 Abstract | | |
The aim of this study is to determine the response to hepatitis B virus (HBV) vaccination in patients on hemodialysis (HD) and to identify the factors that could affect this response. This retrospective study was carried out during the period from January 2009 to December 2009 in the Prince Salman Center for Kidney Diseases (PSCKD), Riyadh, and included 144 patients (78 males and 66 females) on regular HD, all of whom received hepatitis B vaccination. Patients were divided into two groups according to the level of hepatitis B surface antibodies (HBsAb): Responders group (>10 IU/L) and non-responders group (<10 IU/L). The study looked at the factors that may affect the responsiveness to hepatitis B vaccination, like gender, age, co-existence of hepatitis C virus (HCV) infection, dialysis adequacy that was evaluated by urea reduction ratio (URR) and Kt/V, hemoglobin level, albumin level, protein catabolic rate (PCR), body mass index (BMI), subjective global nutritional status (SGA) and HbA1c. There were 129 patients (89.6%) in the responders group including 69 males and 60 females and 15 patients (10.4%) in the non-responders group including nine males and six females. The mean age in the responders group and the non-responders group was 50.56 ± 15.35 and 56.87 ± 12.52 years, respectively (P = 0.128). The mean value of the PCR was 1.03 ± 0.17 and 0.88 ± 0.17 g/kg/day in the responders group and non-responders group, respectively (P = 0.002). There was no statically significant difference between the two groups regarding the presence or absence of HCV infection, age, gender, diabetes mellitus, URR, Kt/V, hemoglobin level and albumin level. We report a high response rate (89%) for HBV vaccination in our HD patients. The PCR was the only factor that affected the response to HBV vaccination in these patients.
How to cite this article:
Al Saran K, Sabry A, Al Halawany Z, Ismail M. Factors affecting response to hepatitis b vaccine among hemodialysis patients in a large Saudi Hemodialysis Center. Saudi J Kidney Dis Transpl 2014;25:185-91 |
How to cite this URL:
Al Saran K, Sabry A, Al Halawany Z, Ismail M. Factors affecting response to hepatitis b vaccine among hemodialysis patients in a large Saudi Hemodialysis Center. Saudi J Kidney Dis Transpl [serial online] 2014 [cited 2021 Jan 18];25:185-91. Available from: https://www.sjkdt.org/text.asp?2014/25/1/185/124572 |
| Introduction | |  |
Patients on hemodialysis (HD) therapy are at a relatively high risk for exposure to hepatitis B virus (HBV) infection. [1] HBV is present in the blood and other body fluids of infected patients. [2] Transmission of infection occurs through blood product transfusions, contamination from dialysis equipment and infection from other environmental sources. [3] Vaccination against HBV has been recommended for all susceptible HD patients since it became available in 1982, but the seroconversion rates are much lower in patients with end-stage renal disease (ESRD). [4] Seroconversion (anti-HBs >10 IU/L) was found in 73-76.6% of HD patients three months after vaccine administration, but an adequate response (anti-HBs >100 IU/L) was observed only in 53.5% in one series. [5] Several population-based genetic studies had indicated that response to booster HBV vaccination as well as long-term immunological response to HBV vaccination are closely related to host genetic factors and are probably modified by recent substance use. [6] Various strategies have been attempted to improve the seroconversion rate, including adding one extra dose of vaccine for a four-vaccine series and/or doubling the dose of vaccine to 40 μg/dose. [7] Some studies have reported a 80% seroconversion with this strategy. [8] However, 41% of the responders had no detectable anti-HBs levels in the serum after three years of follow-up. [5] The causes of the low seroconversion rates in patients with ESRD include malnutrition, uremia, older age and immune-compromised state. [9] Factors that have been associated with good response to HBV vaccination are young age (<40 years), [10] good nutritional status [11] and adequacy of dialysis. [12] After HBV vaccination, specific antibody is produced via activation of B-cells by class II (CD4 + T-Helper) and class I-restricted (CD8 + CTL-cytotoxic T-cells) responses. [13],[14] In HCV-infected HD patients, a low response rate to HBV vaccine has been reported by some studies. [4],[15],[16] The aim of this study is to assess the influence of nutritional status, presence of diabetes mellitus (DM), dialysis adequacy, HCV status, age and gender on the response to HBV vaccination.
