|Year : 2021 | Volume
| Issue : 2 | Page : 75-80
Response rates to hepatitis B vaccine in children with chronic kidney disease on maintenance hemodialysis
Jannatul Ferdous Sonia1, Shireen Afroz2
1 MD (Pediatric Nephrology), Registrar, Anwer Khan Modern Medical College Hospital, Dhanmondi, Dhaka, Bangladesh
2 Department of Critical Care Nephrology & Dialysis, Department of Pediatric Nephrology, Dhaka Shishu (Children) Hospital, Bangladesh Institute of Child Health (BICH), Dhaka, Bangladesh
|Date of Submission||27-Sep-2021|
|Date of Acceptance||15-Dec-2021|
|Date of Web Publication||28-Feb-2022|
Dr. Jannatul Ferdous Sonia
Bangladesh Institute of Child Health (BICH), 22, A/B, 6th Floor, Mazar Road, Gabtoly, Mirpur, Dhaka 1216,
Source of Support: None, Conflict of Interest: None
Context: Patients with chronic kidney disease (CKD) are mostly immunocompromised and more prone to infections. Risk of acquisition of infections is increased during dialysis. Hepatitis B virus (HBV) infection remains a major issue among hemodialysis patients and long-term complications of HBV infection in children are more. Following a regular vaccination schedule and maintenance of adequate antibody titer are the important ways to prevent HB infection in the hemodialysis population. Aims: The aim of this study was to compare the seroconversion rate of hepatitis B vaccine in children with CKD between maintenance dialysis and nondialysis group. Materials and Methods: This interventional study was carried out in the Department of Pediatric Nephrology, Bangladesh Institute of Child Health and Dhaka Shishu (Children) Hospital, from July 2018 to December 2019. Total 36 previously diagnosed advanced stages of patients with CKD were enrolled in the study. Patients were divided into two groups: Group A: maintenance hemodialysis (MHD) patients and Group B: nondialytic patients. Baseline antiHBs titer was done in both groups. In each group, 18 patients were enrolled. Patients who had mean baseline antiHBs >10 mIU/mL (seroconversion) were considered as primary response and patients who had mean antiHBs titer <10 mIU/mL were considered as nonseroconversion. Patients of both groups who had mean antiHBs titer 0.00 mIU/mL were given secondary vaccination by three doses of recombinant hepatitis B vaccine (20 μg) intramuscularly in a 0, 1, and 2 months of schedule. Patients who had mean antiHBs titer > 0.00 but <10 mIU/mL were vaccinated by a single booster dose (20 μg). Four weeks after completion of the vaccination, seroconversion (antiHBs titer >10–100 mIU/mL) and seroprotection (antiHBs titer >100 mIU/mL) rates were measured by immunometric technique in both groups and compared between the groups. Statistical analysis used: Statistical analysis was performed by the Statistical Package for the Social Sciences (SPSS) software program, version 20.0 for Windows (SPSS, Chicago, Illinois). The quantitative observations were indicated by frequencies and percentages. Fisher’s exact test was used to determine the association between categorical variables; Kruskal–Wallis test and unpaired t test were used to determine the association between continuous variables. Results: In this study, all enrolled patients (100%) had developed seroconversion (>10 mIU/mL). In Group A only 1 patient (9%) had seroprotection level and total 11 patients had mean antiHBs titer 46.66 ± 10.90 mIU/mL, whereas in Group B 6 patients (54%) had seroprotection level with mean antiHBs titer 326.15 ± 123.27 mIU/mL. Therefore, more seroprotection level was observed in Group B and the difference between Groups A and B was statistically significant (P = 0.0176). Conclusion: It may be concluded from the study that the immune response of the hepatitis B vaccine was significantly lower in MHD than nondialysis group patients, so it was realized that hemodialysis had effects on reduction of antiHBs titer.
