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Adv Biomed Res 2017,  6:88

The Immune Response of Vaccination Against Hepatitis B virus in Iranian Patients Undergoing Chemotherapy


1 Infectious Diseases and Tropical Medicine Research Center, Isfahan University of Medical Sciences, Isfahan; Infectious Diseases and Tropical Medicine Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
2 Department of Infectious Diseases, Nosocomial Infection Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
3 Department of Oncology and Radiotherapy, Isfahan University of Medical Sciences, Isfahan, Iran
4 Department of Hematology and Oncology, Isfahan University of Medical Sciences, Isfahan, Iran
5 Infectious Diseases and Tropical Medicine Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

Date of Web Publication25-Jul-2017

Correspondence Address:
Farzin Khorvash
Department of Infectious Diseases, Isfahan University of Medical Sciences, Isfahan
Iran
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/abr.abr_330_13

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  Abstract 

Introduction: Hepatitis B virus (HBV) infection and its complications are major public health problems. As it is hard to treat and control the chronic state, control of disease depends on the prevention especially by vaccination. There is an impaired immune response to vaccinations including HBV in patients with some malignancies. The aim of this study is to assess the response rate of patients undergoing chemotherapy to HBV vaccination. Materials and Methods: All patients from two hematology/oncology clinics in Isfahan, Iran with the history of at least 1 month chemotherapy who had the inclusion criteria were enrolled in a case control study. Also a sex- and age-matched control group from healthy population was selected. They were vaccinated in a schedule of 0, 1, and 6 months and were examined for antibody titers 1 month after the last dose. The titers more than 10 mIU/ml were determined as positive response to vaccination. Results: In this study, 50 patients and 50 healthy subjects were enrolled. The two groups were age and sex matched (P > 0.05). Frequency of negative responses to HBV vaccination in case and control groups were 9 (18%) and 1 (2%), respectively (OR = 10.75, CI = 1.30–88.47, P = 0.027). Of 50 patients, 54%, 12%, 22%, and 12% had breast cancer, lymphoma, gastrointestinal, and genitourinary cancers, respectively, and frequency of negative responses were 3 (11%), 1 (16%), 4 (36.4%), and 1 (16%), respectively (P = 0.167). Conclusion: According to our results, malignancy and chemotherapy will have an important effect on the immune system and cause negative response to HBV vaccination. Our results revealed the importance of passive immunity and screening for HBV infection in patients undergoing chemotherapy. Also more studies for better vaccination schedules in this group of patients are recommended.

Keywords: Chemotherapy, hepatitis B virus, malignancy, response, vaccination


How to cite this article:
Meidani M, Khorvash F, Hemati S, Ashrafi F, Ataei B, Daneshmand D. The Immune Response of Vaccination Against Hepatitis B virus in Iranian Patients Undergoing Chemotherapy. Adv Biomed Res 2017;6:88

How to cite this URL:
Meidani M, Khorvash F, Hemati S, Ashrafi F, Ataei B, Daneshmand D. The Immune Response of Vaccination Against Hepatitis B virus in Iranian Patients Undergoing Chemotherapy. Adv Biomed Res [serial online] 2017 [cited 2019 Jan 23];6:88. Available from: http://www.advbiores.net/text.asp?2017/6/1/88/211498


  Introduction Top


Hepatitis B virus (HBV) infection and its complications are major public health problems. It is reported that more than 2 billion people are infected with HBV in the world. In 6% to 10% of patients, acute hepatitis B leads to chronicity and 15% to 25% of them die from chronic liver diseases.[1],[2],[3] The prevalence of chronic carriers in the patients with defective immune system is higher than the general population.[2] As is hard to treat and control the chronic state, control of disease depends on prevention. HBV infections can be prevented by the host immune response stimulated either naturally or by vaccination. A three-dose series of vaccination (administered at 0, 1, and 6 months) against HBV is used to prevent the infection.[4] A response to HBV vaccination is determined by the development of hepatitis B virus surface antigen antibodies (HBs-Ab).[5] About 90% to 95% of healthy subjects achieve a protective titer of antibodies after vaccination. But the response will reduce in some individuals such as older people, males, smokers, overweight individuals, and immunocompromised patients.[6],[7],[8],[9] Also the level of seroprotection will reduce during the time. Some factors such as age and time of the last vaccination are important.[10] The seropositive of 89.4% for healthcares and 87% for children have been reported in 30 and 11 years followup after vaccination, respectively.[11],[12]

