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Keywords:

  • immunogenicity;
  • influenza vaccination;
  • liver transplantation

ABSTRACT

  1. Top of page
  2. ABSTRACT
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. ACKNOWLEDGMENT
  7. DISCLOSURE
  8. REFERENCES

Immunological responses to influenza vaccination administered to liver transplantation recipients are not fully elucidated. To compare inactivated influenza vaccine's immunogenicity between adult and pediatric recipients, 16 adult and 15 pediatric living donor liver transplantation recipients in the 2010–11 influenza season, and 53 adult and 21 pediatric recipients in the 2011–12 season, were investigated. Seroprotection rates (hemagglutinin-inhibition [HI] antibody titer 1:40) were 50–94% to all three antigens among adults and 27–80% among children in both seasons. Seroconversion rates (fourfold or more HI antibody rise) were 32–56% among adults and 13–67% among children in both seasons. No significant differences were observed between the two groups. In addition, 20/53 adult and 13/21 pediatric recipients received a vaccine containing identical antigens in both of these seasons. Geometric mean titer fold increases of all three antigens in adult recipients were significantly lower than those in recipients who had not received a preceding vaccination. In contrast, in pediatric recipients, there were no significant differences between the groups who had and had not received preceding vaccinations. The number of patients with rejection did not differ significantly between the two groups (0/53 vs. 1/21) in the 2011–12 season. The incidence of influenza after vaccination was significantly different between adult and pediatric recipients (0/16 vs. 5/15 in 2010–11 and 0/53 vs. 3/21 in 2011–12, respectively). Overall, there were no significant differences in antibody responses between adult and pediatric groups. Influenza infection was more frequent in pediatric recipients. Long-term response to preceding vaccinations appeared to be insufficient in both groups.

List of Abbreviations
ALT

alanine aminotransferase

AST

aspartate aminotransferase

GMT

geometric mean titers

HI

hemagglutination inhibition

Influenza is a highly infectious viral illness. Because solid organ transplant recipients are treated with immunosuppressive drugs that affect the immune system [1], these patients are at high risk of influenza-related complications, including pneumonia, sepsis, central nervous system disorders and acute graft rejection [2-5]. The World Health Organization, the Advisory Committee on Immunization Practices and the American Society of Transplantation/Transplant Surgeons recommend annual administration of the seasonal inactivated influenza vaccine in post-transplant recipients [6]. Several previous reports have evaluated influenza vaccination in post-liver transplantation adults [7-10] and children [11-13]. We also previously reported safety and immunogenicity of influenza vaccination administered to pediatric living donor liver transplant recipients for four seasons [14, 15]. Although these reports support the safety of inactivated influenza vaccine, evidence about its effectiveness is not conclusive. Safety and effectiveness depend on various factors, such as immune status of recipients, recipient's age, type of vaccine and inoculation method. In terms of age group, the summary efficacy of inactivated influenza vaccines in children was shown to be less than that in adults in a systematic review with meta-analyses of controlled trials [16]. Clarifying the differences between adult and pediatric recipients may provide useful information for planning of additional strategies to prevent influenza in pediatric recipients. Because there are fewer studies of influenza vaccination in pediatric than in adult transplant recipients, assessment, and comparison of safety and immunogenicity of trivalent inactivated influenza vaccine between adult and pediatric living donor liver transplant patients in a single hospital is valuable. Moreover, the vaccine administered in our country included identical influenza antigens through the 2010–11 and 2011–12 seasons, allowing evaluation of long-term persistence of antibody responses and the contribution of preceding vaccinations to boosting responses.

PATIENTS AND METHODS

  1. Top of page
  2. ABSTRACT
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. ACKNOWLEDGMENT
  7. DISCLOSURE
  8. REFERENCES

