Brief Reports

Indian Pediatrics 1999;36: 1243-1248

Clinical Profile and Sero Conversion Pattern of Children with HBsAg Positivity

From the Departments of Pediatrics and Microbiology, Medical College, Kottayam 686 036, Kerala.
Reprint requests: Dr. S Sushama Bai, `Santhi', Amalagiri PO, Kottayam 686 036, Kerala.
Manuscript received: July 9, 1998;
Initial review completed: August 12, 1998;
Revision accepted: June 22, 1999

HBV infection has become a major public health problem world wide. The virus can cause asymptomatic infection, clinical acute hepatitis, fulminant hepatitis, chronic hepatitis or carrier state. Globally nearly 2000 million individuals have serological evidence of prior HBV infection and there are over 300 million chronic carriers, out of which 35 million are in India(1). These carriers provide a source of virus transmission to susceptible individuals and eventually die from these complications(1). Most studies of HBV infection have been conducted in adults, mainly investigating the association between various risk groups and HBV markers. This study was underteken to find out the clinical presentation of children with HBs Ag positivity and their seroconversion pattern including the appearance of anti HBs antibodies.

Subjects and Methods

This study was conducted by the Departments of Pediatrics and Microbiology in a teaching hospital from May 1993 to April 1997. Children admitted to the hospital with clinical picture of viral hepatitis in whom HBsAg was positive formed the study group mainly. Few children with other diseases found to be positive for HBs Ag tested for diagnostic or therapeutic purposes, also were included.

All children had detailed clinical evaluation. In history, immunization status of the child with hepatitis B vaccine and mode of transmission of the illness were also inquired. General nutritional status, signs of hepato-cellular failure, liver size, consistency, associated splenomegaly and ascites were noted in physical examination. Ophthalmologic evaluation to detect KF ring was done in all children above the age of 5 years. Investigations included urine for bile pigments, bile salts and urobilinogen, serum bilirubin (SB) (total and direct), serum alkaline phosphatase (SAP), SGPT, PT, HBsAg and anti HBsAg in all children. Ultrasonic evaluation of abdomen was done in all children to detect liver size and consistency, condition of biliary system and to assess other intra-abdominal organs and was repeated in indicated cases. Parents and siblings of all the children were also screened for HBsAg.

HBsAg was detected by using Hepatitis B Quick test which is a latex slide test for the rapid detection of HBsAg, the kit prepared by Human Gesellschaft Fur Biochemica and Diagnostica mbH, Germany. Anti HBsAg was detected by using Bio ELISA antiHBs supplied by BIO KIT SA., Barcelona, Spain. HBeAg status though important in studying sero conversion of HBV infection could not be done.

Children were followed up every 2 weeks for initial 3 months and then every 3 months till there was complete clinical recovery and when anti HBsAg was found positive. During each visit, general condition of the child, degree of jaundice and signs of chronic hepatitis were evaluated. LFT and HBsAg were repeated every 3 months till LFT became normal and 2 consecutive results of HBsAg estimation were negative. The minimum follow up period was 2 years and the maximum period was 4 years.

Results

Fifty children were included in the study but 5 were lost to follow up. Hence analysis could be completed in only 45 children.

Age and Sex

A male preponderance was observed (24 boys and 21 girls). This reflected the hospital statistics during this period. Age group ranged from 8 months to 12 years, the mean age of presentation being 6 years and 2 months.

Mode of Presentation

Forty children (88.9%) presented as viral hepatitis. Infection was detected on routine screening in three children with nephrotic syndrome before starting prednisolone. Of the remaining two children one presented as neonatal hepatitis and the other presented as acute nephritic syndrome, hepatosplenomegaly, lymphadenopathy and jaundice. In the group which presented as viral hepatitis, 95% had jaundice, 62.5% had fever, 57.5% had anorexia, 47.5% had vomiting, 40% had nausea, 10% each had altered sensorium and seizures and 2.5% had urticaria. All had hepatomegaly and 13.3% had associated splenomegaly also. Table I reveals the clinical presentation of children with hepatitis B virus.

Table I^__ Clinical Presentation of Hepatitis B virus in children (n=40).

The three children with nephrotic syndrome presented with edema, albuminuria and hyper-cholesterolemia. Of this one had moderate hepatomegaly but there was no jaundice or other clinical features. The child who presented as neonatal hepatitis was brought at the age of 8 months after getting treatment from various systems of medicine. This girl was the only child of her parents and was born after 14 years of treatment for infertility. Parents were HBsAg negative. The baby had jaundice from the 2nd day of life onwards. At the time of admission she had Grade-I PEM, deep jaundice and hepatosplenomegaly. Liver biopsy could not be done because of prolonged PT.

