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Saudi Journal of Kidney Diseases and Transplantation
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Table of Contents   
ORIGINAL ARTICLE  
Year : 2019  |  Volume : 30  |  Issue : 2  |  Page : 334-338
Seroconversion following hepatitis B vaccination in children with chronic kidney disease


Department of Pediatric Nephrology, St. John's Medical College Hospital, Bengaluru, Karnataka, India

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Date of Submission19-Dec-2017
Date of Decision31-Jan-2018
Date of Acceptance01-Feb-2018
Date of Web Publication23-Apr-2019
 

   Abstract 


Seroconversion following hepatitis B vaccination is low in children with chronic kidney disease (CKD). This study aimed to assess the seroconversion and persistence of protective immunity following hepatitis B vaccination in children with CKD. This prospective observational study was conducted in a tertiary pediatric nephrology centre to assess the seroconversion and maintenance of antibody titers (>10 mIU/mL) at one year following hepatitis B vaccination (10 μg at 0, 1, and 2 months) in children with CKD Stages II to V. Those who did not seroconvert after the schedule were re-vaccinated, and antibody titers were checked. Categorical data were expressed as proportions and analyzed using the Chi-square test. Pearson’s correlation test was used to determine the correlation of antibody titers with other continuous variables. Seroconversion was observed in 72% (n = 26/36) after vaccination. Only 60% (n = 6/10) had seroconversion after the second course of vaccination. Only 60% of children (n = 12/20) who seroconverted had protective antibody titers at one year. Seroconversion following three doses of hepatitis B vaccine is low in children with CKD. Antibody titers should be monitored periodically as the protective immunity wanes rapidly.

How to cite this article:
Kamath N, Vasudevan A, Iyengar A. Seroconversion following hepatitis B vaccination in children with chronic kidney disease. Saudi J Kidney Dis Transpl 2019;30:334-8

How to cite this URL:
Kamath N, Vasudevan A, Iyengar A. Seroconversion following hepatitis B vaccination in children with chronic kidney disease. Saudi J Kidney Dis Transpl [serial online] 2019 [cited 2019 May 20];30:334-8. Available from: http://www.sjkdt.org/text.asp?2019/30/2/334/256840



   Introduction Top


Children with chronic kidney disease (CKD), especially those on dialysis are at high risk for hepatitis B infection. Hepatitis B infection can be effectively prevented by vaccination.[1]

The Indian Society of Nephrology mandates hepatitis B vaccination in children on dialysis with 10 μg at 0, 1, and 6 months. The antibody titers should be assessed 1–2 months after completing the vaccine schedule and repeated annually thereafter.[2] Vaccination is recommended for pre end-stage renal disease patients to ensure better seroconversion.[3] Different schedules of vaccination have been recommended for hepatitis B, i.e., 0, 1 and 6 months or 0, 1, 2, and 12 months. There is no significant difference in immune response depending on the vaccine schedule used.[4]

There are few studies assessing seroconversion following hepatitis B vaccination in children with CKD,[5],[6],[7] and they are mostly done in the developed countries. There is a need for assessing seroconversion following hepatitis B vaccination in developing countries where the burden of disease is high and the rate of primary immunization is low. The aim of our study was to assess the seroconversion and persistence of protective immunity following hepatitis B vaccination in children with CKD.


   Subjects and Methods Top


This prospective observational study was conducted in the Pediatric Nephrology Department of a tertiary care hospital. Ethical approval was obtained from the Institutional Ethics committee. Children aged 2–18 years with CKD Stages II to V were screened. Children with antibody titers to hepatitis B surface antigen (HBs Ag) <10 mIU/mL were included in the study after obtaining informed consent. Children who were positive for HBs Ag and those who had undergone renal transplantation were excluded from the study. Staging of CKD was done using the estimated glomerular filtration rate by the Schwartz formula according to the National Kidney Foundation-Disease Outcomes Quality Initiative guidelines.[8]

The recombinant hepatitis B DNA vaccine of the same pharmaceutical brand was used in all children. The CDC guidelines for vaccination in CKD recommend for patients aged <20 years, three doses of 10 μg each at 0, 1, and 6 months. Anti-HBs titer ≥10 mIU/mL is considered protective. If the anti-HBs levels are <10 mIU/mL after the primary vaccine series, the person should be revaccinated. Antibody titers must be performed annually thereafter, and if titers are <10 mIU/mL, the patient must be revaccinated.[2],[3]

The CDC guidelines were followed with a modification in the dosing schedule in this study. A recombinant hepatitis B vaccine (10 μg) was administered at 0, 1, and 2 months instead of 0, 1, and 6 months to ensure rapid conversion and compliance and follow-up of our patients.