Study design

During the 2010–11 and 2011–12 influenza seasons, adult (≥16 years) and pediatric (<16 years) living donor liver transplant recipients were enrolled in this study. All recipients were followed up at the Nagoya University Graduate School of Medicine. Information about each participant's underlying illness was collected by reviewing their medical records. Recipients were advised to receive the influenza vaccination if 12 months had elapsed since transplantation. Exclusion criteria for the study were interval of less than 6 months since acute rejection treatment and allergy to egg proteins. Before vaccination, serum concentrations of immunoglobulin A, M and G were measured in all patients and found to be within the normal range. Each vaccine dose was administered as an s.c. injection according to the guidelines in Japan. Patients aged <13 years were given two doses and those aged >13 years one dose of the vaccine. In the 2010–11 season, the doses were 0.2 mL for patients aged 1–5 years, 0.3 mL for those aged 6–12 years (two doses 2–4 weeks apart) and 0.5 mL for those aged ≥13 years. In the 2011–12 season (the guidelines changed between seasons), the doses were 0.25 mL for patients aged 1–3 years; 0.5 mL for those aged 3–12 years (two doses) and 0.5 mL for patients aged ≥13 years. Blood samples for HI testing were obtained at baseline and 4–6 weeks after vaccination (for those who had received one dose of vaccine) or 6–10 weeks after the first vaccination (for those who had received two doses of vaccine). The study design and purpose was approved by the institutional review board of Nagoya University and fully explained to all patients and/or guardians, and informed consent was obtained prior to enrollment.

Sixteen adult and 15 pediatric living donor liver transplant recipients in the 2010–11 season, and 53 adults and 21 children in the 2011–12 season met the above eligibility criteria. Of the 53 adults investigated in the 2011–12 season, 20 had received the same influenza vaccination in the preceding season (2010–11 and 2011–12). Of the 21 children investigated in the 2011–12 season, 13 had received the same influenza vaccination in the preceding season (2010–11 and 2011–12). Therefore, 20 adult and 13 pediatric patients who had received a vaccination in the former influenza season were evaluated for vaccine efficacy over both seasons.

Vaccines

The trivalent influenza vaccine used was derived from A/California/7/2009pdm (H1N1), A/Victoria/210/2009 (H3N2), and B/Brisbane/60/2008. The antigens included in the vaccine were identical over the two influenza seasons. The commercial vaccines (Kitasato Institute Research Center for Biologicals, Saitama, Japan in the 2010–11 season, and Kaketsuken, Kumamoto, Japan in the 2011–12 season) were unadjuvanted, inactivated, split-virus vaccines containing >15 µg of hemagglutinin antigen per 0.5 mL.

Safety assessment

Information regarding the safety of each vaccine was collected at 4 weekly intervals for 6 months post-vaccination. Serum hepatobiliary enzymes were measured as markers of acute allograft rejection. All subjects were assessed for acute febrile illness (>38.0°C) and influenza virus infection was checked for by viral antigen testing (QuickNavi-Flu; Denka-Seiken, Tokyo, Japan) of nasopharyngeal swabs obtained during each acute febrile illness.

Immunogenicity assessment

Influenza-specific HI antibodies for the three influenza strains included in the vaccine were measured at a commercial laboratory (SRL, Tachikawa, Japan). Immunogenicity was evaluated in three ways: seroprotection rates, defined as the percentage of subjects achieving an HI titer ≥40; seroconversion rates, defined as the percentage of subjects achieving at least a fourfold increase in HI titers from seropositive prevaccination titer (≥10) or rise from <10 to ≥40 in those who were seronegative prevaccination; and HI GMT to each influenza antigen at baseline and post-vaccination.

Statistical analysis

Statistical significance for sex, seroprotection rate, and seroconversion rate was assessed by the X2 test or Fisher's exact test (for small samples). For results expressed as median (age, follow-up years, trough concentration of FK506 and geometric mean titer), statistical analysis was performed with the Mann–Whitney U-test. For univariate analysis, the X2 test was used to compare categorical variables. Logistic regression was used for multivariate analysis. A P-value ≤ 0.05 was considered statistically significant. All statistical analyses were performed using SPSS statistics version 20 (IBM, Armonk, NY, USA).

RESULTS

  1. Top of page
  2. ABSTRACT
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. ACKNOWLEDGMENT
  7. DISCLOSURE
  8. REFERENCES

Patient characteristics

Sixteen adult and 15 pediatric living donor liver transplant recipients were studied in the 2010–11 season, and 53 adults and 21 children in the 2011–12 season. Patient characteristics are summarized in Table 1. Many patients were being maintained on tacrolimus-based immunosuppressive regimens. A few patients were also receiving mycophenolate mofetil, prednisolone, azathioprine and cyclosporine. The subjects had no history of anaphylactic reactions to vaccines or eggs. In terms of comorbidities, one (6%) and nine (17%) adult recipients in each season had diabetes mellitus.

