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Jossen J, Lebwohl B, Söderling J, Duberg AS, Aleman S, Sharma R, Hagström H, Green PHR, Ludvigsson JF. No Increased Risk of Hepatitis B Virus Infection in Patients with Celiac Disease: A Population-Based Study. Dig Dis Sci 2025; 70:1521-1529. [PMID: 39984784 PMCID: PMC11972206 DOI: 10.1007/s10620-025-08878-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Accepted: 01/16/2025] [Indexed: 02/23/2025]
Abstract
OBJECTIVES Celiac disease (CeD) has been associated with a low response to hepatitis B (HBV) vaccination, but guidelines for testing and revaccination among individuals with CeD are sparse. We examined the risk of future HBV among individuals with CeD in a population-based Swedish cohort. Furthermore, we examined the rate of prior HBV infection in CeD patients. METHODS All individuals in Sweden diagnosed with biopsy-verified CeD between 1990 and 2017 were identified through the ESPRESSO cohort. Each individual with CeD was matched by age, sex, calendar year, and birth country (Nordic vs. other) with up to 5 reference individuals. RESULTS We identified 44,721 CeD and 222,238 reference individuals. The incidence rates of diagnosed HBV were 2.3 and 2.9 per 100,000 person-years, respectively. This represented no association with CeD (HR 0.77 (0.45-1.30)). This null association was similar for those with a Nordic (HR 0.80 (0.40-1.60)) and non-Nordic ((HR 0.31 (0.09-1.08)) country of birth. Rates of prior HBV infection were low (CeD 0.08%, controls 0.06%). This corresponded to a small but insignificant increase among individuals with CeD (odds ratio, OR 1.41 (0.97-2.05). CONCLUSION In a population-based Swedish cohort, there was no increased risk of developing HBV in individuals with CeD. This finding does not support current practices of testing and revaccination for HBV. Additional studies should be completed in areas with higher endemic rates of HBV. Slightly higher rates of prior HBV infection in CeD may be secondary to increased testing in those seeking medical care for another disease process.
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Affiliation(s)
- Jacqueline Jossen
- Division of Pediatric Gastroenterology, Department of Pediatrics, Columbia University College of Physicians and Surgeons, New York, NY, USA
- Celiac Disease Center, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA
| | - Benjamin Lebwohl
- Division of Digestive and Liver Diseases, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA
- Celiac Disease Center, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA
| | - Jonas Söderling
- Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institute, Stockholm, Sweden
| | - Ann-Sofi Duberg
- Department of Infectious Diseases, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Soo Aleman
- Department of Medicine, Karolinska Institutet, Huddinge, Stockholm, Sweden
- Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden
| | - Rajani Sharma
- Division of Digestive and Liver Diseases, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA
- Center for Liver Disease and Transplantation, Columbia University Irving Medical Center, New York, NY, USA
| | - Hannes Hagström
- Division of Hepatology, Department of Upper GI Diseases, Karolinska University Hospital, Stockholm, Sweden
- Department of Medicine, Karolinska Institutet, Huddinge, Stockholm, Sweden
| | - Peter H R Green
- Division of Digestive and Liver Diseases, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA
- Celiac Disease Center, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA
| | - Jonas F Ludvigsson
- Celiac Disease Center, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA.
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
- Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.
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Asri N, Mohammadi S, Jahdkaran M, Rostami-Nejad M, Rezaei-Tavirani M, Mohebbi SR. Viral infections in celiac disease: what should be considered for better management. Clin Exp Med 2024; 25:25. [PMID: 39731690 DOI: 10.1007/s10238-024-01542-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2024] [Accepted: 12/20/2024] [Indexed: 12/30/2024]
Abstract
Following a gluten-free diet (GFD) is known as the main effective therapy available for celiac disease (CD) patients, which in some cases is not enough to heal all patients presentations completely. Accordingly, emerging researchers have focused on finding novel therapeutic/preventive strategies for this disorder. Moreover, previous studies have shown that celiac patients, especially untreated subjects, are at increased risk of developing viral and bacterial infections, which can become a challenge for the clinician. Viruses, such as Rotavirus, Reovirus, Adenovirus, Enterovirus, Rhinovirus, Astrovirus, Hepatitis virus, COVID-19, Norovirus, and Herpesvirus, have been related to CD pathogenesis. Therefore, clinicians need to pay more attention to evaluate CD patients' viral infection history (especially nonresponders to the GFD), to look for effective preventive strategies and educate patients about important risk factors. In addition, there are still viruses whose role in CD pathogenesis has not been fully studied. In this review, current information on the association between CD and various viral infections was gathered to improve knowledge in this subject area and draw researchers'/clinicians' attention to unstudied/less studied viruses in CD pathogenesis, which might guide future prevention approaches.
