Aralık 2024

57-60

Mehmet AĞIN¹, Muhammet ASENA², Ahmet ORAL²

Departments of Pediatric ¹Gastroenterology, Hepatology and Nutrition and ²Pediatrics, Gazi Yaşargil Education and Research Hospital, Diyarbakır, Turkey

Giriş ve Amaç:Bazı otoimmün hastalıklarda rekombinant hepatit B virüsaşısına karşı yanıtın düşük olduğu bilinmektedir. Fakat bu konu hala tar-tışmalıdır. Çocuk popülasyonun %90-95’i hepatit B aşılamasına yanıt verir-ken, çölyak hastalarında bu oranın daha düşük olabileceği bildirilmektedir.Çalışmamızda çölyak hastalarında hepatit B virüs prevalansını, aşılanmışçölyak hastalarında aşı yanıt oranlarını tespit etmeyi amaçladık.Gereç ve Yöntem:Çalışmaya 2020 ile 2024 yılları arasında polikliniğe başvuran 2-18yaş aralığında 264 çölyak hastası ve 264 kontrol hastası alındı. Hastalardademografik, antropometrik özellikler, hepatit B serolojileri bakıldı. Hepatit Başılanma oranları ve aşı yanıtları belirlendi.Bulgular:Çalışmaya alınan has-taların 346’sı (%60.9) kadın ve 182’si (%39.1) erkek olup hastaların ortala-ma yaşı 10.83 ± 6.9 yıl idi. Hastaların tümünün, standart aşı takvimine göre,aşıları tam idi. Çölyak tanılı olguların 147’sinde (%55.6) aşı yanıtı var iken117’sinde (%44.3) aşı yanıtı yetersiz bulundu. Kontrol grubunda ise, olgula-rın 163’ünde (%61.7) aşı yanıtı var iken 101’inde (%38.2) aşı yanıtı yetersizidi. Çölyak grubunda 4 hastada hepatit B yüzey antijeni pozitifliği saptanır-ken kontrol grubunda sadece 1 hastada hepatit B yüzey antijeni pozitifliğisaptandı.Sonuç:Çölyak hastalarında kronik hepatit B virüsü taşıyıcılığınındaha fazla olduğu düşünüldüğünde, hepatit B virüsüne karşı bağışıklamanınönemi daha da artmaktadır. Bu nedenle tüm çölyak hastalarının aşılanmasonrası aşı yanıtının takip edilmesi ve aşı yanıtı gelişmeyen olguların tekraraşılama programına alınması büyük önem arz etmektedir.

Çölyak hastalığı, hepatit B, aşılanma

<p>Celiac disease (CD) is a chronic autoimmune systemic dis-ease caused by a T cell-mediated immune mechanism that istriggered by gluten contained in grains such as wheat, barley,and rye in genetically predisposed individuals. The frequencyof the disease varies geographically. The highest incidence isin countries where wheat is an important part of daily nutri-tion, such as Turkey, Western Europe, North America, andAustralia. Environmental, immunological, and genetic factorsplay a role in its pathogenesis (1-3).</p><p>The correlation between celiac disease and environmental factors other than gluten has not been fully elucidated yet.Also, inadequate breastfeeding during infancy, viral and oth-er infectious diseases, and smoking may contribute to theonset of the disease (4). Also, it is reported that hepatotropic viruses, together with gluten, may trigger pathophysiologicalprocesses that cause mucosal inflammation and autoimmuneevents during the disease (5).</p><p>Previous studies report that the frequency of chronic viralhepatitis in celiac patients is higher than in the normal pop-ulation (6,7). Also, vaccination against hepatitis B in child-hood is an effective and reliable means of protection againstwidespread hepatitis B virus (HBV) infections, however, ithas been reported that the vaccine response is lower in celiacpatients (5,8).</p><p>The purpose of the present study was to determine the prevalence of the hepatitis B virus in celiac patients and the hep-atitis B response rates in celiac patients vaccinated accordingto the standard vaccination schedule.</p>

