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Original Article
Immunity to hepatitis A virus in liver transplant recipients: A population-based study in Iran
Inmunidad al virus de la hepatitis A en receptores de trasplante de hígado: un estudio poblacional en Irán
Ahamd Rashidia, Fatemeh Sedaghata, Amirali Nejata, Negar Azarpiraa,
Corresponding author
azarpiran@sums.ac.ir

Corresponding author.
, Alireza Shamsaeefarb, Koroush Kazemib, Maryam Moinic,d
a Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
b Shiraz Transplant Center, Abu Ali Sina Hospital, Shiraz University of Medical Sciences, Shiraz, Iran
c Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
d Division of Gastroenterology, Toronto General Hospital, University of Toronto, Canada
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Hepatitis A infection is a self-limited acute viral infection of the liver with an oral-fecal route of transmission&#46; At-risk populations include individuals from endemic regions &#40;India&#44; Africa&#44; and the Middle-East&#41;&#44; infants and children&#44; people living in poorly sanitized conditions&#44; and men who have sex with men &#40;MSM&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">1</span></a> The hepatitis A virus &#40;HAV&#41; has a worldwide distribution with over 1&#46;4 million cases of infection being reported annually&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">2</span></a> However&#44; more recent data suggest a declining rate of infection and a gradual change in epidemiological characteristics&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">3</span></a> Clinical manifestations can vary from a lack of symptoms with only abnormal liver biochemistry to presentations with general symptoms such as nausea&#44; vomiting&#44; and jaundice&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">4</span></a> In its most severe form&#44; acute hepatitis A can lead to liver failure requiring transplantation&#44; which is rare and occurs in less than 1&#37; of cases&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">5</span></a> Mortality from acute HAV infection is seen mainly in older patients and subjects with chronic liver disease&#46;<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">4&#44;6</span></a> The initial antibody response to the HAV infection consists of developing immunoglobulin &#40;Ig&#41; M&#44; IgA&#44; and IgG antibodies&#46; However&#44; the IgG antibody is the major class of antibodies detected during the recovery phase&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">7</span></a> Anti-HAV IgG frequently remains detectable for several decades after acute infection&#44; providing lifelong immunity against reinfection&#46;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">7&#8211;9</span></a> Acute and chronic liver diseases in their most severe and end-stage forms are the main indications for liver transplantation&#46; The post-liver transplant survival rate has significantly increased in recent years due to the development of advanced surgical techniques besides improvements in post-transplant medical care and the successful management of postoperative complications&#44;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">10&#8211;12</span></a> with the one-year post-liver transplantation survival rate exceeding 85&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">13</span></a> To prevent graft rejection&#44; there is a need for prolonged immunosuppressive therapy following transplantation&#44; with greater intensity being required in the first few months&#59; this renders recipients of solid organ transplants vulnerable to different types of infections including viral infections&#46; It should also be noted that infections like hepatitis A and hepatitis E may mimic features of acute cellular rejection in liver transplant recipients&#46;<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">5&#44;14</span></a> Furthermore&#44; following transplantation&#44; the immunosuppressed status of the recipients may alter the kinetics and persistence of protective antibodies against different infections including hepatitis A regardless of whether the antibodies developed from natural infection or through vaccination&#46; Theoretically&#44; there could be a risk of Anti-HAV IgG antibody loss by strong anti-rejection regimens administered following liver transplantation as these immune-suppressing drugs&#44; including high-dose systemic steroids and mycophenolate mofetil&#44; may decimate some pools of memory B-cells&#46;<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">15&#44;16</span></a> Thus&#44; these patients may benefit from immunization against HAV under appropriate situations&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">17</span></a> In most developing countries&#44; a significant number of liver transplant candidates remain unvaccinated for HAV before transplantation because there is the conventional belief of universal natural and life-long immunity against the virus&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">18</span></a> However&#44; vaccination against hepatitis A for non-immune patients in both the pre- and post-liver transplantation phase may fulfill an important role in disease prevention and is recommended by the related guidelines&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">19</span></a> Therefore&#44; determining