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Affiliation(s)
- Nastaran Asri
- Celiac Disease and Gluten Related Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Shahnaz Mohammadi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mahtab Jahdkaran
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Rostami-Nejad
- Celiac Disease and Gluten Related Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Mostafa Rezaei-Tavirani
- Proteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Seyed Reza Mohebbi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Scarmozzino R, Zanoni G, Arcolaci A, Ciccocioppo R. Vaccine Efficacy and Safety in Patients with Celiac Disease. Vaccines (Basel) 2024; 12:1328. [PMID: 39771990 PMCID: PMC11679483 DOI: 10.3390/vaccines12121328] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Revised: 10/18/2024] [Accepted: 10/29/2024] [Indexed: 01/04/2025] Open
Abstract
Celiac disease (CD) is an autoimmune disorder caused by gluten intake in genetically predisposed individuals. This article provides an overview of the available data on the risks of infectious diseases and the mechanisms involved in CD, including a detailed analysis of vaccine efficacy, immunogenicity, and safety. The published articles were retrieved from the PubMed database using the terms "celiac disease", "efficacy", "hyposplenism", "immune response", "infections", "immunization", "immunogenicity", "safety", "vaccination", and "vaccine". CD can be associated with several autoimmune diseases, including selective immunoglobulin A deficiency (SIgAD), altered mucosal permeability, and hyposplenism. These conditions entail an increased risk of infections, which can be prevented by targeted vaccinations, although specific recommendations on immunization practices for subjects with CD have not been released. Regarding vaccinations, the immune response to the Hepatitis B virus (HBV) vaccine can be impaired in patients with CD; therefore, proposed strategies to elicit and maintain protective specific antibody titers are summarized. For patients with conditions that put them at risk of infections, vaccinations against Pneumococcus and other encapsulated bacteria should be recommended. Based on the available evidence, the Rotavirus vaccine offered to children could be useful in preventing CD in at-risk subjects. Overall, except for the HBV vaccine, vaccine efficacy in patients with CD is comparable to that in the general population, and no safety concerns have arisen.
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Affiliation(s)
- Rocco Scarmozzino
- Immunology Unit, Azienda Ospedaliera Universitaria Integrata Policlinico G.B. Rossi & University of Verona, 37134 Verona, Italy;
| | - Giovanna Zanoni
- Immunology Unit, Azienda Ospedaliera Universitaria Integrata Policlinico G.B. Rossi & University of Verona, 37134 Verona, Italy;
| | - Alessandra Arcolaci
- Immunology Unit, Azienda Ospedaliera Universitaria Integrata Policlinico G.B. Rossi & University of Verona, 37134 Verona, Italy;
| | - Rachele Ciccocioppo
- Gastroenterology Unit, Department of Medicine, Azienda Ospedaliera Universitaria Integrata Policlinico G.B. Rossi & University of Verona, 37134 Verona, Italy;
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Bello N, Hudu SA, Alshrari AS, Imam MU, Jimoh AO. Overview of Hepatitis B Vaccine Non-Response and Associated B Cell Amnesia: A Scoping Review. Pathogens 2024; 13:554. [PMID: 39057781 PMCID: PMC11279426 DOI: 10.3390/pathogens13070554] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Revised: 06/18/2024] [Accepted: 06/19/2024] [Indexed: 07/28/2024] Open
Abstract
BACKGROUND The advent of the hepatitis B vaccine has achieved tremendous success in eradicating and reducing the burden of hepatitis B infection, which is the main culprit for hepatocellular carcinoma-one of the most fatal malignancies globally. Response to the vaccine is achieved in about 90-95% of healthy individuals and up to only 50% in immunocompromised patients. This review aimed to provide an overview of hepatitis B vaccine non-response, the mechanisms involved, B cell amnesia, and strategies to overcome it. METHODS Databases, including Google Scholar, PubMed, Scopus, Cochrane, and ClinicalTrials.org, were used to search and retrieve articles using keywords on hepatitis B vaccine non-response and B cell amnesia. The PRISMA guideline was followed in identifying studies, screening, selection, and reporting of findings. RESULTS A total of 133 studies on hepatitis B vaccine non-response, mechanisms, and prevention/management strategies were included in the review after screening and final selection. Factors responsible for hepatitis B vaccine non-response were found to include genetic, immunological factors, and B cell amnesia in healthy individuals. The genetic factors were sex, HLA haplotypes, and genetic polymorphisms in immune response markers (cytokines). Non-response was common in conditions of immunodeficiency, such as renal failure, haemodialysis, celiac disease, inflammatory bowel disease, hepatitis C co-infection, and latent hepatitis B infection. Others included diabetes mellitus and HIV infection. The mechanisms involved were impaired immune response by suppression of response (T helper cells) or induced suppression of response (through regulatory B and T cells). DISCUSSION A comprehensive and careful understanding of the patient factors and the nature of the vaccine contributes to developing effective preventive measures. These include revaccination or booster dose, vaccine administration through the intradermal route, and the use of adjuvants in the vaccine.
