Significance and anamnestic response in isolated hepatitis B core antibody-positive individuals 18 years after neonatal hepatitis B virus vaccination in Taiwan
Fu-Hsiung Sua,b , Chyi-Huey Baia, Fung-Yeh Chuc, Yu-Shiang Lina,c,Chien-Tien Sua,b, Chih-Ching Yeha,d,*
aSchool of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan
b Department of Family Medicine, Taipei Medical University Hospital, Taipei, Taiwan
cDepartment ofClinical Pathology, Far Eastern Memorial Hospital, Pan Chiao, Taipei Hsien, Taiwan
d Department of Public Health, China Medical University, Taichung, Taiwan
Running title: Significance of isolated anti-HBc post- vaccination
Correspondence to:
Chih-Ching Yeh, Ph.D., Associate Professor, School of Public Health, College of Public Health and Nutrition, Taipei Medical University, No. 250, Wu-Hsing Street,
Taipei City, Taiwan 110. [email protected]
Telephone: +886-2-27361661 ext. 6534; Fax: +886-2-27384831
ABSTRACT
Aim: To investigate the significance of isolated hepatitis B core antibody (anti-HBc)
and to analyze the response to hepatitis B virus (HBV) booster vaccination in young adults with isolated anti-HBc who had been fully vaccinated with HBV vaccine as
infants.
Materials and methods: We screened 1734 new university entrants who had been
fully vaccinated against HBV in infancy for the presence of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and anti-HBc upon university entry. Results positive for isolated anti-HBc were reconfirmed by testing for the presence of HBsAg and anti-HBc once more, and further evaluated for anti- HCV, anti-HIV, and HBV DNA status 6 months later. Students were also offered HBV booster vaccinations at that time. Geometric mean titers (GMT) of anti-HBs after one booster dose of HBV were compared between students with isolated anti-
HBc and students with HBV naïve status.
Results: The overall prevalence of isolated anti-HBc in our student cohort was 1.2%
(21 of 1734). No evidence of occult HBV infection was observed. A “booster”
anamnestic response (anti-HBs titer ≥10 mIU/mL) was noted in 95% (20 of 21) of subjects with isolated anti-HBc. After remeasurement of anti-HBc, 13 (62%) of the 21 subjects with isolated anti-HBc were reclassified as having resolved HBV
infection with a loss of anti-HBs. In the remaining 8 subjects (38%), isolated anti- HBc was determined to be false positive. The HBV status of these 8 subjects was HBV naïve due to the waning-off effect of anti-HBs of the neonatal HBV vaccination. There was no significant difference in anamnestic response to a single HBV booster dose of vaccine between students with isolated anti-HBc (n=13) and those with HBV naïve (n=323) status (GMT 50.6 vs 47.7 mIU/mL, P= 0.90).
Conclusion: The presence of isolated anti-HBc 18 years after HBV vaccination can
be attributed to post-HBV infection with a loss of anti-HBs and to a decline in anti- HBs elicited by vaccine. A single HBV booster dose of vaccine is recommended for subjects with isolated anti-HBc who were fully vaccinated with HBV vaccine as infants. This finding needs to be replicated in further studies with larger cohorts.
Key words: HBV, vaccination, isolated anti-HBc, booster, HBV serology
1. Introduction
Hepatitis B core antibodies (anti-HBc) against hepatitis B core antigen peptides develop in response to acute hepatitis B virus (HBV) infection. Core antibodies typically persist for life, regardless of whether the infection resolves or remains chronic . Therefore, anti-HBc acts as a serum marker for evidence of HBV infection.
Testing for the presence of anti-HBc is recommended as a screening test for HBV
infection prior to HBV vaccination in endemic areas .
In asymptomatic populations, anti-HBc positive individuals, that is, subjects with previous natural HBV infection, can be classified into three groups according to the presence or absence of hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (anti-HBs): (1) subjects with HBV immunity through natural infection (anti-HBc positivity, anti-HBs positivity, and HBsAg negativity); (2) subjects with chronic HBV infection (HBsAg positivity); or, (3) subjects with
isolated anti-HBc (anti-HBc positivity, anti-HBs negativity, and HBsAg negativity).