Antibody titers were measured at four months in all children and at 12 months in those who have adequate titers at four months. Children were re-vaccinated according to the same schedule when the antibody titer was <10 mIU/mL following primary vaccination and followed up at four and 12 months. The study protocol is shown in [Figure 1].
Figure 1: The study protocol.

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HBs Ag tested using ELISA. Antibody titers to HBs Ag were assessed.


   Statistical Analysis Top


Sample size estimation: Based on the 70–75% seroconversion rate following hepatitis B vaccination in children with CKD seen with other studies, a sample size of 60 would be able to provide a precision of 10% with a power of 80% and alpha error of 5%.

Quantitative data was expressed as mean and standard deviation. Categorical data was expressed as proportions and analyzed using the Chi-square test. Pearson’s correlation test was used to determine the correlation between continuous variables. A value of P <0.05 was considered statistically significant. Statistical analysis was performed using Statistical Package for the Social Sciences (SPSS) software version 16.0 (SPSS, Chicago, IL, USA).


   Results Top


Of the 98 children who were screened, 55 children in whom the antibody titers were <10 mIU/mL were recruited. The mean age was 11.2 ± 5.26 years. Nineteen patients (33.5%) were girls. Although 44 (80%) of the screened children (n = 98) reported that they had received hepatitis B vaccination, confirmatory records were found only in 17 (30%) children.

Forty-nine children completed the schedule of vaccination as per protocol [Figure 2]. Among these, 30 (62%) had CKD Stage II to IV, 19 (38%) were on dialysis (14 on hemodialysis and 5 on chronic peritoneal dialysis). Thirty-six children completed follow-up at four months and 26 (72%; 16 in CKD Stage II to IV and 10 on dialysis) had adequate seroconversion.
Figure 2: The results of the initial vaccination schedule of Hepatitis B in children with CKD Stages II to V.

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Ten patients who were seronegative at four months following the first dose were revaccinated with the same schedule. Six (60%) had adequate antibody titers, whereas four (40%) had inadequate titers at four months despite the repeat schedule. There was no difference in the seroconversion rates between children who were on dialysis and children with CKD Stages II to IV (P = 0.08).

Twenty out of 36 children who completed one year of follow-up, 12 children (60%) had adequate antibody titers (i.e., titer >10 mIU/mL). However, the mean antibody titers showed a significant decline from 649 mIU/mL at four months to 373 mIU/mL (P = 0.002). There was no significant difference in the decline in antibody titers between various stages of CKD or in those on dialysis.


   Discussion Top


Hepatitis B vaccine is a part of the routine childhood immunization schedule in India. It is alarming to note that only about 40% of our cohort had protective antibody titers to hepatitis B antigen.

Seroconversion following rapid immunization was seen in only 72% of the population with CKD. This is in contrast to 95% seroconversion known in the normal population.[4] This emphasizes the need for primary immunization in childhood. Furthermore, it necessitates the checking of antibody titers following immunization in children with CKD as seroconversion may not happen in about a quarter of patients. It was seen in a similar study, that 91% of children with renal failure had antibody titers >10 mIU/mL after a three-dose schedule of plasma-derived vaccine at 0, 1, and 2 months and 100% responded after four doses.[5] Although we anticipated that children on dialysis would have poor seroconversion, this was not evident in our study, probably due to the small number of children on dialysis. Only 60% of patients who had not seroconverted with the first dose schedule had seroconversion with the second course of vaccination, suggesting poor response to regular vaccination dose in the presence of the CKD.

