Elsevier

Journal of Hepatology

Volume 50, Issue 2, February 2009, Pages 264-272
Journal of Hepatology

Occult hepatitis B virus infection in hepatitis B vaccinated children in Taiwan

https://doi.org/10.1016/j.jhep.2008.09.017Get rights and content

Background/Aims

Presence of occult HBV infection in HBV vaccinated children remains largely unknown. The aim of this study was to investigate the prevalence of occult HBV infection among HBV vaccinated children in Taiwan.

Methods

Forty-six HBsAg negative sera from vaccinated children were enrolled randomly. HBV serum markers were detected by ELISA, and the titers of HBV DNA were determined by quantitative real-time PCR. Pre-S, S and pre-core/core genes were amplified by nested PCR and analyzed.

Results

Anti-HBs was detected in 23 (50%) children, and the positivity decreased according to age. Five (10.9%) children were classified into occult HBV infection by positivity of nested PCR in at least two regions; they had a low titer (mean titer 1.60 × 104 copies/ml). Sequence analyses of S gene showed occult isolates were variants; no G145R but C139S vaccine escape mutant was found. Variation and deletion were found in pre-S region; pre-S deletion was more frequent in 3′ terminus of pre-S1 which leads to loss of immune epitopes and function sites.

Conclusions

This pilot study indicates that the prevalence of occult HBV infection is 10.9% in HBV vaccinated children. Since this is a small study, a study of a large population is needed to confirm the findings herein.

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.

Section snippets

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.

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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.

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