Table 1. Clinical characteristics of subjects receiving influenza vaccine
Characteristic2010–11 season2011–12 season
Adults (n = 16)Children (n = 15)P-valueAdults (n = 53)Children (n = 21)P-value
  • FK 506, tacrolimus; MMF, mycophenolate mofetil; PSL, prednisolone.

  • Bolded values are statistically significant (P ≤ 0.05).

  • other includes Alagille syndrome, alcoholic liver cirrhosis, autoimmune hepatitis, congenital hepatic fibrosis, congenital hypoplasia of the portal vein, hepatoblastoma, liver metastasis of pancreatic solid pseudopapillary tumor, ornithine transcarbamylase deficiency, primary sclerosing cholangitis and Wilson disease.

  • other includes FK 506 and PSL, FK 506 and interferon β-1b, FK 506 and methylprednisolone, FK 506 and MMF and hydrocortisone, or cyclosporine and MMF.

  • §

    X2 test.

  • Mann–Whitney U-test.

Male, n (%)5 (31%)8 (53%)0.213§22 (42%)10 (48%)0.632§
Age in years at vaccination, median (range)53.7 (16.3–70.0)6.4 (2.6–13.8) 56.0 (17.3–71.0)5.9 (1.7–14.8) 
Years since transplantation, median (range)6.2 (3.8–13.3)3.7 (1.1–12.4)0.0215.8 (1.0–23.2)3.0 (1.1–13.4)0.006
Reason for transplantation
Primary biliary cirrhosis40 110 
Biliary atresia313 817 
Hepatitis C30 100 
Fulminant hepatitis20 40 
Hepatitis B10 130 
Other32 74 
Immunosuppressive therapy, n
FK 506512 2518 
FK 506 and MMF31 100 
FK 506 and MMF and PSL30 81 
FK 506 and PSL and azathioprine20 10 
Cyclosporine11 60 
Other21 32 
Trough concentrations of FK 506 in ng/mL; median (range)3.9 (0.6–7.3)2.4 (0.9–6.8)0.0514.8 (0.1–9.1)2.5 (0.6–5.2)<0.001

Safety evaluation

Acute allograft rejection occurred in none of the recipients during the 2010–11 season and in one pediatric recipient during the 2011–12 season. The number of patients with rejection did not differ significantly between adult and pediatric recipients in the 2011–12 season (P = 0.284). In the 2010–11 season, a 4-year-old girl's AST and ALT concentrations increased to 297 and 262 IU/mL, respectively, one day after the first dose of vaccination. However, these values decreased spontaneously and she did not undergo a liver biopsy. In the 2011–12 season, a 2-year-old boy had a mild cough and his AST and ALT concentrations were 80 and 108 IU/mL, respectively, at the time of vaccination. Sixteen days after vaccination, his AST and ALT concentrations increased to 140 and 179 IU/mL, respectively, and he was diagnosed with acute allograft rejection by liver biopsy. He received steroid pulse therapy and did not receive the second vaccination.

Immunogenicity

Immunological responses to influenza vaccine are summarized in Table 2. No significant differences in seroconversion rate or GMT fold increase were observed between adult and pediatric groups in each season. However, adult H1N1 pre-seroprotection rates in the 2010–11 season and post-seroprotection rates in the 2011–12 season were significantly higher than those in the pediatric group. The GMT of all three antigens before vaccination and H1N1 GMT after vaccination in the adult group were significantly higher than in the pediatric group in the 2011–12 season. Interestingly, 20/53 adult and 13/21 pediatric recipients were vaccinated in both seasons with the same vaccine. This allowed comparison of immunogenicity in each season for both patient groups (Table 3). The number of patients who received two consecutive vaccinations did not differ significantly between the adult and pediatric groups (P = 0.059). In the adult group, GMT fold increases in all three antigens in the recipients who received two consecutive vaccinations were significantly lower than in those who did not receive vaccination in the 2010–11 season. In contrast, in the pediatric recipients, there were no significant differences between the groups who had and had not received preceding vaccination. Of the recipients who received vaccination in both seasons, 11/20 adults and 8/11 children underwent examination of HI antibody titers pre- and post-vaccination through both seasons. Kinetics of their titers are shown in Fig. 1.

Table 2. Immunologic responses to influenza vaccine over two influenza seasons
 2010–11 season2011–12 season
Adults (n = 16)Children (n = 15)P-valuesAdults (n = 53)Children (n = 21)P-values
  • Bolded values are statistically significant (P ≤ 0.05).

  • X2 test.

  • Fisher's exact test.