| Patients and Methods | | |
This retrospective study was conducted at the Prince Salman Center for Kidney Diseases (PSCKD), Riyadh, Saudi Arabia, over a period of one year from January 2009 to December 2009. The study included 144 patients (78 males and 66 females); their mean age was 51.21 ± 15.17 years. The subjects were negative for all serological markers of HBV infection. We evaluated levels of HBs antibody (anti-HBs) titer two months after four doses of primary vaccination were administered; the vaccine, Engerix B, 40 μg was administered by intramuscular injection into the deltoid muscle at 0, 1, 2 and 6 months.
The duration of a dialysis session among the study patients was from 3 to 4 h, three times weekly. The blood flow rate ranged from 250 to 400 mL/min, the dialysate flow rate ranged from 500 to 800 mL/min and a bicarbonate-based dialysate was used for all patients. Dialysis adequacy was assessed by monthly calculation of Kt/V and the urea reduction ratio (URR) for all cases. Single pool Kt/V (spKt/V) was assessed using the Daugirdas second-generation formula. [17] The body mass index (BMI) was calculated as body weight in kilograms divided by height in square meters. Subjective global nutritional assessment (SGA) was used to evaluate the overall protein- energy nutritional status before the commencement of hepatitis B vaccination. [18] SGA includes seven subjective assessments. Based on these assessments, each patient was given a score that reflected their nutritional status as follows:
- Weight change over the past two weeks and the last six months.
- Weight gain, no change, mild weight loss (>0.5 kg but <1 kg), score 1-2
- Moderate weight loss (>1 kg but <5%), score 3-5
- Severe weight loss (>5%), score 6-7
- Change in dietary intake.
- No change or slight change for a short duration, score 1-2
- Intake borderline and increasing, score 3-5
- Intake borderline or poor and decreasing, score 6-7
- Presence of gastrointestinal symptoms.
- Few intermittent or no symptoms, score 1-2
- Some symptoms for >2 weeks or severe and improving, score 3-5
- Symptoms daily or frequently >2 weeks, score 6-7
- Functional state.
- No impairment in strength/stamina or mild to moderate loss and now improving, score 1-2
- Mild to moderate loss of strength/stamina in daily activity or severe loss and now improving, score 3-5
- Severe loss of strength/stamina or bed ridden, score 6-7
- Subcutaneous loss of fat.
- Little or no loss, score 1-2
- Mild to moderate in all areas, score 3- 5
- Severe loss in some or most areas, score 6-7
- Muscle wasting.
- Little or no loss, score 1-2
- Mild to moderate in all areas, score 3-5
- Severe loss in some or most areas, score 6-7
- Edema
- Little or no edema, score 1-2
- Mild to moderate edema, score 3-5
- Severe edema
Minimum score = 7, Maximum score = 49; well-nourished score = 1-14, mild to moderate malnourished = 15-35 and severe malnourished = 36-49. [19]
Patients were also subjected to the following biochemical tests for nutritional assessment:
- Pre-dialysis serum albumin,
- PCR as calculated using the following equation:
nPCR = (0.0136 × F) + 0.251
Where F is equal to Kt/V × ({pre-dialysis BUN + post-dialysis BUN} χ 2). [20] - C-reactive protein (CRP) at the commencement of vaccination.
