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H. Sorkhi,¹ M.R.H. Roushan,² G.H. Al Hashemi,³ M.R.E. Dooki⁴ and S. Bai¹

استجابة مرضى الديال الدموي للتلقيح ضد فيروس الالتهاب الكبدي "بي" مع أو بدون العدوى بالالتهاب الكبدي "سي"

هادي سرخي، محمد رضا حسنجاني روشن، قمر الحسيني الهاشمي، محمد رضا اسمعيلي دوكي، سهيلا باي

الخلاصـة: استهدفت هذه الدراسة تحديد مدى نجاعة التلقيح ضد فيروس الالتهاب الكبدي "بي" ومدى استجابة مرضى الديال الدموي للقاح، سواءً منهم المصابون وغير المصابين بعدوى فيروس الالتهاب الكبدي "سي". واستغرقت الدراسة من نيسان/إبريل 2000 إلى أيلول/سبتمبر 2003. وشملت جميع مرضى الديال الدموي الذين أحيلوا إلى مستشفى بابول، والذين تلقوا 4 مكروغرامات من اللقاح على ثلاث حقن عضلية عند قدومهم وبعد شهر وبعد ستة شهور. وقد كانوا جميعاً سلبيِّـين لواسمات العدوى بالالتهاب الكبدي "بي" (المستضد السطحي للالتهاب الكبدي "بي"، الضد السطحي للالتهاب الكبدي "بي" والضد اللبي للالتهاب الكبدي "بي"). ومن بين 62 مريضاً، استجاب 53 (85.5%) للتلقيح، منهم26 (49.1%) استجابوا استجابة عالية. وقد بلغ معدل الاستجابة للتلقيح لدى المرضى الذين تقل أعمارهم عن 30 عاماً 100%، ولدى المرضى الذين تتـراوح أعمارهم بين 30 و49 عاماً 85.7%، ولدى المرضى الذين تتجاوز أعمارهم 50 عاماً 81.1%. وقد استجاب جميع المصابين بعدوى فيروس الالتهاب الكبدي "سي" للتلقيح. ولم يكن لطول مدة تلقي الديال الدموي تأثير على الاستجابة للتلقيح.

ABSTRACT: The aim of this study was to determine the efficacy of hepatitis B virus (HBV) vaccination and the response to vaccine in individuals on haemodialysis with and without HCV infection. From April 2000 to September 2003 all haemodialysis patients referred to the haemodialysis department in a Babol hospital received 4 µg vaccine intramuscularly at 0, 1, and 6 months. All were negative for HBV infection markers (HBcAb, HBsAg and HBsAb). Of 62 patients, 53 (85.5%) responded to vaccination and 26 (49.1%) were high responders. All individuals with HCV infection responded to vaccination. Duration of haemodialysis had no effect on response to vaccination.

Réponse à la vaccination contre le virus de l’hépatite B chez des patients hémodialysés infectés et non infectés par le virus de l’hépatite C

RÉSUMÉ: L’objectif de cette étude était de déterminer l’efficacité de la vaccination contre le virus de l’hépatite B (VHB) et la réponse vaccinale chez des sujets hémodialysés infectés et non infectés par le virus de l’hépatite C (VHC). D’avril 2000 à septembre 2003, tous les patients hémodialysés adressés au service d’hémodialyse d’un hôpital de Babol ont reçu 4 µg de vaccin intramusculaire à 0, 1 et 6 mois. Chez tous ces patients, les marqueurs de l’infection par le VHB – l’antigène (Ag) HBs, les anticorps anti-HBc et les anticorps anti-HBs – étaient négatifs. Tous les sujets infectés par le VHC ont répondu à la vaccination. La durée de l’hémodialyse était sans effet sur la réponse vaccinale.

¹Department of Paediatric Nephrology;
²Department of Infectious Diseases;
³Department of Paediatric Nephrology, Shiraz Medical University, Shiraz, Islamic Republic of Iran.4Department of Paediatric Gastroenterology, Babol Medical University, Babol, Islamic Republic of Iran (Correspondence to H. Sorkhi: This e-mail address is being protected from spambots. You need JavaScript enabled to view it )
Received: 21/11/05; accepted: 02/05/06
EMHJ, 2008, 14(4):798-803

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Introduction

Chronic hepatitis B virus (HBV) infection is one of the most important public health problems in Asia and developing countries [1]. More than 350 million people in the world are suffering from chronic HBV infection [2].

Haemodialysis patients are particularly at risk for developing of HBV infection and are unable to eliminate the virus because of their impaired immune systems. Infected individuals are predisposed to develop chronic liver disease and then renal transplantation problems may occur [3]. So, immunity against HBV infection is essential for all haemodialysis patients [4–7].