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Affiliation(s)
- Nura Bello
- Department of Pharmacology and Therapeutics, Faculty of Basic Clinical Sciences, College of Health Sciences, Usmanu Danfodiyo University, Sokoto 840232, Nigeria;
- Department of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Ahmadu Bello University, Zaria 810107, Nigeria
| | - Shuaibu A. Hudu
- Department of Basic Medical and Dental Sciences, Faculty of Dentistry, Zarqa University, Zarqa 13110, Jordan
- Department of Medical Microbiology and Parasitology, Faculty of Basic Clinical Sciences, College of Health Sciences, Usmanu Danfodiyo University, Sokoto 840232, Nigeria
| | - Ahmed S. Alshrari
- Medical Laboratory Technology Department, Faculty of Applied Medical Science, Northern Border University, Arar 91431, Saudi Arabia;
| | - Mustapha U. Imam
- Centre for Advanced Medical Research and Training, Usmanu Danfodiyo University, Sokoto 840232, Nigeria;
| | - Abdulgafar O. Jimoh
- Department of Pharmacology and Therapeutics, Faculty of Basic Clinical Sciences, College of Health Sciences, Usmanu Danfodiyo University, Sokoto 840232, Nigeria;
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Tahir A, Shinkafi SH, Alshrari AS, Yunusa A, Umar MT, Hudu SA, Jimoh AO. A Comprehensive Review of Hepatitis B Vaccine Nonresponse and Associated Risk Factors. Vaccines (Basel) 2024; 12:710. [PMID: 39066348 PMCID: PMC11281605 DOI: 10.3390/vaccines12070710] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Revised: 06/10/2024] [Accepted: 06/14/2024] [Indexed: 07/28/2024] Open
Abstract
Hepatitis B virus (HBV) infection remains a significant global health concern worldwide, contributing to high rates of mortality and morbidity, including chronic hepatitis B, cirrhosis, and hepatocellular carcinoma (HCC). Universal vaccination programs have significantly reduced the rate of HBV transmission; however, a subset of individuals fail to develop a protective immune response following vaccination and are termed nonresponders. A comprehensive search strategy using the PubMed, Google Scholar, and Web of Science databases was employed to search for relevant studies using keywords including "hepatitis B vaccine", "vaccine nonresponse", "immunogenicity", "immune response to the hepatitis B vaccine", and "associated risk factors". Factors influencing the vaccine's response include demographic factors, such as age and sex, with increased nonresponse rates being observed in older adults and males. Obesity, smoking, and alcohol consumption are lifestyle factors that decrease the vaccine response. Medical conditions, including diabetes, chronic kidney and liver diseases, HIV, celiac disease, and inflammatory bowel disease, affect the vaccine response. Major histocompatibility complex (MHC) haplotypes and genetic polymorphisms linked to immune regulation are genetic factors that further influence the vaccine's effectiveness. To reduce the global burden of hepatitis B infection, it is essential to understand these factors to improve vaccine effectiveness and develop individualized vaccination strategies.
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Affiliation(s)
- Albashir Tahir
- Department of Pharmacology and Therapeutics, Faculty of Basic Clinical Sciences, College of Health Sciences, Usmanu Danfodiyo University, Sokoto 840001, Nigeria; (A.T.); (A.Y.); (M.T.U.)
- Department of Pharmacology, Faculty of Basic Medical Sciences, Bauchi State University, Gadau 751105, Nigeria
| | - Sa’adatu Haruna Shinkafi
- Department of Microbiology and Parasitology, Usmanu Danfodiyo University Teaching Hospital, Sokoto 23270, Nigeria
| | - Ahmed Subeh Alshrari
- Medical Laboratory Technology Department, Faculty of Applied Medical Science, Northern Border University, Arar 91431, Saudi Arabia;
| | - Abdulmajeed Yunusa
- Department of Pharmacology and Therapeutics, Faculty of Basic Clinical Sciences, College of Health Sciences, Usmanu Danfodiyo University, Sokoto 840001, Nigeria; (A.T.); (A.Y.); (M.T.U.)
| | - Muhammad Tukur Umar
- Department of Pharmacology and Therapeutics, Faculty of Basic Clinical Sciences, College of Health Sciences, Usmanu Danfodiyo University, Sokoto 840001, Nigeria; (A.T.); (A.Y.); (M.T.U.)
| | - Shuaibu Abdullahi Hudu
- Department of Basic Medical and Dental Sciences, Faculty of Dentistry, Zarqa University, Zarqa 13110, Jordan
- Department of Microbiology and Parasitology, Faculty of Basic Clinical Sciences, College of Health Sciences, Usmanu Danfodiyo University, Sokoto 840232, Nigeria
| | - Abdulgafar Olayiwola Jimoh
- Department of Pharmacology and Therapeutics, Faculty of Basic Clinical Sciences, College of Health Sciences, Usmanu Danfodiyo University, Sokoto 840001, Nigeria; (A.T.); (A.Y.); (M.T.U.)