Keywords: Chronic kidney disease, hepatitis B vaccine, maintenance hemodialysis, seroconversion rate
|How to cite this article:|
Sonia JF, Afroz S. Response rates to hepatitis B vaccine in children with chronic kidney disease on maintenance hemodialysis. Paediatr Nephrol J Bangladesh 2021;6:75-80
|How to cite this URL:|
Sonia JF, Afroz S. Response rates to hepatitis B vaccine in children with chronic kidney disease on maintenance hemodialysis. Paediatr Nephrol J Bangladesh [serial online] 2021 [cited 2022 May 27];6:75-80. Available from: http://www.pnjb-online.org/text.asp?2021/6/2/75/338565
| Introduction|| |
Patients with chronic kidney disease (CKD) have impaired host defenses against viral infections. Consequently, the risk of acquisition is increased in dialysis populations due to increased exposure to blood products, shared hemodialysis (HD) equipment, breaching of skin, and immunodeficiency.,
The immune response to vaccination is a complex process involving both the innate and the adaptive immune system. It is recommended that children with CKD should receive complete vaccination. In Bangladesh, a mass vaccination program against hepatitis B virus (HBV) was introduced in the EPI schedule in 2003 which covers more than 97%. Compared to a response rate of over 90% in the general population, only 50%–85% of dialysis patients achieve protection level antibody (>10 IU/L) following HB vaccination. There are different recommendations regarding dose and vaccination schedules for children with CKD including a double dose of vaccine (20 μg or 40 μg instead of 10 μg), additional inoculations, the use of adjuvants or adjuncts, and an accelerated schedule (3–4 doses given a month apart).,
After initiation of dialysis, protective hepatitis B antibody levels usually decrease rapidly. Therefore, postvaccinal serological testing is recommended to be done 2–3 months after the end of the vaccination and repeated annually thereafter., Therefore, this study aimed to compare the response rates to hepatitis B vaccine in children with CKD between on maintenance hemodialysis (MHD) patients and nondialysis patients.
| Materials and Methods|| |
This interventional study was carried out in the Department of Pediatric Nephrology, Bangladesh Institute of Child Health and Dhaka Shishu (Children) Hospital, from July 2018 to December 2019. This was done to compare the seroconversion rate of hepatitis B secondary vaccine in children with CKD on MHD and nondialysis patients. All patients with CKD on stages 4–5 were taken as a study population and they were divided into two groups: Group A: cases of patients with CKD on MHD and Group B: cases of patients with CKD on stage 4 and 5 dialysis independent. CKD on MHD: It is defined as glomerular filtration rate (GFR) less than or equal to 15 mL/min/1.73 m2 body surface area and on regular HD, 4 h three times per week. Nondialysis CKD: It is defined as GFR <60 mL/min/1.73 m2 and including GFR <15 mL/min/1.73 m2 but not dialysis dependent. Patients who were being recently vaccinated after diagnosis of CKD, those with a history of previous hepatitis C infection, and those taking immunosuppressive medication were excluded from the study. Then an elaborate history was taken and clinical characteristics of the patients including gender, age, height, weight, underlying disease, duration, and frequency of HD per week were recorded.
Before enrollment, patients were tested for HBsAg at virology laboratory by Abbott Architect i2000SR/Vitros ECi System (J&J) Siemens Advia Centaur XP Random Access Multibatch Immunoassay Analyzer. All the study subjects were HBsAg negative and completely vaccinated with HB vaccine in EPI schedule in the past (primary vaccination). Then baseline antiHBs titer was done in both MHD group and nondialysis group. Of 36 study subjects, 14 (7 in each group) patients had a baseline mean antiHBs titer >10 mIU/mL (seroconversion), which was considered as primary response, and the remaining 22 patients had mean antiHBs titer <10 mIU/mL (nonseroconversion). Of 22 subjects, in Group A three patients and in Group B 4 patients had mean antiHBs titer 0.00 mIU/mL. They were vaccinated with three doses of recombinant hepatitis B vaccine (20 μg) intramuscularly in the deltoid muscle in a 0, 1, and 2 months of schedule (secondary vaccination), and 15 subjects (Group A: eight patients and Group B: seven patients) had antiHBs titer >0.00 but <10 mIU/mL, who were vaccinated with a single booster dose (20 μg). No patient withdrew from the study because of an adverse event. All patients received their vaccination at the hospital. All patients with HD were on 4 h, three times a week regular dialysis and they were vaccinated in stable condition and immediately after the dialysis session. Immunogenicity or antibody response to the vaccine was determined by measuring antiHBs titers 4 weeks following the last dose of vaccine (after 12 sessions of dialysis in the dialysis group). AntiHBs titer was estimated in the serum sample by Abbott Architect i2000SR/Vitros ECi System (J&J) Siemens Advia centaur XP Random Access Multibatch Immunoassay Analyzer. AntiHB titers are expressed in mIU/mL. Serum antiHB level ≥ 10 mIU/mL was considered as seroconversion, whereas those with levels >100 mIU/mL were considered as high immune responders or seroprotection. The other medical records were analyzed to correlate the response to vaccine with several clinical and biological factors.