the HAV immune status of liver transplant recipients is essential as it allows the identification of non-immune patients at risk of infection&#44; thereby facilitating appropriate preventive management&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">The present study was performed to determine the immune status against hepatitis A in a population of unvaccinated liver transplant recipients from a large liver transplant center in Iran&#44; which is considered an endemic region for hepatitis A infection&#46; We also attempted to identify factors associated with natural immunity to hepatitis A in this population of patients&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Materials and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Patients and methods</span><p id="par0015" class="elsevierStylePara elsevierViewall">This cross-sectional study was performed on 261 patients above six years of age who underwent liver transplantation at Abu Ali Sina Organ Transplant Hospital in Shiraz&#44; Iran&#46; Patients were transplanted between January 2014 and December 2016&#46; Immunity to HAV was checked in the post-transplantation follow-up visits between January and April 2017&#44; with a mean follow-up time of 24<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10 months&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Approval for the study was obtained from the Ethics Committee of Shiraz University of Medical Sciences &#40;IR&#46;SUMS&#46;REC&#46;1397&#46;483&#41; and all participants gave written informed consent before participating&#46; Subjects who wished to discontinue taking part in the study at any time were excluded&#46; Baseline data were extracted from the transplantation unit database&#46; Furthermore&#44; information about variables including age&#44; gender&#44; the underlying liver disease leading to transplantation&#44; MELD&#47;PELD scores&#44; socioeconomic status &#40;residential area&#44; ownership of residential place&#44; and monthly income&#41;&#44; education level&#44; and source of drinking water &#40;tap water&#44; bottled water&#44; or well water&#41; was gathered through a questionnaire&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">For laboratory testing&#44; 5<span class="elsevierStyleHsp" style=""></span>ml of the venous blood was taken through venipuncture from each participant under sterile conditions&#46; Centrifugation was done and the sera were isolated and stored at &#8722;20<span class="elsevierStyleHsp" style=""></span>&#176;C&#46; Immunity against hepatitis A was assessed by checking the total HAV antibody level using the DIA&#46;PRO Diagnostic Bioprobes Srl Total HAV Ab kit &#40;Milano&#44; Italy&#41;&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Statistical analysis</span><p id="par0030" class="elsevierStylePara elsevierViewall">For statistical analysis&#44; Statistical Package for Social Sciences &#40;SPSS&#41; version 22&#46;0 &#40;IBM SPSS Statistics for Windows&#44; Armonk&#44; NY&#58; IBM Corp&#41; was used&#46; Results were presented as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviation &#40;SD&#41; for quantitative variables and were summarized as absolute frequencies and percentages for categorical variables&#46; The normality of data distribution was analyzed using the Kolmogorov&#8211;Smirnov test&#46; Categorical variables were compared using the chi-squared test or Fisher&#39;s exact test&#44; while quantitative variables were compared with the <span class="elsevierStyleItalic">t</span>-test or Mann&#8211;Whitney <span class="elsevierStyleItalic">U</span> test&#46; Due to the scarcity of responses&#44; the standard deviation was overestimated&#46; Hence&#44; to evaluate the moderated effect of various factors on hepatitis A immunity&#44; the Fierth method was used instead of the usual logistic regression method&#46; Odds ratios &#40;ORs&#41; were calculated to investigate the power of communication&#46; The enter method was applied in the multivariable model&#46; <span class="elsevierStyleItalic">P</span>-values of 0&#46;05 or less were considered statistically significant&#46;</p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Results</span><p id="par0035" class="elsevierStylePara elsevierViewall">Of 261 patients initially assessed for immunity against hepatitis A&#44; 19 failed to fill the study questionnaire and were thus excluded from the study&#46; Among 242 cases who completed the study course&#44; 151 &#40;62&#46;39&#37;&#41; were male and 91 &#40;37&#46;61&#37;&#41; were female&#46; The mean MELD and PELD scores were 19<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;5 and 11&#46;25<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;5 respectively&#46; The patients&#8217; age range was from 8 to 74 years with a mean and SD of 43&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14&#46;1 years&#46; The most common causes of transplantation were Crigler&#8211;Najjar syndrome and Wilson&#39;s disease in the pediatric group and hepatitis B and primary sclerosing cholangitis among the adult patients&#46; The patients who received liver transplantation for hepatocellular carcinoma were non-cirrhotic&#46; Immunity against hepatitis A was detected in 215 &#40;88&#46;84&#37;&#41; patients&#46; The mean age differed significantly between patients immune and non-immune to