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Cohen R, Mahlab-Guri K, Atali M, Elbirt D. Viruses and celiac disease: what do we know ? Clin Exp Med 2023; 23:2931-2939. [PMID: 37103650 PMCID: PMC10134706 DOI: 10.1007/s10238-023-01070-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Accepted: 04/05/2023] [Indexed: 04/28/2023]
Abstract
The aim of this review is to provide a comprehensive overview about the link between viruses and celiac disease. A systematic search on PubMed, Embase, and Scopus was conducted on March 07, 2023. The reviewers independently selected the articles and chose which articles to include. The review is a textual systemic review, and all relevant articles were included based on title and abstract. If there was a disagreement between the reviewers, they came to a consensus during deliberation sessions. A total of 178 articles were selected for the review and read in full; only part of them was retained. We found studies between celiac disease and 12 different viruses. Some of the studies were done only on small groups. Most studies were on pediatric population. Evidence for an association was found with several viruses (trigger or protective). It seems that only a part of the viruses could induce the disease. Several points are important to keep in mind: firstly, simple mimicry or that the virus induces a high level of TGA is not sufficient to promote the disease. Secondly, inflammatory background is necessary to induce CD with virus. Thirdly, IFN type 1 seems to have an important role. Some of the viruses are potential or known triggers like enteroviruses, rotaviruses, reoviruses, and influenza. Further studies are needed to better understand the role of viruses in celiac disease to better treat and prevent the disease.
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Affiliation(s)
- Ramon Cohen
- Internal Department B, Kaplan Medical Center, Rehovot, Israel.
- Department of Clinical Immunology Allergy and AIDS, Kaplan Medical Center, Rehovot, Israel.
| | - Keren Mahlab-Guri
- Department of Clinical Immunology Allergy and AIDS, Kaplan Medical Center, Rehovot, Israel
| | - Malka Atali
- Internal Department B, Kaplan Medical Center, Rehovot, Israel
| | - Daniel Elbirt
- Department of Clinical Immunology Allergy and AIDS, Kaplan Medical Center, Rehovot, Israel
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Cohen BS, Lebwohl B. COVID-19 and celiac disease: a review. Therap Adv Gastroenterol 2023; 16:17562848231170944. [PMID: 37124373 PMCID: PMC10133858 DOI: 10.1177/17562848231170944] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Accepted: 04/04/2023] [Indexed: 05/02/2023] Open
Abstract
The aim of this review is to broadly cover how the COVID-19 pandemic has affected individuals with celiac disease, including perceived risk, risk of contraction or severe infection, considerations regarding vaccination, access to gluten-free food during the pandemic, and possible long-term changes to the practice of celiac disease management spurred by the pandemic. While initially there was increased perceived risk about COVID-19 in the celiac disease population, studies have found that individuals with celiac disease are not at an increased risk of contracting or having a severe course compared to the general population. There is not yet evidence that COVID-19 infection will lead to an increase in celiac disease incidence, though more research on this topic with longer-term follow-up is necessary to make this determination. Limited access to in-person visits led to an increase in telemedicine, which was adopted swiftly by this patient population and may offer improved access in the long term. In summary, individuals with celiac disease do not appear to be at an increased risk of contracting COVID-19 or having a more severe disease course.
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Affiliation(s)
- Brandon S. Cohen
- Department of Medicine, Celiac Disease Center,
Columbia University Irving Medical Center, New York, NY, USA
| | - Benjamin Lebwohl
- Department of Medicine, Celiac Disease Center,
Columbia University Irving Medical Center, 180 Fort Washington Avenue, Suite
936, New York, NY 10032, USA
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Zingone F, Maimaris S, Auricchio R, Caio GPI, Carroccio A, Elli L, Galliani E, Montagnani M, Valiante F, Biagi F. Guidelines of the Italian societies of gastroenterology on the diagnosis and management of coeliac disease and dermatitis herpetiformis. Dig Liver Dis 2022; 54:1304-1319. [PMID: 35858884 DOI: 10.1016/j.dld.2022.06.023] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Revised: 05/11/2022] [Accepted: 06/19/2022] [Indexed: 12/29/2022]
Abstract
INTRODUCTION Coeliac disease and dermatitis herpetiformis are immune-mediated diseases triggered by the consumption of gluten in genetically predisposed individuals. These guidelines were developed to provide general practitioners, paediatricians, gastroenterologists, and other clinicians with an overview on the diagnosis, management and follow-up of coeliac patients and those with dermatitis herpetiformis. METHODS Guidelines were developed by the Italian Societies of Gastroenterology. Following a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the certainty of the evidence. Statements and recommendations were developed by working groups consisting of gastroenterologists and a paediatrician with expertise in this field. RESULTS These guidelines provide a practical guidance for the diagnosis, management and follow-up of coeliac patients and dermatitis herpetiformis in children and adults, both in primary care and in specialist settings. We developed four sections on diagnosis, gluten-free diet, follow-up and risk of complications in adults, one section focused on diagnosis and follow-up in children and one on the diagnosis and management of dermatitis herpetiformis. CONCLUSIONS These guidelines may support clinicians to improve the diagnosis and management of patients with coeliac disease.