Statistical analysis was performed by Statistical Package for the Social Sciences (SPSS) software program, version 20.0 for Windows (SPSS, Chicago, Illinois). The quantitative observations were indicated by frequencies and percentages. Fisher’s exact test was used to determine the association between categorical variables, whereas Kruskal–Wallis test and unpaired t test were used to determine the association between continuous variables. A value of P < 0.05 was considered statistically significant.
Informed written consent was taken from each patient or legal guardian and assent was taken who were over 7 years old. The consent form clearly described the purpose and methods of study, confidentiality of the interview, risks and benefits of participation in the study, and their rights to participate voluntarily and to refuse at any point of time without consequences.
The protocol was approved by institutional ethical review committee of BICH before commencement of the study.
| Results|| |
Over a period of one and half years, a total of 36 cases of CKD, among them 18 cases in MHD group and 18 cases nondialysis group, were included in the study. Majority of patients (n = 12, 66%) in MHD were in the age group of 6–10 years, whereas nondialysis patients were within 6 months to 5 years of age (n = 8, 44%). Comparatively higher number of males (n = 11, 61%) were found in nondialysis group but ratio (n = 9, 50%) was equal in dialysis group. In the maintenance dialysis group, majority of patients had CKD due to obstructive uropathy (33%), followed by glomerulonephritis (28%), hereditary nephropathy (17%), neurogenic bladder (11%), FSGS (6%) and in nondialysis group the leading cause of CKD was obstructive uropathy (50%) and other CAKUT (17%). Mean systolic blood pressure was significantly higher in the MHD group as compared with nondialysis group [Table 1]. Significantly lower seroprotection level was found in the MHD group [Table 2]. Significant difference in mean antiHBs titer was found in MHD group compared to non-dialysis group [Table 3]. A statistically significant lower rate of seroconversion was found in males (primary response) in comparison to females [Table 4].
|Table 1: Clinical and laboratory characteristics of patients enrolled in the study (n = 36)|
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|Table 2: Comparison of antiHBs titer between MHD and nondialysis group who were given secondary vaccination (n = 22)|
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|Table 3: Comparison of mean antiHBs titers between MHD and nondialysis group who were given secondary vaccination (n = 22)|
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|Table 4: Univariate and multivariate modeling results for predictors of seroconversion (primary response)|
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[Table 1] shows the clinical and biochemical characteristics of study patients. Kruskal–Wallis test was done to measure the level of significance. The statistically significant high mean height was found in the MHD group when compared to nondialysis group (P = 0.004). Mean systolic blood pressure was significantly higher in the MHD group as compared to nondialysis group (P = 0.048).
[Table 5] shows the seroconversion and seroprotection level before secondary vaccination in both MHD and nondialysis group. Fisher’s exact test was used to measure the level of significance. There was no statistically significant difference between the two groups (P = 0.809).
|Table 5: Comparison of baseline antiHBs titer between MHD and nondialysis Group Before secondary vaccination (n = 36)|
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[Table 6] shows a comparison of baseline mean antiHBs titers between MHD and nondialysis groups. Unpaired t test was used to measure the level of significance. The difference was not statistically significant (P = 0.1624).
|Table 6: Comparison of baseline mean antiHBs titers between MHD and nondialysis group (n = 36)|
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[Table 2] shows the rate of seroconversion and seroprotection 1 month following the last dose of secondary vaccination in both MHD and nondialysis groups. Fisher’s exact test was used to measure the level of significance. A significantly lower seroprotection level was found in the MHD group (P = 0.022).
[Table 3] shows a comparison of mean antiHBs titer 1 month following the last dose of secondary vaccination between MHD and nondialysis group. Unpaired t test was done to measure the level of significance. A significant difference in seroprotection level was found in the MHD group as compared to nondialysis group (P = 0.0176).
[Table 4] shows univariate and multivariate logistic regression analysis to predict the probability of seroconversion and factors that influenced nonseroconversion. The predictor variables were the participant’s gender, age, and two GFR categories. This result shows odds for males 74% less to have seroconversion than nonseroconversion than females and this was statistically significant (P = 0.037). For GFR, univariate analysis showed that subjects with GFR >15–60 were two times more likely to have seroconversion than subjects with GFR <15 but which was statistically not significant (P = 0.217).
| Discussion|| |
Patients with CKD are prone to various infections including HBV infection as the results of impaired immune responses. Therfore, these patients need protection against HBV infection, but vaccine dose may be higher or an accelerated vaccination schedule may be needed. Overall, vaccines have acceptable immunogenicity, efficacy, and safety profiles in children with CKD, but the protective antibody levels induced by vaccines and the benefits of booster vaccine doses require to be individualized. This study was done to assess the rate of seroconversion and seroprotection following hepatitis B secondary vaccine in CKD on MHD and nondialysis patients. With this study result, we would be able to recommend an exact dose of hepatitis B vaccine for Patients with CKD.