  • §

    Mann–Whitney U-test.

H1N1
Seroprotection rate (pre)12 (75%)4 (27%)0.00729 (55%)6 (29%)0.069
Seroprotection rate (post)15 (94%)12 (80%)0.27543 (81%)12 (57%)0.033
Seroconversion rate8 (50%)10 (67%)0.34722 (42%)7 (33%)0.516
GMT pre47.618.20.138§37.013.90.015§
GMT post217.0116.00.436§142.238.70.004§
GMT fold increase4.66.40.654§3.82.80.530§
H3N2
Seroprotection rate (pre)3 (19%)5 (33%)0.30319 (36%)4 (19%)0.159
Seroprotection rate (post)11 (69%)10 (67%)0.60239 (74%)12 (57%)0.168
Seroconversion rate9 (56%)6 (40%)0.36623 (43%)9 (43%)0.966
GMT pre12.415.90.560§22.810.30.014§
GMT post95.166.50.380§70.238.70.135§
GMT fold increase7.74.20.338§3.13.70.506§
B
Seroprotection rate (pre)2 (13%)6 (40%)0.09020 (38%)3 (14%)0.049
Seroprotection rate (post)8 (50%)4 (27%)0.18339 (74%)15 (71%)0.851
Seroconversion rate6 (38%)2 (13%)0.13017 (32%)9 (43%)0.381
GMT pre10.415.90.466§21.110.30.007§
GMT post29.517.40.252§51.338.70.275§
GMT fold increase2.81.10.054§2.43.70.069§
Table 3. Immunologic responses to the influenza vaccine in patients receiving identical vaccinations in two consecutive seasons
 AdultsChildrenAdults versus children
2010/11–11/12 (n = 20)2011/12 (n = 33)P-value2010/11–11/12 (n = 13)2011/12 (n = 8)P-value2010/11–11/12
P-value
  • GMT, geometric mean titer.

  • Bolded values are statistically significant (P ≤ 0.05).

  • Recipients who received consecutive influenza vaccine over the two seasons.

  • Recipients who received influenza vaccine exclusively in the 2011–12 season.

  • §

    Mann–Whitney U-test.

  • X2 test.

  • ||

    Fisher's exact test.

Age in years at vaccination, median (range)58.0 (17.3–71.0)54.7 (18.8–69.3)0.869§7.1 (3.6–14.8)2.7 (1.7–10.3)0.006§ 
Trough concentration of FK 506 in ng/mL; median (range)4.6 (1.8–9.1)4.8 (0.1–8.6)0.796§2.1 (0.9–3.7)3.9 (0.6–5.2)0.045§<0.001§
H1N1
Seroprotection rate (pre)13 (65%)16 (49%)0.2425 (39%)1 (13%)0.221||0.135
Seroprotection rate (post)15 (75%)28 (85%)0.295||9 (69%)3 (38%)0.166||0.509||
Seroconversion rate5 (25%)17 (52%)0.0584 (31%)3 (38%)0.557||0.509||
GMT pre54.629.20.137§21.17.10.089§0.087§
GMT post98.5177.70.117§49.525.90.374§0.281§
GMT fold increase1.86.10.008§2.33.70.500§0.478§
H3N2
Seroprotection rate (pre)8 (40%)11 (33%)0.6244 (31%)0 (0%)0.119||0.436||
Seroprotection rate (post)13 (65%)26 (79%)0.27010 (77%)2 (25%)0.029||0.371||
Seroconversion rate6 (30%)17 (52%)0.1267 (54%)2 (25%)0.201||0.171
GMT pre28.320.00.425§16.25.00.045§0.265§
GMT post47.688.90.235§58.120.00.030§0.813§
GMT fold increase1.74.40.027§3.64.00.697§0.068§
B
Seroprotection rate (pre)9 (45%)11 (33%)0.3962 (15%)1 (13%)0.684||0.081||
Seroprotection rate (post)13 (65%)26 (79%)0.27010 (77%)5 (63%)0.410||0.371||
Seroconversion rate3 (15%)14 (42%)0.0385 (39%)4 (50%)0.472||0.132||
GMT pre18.722.70.751§11.19.20.414§0.118§
GMT post31.469.10.031§40.036.70.750§0.730§
GMT fold increase1.73.00.039§3.64.00.804§0.033§
image

Figure 1. HI antibody titers against H1/H3/B pre- and post-influenza vaccination in adult and pediatric living donor liver transplant recipients in the 2010–11 and 2011–12 influenza seasons. Serum samples for HI tests were obtained from 11 adults and 8 children.

