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Seidita A, Latteri F, Pistone M, Giuliano A, Bertoncello L, Cavallo G, Chiavetta M, Faraci F, Nigro A, Termini A, Verona L, Ammannato A, Accomando S, Cavataio F, Lospalluti ML, Citrano M, Di Liberto D, Soresi M, Mansueto P, Carroccio A. Celiac Disease and Liver Damage: The Gut-Liver Axis Strikes Back (Again)? A Retrospective Analysis in the Light of a Literature Review. Nutrients 2024; 17:85. [PMID: 39796519 PMCID: PMC11722968 DOI: 10.3390/nu17010085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2024] [Revised: 12/23/2024] [Accepted: 12/26/2024] [Indexed: 01/13/2025] Open
Abstract
Background/Objectives: An increasing number of studies have reported liver involvement in both children and adults with celiac disease (CD). This often manifests as isolated hypertransaminasemia or hepatic steatosis (HS). The aim of this study was to define the prevalence of hypertransaminasemia and HS in a pediatric population with CD before starting a gluten-free diet (GFD) and to analyze how the introduction of a GFD could modify this condition. We also conducted a state-of-the-art literature review of the association between hypertransaminasemia, metabolic dysfunction-associated steatotic liver disease (MASLD) and CD. Methods: We retrospectively reviewed the clinical charts of pediatric CD patients diagnosed in three different pediatric units of Sicily, analyzing clinical, laboratory, ultrasound, and histology data before and 12 months after the introduction of a GFD. Results: A total of 160 patients (65.0% females, median age 6.4 (0.8-13.2) years) were included; hypertransaminasemia and HS prevalences at diagnosis were 8.1% and 6.1%, respectively. Subjects with hypertransaminasemia were younger (p = 0.01) than those without and had higher frequencies of HS (p = 0.034) and anti-tissue transglutaminase (tTg) immunoglobulin (Ig)G positivity (p = 0.046). Subjects with HS were younger (p = 0.0001) and had a higher frequency of hypertransaminasemia (p = 0.029) compared to non-steatotic ones. After 12 months of a GFD, hypertransaminasemia and HS persisted in 53.8% and 50.0% of patients, respectively. Conclusions: The prevalences of hypertransaminasemia and HS in Sicilian pediatric CD patients seem to be lower than those reported in other geographical areas. A GFD can reverse the trend of liver involvement, although periods of longer than 12 months may be necessary. However, a GFD has been associated with an increased prevalence of HS, and so regular follow-up involving a nutritionist should be recommended to guide physicians in patient management.
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Affiliation(s)
- Aurelio Seidita
- Internal Medicine Unit, “V. Cervello” Hospital, Ospedali Riuniti “Villa Sofia-Cervello”, Via Trabucco, 180, 90146 Palermo, Italy; (A.S.)
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Piazza delle Cliniche, 2, 90127 Palermo, Italy
- Institute for Biomedical Research and Innovation (IRIB), National Research Council (CNR), 90146 Palermo, Italy
| | - Federica Latteri
- Gastroenterology Unit, “V. Cervello” Hospital, Ospedali Riuniti “Villa Sofia-Cervello”, Via Trabucco, 180, 90146 Palermo, Italy
| | - Mirco Pistone
- Internal Medicine Unit, “V. Cervello” Hospital, Ospedali Riuniti “Villa Sofia-Cervello”, Via Trabucco, 180, 90146 Palermo, Italy; (A.S.)
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Piazza delle Cliniche, 2, 90127 Palermo, Italy
| | - Alessandra Giuliano
- Internal Medicine Unit, “V. Cervello” Hospital, Ospedali Riuniti “Villa Sofia-Cervello”, Via Trabucco, 180, 90146 Palermo, Italy; (A.S.)
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Piazza delle Cliniche, 2, 90127 Palermo, Italy
| | - Luca Bertoncello
- Internal Medicine Unit, “V. Cervello” Hospital, Ospedali Riuniti “Villa Sofia-Cervello”, Via Trabucco, 180, 90146 Palermo, Italy; (A.S.)
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Piazza delle Cliniche, 2, 90127 Palermo, Italy
| | - Giorgia Cavallo
- Internal Medicine Unit, “V. Cervello” Hospital, Ospedali Riuniti “Villa Sofia-Cervello”, Via Trabucco, 180, 90146 Palermo, Italy; (A.S.)
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Piazza delle Cliniche, 2, 90127 Palermo, Italy
| | - Marta Chiavetta
- Internal Medicine Unit, “V. Cervello” Hospital, Ospedali Riuniti “Villa Sofia-Cervello”, Via Trabucco, 180, 90146 Palermo, Italy; (A.S.)