The prevalence of isolated anti-HBc in different populations ranges from 0.1%
to 20%, depending upon whether HBV is endemic in a particular region . In areas with low endemicity, such as most parts of Europe and the United States, the prevalence of isolated anti-HBc is about 1%–4% of the population . In contrast, in endemic countries such as those in South East Asia and sub-Saharan Africa, the
prevalence of isolated anti-HBc is much higher . Prior to the introduction of the universal HBV vaccination program in 1984, the prevalence of isolated anti-HBc in the adult population in Taiwan was 15%. In addition, Chan et al. reported that majority of their adult subjects (>75%) with isolated anti-HBc had evidence of previous infection with HBV . Although the prevalence of HBV infection has decreased markedly in Taiwan since the introduction of the neonatal HBV
vaccination program, infection still remains endemic to the area .
Isolated anti-HBc seropositivity may result from (1) resolved HBV infection with waning titers of anti-HBs (type I); (2) a false positive anti-HBc result (type II);
(3) occult chronic HBV infection with undetectable HBsAg (type III); or, (4) the presence of anti-HBc during the “window period” following acute HBV infection, when antigenemia with HBsAg has resolved and anti-HBs has not yet developed (type IV). The possibility of isolated anti-HBc reactivity being due to the anti-HBc
window period, however, is highly unlikely with current sensitive HBsAg assays . The clinical approach to the evaluation and management of isolated anti-HBc depends on the clinical situation. For subjects who are at risk for HBV infection, such as individuals living in areas that are endemic for HBV infection, some experts suggest vaccination with a complete HBV immunization series while others suggest that total anti-HBc testing be repeated. If the repeat test result is negative, suggesting
a false-positive result in the initial test, patients are recommended to receive a complete HBV immunization series. If the repeat anti-HBc test result is positive, the patient most likely has resolved HBV infection with waning anti-HBs titers. There is a lack of consensus regarding whether these patients should receive HBV vaccination. The options for these patients include (1) not vaccinating, (2) administering one dose and then checking the anti-HBs titers to see whether there is a "booster" anamnestic response (anti-HBs titer greater than 10 mIU/mL), or (3) administering a complete vaccination series. Hence, whether patients with isolated
anti-HBc require vaccination against HBV remains controversial.
The purposes of this study are to investigate the significance of isolated anti- HBc and to analyze the response to HBV booster vaccination in young adults with
isolated anti-HBc who had been fully vaccinated with HBV vaccine in infancy.
2. Materials and Methods
2.1 National vaccination program
The HBV vaccination program was launched in July 1984 as a measure to reduce the prevalence of HBV infection in Taiwan. Vaccination was available free-of- charge to infants born to HBsAg carrier mothers. From July 1986, all newborn infants were immunized against HBV with plasma-derived vaccine at birth, and at 1 month, 2 months, and 12 months of age. Additionally, subsequent to 1 November
1992, the plasma-derived vaccine used for vaccination was replaced by a recombinant yeast-derived vaccine, which consisted of a three-dose regimen, administered at birth and at the ages of 1 month and 6 months. Details of the HBV vaccination program have been described previously . Currently in Taiwan, it is not recommended that booster doses of HBV vaccine be administered to infants, children, and adolescents who have received a complete vaccination course. Booster doses of HBV vaccine are recommended only in high risk groups such as hemodialysis patients, HIV-infected persons, hematopoietic stem-cell transplant
recipients, persons receiving chemotherapy, and health workers etc.
2.2 Study participants
This study comprised 3125 new university entrants who were born after 1 July 1986 and had completed a four-dose course of plasma-derived vaccine in infancy.
Upon university enrolment during the period between September 2006 and October 2008, all of the participants underwent a compulsory health screening examination, which included the evaluation of serum HBsAg, anti-HBs, and anti-HBc status.
Participants were excluded from the study if they were unable to provide a record of having completed a full course of HBV immunization with plasma-derived vaccine or if they had received a previous HBV-booster inoculation in their childhood and/or adolescence. From the initial cohort, 1734 students (1037 males, 697 females, mean age = 18.6 ± 0.9 years) were enrolled. Among this cohort, 90 subjects with anti-HBc
reactivity (including 21 subjects with isolated anti-HBc) were identified.