<p><b>selection of Patients</b></p><p>The study included 264 patients who were diagnosed withceliac disease and 264 healthy children without celiac dis-ease who were followed up by the Health Sciences Universi-ty Diyarbakir Gazi Yaşargil Training and Research Hospital,Pediatric Gastroenterology Polyclinic between November2020 and December 2024. The ages of the patients includedin the study ranged from 2 to 18 years. Since it may affectthe antibody response, those with a systemic disease or thosereceiving treatment for systemic disease, those with anotherinflammatory or infectious disease, those with malignancy,those with renal failure, cardiac failure and liver failure, di-abetes mellitus, inflammatory bowel disease, and hemato-logical diseases were excluded from the study. In all groups,only patients who had received 3 doses of hepatitis B vaccinewere included in the study and patients who had receivedadditional doses or incomplete doses were excluded from thestudy.</p><p><b>Data Evaluation</b></p><p>Demographic data (i.e., age, sex), vaccination status, hepati-tis B surface antigen (HBsAg), and anti-HBsAg of all patientswere recorded. The endoscopic appearance and histopatho-logical data of the patients were documented.</p><p>Biochemical Measurements</p><p>Biochemical parameters were measured from antecubital ve-nous blood samples that were taken in the morning hoursfollowing an 8-hour fast.</p><p><b>Endoscopic Evaluation</b></p><p>Endoscopies of the patients were performed by using a Fu-jinon EG530WR endoscopy device at the Gazi Yasargil Ed-ucation and Research Hospital, Gynecology and PediatricsHospital Endoscopy Unit. Verbal and written consent wasobtained from the families before endoscopy. All patientswere fasted for 6 hours before endoscopy, and following localpharyngeal xylocaine anesthesia, the patients were sedatedwith 0.1 mg/kg midazolam and 1 mg/kg ketamine, and thenthe endoscopic procedure was performed. During endosco-py, the esophagus, stomach, and duodenum were examinedin detail and multiple biopsies were taken from different sitesfor the diagnosis of celiac disease, as previously reported.</p><p><b>Histopathological Evaluation</b></p><p>Endoscopically obtained esophageal, corpus, antrum, andduodenum biopsies were sent to the pathology laboratoryin 10% formaldehyde. Following routine tissue follow-upprocedures, paraffin-embedded tissue samples were cutinto 5-micron thicknesses, stained with routine hematox-ylin-eosin (H-E), and evaluated under a light microscope.Histopathological evaluation was performed according to theMarsh classification. The diagnosis of CD was based on thecharacteristic histological finding of increased intraepitheliallymphocytes, villous atrophy, and crypthyperplasia classifiedaccording to the standard classification proposed by Marsh(2,9)</p><p><b>Hepatitis B Serology</b></p><p>Hepatitis B surface antigen (HBsAg), hepatitis B surface an-tibody (anti-HBs), hepatitis B e-antigen (HBeAg), hepatitis Bvirus e-antibody (Anti-HBe), immunoglobuline M antibodyagainst hepatitis B core antigen (anti-HBc IgM), immunoglob-uline G antibody against hepatitis B core antigen (anti-HBcIgG), and when necessary antibodies against hepatitis deltavirus (Anti-HDV), HBV-DNA (Amplicor HBV MonitorTMtest, Roche Diagnostic Systems, Inc., Branchburg, NJ) wereinvestigated. Enzyme-Linked Immunosorbent Assay (ELISA)method was employed to evaluate HBsAg, HBeAg, anti-HBe,anti-HDV, anti-HCV, and anti-HIV tests in all patients, HBV-DNA was tested using quantitative polymerase chain reaction(PCR).</p><p>Seroconversion or antibody response was taken as anti-HBstiter > 10 IU/L. When the anti-HBs titer was < 10 IU/L, it wasaccepted as unresponsive or seroconversion negative.</p><p><b>Ethics Statement</b></p><p>All participants provided written consent to participate in thestudy. Ethical approval for the study was obtained from ourhospital’s Ethics Committee (No: 287, Diyarbakır, Turkey).All procedures followed the ethical standards of our institu-tion’s human experimentation committee and the Declarationof Helsinki. Written informed consent forms were obtainedfrom all participants, who were evaluated by a gastroenterol-ogist and included in the study.</p><p><b>Statistical Analysis</b></p><p>The normality of the distribution of continuous variables wastested by the Shaphiro-Wilk test. The Mann-Whitney U testwas used for non-normal data in the comparison of two inde-pendent groups and the Wilcoxon test was used to comparebefore and following measurements for non-normal data. TheChi-Square test was used to evaluate the relation betweencategorical variables. Statistical analysis was performed withSPSS for Windows version 24.0 and a p-value < 0.05 wasaccepted as statistically significant.</p>

Among the patients who were included in the study, 346(60.9%) were female, 182 (39.1%) were male, and the mean age of the patients was 10.83 ± 6.9 years. All patients werefully vaccinated according to the standard vaccination sched-ule. There were no significant differences between the ageand gender distribution of the cases.<p>When the vaccination status was evaluated, all patients in theceliac and control groups had received a total of three dosesof the hepatitis B vaccine regularly according to the standardvaccination schedule. Although the number of those who re-sponded to the vaccine (anti-HBs ≥ 10 I/U) in the celiac pa-tients was 147 (55.6%), the number of those who did not re-spond to the vaccine was 117 (44.3%). The number of thosewho responded to the vaccine (anti-HBs ≥ 10 I/U) was 163(61.7%) and the number of those who did not respond tothe vaccine was 101 (38.2%) in the control group (Table 1).HBsAg positivity was detected in 4 cases in the celiac group,but it was detected in only 1 case in the control group.</p>