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Affiliation(s)
- Fabiana Zingone
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Italy; Gastroenterology Unit, Azienda Ospedale Università, Padova, Italy.
| | - Stiliano Maimaris
- Dipartimento di Medicina Interna e Terapia Medica, Università di Pavia, Italia
| | - Renata Auricchio
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy
| | - Giacomo Pietro Ismaele Caio
- Department of Morphology, Surgery and Experimental Medicine, St. Anna Hospital, University of Ferrara, Ferrara, Italy
| | - Antonio Carroccio
- Unit of Internal Medicine, "V. Cervello" Hospital, Ospedali Riuniti "Villa Sofia-Cervello", 90146 Palermo, University of Palermo, Italy
| | - Luca Elli
- Gastroenterology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
| | - Ermenegildo Galliani
- UOC Gastroenterologia ed Endoscopia Digestiva, AULSS1 Dolomiti Veneto, Ospedale San Martino, Belluno, Italy
| | - Marco Montagnani
- Department of Medical and Surgical Sciences, University of Bologna, Italy; Gastroenterology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Italy
| | - Flavio Valiante
- UOC Gastroenterologia ed Endoscopia Digestiva, AULSS1 Dolomiti Veneto, Feltre (BL), Italy
| | - Federico Biagi
- Istituti Clinici Maugeri, IRCCS, Unità di Gastroenterologia dell'Istituto di Pavia, Italy
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COVID-19 Vaccine: A Survey of Hesitancy in Patients with Celiac Disease. Vaccines (Basel) 2021; 9:vaccines9050511. [PMID: 34065654 PMCID: PMC8156726 DOI: 10.3390/vaccines9050511] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2021] [Revised: 05/12/2021] [Accepted: 05/12/2021] [Indexed: 02/06/2023] Open
Abstract
(1) Background: COVID-19 vaccination campaigns offer the best hope of controlling the pandemic. However, the fast production of COVID-19 vaccines has caused concern among the general public regarding their safety and efficacy. In particular, patients with chronic illnesses, such as celiac disease (CD), may be more fearful. Information on vaccine hesitancy plays a pivotal role in the development of an efficient vaccination campaign. In our study, we aimed to evaluate COVID-19 vaccine hesitancy among Italian CD patients. (2) Methods: an anonymous questionnaire was sent to CD patients followed at our tertiary referral center for CD in Milan, Italy. Patients were defined as willing, hesitant and refusing. We evaluated the reasons for hesitancy/refusal and the possible determinants, calculating crude and adjusted odds ratios [AdjORs] with 95% confidence intervals [CIs]. (3) Results: the questionnaire was sent to 346 patients with a response rate of 29.8%. Twenty-six (25.2%) of the 103 respondents were hesitant, with a total refusal rate of 4.8%. The main reason was fear of adverse events related to vaccination (68.2%). Among hesitant patients, 23% declared that their opinion was influenced by their CD. The determinants positively influencing willingness to be vaccinated against COVID-19 were adherence to a GFD, perception of good knowledge about COVID-19 and its vaccines, and a positive attitude to previous vaccines (AdjOR 12.71, 95% CI 1.82-88.58, AdjOR 6.50, 95% CI 1.44-29.22, AdjOR 0.70, 95% CI 0.11-4.34, respectively). (4) Conclusions: CD patients should be vaccinated against COVID-19 and a specific campaign to address the determinants of hesitancy should be developed.
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Association between Elevated TGA-IgA Titers and Older Age at Diagnosis with Absence of HBV Seroconversion in Celiac Children. Vaccines (Basel) 2021; 9:vaccines9020101. [PMID: 33525661 PMCID: PMC7912643 DOI: 10.3390/vaccines9020101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Revised: 01/24/2021] [Accepted: 01/25/2021] [Indexed: 11/17/2022] Open
Abstract
Patients with celiac disease can have a low rate of protective hepatitis B (HBV) antibody titers after vaccination. We aimed to evaluate the HBV seroconversion in celiac disease (CD) children at the time of diagnosis as well as to identify the presence of possible predictive factors. Celiac disease children were prospectively enrolled and tested for antibodies against the S protein of HBV (HBsAg) at time of diagnosis between January 2009 and February 2020. Based on the serologic response to the vaccine, “responders” and “non-responders” were identified. Statistical analysis has been performed through R statistical software (3.5.1 version, R core Team) Of 96 CD children evaluated, 41.7% (n = 40) showed non-protective or absent antibody titers against HBV. Elevated IgA-antibodies against transglutaminase 2 (TGA-IgA) values and older age at diagnosis were associated with an absent seroconversion to HBV vaccine, while presenting symptoms were not significant. An elevated prevalence of absent seroconversion to HBV vaccine exists in this cohort of CD patients at the time of disease diagnosis. Elevated TGA-IgA titers and older age at diagnosis seem to negatively predict seroconversion. Further studies are needed to identify the real profile of “non-responders”, aiming to organize surveillance and eventual revaccination strategy.