2.3 Study design
Six months later, HBV DNA testing was performed on specimens from the 90 students with anti-HBc positivity as well as on specimens from subjects who demonstrated anti-HBc and anti-HBs positivity to rule out possible HBsAg escape mutants. Subjects with isolated anti-HBc were retested for reactivities to anti-HBc and HBsAg, in addition to hepatitis B e antigen (HBeAg), and antibodies to hepatitis B e antigen (anti-HBe). Subjects also underwent HIV and HCV testing. (figure 1) A result re-demonstrating anti-HBc positivity was considered a true positive result. For samples that were negative for anti-HBc, we assumed that the first positive anti-HBc result was a false positive. All subjects with isolated anti-HBc were offered one dose of recombinant HBV vaccine (Engerix-B, recombinant hepatitis B surface antigen, 20 µg/mL/vial, GlaxoSmithKline, Belgium) for booster immunization in the same manner as previously described in the literature for HBV naïve subjects A blood sample was taken for serum anti-HBs level assessment 4 weeks after the booster vaccination. Two subsequent booster vaccinations with a recombinant HBV vaccine were offered at the end of the first and sixth months if a subject’s sample had an anti-HBs titer less than 10 mIU/mL after receiving the first dose of HBV booster vaccine. A second blood sample was taken to assess serum anti-HBs titers 7 months
after the first booster had been administered. An anamnestic response to the HBV vaccine booster was defined as a rise in anti-HBs titers from less than 10 mIU/mL (pre-booster) to greater than or equal to 10 mIU/mL and at least a doubling in original titer 1 month following administration of the booster vaccination . This study was approved by the Research Ethics Review Committee of the Far Eastern Memorial Hospital, Taiwan. Written consent was obtained from all volunteers at the
time of sampling.
2.4 Serological markers and definition of HBV status
The serum HBsAg, anti-HBs, and anti-HBc levels were determined using a commercially available enzyme immunoassay kit (AxSYM, Abbott Laboratories, North Chicago, IL, USA). The detection limit of the anti-HBs enzyme immunoassay kit was 0.1 mIU/mL. Samples were considered positive for anti-HBc if the S/CO (sample rate/cut-off rate) was less than or equal to 1.000, and were considered negative if the S/CO value was in the range of 1.001–3.000. All initially reactive anti-HBc samples were retested in duplicate before the samples were classified as being reactive for anti-HBc. Serum samples with an anti-HBs level equal to or greater than 10 mIU/mL and HBsAg negative were interpreted as being seroprotective against HBV infection. HBV DNA was determined using the COBAS AmpliPrep/COBAS TaqMan HBV Test (Roche Molecular Systems, Branchburg,
NJ), which has a detection limit of 6 IU/ml for HBV DNA. Testing for the presence of HBeAg, anti-HBe, and antibodies to hepatitis C virus (anti-HCV) was carried out with a commercially available enzyme immunoassay (Ortho-Clinical Diagnostics, Amersham). A microparticle enzyme immunoassay (AxSYM HIV 1/2 gO, Abbott Laboratories, Wiesbaden, Germany) was used to test for serological markers of HIV
in subjects with isolated anti-HBc.
2.5 Statistical analysis
Anti-HBs titers were log-transformed to calculate the geometric mean titer (GMT). For the calculation of GMT, persons who had an undetectable anti-HBs titer were assigned a nominal serum anti-HBs-titer value of 0.1 mIU/mL and persons with a titer higher than 1,000 mIU/mL were assigned a value of 1,000 mIU/mL . The Pearson’s Chi-square test was used to compare the proportions of males and females with different HBV statuses. The two-sample T-test was used to compare pre- and post-booster differences (GMT) in anti-HBs level (mIU/mL) among the subjects with isolated anti-HBc and subjects with HBV naïve status. The McNemar test was used to compare the frequency distribution of the post-boosted serum anti-HBs titers among the isolated anti-HBc subjects with different levels of pre-boosted serum anti-HBs. The non-parametric Man-Whitney U test was used to compare the post- boosted serum anti-HBs titers between isolated anti-HBc subjects with different
levels of pre-boosted serum anti-HBs. An alpha level of less than 0.05 was considered statistically significant in all tests.
3. Results
3.1 HBV seroprevalence
The overall prevalence of serum anti-HBc positivity at the beginning of the study was 5.2% (90 of 1734) (Table 1). The overall prevalence of isolated anti-HBc was 1.2% (n=21) (1.4% for males and 1.0% for females). Among the 90 subjects with anti-HBc positivity, 9 subjects were excluded from HBV DNA testing because they had insufficient blood samples. Therefore, 81 of the 90 subjects underwent HBV DNA testing. The results were negative for HBV DNA in all of the 21 subjects with isolated anti-HBc and in 30 subjects with HBV immunity through natural infection. In addition, all 30 chronic HBV carriers were HBV DNA positive, including two subjects with anti-HBs positivity. No HBsAg escape mutants were identified in the anti-HBc positive group. The prevalence of HBV-naïve status among the study subjects was 58.2% (58.9% for males and 57.2% for females). The overall prevalence of HBV immunity through vaccination was 35.9% (34.8% for males and 37.6% for females). There was no significant difference in distribution of HBV status between male and female undergraduate new entrants who were born after commencement of the national HBV vaccination program.