We also measured the levels of other factors that may have an impact on the effectiveness of vaccination, including HbA1c, hemoglobin (Hb) and anti-HCV antibodies by routine laboratory techniques.
| Statistical Analysis | | |
The results were summarized as mean ± standard deviation (SD). Student's t test was used for testing the significance of differences of values measured between responders and non-responders and P value <0.05 was taken as statistically significant. For the primary cause of ESRD, Chi-square test was used. All analyses were performed using SPSS version 16.
| Results | | |
Demographic data
A total of 144 chronic HD patients were enrolled in our study (78 males and 66 females). The mean age was 51.21 ± 15.17 years (range 18-85 years); it was lower in the responder compared with the non-responder group (50.56 ± 15.35 vs 56.87 ± 12.52 years, respectively, P = 0.128). The etiology of ESRD included DM in 54 cases (37.5%), hypertension in 43 cases (30.6%), interstitial nephritis in ten cases (6.9%), obstructive uropathy in six cases (4.2%), drug induced in four cases (2.7%) and unknown causes in 27 cases (18.1%). There was no significant difference between responders and non-responders regarding the original renal disease (P = 0.505) [Figure 1] and [Table 1], [Table 2] and [Table 3]. | Figure 1: The etiology of end-stage renal disease in the study patients.
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 | Table 1: Demographic and laboratory criteria of the 144 patients included in our study.
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 | Table 2: Comparison between responders and non-responders with vaccination against hepatitis B virus infection.
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 | Table 3: The primary renal disease causing end-stage renal disease and its effect on response to vaccination against hepatitis B virus infection.
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The hemodialysis prescription
The mean duration on HD therapy among the study patients was 3.31 years (range 1-17 years), and was similar in responders and non-responders (3.35 ± 1.62 vs 3.03 ± 0.972 years, respectively; P = 0.467) [Table 2]. All patients received 3-4 h of HD using volumetric machines and high-flux polysulfone membrane with different surface areas (1.2, 1.4, 1.6 and 1.8 m 2 ). The dialysate flow ranged from 500 to 800 mL/min and the blood flow rate ranged from 250 to 400 mL/min. Ninety-seven percent of the patients had thrice-weekly dialysis sessions and 3% had twice-weekly dialysis sessions. There was flexibility in extending the dialysis duration beyond 4 h as well as offering daily dialysis, if indicated.
The mean and standard deviation of URR and Kt/V for the whole group were 70.64 ± 5.45% and 1.46 ± 0.19, respectively [Table 1]. The mean URR and Kt/V in the responder group was not significantly different from the non-responder group (70.64 ± 5.45 vs 69.12 ± 5.65%, P = 0.11 and 1.46 ± 0.19 vs 1.40 ± 0.18, P = 0.24) [Table 2].
Response to hepatitis B virus vaccine
A total of 144 patients were studied, of whom 129 patients (89.58%) became sero-positive (responders) two months after HBV vaccination with antibody titer more than 10 IU/L and 15 patients were non-responders with antibody titer less than 10 IU/L (10.42%). Among the responders, 119 patients (82.64%) had antibody titer more than 100 IU/L.
Effect of nutritional status on antibody response
The mean and standard deviation of SGA score for the whole group was 5.69 ± 1.56 [Table 1], and there was no significant difference between the responder group and the non-responder group [Table 2]. Similarly, as shown in [Table 2], there was no significant difference in the serum albumin levels and the BMI between the two groups. The mean and standard deviation of the PCR for the whole group was 1.02 ± 0.24 g/kg/day [Table 1]. The mean PCR in the responder group was significantly higher than that in the non-responder group (1.02 ± 0.24 vs 0.88 ± 0.22 g/kg/day, respectively, P < 0.006) [Table 2].
Effect of diabetes mellitus, hemoglobin, C-reactive protein and hepatitis C virus status on antibody response
We used HbA1C as an indicator of glycemic control for diabetic patients included in the study. There was no significant difference between the responder group and the non-responder group in the HbA1C, Hb and CRP levels [Table 2].
In our study group, 40 patients (27.8%) were anti-HCV positive, and included 35 responders and five non-responders. This difference was not statistically significant (P = 0.61) [Figure 2]. | Figure 2: The number of responders and nonresponders in hepatitis C virus-negative and - positive patients.