HAV &#40;46&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&#46;5 years and 24&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#46;8 years&#44; respectively&#59; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; The subjects were divided into three age groups&#58; 0&#8211;18 years &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>10&#41;&#44; 19&#8211;30 years &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>45&#41;&#44; and over 30 years of age &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>187&#41;&#59; immunity against hepatitis A was investigated separately in each group&#46; The rate of immunity against hepatitis A in the first&#44; second&#44; and third age groups was 40&#37;&#44; 60&#37;&#44; and 98&#37;&#44; respectively&#46; The minimum immunity rate was seen in patients below 18 years of age&#44; with the immunity rate against hepatitis A increasing with age &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">As shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#44; the immunity rate was univariately independent of patient gender &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;823&#41;&#44; area of residence &#40;urban&#58; 87&#46;8&#37;&#44; rural&#58; 94&#46;4&#37;&#59; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;389&#41;&#44; ownership of residential place &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;715&#41;&#44; monthly income &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;173&#41;&#44; and source of drinking water &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;771&#41;&#46; However&#44; the rate of immunity showed an inverse relationship with the level of education &#40;illiterate&#58; 100&#37;&#59; undergraduate&#58; 95&#46;5&#37;&#59; diploma&#58; 93&#46;6&#37;&#59; academic degree&#58; 69&#46;4&#37;&#59; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; The immunity rate was significantly different among different indications of liver transplantation &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#44; with the lowest immunity rate &#40;33&#46;3&#37;&#41; being found among the three patients with Crigler&#8211;Najjar syndrome&#44; followed by an immunity rate of 54&#46;5&#37; among 11 patients who had Wilson&#39;s disease &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; Crigler&#8211;Najjar syndrome and Wilson&#39;s disease were common indications of liver transplantation in our pediatric population of patients but not among the adults&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">In the multivariable logistic regression model&#44; younger age &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;175&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; and higher education level &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#46;142&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;040&#41; represented the two main determinants of HAV non-immune status in our population of patients &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Discussion</span><p id="par0050" class="elsevierStylePara elsevierViewall">According to the universal survey conducted by the World Health Organization &#40;WHO&#41; in 2009&#44; there has been a significant decline in HAV infection rates among children and young adults worldwide&#46; This is while greater susceptibility to HAV infection is expected during adulthood if there is less exposure to the virus during childhood&#46;<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">20&#44;21</span></a> As a developing country&#44; Iran remains an intermediate-endemic area for HAV infection according to a WHO study that divided the whole globe into 21 divisions in terms of HAV epidemiology&#46;<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">20&#44;22</span></a> However&#44; based on the most recent local epidemiologic studies&#44; there might be a move toward low endemicity with improving socioeconomic status and hygiene&#44; at least in some parts of the country&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">23</span></a> In high-endemic areas&#44; mass vaccination is not recommended as most individuals develop natural immunity to hepatitis A secondary to asymptomatic childhood exposure&#46; For countries transitioning from high to intermediate endemicity&#44; a considerable percentage of the adult population possesses no history of exposure to the virus and remain non-immune&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">24</span></a> In such countries&#44; the inclusion of the hepatitis A vaccine in large-scale vaccination programs seems to be reasonable and cost-effective for disease prevention beyond childhood&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">24</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">Hepatitis A vaccination is also recommended in high-risk individuals including patients with chronic liver disease and recipients of organ transplantations&#46; In patients with chronic liver disease&#44; the incidence of hepatitis A infection does not rise&#44; though these patients are at risk of a complicated clinical course &#40;fulminant hepatitis and even death&#41; upon exposure&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">25</span></a> It has been proven that the immunologic response to vaccination against HAV decreases with the progression of chronic liver disease&#46; In