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Passanisi S, Dipasquale V, Romano C. Vaccinations and Immune Response in Celiac Disease. Vaccines (Basel) 2020; 8:vaccines8020278. [PMID: 32517026 PMCID: PMC7349995 DOI: 10.3390/vaccines8020278] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Revised: 05/31/2020] [Accepted: 06/02/2020] [Indexed: 12/16/2022] Open
Abstract
Immune response to vaccinations in celiac patients is of growing scientific interest. However, some aspects of the relationship between celiac disease (CD) and vaccines are still unclear. A comprehensive search of published literature using the PubMed database was carried out using the following key terms: "adaptive immunity", "celiac disease", "humoral immune response", "immunization", and "vaccination". To date, there is no evidence showing any causative association between vaccines and CD development. Therefore, vaccinations may be administered according to the modalities and timing of the National Immunization Schedule for each country. The rotavirus vaccine is currently recommended for the general population, and according to some data, it appears to reduce the risk for the development of CD autoimmunity in the early years of life. Regarding the hepatitis B virus, a booster dose of the vaccine is often required due to the low or the lost immune response rate in CD. Furthermore, determination of hepatitis B antibody titers could be useful in newly diagnosed CD subjects regardless of age at diagnosis. Finally, pneumococcal vaccines may be administered in patients with advancing age at diagnosis and concomitant risk factors. Future clinical practice guidelines for vaccination and monitoring programs in celiac patients could be recommended.
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Abstract
There is substantial variation between individuals in the immune response to vaccination. In this review, we provide an overview of the plethora of studies that have investigated factors that influence humoral and cellular vaccine responses in humans. These include intrinsic host factors (such as age, sex, genetics, and comorbidities), perinatal factors (such as gestational age, birth weight, feeding method, and maternal factors), and extrinsic factors (such as preexisting immunity, microbiota, infections, and antibiotics). Further, environmental factors (such as geographic location, season, family size, and toxins), behavioral factors (such as smoking, alcohol consumption, exercise, and sleep), and nutritional factors (such as body mass index, micronutrients, and enteropathy) also influence how individuals respond to vaccines. Moreover, vaccine factors (such as vaccine type, product, adjuvant, and dose) and administration factors (schedule, site, route, time of vaccination, and coadministered vaccines and other drugs) are also important. An understanding of all these factors and their impacts in the design of vaccine studies and decisions on vaccination schedules offers ways to improve vaccine immunogenicity and efficacy.
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Manti S, Cuppari C, Parisi GF, Tardino L, Salpietro C, Leonardi S. HMGB1 values and response to HBV vaccine in children with celiac disease. Nutrition 2017; 42:20-22. [PMID: 28870474 DOI: 10.1016/j.nut.2017.05.012] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2017] [Revised: 04/30/2017] [Accepted: 05/15/2017] [Indexed: 12/17/2022]
Abstract
OBJECTIVES In addition to its wide clinical variability, celiac disease (CD) can also cause a lower response to the hepatitis B virus (HBV) than healthy individuals. The aim of this study was to examine high mobility group box 1 (HMGB1) as a new potential marker of an inadequate response to HBV vaccine in children with CD at diagnosis before starting a gluten-free diet. METHODS We recruited 49 children with CD who were tested at admission for immunization against HBV. Serum HMGB1 levels were measured by an enzyme-linked immunosorbent assay test. RESULTS Serum HMGB1 levels were significantly higher in nonresponders than in responders (P < 0.05). In the responders group in particular, with reference to the titer of vaccine response, we found a significantly higher serum HMGB1 level in the low responders (P < 0.001). We detected statistically significant higher values of HMGB1 in the typical form of disease presentation than in the atypical or silent form (P < 0.05). In the typical form, we showed even significantly higher HMGB1 values in low responders than in high responders (P < 0.001). With regard to the HLA haplotype and serum HMGB1 levels, any statistically significant difference was detected (P > 0.05). CONCLUSIONS In patients with CD, HMGB1 could represent a new marker that is able to reflect the immune impairment that results in failure of the HBV vaccination.