Mode of Infection

Twenty six children (57.8%) had received injections within the past 3 months. Of this 24 had antibiotic injections for pneumonia, pyogenic meningitis or for enteric fever from various hospitals. One had DT as routine immunization. One child had ALL and had several blood transfusions which were properly screened from our institution itself. Five children had family members with positive HBsAg. The infant with neonatal hepatitis is the single case in this study in whom perinatal transmission could be considered. The details of mode of transmission of HBV infection are shown in Table II.

Table II^__ Mode of Transmission of HBV Infection (n=45).

Liver Function Tests

SB was elevated in 40 (88.9%) children. This included 38 children presenting as viral hepatitis, and the children with neonatal hepatitis and acute nephritic syndrome. SB above 10 mg/dl was observed in 4 children, i.e., one child with neonatal hepatitis and 3 children with viral hepatitis. SGPT and SAP were elevated in 37 (82.2%) patients each who included children with neonatal hepatitis, acute nephritic syndrome, one child with nephrotic syndrome and 34 children with hepatitis. Among them 11 (24.4%) had SGPT values above 100 IU/L and 12 (26.6%) has SAP values above 300 KA units. Prolongation of PT was observed in 9 children (20%). Six of them had values above 20 seconds and of them 3 children expired. There was no correlation between LFT values and the clinical presentation of the illness. Except for the child with chronic hepatitis, PT was the earliest LFT to become normal, mean duration being 2 weeks followed by SB, SAP and SGPT, respectively.

Clinical Outcome

Forty patients (88.9%) recovered completely both clinically and biochemically by the end of 3 months. This included 37 children with hepatitis including the child with ALL and all children with nephrotic syndrome. In the hepatitis group anorexia was the earliest symptom to disappear, the mean duration being 18 days, followed by fever, jaundice and hepa-tomegaly. Hepatic encephalopathy developed in 4 children (8.89%) out of whom 3 expired, the overall mortality rate being 6.6%. Two of the expired had Wilson disease and one child had septicemia. Carrier state(1-3) developed in 7 children (15.5%) but 5 of them recovered completely. Of the remaining two children one child continued to remain as asymptomatic carrier. The other was the infant with neonatal hepatitis and even though antigenemia dis-appeared in this child, she had waxing and waning of jaundice, irregular fever, hepato-splenomegaly and abnormal LFT with persis-tently prolonged PT.

Seroconversion

Of the surviving forty two children, 41 (91.1%) became HBsAg negative by the end of 3 years, annual sero conversion rate of antigenemia being 30.3% (Table III). Among them, 27 (60%) became seronegative by 3 months, 8 of them (17.7%) between 4 to 6 months whereas 7 of them (15.5%) turned out as carriers. Thus, altogether 35 children (77.8%) became seronegative before 6 months and these were 31 children from the hepatitis group, one child with acute nephritic syndrome and 3 child-ren with nephrotic syndrome. No difference could be observed among these children in their clinical or biochemical recovery.

Table III^__Serological Outcome of HBV Infection (n=45).

Anti HBsAg developed in 11 children (24%) at the completion of the study, annual rate of seroconversion being 6.1%. The minimum period of appearance of antibody was 7 months and the maximum period was 4 years. All children with anti HBsAg conversion presented as viral hepatitis and did not include children with acute nephritic syndrome, nephrotic syn-drome or chronic hepatitis. Here also no cor-relation could be drawn between seroconver-sion and clinical or biochemical recovery. The disappearance of HBsAg in relation to age at presentation is depicted in Table IV.

Table IV^__Disappearance of HbsAg in Relation to Age at Presentation (n=41).

Carriers

Altogether seven children (15.5%) became carriers but at the end of 5 years only one child continued to remain as persistent carrier. This was a boy of 5 years who presented as viral hepatitis with mild jaundice. His SAP was normal and SGPT was only 64 IU/L. Except for mild hepatomegaly he did not have any other clinical or biochemical abnormality throughout the study period. Of the remaining 6 children, the child with perinatal transmission progressed to chronic hepatitis. She was found to be HBsAg negative at 9th month of follow up, i.e., at the age of 17 months. The remaining 5 patients presented as viral hepatitis. Four of them attained seronegativity between 9 months to 1 year after the onset of illness and the last patient became seronegative between 2� to 3 years of follow up period. There was no correlation between clinical presentation and LFT in these children and none of them developed anti-HbsAg.