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In the 2011–12 season, factors associated with seroprotection were assessed in 74 patients (53 adults and 21 children). Univariate analysis showed that being an adult and number of years since transplantation were significantly correlated with seroprotection. However, this finding was not significant according to multivariate analysis (Table 4). Factors associated with seroprotection or seroconversion in the 2010–11 season, and those associated with seroconversion rate in the 2011–12 season were also assessed. No significant factors were found by multivariate analysis (data not shown).

Table 4. Factors associated with seroprotection in the 2011–12 season
FactorNo. of patients (with factor/total)No. of patients (with seroprotection/with factor; %)Univariate analysisMultivariate analysis
OR (95% CI)P-valueOR (95% CI)P-value
  • CI, confidence interval; FK 506, tacrolimus; OR, odds ratio.

  • Bolded values are statistically significant (P ≤ 0.05).

  • Median.

H1N1
Group (adult)53/7443/53 (81.1)3.23 (1.07–9.73)0.0333.23 (1.07–9.73)0.038
Vaccine schedule (1 dose)55/7444/55 (80.0)2.91 (0.94–8.96)0.057  
Follow up years after transplantation (>5.4 years)38/7432/38 (84.2)3.01 (1.00–9.11)0.045  
FK 506 trough (>4.2 ng/mL)33/6727/33 (81.8)2.15 (0.69–6.73)0.186  
H3N2
Group (adult)53/7439/53 (73.6)2.09 (0.73–6.02)0.168  
Vaccine (1 dose)55/7440/55 (72.7)1.94 (0.65–5.75)0.228  
Follow up years after transplantation (>5.4 years)38/7428/38 (73.7)1.58 (0.59–4.27)0.363  
FK 506 trough (>4.2 ng/mL)33/6724/33 (72.7)1.46 (0.51–4.12)0.479  
B
Group (adult)53/7439/53 (73.6)1.11 (0.36–3.44)0.851  
Vaccine (1 dose)55/7441/55 (74.5)1.35 (0.43–4.23)0.604  
Follow up years after transplantation (>5.4 years)38/7428/38 (73.7)1.08 (0.39–3.01)0.887  
FK 506 trough (>4.2 ng/mL)33/6724/33 (72.7)0.82 (0.27–2.47)0.725  

Surveillance for influenza virus infection

During the post-vaccination period, five pediatric recipients were diagnosed with influenza in the 2010–11 season; viral antigen testing showed that one was infected with type A and four with type B. Three pediatric recipients were infected with influenza in the 2011–12 season; two with type A and one with type B. In contrast, no adult recipient was diagnosed with influenza during either season. There were significant differences between the two groups in the number of influenza patients after vaccination in both seasons (P = 0.018 in the 2010–11 season and P = 0.021 in the 2011–12 season). All influenza patients were treated with oseltamivir or zanamivir and recovered without serious complications.

DISCUSSION

  1. Top of page
  2. ABSTRACT
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. ACKNOWLEDGMENT
  7. DISCLOSURE
  8. REFERENCES

Previous reports have demonstrated the effectiveness of inactivated influenza vaccine for liver transplant recipients. However, evidence concerning immunological responses to influenza vaccination in liver transplantation recipients is still not conclusive. Several reports have demonstrated benefits from influenza vaccination; seroprotection rates after vaccination in adult liver transplant patients were 91–92%/77–92%/68–95% for H1N1/H3N2/B respectively [7, 8], and in pediatric recipients 38–75%/38–71%/23–75% for H1N1/H3N2/B, respectively [12-15]. GMTs after vaccination in adults were 52–192/56–190/22–55 for H1N1/H3N2/B, respectively [8-10], and titers in children were 57–119/26–98/13–69 for H1N1/H3N2/B, respectively [13-15]. GMT fold increases after vaccination in adults were 1.9–10.6/2.4–8.1/2.4–9.3 for H1N1/H3N2/B, respectively [7, 9, 10], and in children 1.3–2.1/1.5–2.6/1.0–3.0, respectively [13, 15]. In the present study, seroprotection rates were 50–94% to all three antigens among adults and 27–80% among children in both seasons. GMT fold increases after vaccination were 2.8–7.7 for all three antigens in adults and 2.4–3.8 in children. These results are similar to the above-mentioned previous results, suggesting that inactivated influenza vaccine was effective in the two seasons studied in our hospital. In addition, although the cited previous studies did not compare data between adult and pediatric liver transplant recipients in a single study, antibody responses in adult recipients appear to be higher than in pediatric recipients. Mack et al. reported that younger age and shorter post-transplant time are risk factors for poor vaccine response [11]. The present study was carried out in a single hospital with the same vaccine and may therefore provide more definitive information regarding differences between adult and pediatric liver transplant recipients. Our data show that immunogenicity of influenza vaccination to adult living donor liver transplant recipients was generally not significantly higher in comparison with pediatric recipients in either the 2010–11 or the 2011–12 season.