<p>HBV infection is a significant public healthcare concernon aglobal scale. However, the occurrence of chronic liver disease,morbidity, and mortality have decreased significantly withvaccination. After the implementation of mass immunizationprograms recommended by the World Health Organizationin 1991, the incidence of HBV infection among infants, chil-dren, and adolescents decreased significantly in many coun-tries. In previous studies, although the immune response rateto HBV vaccination was found to be around 90%, it was re-ported that the immune response rate to HBV vaccine in celi-ac patients was 4%-10% lower than in the healthy population(10,11). In our study, similar to the literature, the vaccineresponse rate in celiac patients was 6.1% lower than in thehealthy control group. The ability to respond to recombinantHBV vaccine has been associated with many genes. In thisrespect, it is accepted that the most important specific genesare human leukocyte antigen (HLA) haplotypes. It has beenthought that the high prevalence of hepatitis and the low vac-cine response rate in celiac patients may be related to theunresponsiveness of the immune system (12). In a study con-ducted in our country in the adult age group, the prevalenceof HBV was found to be 2-4%. When this rate is considered,it is seen that there is a moderate increase in the prevalence ofchronic hepatitis B in celiac patients (13).</p><p>In previous years, although it varied among regions, HBsAgseroprevalence was found to be between 3.9-12.5%, and an-ti-HBs seroprevalence was found to be between 20.6 - 52.3% in our country (14,15). In previous studies conducted in lat-er years, Aypak et al. found HBsAg positivity at 0.0% andanti-HBs positivity at 66.4% in a study that was conductedin Ankara between 2010 and 2011; Kaya et al. found HBsAgpositivity at 0.2% and anti-HBs positivity at 71.3% in anotherstudy conducted in Van; Ayvaz et al. found HBsAg positivi-ty at 0.16% and anti-HBs positivity at 73.9% in a previousstudy conducted in Sivas in 2008 (16-18). In another studyconducted by Bardella et al., it was reported that HBsAg pos-itivity was 2.5% in celiac patients and that there may be arelationship between celiac disease and HBV infection (19).Similarly, in another study conducted by Gamal et al., HBsAg positivity was detected in 9.9% of the cases and this ratewas reported to be significantly higher than the prevalence ofchronic hepatitis B in the country (6). In our study, HBsAgpositivity was detected in 4 (1.9%) of the celiac cases, whileonly 1 case of the control cases was found to be HBsAg pos-itive. These results show that HBsAg positivity is higher inceliac cases than in the normal population.</p><p>It is speculated that the HLA DQ2 genotype plays a role in thedevelopment of low immune response to recombinant HBVvaccine (20). Also, other studies reported that gluten intakeduring vaccination may have a possible effect (21). For thisreason, vaccine non-response will be seen more frequently inthose who do not comply with a gluten-free diet.</p><p>In conclusion, although it was not statistically significant inthe present study, the researchers found that celiac cases hadlower vaccine response to the HBV vaccine compared to thecontrol group. Also, chronic HBV carriage was observed tobe higher in cases diagnosed with celiac disease. Consideringthat chronic HBV carriage is higher in celiac patients, the im-portance of vaccination against HBV increases even more. Forthis reason, it is of great importance to monitor the vaccineresponse of all celiac patients following vaccination and toinclude those who do not develop a vaccine response in therevaccination program.</p><p><b>Ethics:</b> All participants provided written consent to partici-pate in the study. Ethical approval for the study was obtainedfrom Gazi Yaşargil Training and Research Hospital, Clinical</p><p>Research Ethics committee (No: 287, Diyarbakır, Turkey).</p><p><b>Disclosure statements:</b> The authors declare no conflicts ofinterest.</p><p><b>Acknowledgments:</b> The authors declare that this study hasreceived no financial support.</p><p><b>Authorship contribution: </b>M.A. and A.O. developed thestudy protocol, screened and enrolled the patients, evaluat-ed the outcomes, preliminarily analyzed the data, and wrotethe manuscript. M.A. and A.O. developed the study protocoland analytical framework for the study and contributed to the writing of the manuscript. M.A., A.O., and M.A. screened thepatients. M.A. and A.O. supervised the design and execution ofthe study, performed the final data analyses, and contributed to the writing of the manuscript. All authors have read andapproved the final manuscript.</p>

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