The response rates to HBV vaccine in this group of patients differ in several studies [6,8–13]. Haemodialysis patients have poor immunity, so the response to HBV vaccine is much lower than in healthy people [5,14]. 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) T-cell responses. Insufficient T- and B-cells responses can cause chronic liver disease in 30% of HBV infected haemodialysis patients [15,16]. Second-generation recombinant vaccine (expressing the “s” gene) is safer and more immunogenic than plasma-derived vaccines [4,11,17]. In addition, some studies have shown a low response rate to HBV vaccine in haemodialysis patients infected with hepatitis C virus (HCV) and some authors could not find the effective conversion rate of HCV infection on response to HBV vaccine [14,18–22].

The purpose of this study was to assess the efficacy of HBV vaccine in a group of haemodialysis patients and HCV-infected individuals in Babol city, Islamic Republic of Iran.

Methods

From April 2000 through September 2003, all haemodialysis patients referred to the haemodialysis department of Shahid Beheshti Hospital, Babol Medical University were enrolled in this study. The department serves all haemodialysis patients living in Babol city and the villages around it. Haemodialysis patients who were positive for hepatitis B virus surface antigen (HBsAg), antibody to hepatitis B surface antigen (anti-HBs) and antibody to hepatitis B core antigen (anti-HBc) were excluded.

All patients received 2 cm3 Engerix-B vaccine (40 μg) HBsAg (Herberbiovac HB, Cuba) intramuscularly in the deltoid muscle in 3 doses (at 0, 1 and 6 months). One month after the last dose of vaccine, the HBsAb (anti-HBS) titre was determined using an enzyme-linked immunosorbent assay (ELISA) method, and antibody titres > 10 mIU/mL were considered as seroprotective. HCVAb, HBcAb, HBsAg and HBsAb were assayed with ELISA methods (Randox, England). Antibody levels between 10–99 mIU/mL  were defined as responder and > 100 mIU/mL as high responder.

The local ethics committee approved the study and informed consent was obtained from all patients.

Statistical analysis was performed using SPSS, version 10. Chi-squared and Fisher exact tests were used to compare the antibody levels by age, sex, duration of haemodialysis and concurrent HCV infection. P-values < 0.05 were considered as significant.

Results

During this study 62 patients (28 males and 34 females) were evaluated (16 patients were excluded due to early transplantation, elevated liver enzyme tests or death). The mean age of the patients was 50.95 (SD 17.82) years, range 10 to 79 years. Eleven (17.7%) patients were 5 years in 4 (6.5%).

Fifty-three (85.5%) of the patients had an antibody response to HBV vaccine: 25 (89.2%) males and 28 (82.4%) females (P > 0.05). Almost half of them (26, 49.1%) were high responders.

There was no significant difference in antibody response by age (P > 0.05). All (100%) of the 11 patients who were 0.05); 80.0% with duration < 2 years responded compared with 100% of those with longer durations (Table 1).

HCV infection was also detected in 19 (30.6%) patients. All of the HCV-infected individuals responded to HBV vaccine and 8 of them were high responders.

Discussion

Haemodialysis patients have impaired immunologic function and are predisposed to development of infections. In the United States of America (USA), complications of HBV infection are the second cause of death in these patients [23]. They have high risk for HBV infection, and recombinant HBV vaccine has been recommended for all patients undergoing haemodialysis since 1980. However, the success rate of vaccination is lower than in the general population [5,14,24].

It is noteworthy that 85.5% of our pa-tients responded with had an anti-HBS titre > 10 mIU/mL. The reason for this high rate of response is not clear. In our study there was no significant difference in the antibody response comparing age groups < 30, 30–50 and 50+ years of old. Elderly haemodialysis patients have been found to have a lower antibody titre to HBV vaccine [25–28]. In Mitwalli’s report the rate of seroconversion was higher in younger patients ( 50 years) [13]. Chin reported a better response rate to HBV vaccine in patients with a mean age of 51 years compared with 59 years of age [28]. Vlassopoulos et al. used intradermal vaccination and reported that age and sex had no influence on the immune response [29].

Peces et al. used 4 doses of vaccine and did not find any difference in response rate regarding sex, duration of haemodialysis, malnutrition status and haemoglobin level, but the response rate was better in patients 0.05).

Some authors have shown a decreased immune response to HBV vaccine in pa-tients with HCV infection. They reported very low antibody titres in these patients and suggested a possible genetic basis for the low response rate to both viruses [14,19–22]. Navarro et al. reported a low response to HBV vaccination in HCV-infected haemodialysis patients in 2 studies. In the first study, the effective immunization rate (antibody titre ≥ 100 mIU/mL) was lower in HCV infected patients (33.3% versus 70.3%, P 100 mIU/mL (P < 0.01). They suggested that HCV infection may reduce the effectiveness of HBV vaccination in haemodialysis patients [22].