The prevalence of HBsAg positivity is less than 1% in general population but 10% to 20% in individuals with cancer.[13],[14] Studies have reported an impaired immune response to vaccinations including HBV in patients with malignancies.[15],[16] Anticancer therapy causes an immunosuppressive state and increases susceptibility to viral infections such as HBV. Also bacterial and fungal infections are more probable in this group of patients.[13] The aim of this study is to assess the response rate of patients undergoing chemotherapy to HBV vaccination.


  Materials and Methods Top


A case-control study was conducted from March 2011 till March 2012. All the patients from two hematology/oncology clinics in the Isfahan city of Iran that were receiving chemotherapy (for at least one month) who did not receive HBV vaccination or did not have HBV infections in the past were enrolled and the final case group was selected considering the exclusion criteria. The control group was selected from healthy people without any immune diseases and history of chemotherapy who did not receive HBV vaccination or did not have HBV infections. The data were obtained from interview, medical history and blood testing. Participants who took any immunosuppressive drugs were excluded from the control group. Also patients with incomplete or suspicious medical documents were excluded. Fifteen patients with malignancies undergoing chemotherapy completed our criteria and were enrolled as a case group. Also 50 healthy subjects (control group) were involved.

The participants were advised that participation in the study is on a voluntary basis and an informed consent was obtained. Demographic characteristics such as sex and age were obtained through interview. A type of malignancy and duration of chemotherapy were obtained from medical documents of the patients.

Screening for antihepatitis B antibody (HBsAb) was done by performing enzyme-linked immunosorbent assay (ELISA) method and positive subjects were excluded. The negative individuals were vaccinated by HBV vaccine intramuscularly in the deltoid muscle by fallowing a schedule of 0, 1, and 6 months. The antibody titer was tested after one month (seven months after the first dose) by ELISA method and the titers more than 10mIU/ml were determined as positive response to vaccination.

Data analysis

Statistical analysis was performed using SPSS for windows (Version 16.0, 2007, SPSS Inc, Chicago, IL, USA). The Student t-test (for comparison of age) and Chi-square test (for other variables) were used to compare variables. Univariate analysis was done to estimate odds ratio (OR) and 95% confidence intervals (CI). Statistical significance was assessed at the 0.05 probability level in all analyses and the data are given as mean ± standard deviation (SD) or frequency.

Ethics

The research protocol was approved by the Ethical committee of Isfahan University of Medical Sciences in Iran.


  Results Top


The mean age of study sample was 39.62 ± 7.81 (mean ± SD). Of all participants, 30 and 70 subjects were male and female, respectively. The mean age of case and control groups were not statistically significant different (40.44 ± 8.56 and 38.80 ± 6.96, respectively, P = 0.296). In each group 15 subjects were male and 35 were female. Table one reports the frequency of malignancies. Because of the small sample size, some groups are merged and new classification is also shown in the [Table 1].
Table 1: Frequency classification of different types of alignancies in the case group (n=50)

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Frequency of the negative responses to HBV vaccination 6 months after last dose of vaccine injection were nine (18%) and one (2%) in the case and control groups, respectively (OR = 10.75, confidence interval = 1.30–88.47, P = 0.027). [Table 2] shows the negative response frequencies of patients undergoing chemotherapy in each malignancy type. We classified GI, GU, and breast cancers as solid cancers and lymphoma as hematologic malignancy. Frequency of positive response in patients with solid cancers and hematologic malignancies were 81.8% (36 of 44 patients) and 83.3% (5 of 6 patients), respectively (P = 0.916).
Table 2: Negative response frequency of patients undergoing chemotherapy divided by the malignancy type