Among those who seroconverted, only 60% of patients remained protected at one year following vaccination. Even in those who remained protected, there was a significant decline in antibody titers. This emphasizes the need for periodic monitoring of hepatitis B titers in children with CKD. Drachman et al showed that children on dialysis who received three doses of 20 μg at 0, 1, and 2 months showed seroconversion in 33% of patients, and seroconversion was seen after 40 μg in 33%, 76%, and 85% after 3, 4, and 5 doses, respectively.[6] Watkins showed that three doses of 20 μg achieved seroconversion in 100% of predialysis, 94% of dialysis, and 64% of transplant recipient patients. Around 88% of the children retained protective immunity one year later.[7] Sheth et al showed that the mean duration of immunity in children is 106.3 months in CKD and 37.1 months in those on dialysis. Children immunized after initiating dialysis had a hazard ratio of 6.13 for losing immunity as compared to those immunized as infants.[9]

In adults with CKD, as seroconversion is suboptimal and antibody titers wane off early, the Advisory Committee on Immunization Practices ACIP guidelines recommend a double dose of vaccine for patients on hemodialysis.[2] Whether a similar schedule needs to be adopted in children needs further study. Although the various studies in children are not comparable due to the differences in dose and schedule, all these studies including our study emphasize the need to focus on primary immunization in all children, to check hepatitis B titers periodically in children with CKD and revaccinate children with inadequate antibody titers. Further randomized control trials are required comparing double dose or additional doses in children with CKD.

The limitations of our study were that we had a small sample size and there were a considerable number of patients who were lost to follow-up.


   Conclusions Top


Seroconversion following three doses of hepatitis B vaccine is low in children with CKD and those on dialysis. Antibody titers need to be assessed after vaccination in these children. The immunity acquired following vaccination dwindles rapidly; hence, periodic monitoring of antibody titers is required.



 
   References Top

1.
Janus N, Vacher LV, Karie S, Ledneva E, Dearay G. Vaccination and chronic kidney disease. Neprol Dial Transpl 2008;23:800-7.  Back to cited text no. 1
    
2.
Vaccine recommendations for patients of chronic kidney disease. Indian J Nephrol 2005; 15 Suppl 1:72-4.  Back to cited text no. 2
    
3.
Chi C, Patel P, Pilishvili T, Moore M, Murphy T, Strikas R. Guidelines for vaccinating dialysis patients and patients with chronic kidney disease. US Department of Health and Human Services, CDC, Advisory Committee on Immunization Practices (ACIP); 2012, p. 12.  Back to cited text no. 3
    
4.
Mast EE, Margolis HS, Fiore AE, et al. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: Recommendations of the Advisory Committee on Immunization Practices (ACIP) part 1: Immunization of infants, children, and adolescents. MMWR Recomm Rep 2005;54:1-31.  Back to cited text no. 4
    
5.
Pillion G, Chiesa M, Maisin A, Schlegel N, Loirat C. Immunogenicity of hepatitis B vaccine (HEVAC B) in children with advanced renal failure. Pediatr Nephrol 1990;4:627-9.  Back to cited text no. 5
    
6.
Drachman R, Isacsohn M, Rudensky B, Drukker A. Vaccination against hepatitis B in children and adolescent patients on dialysis. Nephrol Dial Transplant 1989;4:372-4.  Back to cited text no. 6
    
7.
Watkins SL, Alexander SR, Brewer ED, et al. Response to recombinant hepatitis B vaccine in children and adolescents with chronic renal failure. Am J Kidney Dis 2002;40:365-72.  Back to cited text no. 7
    
8.
Hogg RJ, Furth S, Lemley KV, et al. National kidney foundation’s kidney disease outcomes quality initiative clinical practice guidelines for chronic kidney disease in children and adolescents: Evaluation, classification, and stratification. Pediatrics 2003;111:1416-21.  Back to cited text no. 8
    
9.
Sheth RD, Peskin MF, Du XL. The duration of hepatitis B vaccine immunity in pediatric dialysis patients. Pediatr Nephrol 2014;29: 2029-37.  Back to cited text no. 9
    

Top
Correspondence Address:
Nivedita Kamath
Department of Pediatric Nephrology, St. John's Medical College, Sarjapur Road, Bengaluru - 560 034, Karnataka
India
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DOI: 10.4103/1319-2442.256840

PMID: 31031369

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    Figures

  [Figure 1], [Figure 2]



 

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    Abstract
   Introduction
   Subjects and Methods
   Statistical Analysis
   Results
   Discussion
   Conclusions
    References
    Article Figures
 

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