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Affiliation(s)
- Sara Manti
- Department of Pediatrics, Unit of Pediatric Genetics and Immunology, University of Messina, Messina, Italy
| | - Caterina Cuppari
- Department of Pediatrics, Unit of Pediatric Genetics and Immunology, University of Messina, Messina, Italy
| | - Giuseppe F Parisi
- Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
| | - Lucia Tardino
- Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
| | - Carmelo Salpietro
- Department of Pediatrics, Unit of Pediatric Genetics and Immunology, University of Messina, Messina, Italy
| | - Salvatore Leonardi
- Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy.
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Anania C, Olivero F, Spagnolo A, Chiesa C, Pacifico L. Immune response to vaccines in children with celiac disease. World J Gastroenterol 2017; 23:3205-3213. [PMID: 28566880 PMCID: PMC5434426 DOI: 10.3748/wjg.v23.i18.3205] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2017] [Revised: 03/07/2017] [Accepted: 04/12/2017] [Indexed: 02/07/2023] Open
Abstract
Celiac disease (CD) is an immune-mediated systemic condition evoked by ingestion of gluten and related prolamines in genetically susceptible subjects. The disease is featured by a variable combination of clinical signs, specific antibodies, HLA-DQ2 and HLA-DQ8 haplotypes, and enteropathy. Vaccination is the most potent intervention for infectious disease prevention. Several factors including age, gender, ethnicity, quality and quantity of vaccine antigen, doses, and route of administration can influence immune response to vaccination, although the main cause of variation in the responsiveness among vaccine recipients is host genetic variability. The HLA system has a fundamental role in identifying the antigens introduced into the host with the vaccines and in the development of specific antibodies, and some HLA phenotypes have been associated with a less effective immunological response. The available literature indicates that the immunological response to vaccines in CD children does not differ markedly from that of general population and antibody titres are high enough to provide long-term protection, except for hepatitis B virus vaccine. In this article, we review and discuss the scarce literature in this field in order to provide clinical practice guidelines to achieve the most efficient monitoring of the response to vaccines in pediatric CD patients.
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Abstract
AIM To evaluate hepatitis B virus (HBV) vaccine response and correlation with human leukocyte antigens (HLA) and/or gluten intake in celiac patients at diagnosis. METHODS Fifty-one patients affected by celiac disease, diagnosed at the Department of Pediatrics of the University of Catania (Italy), were recruited. All patients were tested at admission for immunization against HBV, according to findings from analysis of quantitative HBV surface antibody (anti-HBs). The anti-HBs titer was measured by enzyme-linked immunosorbent assay. Following the international standards, subjects with antibody titer < 10 IU/L were defined as non-responders. The prevalence of responders and non-responders among celiac subjects and the distribution of immunization for age were examined. In addition, the prevalence of responders and non-responders was assessed for correlation to HLA and clinical features at diagnosis of celiac disease. RESULTS The entire study population was divided into three groups according to age: 24 patients aged between 0 to 5.5 years (48.9%, group A); 16 aged between 5.5 and 9.5 years (30.61%, group B); 9 aged between 9.5 and 17 years (18.75%, group C). Comparison of the percentage of responders and non-responders between the youngest and the oldest age group showed no significant difference between the two groups (P > 0.05). With regard to the HLA haplotype, comparison of the distribution of vaccination response showed no statistically significant difference between the different genotypes (homozygosity for the HLADQ2 haplotype compared with HLADQ2/DQ8 heterozygosity or other haplotypes; P > 0.05). Moreover, distribution of the responders according to clinical features of celiac disease showed no statistically significant differences (P > 0.05). CONCLUSION This prospective study confirmed the lower percentage of response to HBV vaccine in celiac subjects. However, the underlying mechanism remains unclear and further studies are needed.
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Filippelli M, Garozzo MT, Capizzi A, Spina M, Manti S, Tardino L, Salpietro C, Leonardi S. Immune response to hepatitis B virus vaccine in celiac subjects at diagnosis. World J Hepatol 2016; 8:1105-1109. [PMID: 27660678 PMCID: PMC5026993 DOI: 10.4254/wjh.v8.i26.1105] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2016] [Revised: 07/14/2016] [Accepted: 08/01/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate hepatitis B virus (HBV) vaccine response and correlation with human leukocyte antigens (HLA) and/or gluten intake in celiac patients at diagnosis.
METHODS Fifty-one patients affected by celiac disease, diagnosed at the Department of Pediatrics of the University of Catania (Italy), were recruited. All patients were tested at admission for immunization against HBV, according to findings from analysis of quantitative HBV surface antibody (anti-HBs). The anti-HBs titer was measured by enzyme-linked immunosorbent assay. Following the international standards, subjects with antibody titer < 10 IU/L were defined as non-responders. The prevalence of responders and non-responders among celiac subjects and the distribution of immunization for age were examined. In addition, the prevalence of responders and non-responders was assessed for correlation to HLA and clinical features at diagnosis of celiac disease.