compensated liver disease&#44; the immune response to vaccination is comparable to that of healthy individuals&#46; However&#44; the rate of response declines with the progression of liver disease&#44; and response rates as low as 26&#37; have been reported with advanced liver disease in comparison with 99&#37; in the normal population&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">26</span></a> The seroprevalence of hepatitis A has been evaluated in normal populations&#59; however&#44; data on patients undergoing liver transplantation is limited&#44; especially in the early pre-operation period&#46; It is still unclear whether high pre-transplant serum HAV IgG levels predict protection against hepatitis A infection after transplantation&#46;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">7&#44;9</span></a> Currently&#44; pre-transplant vaccination for the prevention of post-transplant hepatitis A infection is recommended due to its high safety and efficacy&#46;<a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">27&#44;28</span></a> However&#44; the vaccine-related longevity of protection in such patients has not exclusively been studied&#46; In a study from the United States done in 2000&#44; Arslan et al&#46; reported HAV IgG loss rates of 18&#37; and 29&#37; among their patients one and two years after transplantation&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">17</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Reviewing the literature shows that immunity against hepatitis A infection is associated with several factors such as age&#44; water supply source&#44; level of sanitation&#44; and even ethnic background&#46; In the United States&#44; the seroprevalence of the hepatitis A antibody is higher among males than females&#44; among older patients than the younger&#44; and among Hispanic population than African Americans and whites&#46;<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">29&#44;30</span></a> In our study&#44; the rate of immunity against HAV among recipients of liver transplantation was around 88&#37;&#46; Vaccination against hepatitis A is not routinely done in Iran and the vaccine is not administered to cirrhotic patients and liver transplant candidates&#46; Hence&#44; this immunity rate of 88&#37; represents the natural immunity in our population of patients&#46; As expected&#44; the immunity rate against hepatitis A was variable among different age groups&#46; In the population of pediatric liver recipients&#44; 40&#37; were immune to hepatitis A&#44; while among young adults aged between 19 and 30 years&#44; the immunity rate was 60&#37;&#46; This shows that 60&#37; of pediatric and 40&#37; of young adult liver transplant recipients aged below 30 years are susceptible to hepatitis A infection&#46; This is very important as this susceptible population becomes immunosuppressed following the administration of post-liver transplant medications&#46; High rates of susceptibility to infection are perhaps even more alarming in adult recipients as a more severe clinical disease is expected following acute hepatitis A&#46; In a recent nationwide study by Bagheri Lankarani et al&#46;&#44; the hepatitis A immunity rate in Iran was shown to be 82&#46;6&#37; by the age of 29 years&#44; which is higher than that of our patients within the same age group&#46; In their nationwide study&#44; they showed an immune rate of 41&#46;1&#37; in children by the age of 15 years&#44; which is comparable to our result of 40&#37; immunity in children under the age of 18 years&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">31</span></a> In another study by Izadi et al&#46; on Iranian soldiers aged 18&#8211;34 years&#44; an immunity rate of 80&#46;3&#37; was reported&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">32</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">In this study&#44; we also showed that the rate of immunity increases with age&#44; which is expected due to the increased chance of exposure to the virus over time&#46; However&#44; no significant difference was observed in the rate of immunity to hepatitis A between male and female patients&#59; this is while some studies describe a higher immunity rate among men&#46; In a study from the United States&#44; the rate of immunity to hepatitis A was about 20&#37; more among men than women&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">17</span></a> As another determinant for the rate of immunity against hepatitis A&#44; those with lower education levels showed increased rates of immunity against HAV&#44; representing a higher rate of previous exposure to the virus in this group of patients&#46; Merat et al&#46; presented a similar finding from their study on HAV immune status in three large cities of Iran&#46; They showed a significant correlation between a higher level of paternal education and the non-immune status against hepatitis A in their pediatric population of patients&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">20</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Multiple similar studies have been conducted on the subject of hepatitis A immune status of recipients of liver transplants&#46; In a study from Spain in 2008 by Aoufi et al&#46;&#44; the rate of immunity against HAV was reported to be 93&#46;3&#37; among cirrhotic patients being evaluated for liver