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Piazza delle Cliniche, 2, 90127 Palermo, Italy
| | - Francesco Faraci
- Internal Medicine Unit, “V. Cervello” Hospital, Ospedali Riuniti “Villa Sofia-Cervello”, Via Trabucco, 180, 90146 Palermo, Italy; (A.S.)
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Piazza delle Cliniche, 2, 90127 Palermo, Italy
| | - Alessia Nigro
- Internal Medicine Unit, “V. Cervello” Hospital, Ospedali Riuniti “Villa Sofia-Cervello”, Via Trabucco, 180, 90146 Palermo, Italy; (A.S.)
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Piazza delle Cliniche, 2, 90127 Palermo, Italy
| | - Alessandro Termini
- Internal Medicine Unit, “V. Cervello” Hospital, Ospedali Riuniti “Villa Sofia-Cervello”, Via Trabucco, 180, 90146 Palermo, Italy; (A.S.)
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Piazza delle Cliniche, 2, 90127 Palermo, Italy
| | - Laura Verona
- Internal Medicine Unit, “V. Cervello” Hospital, Ospedali Riuniti “Villa Sofia-Cervello”, Via Trabucco, 180, 90146 Palermo, Italy; (A.S.)
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Piazza delle Cliniche, 2, 90127 Palermo, Italy
| | - Agnese Ammannato
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Piazza delle Cliniche, 2, 90127 Palermo, Italy
| | - Salvatore Accomando
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Piazza delle Cliniche, 2, 90127 Palermo, Italy
- Department of Pediatrics, University Hospital of Palermo, 90134 Palermo, Italy
| | - Francesca Cavataio
- Pediatric Gastroenterology Unit, “Di Cristina” Hospital, Palermo, 90134 Palermo, Italy
| | | | - Michele Citrano
- Pediatrics Unit, “V. Cervello” Hospital, Ospedali Riuniti “Villa Sofia-Cervello”, Via Trabucco, 180, 90146 Palermo, Italy
| | - Diana Di Liberto
- Department of Biomedicine, Neurosciences and Advanced Diagnostics (BIND), Institute of Biochemistry, University of Palermo, 90127 Palermo, Italy
| | - Maurizio Soresi
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Piazza delle Cliniche, 2, 90127 Palermo, Italy
| | - Pasquale Mansueto
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Piazza delle Cliniche, 2, 90127 Palermo, Italy
| | - Antonio Carroccio
- Internal Medicine Unit, “V. Cervello” Hospital, Ospedali Riuniti “Villa Sofia-Cervello”, Via Trabucco, 180, 90146 Palermo, Italy; (A.S.)
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Piazza delle Cliniche, 2, 90127 Palermo, Italy
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Subedi R, Soulat A, Rauf Butt S, Mohan A, Danish Butt M, Arwani S, Ahmed G, Majumder K, Mohan Lal P, Kumar V, Tejwaney U, Ram N, Kumar S. Exploring the association between atrial fibrillation and celiac disease: a comprehensive review. Ann Med Surg (Lond) 2024; 86:7155-7163. [PMID: 39649916 PMCID: PMC11623827 DOI: 10.1097/ms9.0000000000002259] [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: 06/24/2023] [Accepted: 05/10/2024] [Indexed: 12/11/2024] Open
Abstract
Objective This paper aims to provide a comprehensive overview of the pathophysiology of atrial fibrillation (AF) and celiac disease (CD) individually while also exploring the emerging evidence of a potential association between the two conditions. Methods The pathophysiology of AF, the most prevalent arrhythmia globally, and CD, an autoimmune condition triggered by gluten consumption, is examined. Genetic, structural, electrophysiological, and inflammatory factors contributing to their development are explored. Results AF involves irregular atrial activity leading to electrical and structural remodeling of the atrium. CD is characterized by an immune response to gluten, primarily associated with HLA-DQ2 and HLA-DQ8 genetic mutations, resulting in damage to intestinal tissue. Emerging research suggests a link between AF and CD, possibly mediated through inflammation, fibrosis, and electromechanical delays in the atrium. Conclusion Understanding the association between AF and CD carries significant clinical implications. Recognition of this relationship can assist in identifying individuals at higher risk for AF and inform proactive management strategies. Additionally, it underscores the importance of comprehensive care for CD patients, considering potential cardiac implications. Further research is warranted to elucidate precise mechanisms and explore potential therapeutic interventions targeting common pathways, opening avenues for enhanced patient care and future investigations.