RESULTS The entire study population was divided into three groups according to age: 24 patients aged between 0 to 5.5 years (48.9%, group A); 16 aged between 5.5 and 9.5 years (30.61%, group B); 9 aged between 9.5 and 17 years (18.75%, group C). Comparison of the percentage of responders and non-responders between the youngest and the oldest age group showed no significant difference between the two groups (P > 0.05). With regard to the HLA haplotype, comparison of the distribution of vaccination response showed no statistically significant difference between the different genotypes (homozygosity for the HLADQ2 haplotype compared with HLADQ2/DQ8 heterozygosity or other haplotypes; P > 0.05). Moreover, distribution of the responders according to clinical features of celiac disease showed no statistically significant differences (P > 0.05).
CONCLUSION This prospective study confirmed the lower percentage of response to HBV vaccine in celiac subjects. However, the underlying mechanism remains unclear and further studies are needed.
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Leonardi S, Filippelli M, Manti S, Cuppari C, Salpietro C. Extending the Debate on Poor Response to Hepatitis B Virus Vaccination in Children With Celiac Disease: Which Question Remains? HEPATITIS MONTHLY 2015; 15:e30888. [PMID: 26587037 PMCID: PMC4644565 DOI: 10.5812/hepatmon.30888] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 06/19/2015] [Accepted: 07/29/2015] [Indexed: 12/11/2022]
Affiliation(s)
- Salvatore Leonardi
- Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
- Corresponding Author: Salvatore Leonardi, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy. Tel: +39-0953782764, Fax: +39-0953782385, E-mail:
| | - Martina Filippelli
- Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
| | - Sara Manti
- Department of Pediatrics, Unit of Pediatric Genetics and Immunology, University of Messina, Messina, Italy
| | - Caterina Cuppari
- Department of Pediatrics, Unit of Pediatric Genetics and Immunology, University of Messina, Messina, Italy
| | - Carmelo Salpietro
- Department of Pediatrics, Unit of Pediatric Genetics and Immunology, University of Messina, Messina, Italy
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Opri R, Veneri D, Mengoli C, Zanoni G. Immune response to Hepatitis B vaccine in patients with celiac disease: A systematic review and meta-analysis. Hum Vaccin Immunother 2015; 11:2800-5. [PMID: 26378476 DOI: 10.1080/21645515.2015.1069448] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
It is debated whether patients with celiac disease (CD) have non-protective antibody responses to HBV vaccination more frequently than non-affected subjects. To perform a literature review and meta-analysis on protective response to HBV vaccination in CD patients. RCTs and observational controlled studies were eligible. Outcome of interest was an anti-HBs (HBsAb) titer ≥ 10 IU/L after last vaccine dose. Comparative index was rate ratio (RR). Heterogeneity between studies was addressed and funnel plots were analyzed. Meta-regression models were applied to investigate effect size due to study-specific variables. Twelve retrospective studies on a total of 1,447 participants and 4 prospective studies on 184 subjects were selected. The RR was 0.732 (95% C.I.: 0.664-0.808) and 0.777 (95% C.I.: 0.629-0.960) in the prospective and retrospective studies, respectively. The I(2), indicating heterogeneity, was 51.1% in retrospective, 39.8% in prospective studies. Non-protective antibody responses occurred more frequently in patients than controls. Due to limitations in the available studies, additional trials to evaluate post-vaccination HBsAb titer in CD patients are needed.
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Affiliation(s)
- R Opri
- a Department of Pathology and Diagnostics ; Section of Immunology; University of Verona ; Verona , Italy
| | - D Veneri
- b Department of Medicine ; Section of Hematology; University of Verona ; Verona , Italy
| | - C Mengoli
- c Infectious Diseases; University of Padua ; Padua , Italy
| | - G Zanoni
- a Department of Pathology and Diagnostics ; Section of Immunology; University of Verona ; Verona , Italy
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Filippelli M, Lionetti E, Pulvirenti A, Gennaro A, Lanzafame A, Marseglia GL, Salpietro C, Rosa ML, Leonardi S. New approaches in hepatitis B vaccination for celiac disease. Immunotherapy 2015; 6:945-52. [PMID: 25313572 DOI: 10.2217/imt.14.64] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Celiac disease (CD) is a gluten-induced immune-mediated disorder that has been associated with a defective response to the hepatitis B virus (HBV) vaccination. This unresponsiveness could lead to a world health problem, because non-responder patients could represent a reservoir of HBV-susceptible people that will persist as healthy carriers, leading to the diffusion of the disease. This article presents a literature review of both intramuscular (IM) and intradermal (ID) routes for boosters in celiac patients. We used PubMed database and generated the odds ratio (OR) of the response on the basis of electronic searches of clinical trials. Although our results confirm the positive response of celiac patients to IM vaccination, the ID route seems to be better than the conventional one, since it could provide a saving in cost and a greater immunogenicity.
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Affiliation(s)
- Martina Filippelli
- Department of Medical & Pediatric Science, University of Catania, Catania, Italy
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