transplantation&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">33</span></a> In another study from the same center in 2012 by Guti&#233;rrez Domingo et al&#46; on a larger population of candidates for liver transplantation&#44; a similar rate of immunity was reported &#40;91&#46;8&#37; immunity&#59; 8&#46;2&#37; non-immunity&#41;&#46; In that study&#44; patients in the non-immune group shared the characteristics of being younger&#44; non-diabetic&#44; non-alcoholic&#44; and negative for hepatitis B markers&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">34</span></a> Both study results represented lower HAV immunity rates in younger patients&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">From our study&#44; it was concluded that&#44; as expected&#44; the rate of immunity in younger recipients of liver transplants is significantly lower relative to older patients&#46; The rate of non-immunity in our total patient population was detected as 11&#46;16&#37;&#46; However&#44; the rate of non-immunity against hepatitis A was found to be as high as 61&#46;1&#37; among patients younger than 22 years of age&#46; These findings show that a significant proportion of young liver transplant recipients in our center are at increased risk of HAV infection due to a lack of natural immunity against the virus&#46; This indicates the importance of preventive measures&#44; particularly hepatitis A vaccination&#44; in this population of patients as non-immune individuals possess a higher risk of serious complications following post-transplantation hepatitis A infection&#46; For the best results&#44; the advice on HAV vaccination could be generalized to the pre-transplantation period and even to patients with compensated cirrhosis before immediate transplantation becomes necessary&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">The main limitation of our study was the fact that it was conducted in a single center&#46; It should be noted&#44; however&#44; that our center is the largest and leading liver transplant center in the country&#44; accepting a high volume of liver transplant candidates from the whole country&#46; Furthermore&#44; our center dominates among a limited number of centers that perform pediatric liver transplantation&#46; Another limitation is the lack of information about the pre-transplant HAV immune status of our patients&#46; It is also important to note that the underlying liver disease leading to transplantation may differ from other countries given the lack of alcohol-related liver disease in our patient population&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Conclusion</span><p id="par0085" class="elsevierStylePara elsevierViewall">This study found a considerable rate of non-immunity to hepatitis A among younger recipients of liver transplants in our center&#46; Appropriate testing to measure HAV immune status is indicated in these patients&#44; preferably in the pre-transplantation period&#59; vaccination against hepatitis A should be considered for non-immune candidates&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conflicts of interest</span><p id="par0090" class="elsevierStylePara elsevierViewall">The authors declare no conflicts of interest&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Acute hepatitis A is usually a self-limited viral disease but can be severe and even fatal in special groups of patients including those with chronic liver disease and recipients of liver transplantation&#46; To take appropriate preventive measures&#44; it is important to determine the immune status against the hepatitis A virus in patients at risk of grave clinical outcomes following infection&#46; To assess the need for immunization against hepatitis A&#44; we aimed to determine the immune status against hepatitis A in a population of liver transplant recipients&#46; We also investigated the association between hepatitis A immune status and demographic factors such as age and sex&#44; underlying liver disease&#44; source of drinking water&#44; geographical area of residence and socioeconomic status&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">This cross-sectional study was performed on 242 recipients of allogenic liver transplants at Abu Ali Sina Organ Transplant Hospital in Shiraz&#44; Iran&#44; between January 2017 and April 2017&#46; The level of immunity was assessed using hepatitis A antibody detection kits&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The rate of immunity against hepatitis A was detected as 88&#46;8&#37; in our study population&#46; In the multivariable logistic regression model&#44; younger age &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#46;175&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; and higher education level &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#46;142&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;040&#41; were the main determinants of non-immune status&#46; However&#44; hepatitis A immunity was independent of gender&#44; monthly family income&#44; water supply source&#44; residential area and underlying liver disorder&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Although a significant proportion of liver transplant recipients in this study showed evidence of natural immunity to hepatitis A&#44; a considerable proportion of younger patients and those with a higher level of