In this study, primary immunization responses were compared between maintenance dialysis and nondialysis groups. It revealed 39% seroconversion (antiHBs >10 IU/L) in both MHD and nondialysis groups. There was no difference in baseline immune response to HB vaccine of MHD when compared with nondialysis group. Jason et al. also found similar results. Mast et al. reported 95% seroconversion known in the normal population. This emphasizes the need for primary immunization in childhood and assessing the antibody titers following immunization in children with CKD as quarter of patients did not achieve seroconversion. Jason et al. also found similar results, in patients on HD in their study.
In this study after getting secondary vaccination of hepatitis B vaccine in both groups, 100% of patients achieved seroconversion in both MHD and nondialysis groups, but a statistically significant difference in seroprotection level (1/11 vs 6/11) was found (P = 0.038). These observations were consistent with other studies.
Watkins et al. showed that three doses of 20 μg achieved seroconversion in 100% of predialysis, 94% of dialysis, and 64% of transplant patients. Kamath et al. showed no difference in the seroconversion rates between children who were on dialysis and children with CKD stages II to IV. These results were consistent with this study.
In this study, 1 month after giving the last dose of HB vaccine, the mean antiHB titers was 46.66 ± 10.90 mIU/mL in MHD group and 326.15 ± 123.27 mIU/mL in nondialysis group. The difference between two groups was statistically significant (P = 0.0176). This was consistent with other studies., 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 and children immunized after initiating dialysis as compared to those immunized as infants. DaRoza et al. reinforced this result by stating that the earlier the patient with CKD is subjected to vaccination, the more susceptible the seroconversion will be.
In this study, there were no statistically significant differences in terms of age, gender, BMI, and other biochemical parameters between dialysis and nondialysis group but on MHD group patients were more hypertensive compared to nondialysis group, which was similar to other studies.,
This study showed that patients with GFR levels >15–60 mL/min/1.73 m2 had two times more likely to have seroconversion than patients with GFR < 15 mL/min/1.73 m2, although it was not statistically significant. Other studies also reported similar findings., This study showed male gender had a significant chance of decreased immunogenicity concerning the vaccine against HB, but females showed better response which was consistent with other studies.,, Hannah et al. said that genes for toll-like receptor pathway and type-1 interferon induction justify these differences because of several genes that are immune-related are located on the X chromosome and play a pivotal role in immune competence.
The findings can be summarized as follows currently; it is not clear whether the different stages of CKD, as well as gender could be an independent predictor of better seroprotection after administration of HB vaccine. However, this study found that in nondialysis stages of CKD, vaccination is more likely to induce seroprotection compared with the dialysis stage. Therefore, dialysis appears to be an independent predictor of seroprotection.
This study had some limitations. The study population was selected from one selected hospital in Dhaka city, so that the results of the study may not reflect the exact picture of the entire community.
Long-term follow-up with routine HB titer could not be done because of time limitations.
It may be concluded that seroconversion (100%) was satisfactory in both MHD and nondialysis patients but a significantly lower seroprotection rate and mean antibody titers were observed in patients with MHD compared to nondialysis group. Therefore, it was realized that repeated dialysis had effects for reduction of antibody titer.
From this study, we can recommend that before starting RRT HBV infection screening is must. Antibody titers should be monitored periodically and maintenance of antiHBs titer in a seroprotection level by secondary vaccination should be recommended.
I am highly grateful to all the doctors, staff, nurses, and dialysis technicians of Department of Pediatric Nephrology of Dhaka Shishu Hospital for their kind cooperation and also indebted to BSMMU Pediatric Nephrology authority for support me in intellectual inputs.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Wong PN, Fung TT, Mak SK, Lo KY, Tong GM, Wong Y, et al
. Hepatitis B virus infection in dialysis patients. J Gastroenterol Hepatol 2005;20:1641-51.
Fabrizi F, Martin P, Dixit V, Bunnapradist B, Dulai G Meta-analysis: The effect of age on immunological response to hepatitis B vaccine in end-stage renal disease. Aliment Pharmacol Ther 2004;20:1053-62.
Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012, practice guideline for the evaluation and management of chronic kidney disease, Suppl 3. Kidney Int2013;3:1-150.
Fabrizi F, Ganeshan SV, Dixit V, Martin P Meta-analysis: The adjuvant role of granulocyte macrophage-colony stimulating factor on immunological response to hepatitis B virus vaccine in end-stage renal disease. Aliment Pharmacol Ther 2006;24:789-96.