3.2 Reclassification of subjects with isolated anti-HBc after HBV vaccine booster
The 21 subjects who initially tested positive for isolated anti-HBc were screened for the presence of HBeAg, anti-HBe, HIV, and HCV six months later. The subjects were also retested for reactivities to anti-HBc and HBsAg. None of the subjects tested positive for serum HBeAg, anti-HBe, or markers of HIV and HCV infection. The second test showed that the initial findings of isolated anti-HBc in 13 (62%) of the 21 students were true-positive results and that there were false-positive results in 8 (38%) of the 21 students. One of the 13 students with true-positive isolated anti-HBc status did not maintain seroprotective levels of anti-HBs (< 10 mIU/mL) after the first HBV booster; however, his titer was within the protective range after completing a three-dose course of HBV vaccine. Although we re- classified this student as having resolved HBV infection with loss of anti-HBs (type I), type II (a false positive isolated anti-HBc) cannot be completely ruled out. Type III (occult HBV infection) was highly unlikely as the HBV DNA and anti-HBe test results in this student were negative. All 8 subjects with false-positive isolated anti-
HBc status maintained seroprotective levels of anti-HBs after the first HBV booster.
3.3 Comparison of the HBV booster effect between subjects with isolated anti-HBc and subjects with HBV naïve status
Of the 1010 subjects with HBV-naïve status, 315 (31.3%) voluntarily received
a single booster dose of recombinant HBV vaccine (data not shown). Differences in anti-HBs levels before and after booster vaccination were compared between the 13 subjects with true isolated anti-HBc and 323 HBV naïve subjects (315 subjects with HBV naïve status and 8 subjects with false isolated anti-HBc) (Table 2). There was no significant difference in anamnestic response to the HBV vaccine booster dose between subjects with true isolated anti-HBc (50.6 mIU/mL) and subjects with naïve
HBV status (47.7 mIU/mL) (P = 0.90).
3.4 Anamnestic response to HBV vaccination among isolated anti-HBc subjects
In order to assess the anamnestic response to HBV vaccination in the 13 subjects with true isolated anti-HBc, the students were stratified into two groups according to pre-boosted anti-HBs titers: group I, an anti-HBs level <1.0 mIU/mL and group II, an anti-HBs level ranging from 1.0 to <10.0 mIU/mL (Table 3). The responses to booster vaccination were subdivided into three groups based on serum post-boosted anti-HBs titers, namely, an anti-HBs level <10 mIU/mL, a level ranging from 10 to <100 mIU/mL, and a level ≥100 mIU/mL. The mean increase in GMT after booster vaccination was 26.8 mIU/mL in subjects with pre-booster anti- HBs levels <1.0 and 106.0 mIU/mL in subjects with pre-booster anti-HBs levels ranging from 1.0 to <10.0 mIU/mL. The differences in mean GMT were significant in both groups (P < 0.0001). In addition, the results of the McNemar test provided
additional evidence that individuals with high anti-HBs titers after primary vaccination tend to have greater long-term immunogenicity (P < 0.05).
4. Discussion
Among the 1734 students surveyed, we have found that 90 (5.2%) were anti- HBc positive individuals and 21 (1.2%) had isolated anti-HBc according to their initial serum HBV screening results. (Table 1) In Taiwan, a country with a high rate of HBV infection, isolated anti-HBc without concurrent HBsAg or anti-HBs is found in 10% to 15% of the adult population . In a study conducted prior to the national HBV program in Taiwan, Chan et al. reported that 15% of the adult population had isolated anti-HBc and that the majority (>75%) of the subjects with isolated anti-HBc had evidence of previous HBV infection. Among their 50 isolated anti-HBc subjects, only one showed anamnestic anti-HBs responses after one dose of HBV vaccine . Since the implementation of the national HBV vaccination program, the prevalence of isolated anti-HBc has been gradually decreasing. In this study, the low prevalence (approximately 1.2% (95% CI: 0.78%- 1.86%)) of isolated anti-HBc observed in the undergraduate new university entrants more than 18 years after the commencement of the nationwide HBV vaccination program is compatible with Lu et al. reported in a 15-year follow-up study (1.2%) . Thus, the national
neonatal HBV vaccination program has contributed to the lower prevalence of
isolated anti-HBc in Taiwan.