education were non-immune&#46; The results of this study signify the importance of screening for hepatitis A immunity in this at-risk population of patients and the need for vaccinating non-immune patients&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Antecedentes</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">La hepatitis A aguda suele ser una enfermedad viral autolimitada&#44; pero puede ser grave e incluso mortal en grupos especiales de pacientes&#44; incluidos aquellos con enfermedad hep&#225;tica cr&#243;nica y los receptores de un trasplante de h&#237;gado&#46; Para tomar las medidas preventivas adecuadas&#44; es importante determinar el estado inmunol&#243;gico frente al virus de la hepatitis A en pacientes con riesgo de sufrir resultados cl&#237;nicos graves despu&#233;s de la infecci&#243;n&#46; Para evaluar la necesidad de inmunizaci&#243;n contra la hepatitis A&#44; nuestro objetivo fue determinar el estado inmunol&#243;gico contra la hepatitis A en una poblaci&#243;n de receptores de trasplante de h&#237;gado&#46; Tambi&#233;n investigamos la asociaci&#243;n entre el estado inmunol&#243;gico de la hepatitis A y factores demogr&#225;ficos como la edad y el sexo&#44; la enfermedad hep&#225;tica subyacente&#44; la fuente de agua potable&#44; el &#225;rea geogr&#225;fica de residencia y el nivel socioecon&#243;mico&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">este estudio transversal se realiz&#243; en 242 receptores de trasplantes de h&#237;gado alog&#233;nicos en el hospital de trasplantes de &#243;rganos &#8220;Abu Ali Sina&#8221; en Shiraz&#44; Ir&#225;n&#44; entre enero de 2017 y abril de 2017&#46; El nivel de inmunidad se evalu&#243; mediante kits de detecci&#243;n de anticuerpos contra la hepatitis A&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">La tasa de inmunidad contra la hepatitis A se detect&#243; como 88&#44;8&#37; en nuestra poblaci&#243;n de estudio&#46; En el modelo de regresi&#243;n log&#237;stica multivariable&#44; la edad m&#225;s joven &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44;175&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; y el nivel de educaci&#243;n superior &#40;OR<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#44;142&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;040&#41; fueron los principales determinantes del estado no inmunitario&#46; Sin embargo&#44; la inmunidad contra la hepatitis A fue independiente del sexo&#44; el ingreso familiar mensual&#44; la fuente de suministro de agua&#44; el &#225;rea residencial y la enfermedad hep&#225;tica subyacente&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusi&#243;n</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Aunque una proporci&#243;n significativa de los receptores de trasplante de h&#237;gado en este estudio mostr&#243; evidencia de inmunidad natural a la hepatitis A&#44; una proporci&#243;n considerable de pacientes m&#225;s j&#243;venes y aquellos con un mayor nivel de educaci&#243;n no eran inmunes&#46; Los resultados de este estudio demuestran la importancia del cribado de la inmunidad contra la hepatitis A en esta poblaci&#243;n de pacientes en riesgo y la necesidad de vacunar a los pacientes no inmunes&#46;</p></span>"
        "secciones" => array:4 [
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            "identificador" => "abst0025"
            "titulo" => "Antecedentes"
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          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
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          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusi&#243;n"
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        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
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          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Immunity status against HAV &#40;hepatitis A virus&#41; in different age groups of liver transplant recipients&#46;</p>"
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      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Figure 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
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          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">The rate of immunity to hepatitis A in liver transplant recipients according to the type of underlying liver disease&#46; PBC&#44; primary biliary cholangitis&#59; HCV&#44; hepatitis C virus&#59; HBV&#44; hepatitis B virus&#59; PSC&#44; primary sclerosing cholangitis&#59; NASH&#44; non alcoholic steatohepatitis&#59; AIH&#44; autoimmune hepatitis&#59; HAV&#44; hepatitis A virus&#46;</p>"
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                  \t\t\t\t">46&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&#46;5&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;451&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">11&#46;25<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;5&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">10&#46;75<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;384&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">2 &#40;7&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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ISSN: 24443824
Original language: English
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