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  Discussion Top


This study was conducted to evaluate the effect of chemotherapy on the human response to HBV vaccination. Of the participants, 18% of case and 2% of control group had negative response to vaccination. In comparison to study of Ramesh et al.,[13] who showed that 28.6% of children receiving chemotherapy had protective antibody titers and also study of Entacher et al.,[16] who showed 32% positive response to vaccination, our results revealed a higher response (82%). Entecher et al. showed that the vaccination response in patients undergoing chemotherapy with solid malignancies is higher than hematologic malignancies (28.5% vs 0%). our results revealed that 81.8% of subjects with solid tumors and 83.3% of patients with hematologic malignancy had a positive response and are statistically equal (P > 0.05). Another study conducted by Hovi et al.[17] showed that 45.4% and 88% of patients with solid tumors and hematological malignancies, respectively, had a positive response to HBV vaccination.

The results showed that subjects with malignancy undergoing chemotherapy had 10.75 fold risk of negative response to HBV vaccination in comparison to healthy people. Hovi et al. reported that children receiving chemotherapy have weaker responses to HBV vaccine than children not receiving chemotherapy.[17] Berberoglu et al. showed that 6 months after first dose of vaccination in children with cancers, 56% were positive for antibody titration. They also reported that 67.5% and 70.5% were positive after nine and 12 months, respectively.[18] Rosen et al. in a study reported that six out of seven healthy controls had protective antibody titers but six out of 32 patients with breast cancer responded to HBV vaccination.[19]

There are some possible reasons in addition to chemotherapy for the weaker response in the case group such as immunodeficiency after malignancy, genetic factors, malnutrition, associated life styles and environmental factors in some malignancies and possible effect of chemotherapy on vaccine directly. As our results showed that there is a higher risk of weak response to HBV vaccination in patients with malignancies undergoing chemotherapy in comparison to healthy population. As 82% of patients with malignancies undergoing chemotherapy showed a positive response to HBV vaccination we think it is better to vaccinate them all for HBV and then screen them. The vaccination and screening are worth doing because of higher risk of negative response in these patients than normal population. Because of sever damages caused by hepatitis B infection, passive immunity will be helpful when we find not responding patients. Our results showed a profound immune deficiency after chemotherapy and more studies on HBV vaccination schedule in this group is necessary. Studies with a higher sample size and also study of comparison of patients with malignancy without chemotherapy with patients with malignancy undergoing chemotherapy will be helpful.


  Conclusion Top


In concussion, according to our results, malignancy and chemotherapy will have an important effect on the immune system and cause negative response to HBV vaccination. Our results revealed the importance of passive immunity and screening for HBV infection in patients undergoing chemotherapy. Also more studies for better vaccination schedules are recommended.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no confl icts of interest.

 
  References Top

1.
McMahon BJ. Epidemiology and natural history of hepatitis B. Semin Liver Dis 2005;25(Suppl 1):3-8.  Back to cited text no. 1
    
2.
Nahar K, Jahan M, Nessa A, Tabassum S. Antibody responses after hepatitis B vacination among maintenance haemodialysis patients. Bangladesh Med Res Coun Bull 2011;37:88-91.  Back to cited text no. 2
    
3.
Mohammad Nejad E, Jafari S, Mahmoodi M, Begjani J, Roghayyeh Ehsani S, Rabirad N. Hepatitis B virus antibody levels in high-risk health care workers. Hepat Mon 2011;11:662-3.  Back to cited text no. 3
    
4.
Wistrom J, Ahlm C, Lundberg S, Settergren B, Tarnvik A. Booster vaccination with recombinant hepatitis B vaccine four years after priming with one single dose. Vaccine 1999;17:2162-5.  Back to cited text no. 4
    