Peces et al., however, reported 80 vac-cinated seronegative haemodialysis pa-tients. They used 4 vaccine doses (0, 1, 2 and 6 months) and 77.5% of patients had a high response. There was no difference between responder and nonresponder patients concerning HCV infection [20]. Cheng et al. used 5 vaccine doses and the effective conversion rates of the anti-HCV(+) and anti-HCV(–) groups were 75.0% and 77.3% respectively (P = 0.867) [21]. We also found that all cases of HCV infection had a good response to vaccination and 42% of them had a high response. So further large-scale studies are needed to confirm the response to HBV vaccination in HCV-infected haemodialysis patients.

In conclusion, sex, age, duration of haemodialysis and HCV had no association with low response to HBV vaccine, and vaccination can induce sufficient response.

Acknowledgements

The authors would like to thank all person-nel of the haemodialysis unit of Shahid Beheshti Hospital, and Dr Firousjahi for excellent assistance.

References

1. Tandon BN, Acharya SK, Tandon A. Epidemiology of hepatitis B virus infection in India. Gut, 1996, 2:s56–9.
2. Purcell RH. The discovery of the hepatitis viruses. Gasteroentology, 1993, 104:55–63.
3. Kohler H. Hepatitis B immunization in dialysis patients—is it worthwhile? Nephrology, dialysis, transplantation, 1994, 9:1719–20.
4. Rapicetta M. Hepatitis B vaccination in dialysis centers: advantages and limits. Nephron, 1992, 61:284–6.
5. Girndt M, Pietsch M, Kohler H. Tetanus immunization and its association to hepatitis B vaccination in patients with chronic renal failure. American journal of kidney diseases, 1995, 26(3):454–60.
6. Miller ER, Alter MJ, Tokars JI. Protective effect of hepatitis B vaccine in chronic haemodialysis patients. American journal of kidney diseases, 1999, 33(2):356–60.
7. Drachman R et al. Vaccination against hepatitis B in children and adolescent patients on dialysis. Nephrology, dialysis, transplantation, 1989, 4:372–4.
8. Pol S et al. Genetic basis to hepatitis B vaccine in hemodialyzed patients. Journal of hepatology, 1990, 11:385–7.
9. Caillat-Zucman S et al. Distinct HLA class II alleles determine antibody response to vaccination with hepatitis B surface antigen. Kidney international, 1998, 53:1626–30.
10. Lewis-Ximenez LL et al. Serological and vaccination profile of hemodialysis patients during an outbreak of hepatitis B virus infection. Nephron, 2001, 87:19–26.
11. Dukes CS et al. Hepatitis B vaccination and booster in predialysis patients: a 4-year analysis. Vaccine, 1993, 11(12):1229–32.
12. Kohler H et al. Active hepatitis B vaccina-tion of dialysis patients and medical staff. Kidney international, 1984, 25:124–8.
13. Mitwalli A. Responsiveness to hepatitis B vaccine in immunocompromised patients by doubling the dose scheduling. Neph-ron, 1996, 73:417–20.
14. Vlassopoulos D et al. Factors involved in low response to HBV vaccine in health and end-stage renal failure. Nephrology, dialysis, transplantation, 1998, 13:A191.
15. Descamps-Latscha B, Chatenoud L. T cells and B cells in chronic renal failure. Seminars in nephrology, 1996, 16(3):183–91.
16. Rahman F et al. Cellular and humoral responses induced by intradermal or intramuscular vaccination with the major hepatitis B surface antigen. Hepatology, 2000, 31:521–7.
17. Carletti P et al. HBV infection in haemo-dialysis patients: monitoring and preven-tion. Nephron, 1992, 61:269–70.
18. Fabrizi F et al. Intradermal versus intra-muscularly hepatitis B vaccination in non-responding chronic dialysis patients: a prospective randomized study with cost-effectiveness evaluation. Nephrology, dialysis, transplantation, 1997, 12:1204–11.
19. Navarro JF et al. Hepatitis C virus infection decreases the effective antibody respon-se to hepatitis B vaccine in haemodialysis patients. Clinical nephrology, 1994, 41(22):113–6.
20. Peces R et al. Prospective analysis of the factors influencing the antibody response to hepatitis B vaccine in hemodialysis patients. American journal of kidney diseases, 1997, 29(2):239–45.
21. Cheng CH et al. Hepatitis B vaccine in hemodialysis patients with hepatitis C viral infection. Vaccine, 1997, 15(12–13):1353–7.
22. Navarro JF et al. Antibody level after hepatitis B vaccination in haemodialysis patients: influence of hepatitis C virus infection. American journal of nephrology, 1996, 16(2):95–7.
23. 2002 annual data report (ADR)/Atlas. Bethesda, Maryland, United States Renal Data System, 2000 (NIH/NIDDK/DKUHD).
24. Bel’eed K et al. Vaccination against hepatitis B infection in patients with end stage renal disease. Postgraduate medical journal, 2002, 78(923):538–40.
25. Fernandez E et al. Response to the hepatitis B virus vaccine in haemodialysis patients: influence of malnutrition and its importance as a risk factor for morbidity and mortality. Nephrology, dialysis, transplantation, 1996, 11(8):1559–63.