HBcAg pattern (less than 40% positive nuclei), whereas 87% of antibody negative cases exhibited a diffuse HBcAg expression (more than 60% stained nuclei). During follow-up, seroconversion from HBeAg to anti-HBe with subsequent remission of liver disease occurred in 82% of patients presenting with detectable levels of anti-HBc, including three out of seven cases with chronic persistent hepatitis, but in none of the cases that were initially negative (P<0.01). These results indicate that during the natural course of chronic hepatitis B in children, anti-HBc IgM levels in serum reflect the degree of host immune response to infected hepatocytes. The close correlation between anti-HBc IgM seropositivity and seroconversion from HBeAg to anti-HBe suggests that anti HBc IgM may have a prognostic value during the follow-up of children with chronic HBeAg positive hepatitis B.Abbreviations anti-HBc IgM IgM antibody to hepatitis B core antigen - HBeAg hepatitis B antigen - HBcAg hepatitis B core antigen - HBV hepatitis B virus - ALT alanine aminotransferase - CAH chronic active hepatitis - CPH chronic persistent hepatitis     

Long-term outcome of chronic hepatitis B in adolescents or young adults in follow-up from childhood

BACKGROUND: It has not yet been defined whether children with chronic hepatitis B are likely to develop severe liver disease in the future. The purpose of this study was to evaluate the evolution of chronic hepatitis B acquired in childhood. METHOD: Fifty-two children in the age range of 0 to 15 years who were positive for hepatitis B surface antigen and hepatitis B e antigen in serum for at least 6 months were enrolled in this study. In the majority of the 52 children, hepatitis B virus infection was acquired by perinatal transmission. All 52 showed abnormal liver function test findings for more than 6 months before enrollment, and the subjects were followed up longitudinally for 3 to 22 years (mean, 11 years). They are now more than 15 years of age (15-27 years old). RESULTS: During the follow-up period, 26 (50%) children had spontaneous seroconversion to anti-hepatitis B e. Serum levels of alanine aminotransferase normalized in these 26 children. In one child of these children, hepatocellular carcinoma developed at the age of 21 years, 16 years after seroconversion, although his liver function profiles remained normal. The other 26 children remained hepatitis B e antigen positive, most with unchanged biochemical features. Sixteen (62%) children among these 26 children were treated with interferon-alpha. Eleven (69%) children had seroconversion to anti-hepatitis B e within the first year after the cessation of therapy. Hepatocellular carcinoma developed in 1 of these 11 children at the age of 16 years, 6 years after interferon therapy. Thus, hepatocellular carcinoma developed in two children in an anti-hepatitis B e positive phase. CONCLUSION: All children carrying hepatitis B surface antigen should be observed carefully to monitor the possible development of hepatocellular carcinoma, especially in the antihepatitis B e-positive phase after spontaneous seroconversion or even after interferon treatment.