5.
Ganczak M. A cross-sectional study on anti hepatitis B immune status in vaccinated healthcare workers in the west pomeranian region of poland. Hepat Mon 2012;12:185-9.  Back to cited text no. 5
    
6.
Wong EK, Bodsworth NJ, Slade MA, Mulhall BP, Donovan B. Response to hepatitis B vaccination in a primary care setting: Influence of HIV infection, CD4+ lymphocyte count and vaccination schedule. Int J STD AIDS 1996;7:490-4.  Back to cited text no. 6
    
7.
Fisman DN, Agrawal D, Leder K. The effect of age on immunologic response to recombinant hepatitis B vaccine: A meta-analysis. Clin Infect Dis 2002;35:1368-75.  Back to cited text no. 7
    
8.
Sabido M, Gavalda L, Olona N, Ramon JM. Timing of hepatitis B vaccination: Its effect on vaccine response in health care workers. Vaccine 2007;25:7568-72.  Back to cited text no. 8
    
9.
Wood RC, MacDonald KL, White KE, Hedberg CW, Hanson M, Osterholm MT. Risk factors for lack of detectable antibody following hepatitis B vaccination of Minnesota health care workers. JAMA 1993;270:2935-9.  Back to cited text no. 9
    
10.
Alavian SM, Mahboobi N. Anti-HBs antibody status and some of its associated factors in dental health care workers in Tehran University of Medical Sciences: Anti-HBs Ab and associated factors in dental society. Hepat Mon 2011;11:99-102.  Back to cited text no. 10
    
11.
Grosso G, Mistretta A, Marventano S, Ferranti R, Mauro L, Cunsolo R, et al. Long-term persistence of seroprotection by hepatitis B vaccination in healthcare workers of southern Italy. Hepat Mon 2012;12:e6025.  Back to cited text no. 11
    
12.
Coppola RC, Meloni A, Campagna M. Impact of universal vaccination against hepatitis B: The italian model. Hepat Mon 2012;12:417-9.  Back to cited text no. 12
    
13.
Ramesh M, Marwaha R, Chawla Y, Trehan A. Seroconversion after hepatitis B vaccination in children receiving cancer chemotherapy. Indian Pediatr 2000;37:882-5.  Back to cited text no. 13
    
14.
Alavian SM, Tabatabaei SV, Ghadimi T, Beedrapour F, Kafi-Abad SA, Gharehbaghian A, et al. Seroprevalence of Hepatitis B Virus Infection and Its Risk Factors in the West of Iran: A Population-based Study. Int J Prev Med 2012;3:770-5.  Back to cited text no. 14
    
15.
Siber GR, Weitzman SA, Aisenberg AC, Weinstein HJ, Schiffman G. Impaired antibody response to pneumococcal vaccine after treatment for Hodgkin's disease. N Engl J Med 1978;299:442-8.  Back to cited text no. 15
    
16.
Entacher U, Jurgenssen O, Thun-Hohenstein L, Simbruner G, Khoss A, Wank H, et al. Hepatitis B vaccination and immune response in children with malignant diseases. Eur J Pediatr 1985;144:160-3.  Back to cited text no. 16
    
17.
Hovi L, Valle M, Siimes MA, Jalanko H, Saarinen UM. Impaired response to hepatitis B vaccine in children receiving anticancer chemotherapy. Pediatr Infect Dis J 1995;14:931-5.  Back to cited text no. 17
    
18.
Berberoglu S, Büyükpamukcu M, Sarialioglu F, Akyüz C, Ilhan I. Hepatitis B vaccination in children with cancer. Pediatr Hematol Oncol 1995;12:171-8.  Back to cited text no. 18
    
19.
Rosen HR, Stierer M, Wolf HM, Eibl MM. Impaired primary antibody responses after vaccination against hepatitis B in patients with breast cancer. Breast Cancer Res Treat 1992;23:233-40.  Back to cited text no. 19
    



 
 
    Tables

  [Table 1], [Table 2]



 

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