However, our study has some limitations. First, because healthy controls were not included, we could not compare recipients with healthy controls. Second, the study included relatively few patients.

The virus strains in the 2011–12 seasonal influenza vaccine were identical to those in the 2010–11 vaccine. Therefore, in this study, we were able to investigate long-term persistence of antibodies induced by influenza vaccine, and antibody responses in patients who had and had not been vaccinated in the preceding year. Annual repeated vaccination may have a cumulative effect and be a confounding factor in the magnitude and duration of antibody reactions; however, such effects are difficult to analyze. Several reports have demonstrated that post-vaccination antibody titers decline over the course of a year in both healthy children and adults [17-19]. Otherwise, there are few studies concerning persistence of influenza vaccine-induced antibodies in solid organ transplant patients [20-22]. Moran et al. reported that post-immunization antibody titers among healthy adult controls were higher than in adult lung transplant recipients; however, few differences in antibody titers were observed 11 months after vaccination in these adult recipients [20]. In particular, about 70% of recipients maintained seroprotective antibody concentrations to most vaccine antigens. In contrast, Cordero et al. reported detection of long-term antibody titers to previous vaccination in 30% of recipients aged ≥15 years [21]. In the present study, pre-vaccination seroprotection rates in adult patients were 45–65% and GMT 18.7–54.6 to the three antigens. Unexpectedly, GMT fold increases of all three antigens in recipients who received two consecutive vaccinations were significantly lower than in recipients who had not been vaccinated in the previous season. This result may be attributable to relatively high pre-vaccination titers to both H1 and H3 antigens; however, the reason for this finding is not clear. Moreover, there were no significant differences in general antigen responses between the adult and pediatric groups who had received preceding vaccinations. Long-term responses to preceding vaccinations were insufficient in our adult and pediatric liver transplantation recipients in that they did not contribute to boosted responses. Immune-enhancing vaccine strategies, such as high-dose vaccines [23, 24], booster dose re-vaccination [25] or adjuvanted vaccines [26, 27] should be considered.

We consider the incidence of influenza infection after vaccination the most important indicator of the effectiveness of the vaccine. In the present study, 5/15 and 3/21 pediatric liver transplant recipients were infected with influenza in the 2010–2011 2011–12 season, respectively, whereas no adult recipient was infected. Thus, there was a significant difference between pediatric and adult patients in the frequency of influenza. Madan et al. demonstrated that cell-mediated immune responses to influenza vaccination are diminished in pediatric liver transplant recipients, whereas seroprotection and seroconversion rates are similar to those in healthy siblings [12]. Although cell-mediated immune responses to influenza vaccination have not been shown in adult recipients, it is possible that they are weaker in pediatric than in adult recipients. This may affect the morbidity rate of influenza after vaccination. Further studies are needed to clarify differences in incidence of influenza between pediatric and adult recipients.

In conclusion, in this single hospital study, adult and pediatric liver transplant recipients generated immune responses to inactivated seasonal influenza vaccine and no significant differences were seen between adult and pediatric liver transplant recipients in immunogenicity of influenza vaccination over two influenza seasons. Long-term persistence and contribution to a boosted response were insufficient in both recipient groups. The number of patients with severe adverse reactions did not differ significantly between the two recipient groups. Immune-enhancing vaccine strategies for liver transplant recipients should be considered in future.

ACKNOWLEDGMENT

  1. Top of page
  2. ABSTRACT
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. ACKNOWLEDGMENT
  7. DISCLOSURE
  8. REFERENCES

This work was not supported by any funding source.

REFERENCES

  1. Top of page
  2. ABSTRACT
  3. PATIENTS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. ACKNOWLEDGMENT
  7. DISCLOSURE
  8. REFERENCES
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