In our study, possible reasons for isolated anti-HBc in subjects who were fully vaccinated with HBV vaccine as infants include (1) resolved HBV infection in subjects with very low anti-HBs titers or loss of anti-HBs positivity, and (2) false positive anti-HBc results. Of the 21 subjects with isolated anti-HBc, 8 (38%) were re-classified as having false-positive isolated anti-HBc because they showed negative results in repeated anti-HBc testing. As they all had received a completed series of neonatal HBV vaccination, the HBV status of the 8 subjects most likely was HBV naïve due to the waning-off effect of anti-HBs of the neonatal HBV vaccination. In addition, 62% (13 of 21) of the subjects with isolated anti-HBc were defined as having true-positive isolated anti-HBc results. Of these subjects with true- positive isolated anti-HBc, 92% (12/13) demonstrated anamnestic anti-HBs responses after receiving one booster of HBV vaccine, indicating that isolated anti- HBc in those subjects was due to resolved HBV infection with a loss of anti-HBs.
These findings are in sharp contrast to those reported in a study conducted prior to the commence of the national HBV vaccination in Taiwan in that the vast majority of cases of isolated anti-HBc did not respond to one dose of HBV vaccine .
HBV DNA is detected in approximately 10% of subjects with isolated anti-
HBc . In a study by Chan et al., 37 of 50 subjects with true isolated anti-HBc (74%) showed positive HBV DNA and/or anti-HBe results prior to the initiation of the HBV national vaccination program in Taiwan . In our study, none of the subjects with isolated anti-HBc had evidence of HBV DNA. A recent study in Korea also reported a very low prevalence (4 of 230) of HBV DNA among subjects with isolated anti-HBc . These discrepancies may be explained by the different sensitivities and specificities of the methods selected to detect HBV DNA, differences in the populations studied, the clinical specimens and specimen selection criteria used for the HBV DNA tests, in addition to differences in endemicity . In Chan et al study conducted prior to commencement of the national HBV vaccination program in Taiwan, they had observed the high prevalence of prior HBV infection with loss of anti-HBs, the high prevalence of HBV DNA and anti-HBe markers, and the low response rate to HBV vaccine booster among healthy Taiwan adults . In contrast, our study found a high percentage of false-positive isolated anti-HBc, a high anamnestic response to one HBV vaccine booster dose, and no evidence of HBV DNA or anti-HBe among the students who were fully vaccinated with HBV vaccine as infants. We speculate that the high percentage of false-positive isolated anti-HBc in this cohort is associated, at least in part, with a decrease in prevalence of true-positive isolated anti-HBc cases rather than an increase in the number of false-
positive isolated anti-HBc cases. Hence, our study showed no evidence of on-going HBV infection among isolated anti-HBc subjects in post-HBV vaccination era compared to high prevalence of HBV DNA among the true isolated anti-HBC prior to HBV vaccination era. Our finding implies that mass neonatal HBV vaccination
may have altered the significance and prevalence of true isolated anti-HBc.
Isolated anti-HBc is also a common finding in HIV–infected persons (14-81%) . This wide variation in the prevalence of isolated anti-HBc among HIV patients is probably due to the various epidemiologic characteristics of the patients enrolled in these studies and the background seroprevalence of HBV infection. An association between isolated anti-HBc and HCV has also been reported . Co-infection of HBV with HIV or HCV can lead to down-regulation or interference of HBsAg production . In contrast to the findings reported by Jilg et al., in which 14.3% of isolated anti-HBc samples were also positive for HIV and 40.5% of samples were positive for HCV, none of our 21 subjects with isolated anti-HBc had serological markers of infection with HIV or HCV. One possible explanation for the discrepancy is that the previous studies were mainly conducted among HIV patients whereas our subjects were young adults, a population with very low prevalence of HIV and HCV infection . Another possibility for the discrepancy is the small number of isolated anti-HBc subjects we investigated.
Isolated anti-HBc can also be due to false-negative HBsAg test results.