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| Discussion | | |
Infection with HBV carries high mortality and is more likely to result in a carrier state in uremic patients. The introduction of universal precautions and the reduced use of blood products facilitated by the widespread use of erythropoietin (EPO) have contributed significantly in bringing the prevalence of hepatitis B down in patients on HD. With the introduction of the vaccine against HBV in 1982, it was hoped that hepatitis B would be eliminated from dialyzed patients, but the vaccine showed sub-optimal efficacy.21 The low response rate to the HBV vaccine in HD patients has prompted clinicians to use a higher dose (40 μg) and more frequent injections (0, 1, 2 and 6 months). [4] HBV infection remains an important problem in HD patients; however, only 50- 60% of the patients develop seroconversion after intramuscular HBV vaccine. [22] Prior studies had shown that the unresponsiveness to HBV vaccine is of multi-factorial etiology and is related to the presence of several modulators. [8],[23],[24]
Based on the serum HbsAb levels, the subject population has been classified as non-immune (<10 IU/L), moderately immune (between 10 and 100 IU/L) and fully immune (>100 IU/L). [21]
The present study showed a very high response to hepatitis B vaccination among HD patients, with 129 patients (89.58%) showing antibody response and 119 patients (82.64%) becoming fully immune after a full course of vaccination. Previous studies in HD patients have shown variable response rates to hepatitis B vaccination ranging from 47 to 73%. [4] Similar fully immune response to hepatitis B vaccination in HD patients has also been observed in areas such as Brazil [23] (89.5%) and Egypt (89.65%). [25]
In the present study, age, gender, the primary cause of ESRD, duration on HD, Hb albumin levels, BMI and SGA scores did not affect the response to hepatitis B vaccine. These results are in agreement with those reported by Peces et al, [26] Daco et al [12] and Tele et al. [24] Similarly, Roozbeh et al [27] showed that age, gender, BMI and serum albumin concentration did not differ between responders and non-responders to hepatitis B vaccine. A recent meta-analysis of 17 clinical trials showed a decreased response to hepatitis B vaccination among older dialysis patients, [15] which might be attributed to age-associated changes in immune status. This effect was not evident in our study, as the cohort of our dialysis patients was relatively younger compared with the other studies. [4],[12],[28]
The present study showed that malnutrition impairs the ability to form antibodies, as evidenced by significantly higher levels of PCR in responders compared with non-responders. This result is in agreement with the results of Fernandez et al, [11] who stated that malnutrition negatively influences the response to HBV vaccine in HD patients. This result is not in agreement with the results of Peces et al [26] and Tele et al. [24] Another interesting finding in our study is that DM was not a significant predictor of response to HBV vaccine. This is not in agreement with the results of Chin et al, [29] who showed poor vaccine response in diabetic patients. Peces et al, Majdan et al and Urbanowicz et al [26],[30],[31] found that the positivity of anti-HCV did not pose a negative effect on HBV vaccination in HD patients, which is in agreement with our study, while Sezer et al, Jadoul et al, Novarro et al and Muszytowaski et al [8],[23],[4],[32] have reported that co-existing HCV infection reduces the effectiveness of hepatitis-B vaccine in HD patients.
In the present study, dialysis efficiency had no effect on responsiveness to HBV vaccine, which could be explained by the efficient dialysis offered in our center. This result was not in agreement with the results of Kovacic et al, [33] who showed a weaker response to HBV vaccine associated with inadequate HD.
| Conclusion | | |
We report a high response rate to hepatitis-B vaccination among our patients. Gender, age, efficiency of dialysis, DM, anemia, HCV antibody status and systemic inflammation had no association with response to HBV vaccine. Only good nutritional state was associated with good response to hepatitis B vaccine.
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Correspondence Address:
Khalid Al Saran
Prince Salman Center for Kidney Diseases P. O. Box 27604, Riyadh
Saudi Arabia
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DOI: 10.4103/1319-2442.124572 PMID: 24434410 
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3] |