Discussion

HBsAg, previously known as the Australia antigen, is the surface subunits of HBV produced abundantly during infection. The antigen appears in blood about 6 weeks after infection and disappears by 3 months(3). The persons who continue to harbour the antigen for 6 months or more are termed chronic carriers. All HBsAg positive persons are considered potentially infectious(1). Immunosuppressed children may have hepatitis B infection within the liver, without serological evidence(4).

Anti HBsAg appears late some 3 months after the onset of illness and its presence indicates recovery and immunity. Anti HBsAg values are rarely high. Between 10 to 15% of patients with acute type of B hepatitis never develop antibody. Simultaneous infection with different subtypes of HBV may show coexistence of HBsAg and anti HBs(5-7) but such a finding was not observed in our study.

This study on at risk children from neonatal period to 12 years of age has revealed annual rates of disappearance of HBsAg and sero-conversion to anti HBsAg as 30.3% and 6.1%, respectively. Comparable data for at risk children are not available. In a study conducted at Prague on 37 patients with chronic hepatitis B infection who were followed up for 8 years, the annual sero conversion rate of HBsAg was documented to be 2.4%(8).

The risk of carrier state and chronic infection are inversely related to the age of the person(4). Over 80% of those infected in the first 6 months of life become carriers as opposed to less than 20% of children infected between 2 and 3 years(3). The lower rate of carrier state (15.5%) in this study may be attributed to the higher age at presentation as revealed in Table IV. The risk of chronicity in children under 6 years has been reported as 30%(9), but in our study the risk of chronicity was 2.2% indicating better prognosis.

Fifty eight per cent of children in the study group had infection through contaminated needles whereas infection could be traced through family contacts in 11.1% and through perinatal transmission in 2.2% only. In areas of intermediate endemicity for HBV infection, the group in which India belongs, transmission patterns are mixed and transmission occurs in all age groups(1). Hence, hepatitis B vaccine if not given at birth should be given along with primary vaccination for benefit. Close physical contact with carriers and vector bites are possible modes of transmisson of HBV in children with family contacts in whom source is not clear(10,11).

In conclusion this study has revealed higher rates of seroconversion, lower risk for carrier state and chronicity and thus better prognosis in children presenting with HBV infection. Since needle transmission was seen as a major route of infection, HB vaccine if not given at birth should definitely be administered along with primary vaccination.

References

1. Lalit K, Andrew JH. Epidemiology of childhood hepatitis B in India. Indian J Pediatr 1995; 62: 635-653.

2. Ballistreri F. Viral hepatitis. Pediatr Clin N Am 1988; 35: 637-663.

3. Mowat AP, Baker AJ. Chronic liver disease. In: Forfar and Arneil's Text Book of Paediatrics, 5th edn. Eds. Campbell AGM, McIntosh N. Edinburgh. Churchill Livingstone, 1998; pp 480-481.

4. John DS, Larry KP. Hepatitis A through E. In: Nelson Text Book of Pediatrics, 15th edn. Eds. Berhrman KE, Kliegman RM, Arvin AM. Bangalore, Prism Books, 1996; pp 909-914.

5. NKGP, Saw TI. Concurrence of hepatitis B surface antigen and antibody in acute and chronic hepatitis B cases. Med J Malaysia 1994; 49: 117-121.

6. Styezy, Haltoa W, Balcar-Boron A, Dorave M. Concurrence of HBsAg and anti HBs antibodies in children infected with HBV. Przegl Epidemiol 1995; 49: 317-319.

7. Sherlock S, Dooley J. Type B (HBV) hepatitis. In: Diseases of the Liver and Biliary System, 9th edn. London, Oxford Blackwell Scientific Publica-tions, 1993; pp 269-280.

8. Str. Ansk YJ, Chlumska A. Prevalence of HBeAg and HBsAg sero-conversion in patients with chronic hepatitis B. Sb Lek 1993; 94: 317-325.

9. Hyams KC. Risks of chronicity following acute hepatitis virus infection_A review. Clin Infct Dis 1995; 20: 992-1000.

10. Portoso, Cordoso DD, Quieroz DA, Rosa H, Andrade AL, Zeker F, et al. Prevalence and risk factors for HBV infection among street youth in central Brazil. J Adolesc Health 1994; 15: 577-581.

11. Chotard J, Lindsay SW, Coromia E, Mendy M, Alonso PL, Whittle H. Risk factors for transmission of hepatitis B virus to Gambian children. Lancet 1990; 336: 1107-1109.

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