Occult hepatitis B virus infection in hepatitis B vaccinated children in Taiwan☆
Introduction
Chronic hepatitis B virus (HBV) infection is a major health problem worldwide, affecting approximately 350 million individuals. The clinical outcomes of chronic HBV infection include inactive carrier state, chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC) [1], [2]. Some reports demonstrated that HBV-DNA could be detected in hepatitis B surface antigen (HBsAg) negative individuals and named it occult hepatitis B virus (oHBV) infection. The causes of undetectability of HBsAg in serum may include mutations in the S regions of the virus genome and decrease in viral load. The clinical consequence of occult HBV infection has yet to be determined. Some researchers indicated that occult HBV could be associated with fulminant hepatic failure, unexplained chronic hepatitis, cirrhosis and hepatocellular carcinoma [3], [4], [5], [6], therefore, the issue of occult HBV could not be neglected.
HBV infection is higly endemic in Taiwan. In order to control HBV infection, a nationwide vaccination program was launched in 1984 [7] that resulted in a significant carrier reduction rate in children from 10% to <1% over 10 years [8]. Several studies have documented that the long lasting protective efficacy of HBV vaccination could be maintained until ages 5–12 years [9], [10], [11], [12], and the positivity of protective anti-HBs gradually decreased from 71.1% at age 7 years to 37.4% at age 12 years in Taiwan [13]. Due to loss of protection, these anti-HBs negative children may have a higher risk for HBV infection.
To date, documentation of occult HBV prevalence rates has been limited to blood or organ donors and selected patient populations [14], [15], [16]. To our knowledge, there have been no published reports focusing on occult HBV in HBV vaccinated children. The purpose of the present study was to investigate the prevalence of occult HBV infection in this population.
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Patients
Forty-six HBsAg negative sera of HBV vaccinated children from 44 families were recruited randomly from June to November 2007 in the Shin Kong Wu Ho-Su Memorial Hospital. Most of these children had some medical problems such as IgE-related allergy, respiratory tract infection or gastroenteritis under observation by a general paediatrician. The history of familial clustering of HBV infection and hepatitis B vaccination were recorded. All subjects gave informed consent for their participation in
The relationship of HBV serum marker with age
The demographic, serological and virological characteristics of 46 HBsAg negative children are shown in Table 1. Among 46 HBV vaccinated children, 23 (50%) were anti-HBs positive; three (6.5%) were anti-HBc positive; all of them were HBeAg negative. One out of three anti-HBc positive children was also positive with anti-HBs; two were anti-HBc positive alone and came from the same family. The positivity of anti-HBs gradually decreased from 100% at age distribution of 1–2.9 years old to 40% at
Discussion
The results of this study indicate that the overall positivity of anti-HBs was 50% and decreased according to age, from 100% at age 1–2.9 years old to 40% at age 9–12.9 years old. This result is similar to the finding of Prof. Chang’s large cohort study (18,779 subjects) in Taiwan [24]: the overall prevalence rate of anti-HBs was 50.3% in 2004 and decreased from 80% at age <1 year to 42.2% at age 11–12. Comparison with the results reported from Prof. Chang, the positive rate of anti-HBs
Acknowledgments
The study was supported by grants (SKH-FJU-95-10 and SKH-FJU-96-08) from Shin-Kong Wu Ho-Su Memorial Hospital, Taiwan.
References (40)
- et al.
Global control of hepatitis B virus infection
Lancet Infect Dis
(2002) - et al.
Prevalence of herpesviridae and hepatitis B virus DNA in the liver of patients with non-A, non-B fulminant hepatic failure
Hepatology
(1996) - et al.
Hepatitis B virus maintains its pro-oncogenic properties in the case of occult HBV infection
Gastroenterology
(2004) - et al.
Twelve-year follow-up study of hepatitis B immunization of Senegalese infants
J Hepatol
(1994) - et al.
Long-term efficacy of recombinant hepatitis B vaccine and risk of natural infection in infants born to mothers with hepatitis B e antigen
J Pediatr
(1995) - et al.
Persistent hepatitis B virus infection in subjects without hepatitis B surface antigen: clinically significant or purely ‘occult’?
Hepatology
(2001) - et al.
Occult hepatitis B virus infection
J Hepatol
(2007) - et al.
Quantification and genotyping of hepatitis B virus in a single reaction by real-time PCR and melting curve analysis
J Hepatol
(2004) - et al.
Two decades of universal hepatitis B vaccination in Taiwan: impact and implication for future strategies
Gastroenterology
(2007) - et al.
Occult hepatitis B virus infection in chronic liver disease full-length genome and analysis of mutant surface promoter
Gastroenterology
(2004)
Both pre-S1 and S domains of hepatitis B virus envelope proteins interact with the core particle
Virology
Impact of hepatitis B vaccination on hepatitis B disease and nucleic acid testing in high-prevalence populations
J Clin Virol
Hospital admission is a relevant source of hepatitis C virus acquisition in Spain
J Hepatol
High prevalence and mapping of pre-S deletion in hepatitis B virus carriers with progressive liver diseases
Gastroenterology
Occult hepatitis B virus infection in a North American community-based population
J Hepatol
The characteristics of the cell-mediated immune response identify different profiles of occult hepatitis B virus infection
Gastroenterology
Hepatitis B virus biology
Microbiol Mol Biol Rev
Hepatitis B virus DNA in serum and liver is commonly found in Chinese patients with chronic liver disease despite the presence of antibodies to HBsAg
Hepatology
Hepatitis B virus DNA in patients with chronic liver disease and negative tests for hepatitis B surface antigen
N Engl J Med
A mass vaccination program in Taiwan against hepatitis B virus infection in infants of hepatitis B surface antigen – carrier mothers
JAMA
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The authors declare that they do not have anything to disclose regarding funding from industries or conflict of interest with respect to this manuscript.