Concentrations of HBsAg that are below detection limits or mutations in the major antigenic determinant, namely the “a” determinant, of HBsAg that are associated with occult HBV infection can lead to false-negative HBsAg results . In our study, samples from the 21 subjects with isolated anti-HBc status were all negative for serum HBsAg, anti-HBe, and HBV DNA. Hence, isolated anti-HBc due to false- negative HBsAg test results and the presence of occult HBV infection is unlikely to be the cause of isolated anti-HBc in this study. In addition, isolated anti-HBc seropositivity may result from the presence of anti-HBc during the “window period”
following acute HBV infection, when antigenemia with HBsAg has resolved and anti-HBs has not yet developed. In our study, the fact that the results were still negative for HBV markers 6 months later ruled out this possibility.
In order to evaluate whether isolated anti-HBc among these post-vaccinated young adults could be related to a prior exposure to HBV, one booster dose of a recombinant HBV vaccine was given to determine the immunological response as reported previously . HBV-immune individuals with undetectable levels of anti-HBs typically develop a strong secondary immune response after the first dose of HBV vaccine. On the other hand, chronic low-level HBV carriers, when challenged by vaccination, typically are not able to produce anti-HBs antibodies. In our study,
although the mean increase in anti-HBs level after one booster vaccination was not statistically greater in subjects with isolated anti-HBc than in subjects in the HBV naïve group, the increase can be interpreted as an anamnestic response in subjects with isolated anti-HBc. Furthermore, we found that subjects with high anti-HBs titers subsequent to primary neonatal HBV vaccination had better long-term immunogenicity. As a result, it is not likely that chronic low-level HBV carriage was the main mechanism mediating isolated anti-HBc in young adults 18 years after
neonatal HBV vaccination.
Some previous reports revealed higher anamnestic anti-HBs responses among subjects with isolated anti-HBc in countries endemic for HBV infection . However, a report from Taiwan found that individuals with isolated anti-HBc had low anamnestic anti-HBs responses (1 of 50) and high primary anti-HBs responses (44 of 45) prior to commencement of the nationwide vaccination program, and that most (nearly 75%) of the subjects with isolated anti-HBc exhibited evidence of previous HBV exposure . In contrast, the anamnestic response in our 13 subjects with true isolated anti-HBc who were born after the implementation of the universal HBV vaccination program was 92% (12 of 13). A recent study also reported a higher anamnestic response and a lower primary response among subjects with isolated anti-HBc after implementation of a universal HBV vaccination program . The high
rate of anti-HBs positivity after vaccination boosting in subjects who were originally anti-HBs negative indicates that anamnestic rise in anti-HBs in response to HBsAg exposure confers long-term immunity despite the overall decline in anti-HBs titers
with the passage of time .
One of the limitations of this study is that results of the test used to detect mean differences in anti-HBs levels may have been affected by the small number of subjects with isolated anti-HBc. However, the findings of isolated anti-HBc were reconfirmed six months after the initial assessment and were given with the HBV booster vaccination, thereby increasing the validity of the study. Further studies with larger sample sizes are needed to examine this effect. Another limitation of the study is that we used blood samples rather than liver tissue to screen for the presence of HBV antigens and antibodies. It has been reported that the detection rate of HBV DNA in subjects with isolated anti-HBc is higher in liver tissue (16 of 39 (41.0%)) than in blood (44 of 545 (8.1%)) . Thus, we speculate that the real prevalence of
occult HBV infection in subjects with isolated anti-HBc is underestimated.
In summary, the overall prevalence of isolated anti-HBc was 1.2% among our 1734 young adults who were fully vaccinated with HBV vaccine as infants. After repeating the anti-HBc measurements, we found that 38% (8 of 21) of the subjects with isolated anti-HBc had false-positive results. The HBV status of these 8 subjects
most likely was HBV-naïve with loss of anti-HBs through years after neonatal HBV vaccination. In the group of subjects with true isolated anti-HBc (13 of 21), isolated anti-HBc was due to resolved HBV infection with waning titers of anti-HBs.
Although there is no consensus on the clinical management of patients with isolated anti-HBc, we believe that one dose of HBV booster is a cost-effective option in young adults as 92.3% (12/13) of our true isolated anti-HBc subjects responded to one dose of booster vaccine.
Acknowledgements
Funding source: The study had no external funding source.
Conflict of interest statement: None declared.
Ethical approval: The study-protocol was approved by the Research Ethics Review Committee of the Far Eastern Memorial Hospital (FEMH No.:96035).
References
Figure Legends:
Fig. 1. Study flow chart.