Chi C, Patel P, Pilishvili T, Moore M, Murphy T, Strikas R Guidelines for Vaccinating Kidney Dialysis Patients and Patients with Chronic Kidney Disease 2012. Available from: http://www.cdc.gov/ vaccines/ pubs /downloads/ dialysis guide- 2012.pdf. [Last accessed on 20 February 2016].
Esposito S, Mastrolia MV, Prada E, Pietrasanta C, Principi N Vaccine administration in children with chronic kidney disease. Vaccine 2014;32:6601-6.
Bock M Vaccination against Hepatitis B in Patients in Hemodialysis and Analysis of Associated Factors: Non-seroconversion. Dissertation, Porto Alegre: Federal University of Rio Grande do Sul; 2007.
Ng KH, Teo S, Yap HK, Sathe KP Hemodialysis orders. In: Yap HK, Liu ID, Ng KH, editors. Pediatric Nephrology (On-The-Go). 3rd ed. Singapore: Shaw-NKF-NUH Children’s Kidney Center; 2018. p. 473-88.
Mohammad H, Ghadiani , Besharati S, Mousavinasab N, Jalalzadeh M Respone rates to HB vaccine in CKD stages 3-4 and hemodialysis patient. J Res Med Sci2012;17:527-33.
Hu Y, Li Q, Chen Y Timeliness of childhood primary immunization and risk factors related with delays: Evidence from the 2014 Zhejiang provincial vaccination coverage survey. Int J Environ Res Public Health 2017;14:1086.
Centers for Disease Control. Guidelines for Vaccinating Kidney Dialysis Patients and Patients with Chronic Kidney Disease. Summary of ACIP Recommendations; 2012. Available from: http://www.cdc.gov/dialysis/PDFs/Vaccinating Dialysis Patients and patients dec 2012.pdf. [Last accessed on 24 June 2015].
Misurac JM, VanDeVoorde RG, Kallash M, Lorember FM, Luckritz KE, Rheault MN, et al
Immunogenicity of augmented compared with standard dose hepatitis B vaccine in pediatric patients on dialysis: A midwest pediatric nephrology consortium study. Clin J Am Soc Nephrol 2017;12:772-8.
Mast EE, Margolis HS, Fiore AE, Brink EW, Goldstein ST, Wang SA 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) part1: Immunization of infants, children, and adolescents. MMWR Recomm Rep 2005;54:1-31.
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.
Watkins SL, Alexander SR, Brewer ED, Hesley TM, West DJ, Chan IS, et al
; Southwest Pediatric Nephrology Study Group. Response to recombinant hepatitis B vaccine in children and adolescents with chronic renal failure. Am J Kidney Dis 2002;40:365-72.
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.
Hosam I, Mohammed SME, Shaymaa F, Mohamed . Assessment of immune response to hepatitis B virus vaccine in chronic hemodialysis patients. Menoufia Med J 2017;30:184-9.
Sheth RD, Peskin MF, Du XL The duration of hepatitis B vaccine immunity in pediatric dialysis patients. Pediatr Nephrol 2014;29:2029-37.
DaRoza G, Loewen A, Djurdjev O, Love J, Kempston C, Burnett S, et al
. Stage of chronic kidney disease predicts seroconversion after hepatitis B immunization: Earlier is better. Am J Kidney Dis 2003;42:1184-92.
Samir H, Almueillo . Evaluation of response to hepatitis B vaccination in chronic hemodialysis patients. Saudi J Med Med Sci 2016;5:218-23.
Staples A, Wong C Risk factors for progression of chronic kidney disease. Curr Opin Pediatr 2010;22:161-9.
Taheri S, Shahidi S, Moghtaderi J, Seirafian S, Emami A, Eftekhari SM Response rate to hepatitis B vaccination in patients with chronic renal failure and end-stage-renal_disease: Influence of Diabetes Mellitus. J Res Med Sci2005;10:384-90.
Trevisan A, Giuliani A, Scapellato ML, Carsetti SR, Zaffina S, Brugaletta R, et al
. Sex disparity in response to hepatitis B vaccine related to the age of vaccination. Int J Environ Res Public Health 2020;17:327.
Klein SL, Jedlicka A, Pekosz A The Xs and Y of immune responses to viral vaccines. Lancet Infect Dis 2010;10:338-49.
Hannah MF, Bajic VB, Klein SL Sex differences in the recognition of and innate antiviral responses to Seoul virus in Norway rats. Brain Behav Immun 2008;22:503-16.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]