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Affiliation(s)
- Rasish Subedi
- Universal College of Medical Sciences, Siddharthanagar
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- Aga Khan University Hospital, Karachi
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Cazac GD, Mihai BM, Ștefănescu G, Gîlcă-Blanariu GE, Mihai C, Grigorescu ED, Onofriescu A, Lăcătușu CM. Celiac Disease, Gluten-Free Diet and Metabolic Dysfunction-Associated Steatotic Liver Disease. Nutrients 2024; 16:2008. [PMID: 38999756 PMCID: PMC11243569 DOI: 10.3390/nu16132008] [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: 06/05/2024] [Revised: 06/21/2024] [Accepted: 06/22/2024] [Indexed: 07/14/2024] Open
Abstract
Celiac disease (CD) is a chronic autoimmune disorder triggered by the ingestion of gluten-containing food by genetically predisposed individuals. Hence, treatment of CD consists of permanent avoidance of wheat, rye, barley, and other gluten-containing foods. Lifelong adherence to a gluten-free diet (GFD) improves the symptoms of CD, but recent evidence suggests it is also associated with a higher risk for hepatic steatosis and the coexistence or emergence of other cardiometabolic risk factors. Moreover, a higher risk for liver steatosis is also reported by some authors as a potential extraintestinal complication of the CD itself. Recent nomenclature changes designate the association between hepatic steatosis and at least one of five cardiometabolic risk factors as metabolic dysfunction-associated steatotic liver disease (MASLD). An extended network of potentially causative factors underlying the association between MAFLD and CD, before and after dietary therapy is implemented, was recently described. The individualized treatment of these patients is less supported by evidence, with most of the current recommendations relying on empiric clinical judgment. This review focuses on the causative associations between CD and hepatic injury, either as an extraintestinal manifestation of CD or a side effect of GFD, also referring to potential therapeutic strategies for these individuals.
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Affiliation(s)
- Georgiana-Diana Cazac
- Unit of Diabetes, Nutrition, and Metabolic Diseases, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania; (G.-D.C.); (A.O.); (C.-M.L.)
- Clinical Center of Diabetes, Nutrition and Metabolic Diseases, “Sf. Spiridon” County Clinical Emergency Hospital, 700111 Iași, Romania
| | - Bogdan-Mircea Mihai
- Unit of Diabetes, Nutrition, and Metabolic Diseases, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania; (G.-D.C.); (A.O.); (C.-M.L.)
- Clinical Center of Diabetes, Nutrition and Metabolic Diseases, “Sf. Spiridon” County Clinical Emergency Hospital, 700111 Iași, Romania
| | - Gabriela Ștefănescu
- Unit of Medical Semiology and Gastroenterology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (G.Ș.); (G.-E.G.-B.); (C.M.)
- Institute of Gastroenterology and Hepatology, “Sf. Spiridon” County Clinical Emergency Hospital, 700111 Iași, Romania
| | - Georgiana-Emmanuela Gîlcă-Blanariu
- Unit of Medical Semiology and Gastroenterology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (G.Ș.); (G.-E.G.-B.); (C.M.)
- Institute of Gastroenterology and Hepatology, “Sf. Spiridon” County Clinical Emergency Hospital, 700111 Iași, Romania
| | - Cătălina Mihai
- Unit of Medical Semiology and Gastroenterology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (G.Ș.); (G.-E.G.-B.); (C.M.)
- Institute of Gastroenterology and Hepatology, “Sf. Spiridon” County Clinical Emergency Hospital, 700111 Iași, Romania
| | - Elena-Daniela Grigorescu
- Unit of Diabetes, Nutrition, and Metabolic Diseases, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania; (G.-D.C.); (A.O.); (C.-M.L.)
- Clinical Center of Diabetes, Nutrition and Metabolic Diseases, “Sf. Spiridon” County Clinical Emergency Hospital, 700111 Iași, Romania
| | - Alina Onofriescu
- Unit of Diabetes, Nutrition, and Metabolic Diseases, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania; (G.-D.C.); (A.O.); (C.-M.L.)
- Clinical Center of Diabetes, Nutrition and Metabolic Diseases, “Sf. Spiridon” County Clinical Emergency Hospital, 700111 Iași, Romania
| | - Cristina-Mihaela Lăcătușu
- Unit of Diabetes, Nutrition, and Metabolic Diseases, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iași, Romania; (G.-D.C.); (A.O.); (C.-M.L.)
- Clinical Center of Diabetes, Nutrition and Metabolic Diseases, “Sf. Spiridon” County Clinical Emergency Hospital, 700111 Iași, Romania
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Yoosuf S, Singh P, Khaitan A, Strand TA, Ahuja V, Makharia GK. Prevalence of Celiac Disease in Patients With Liver Diseases: A Systematic Review and Meta-Analyses. Am J Gastroenterol 2023; 118:820-832. [PMID: 36599134 DOI: 10.14309/ajg.0000000000002123] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Accepted: 11/02/2022] [Indexed: 01/06/2023]
Abstract
INTRODUCTION A subset of patients with celiac disease (CeD) has liver involvement in the form of hypertransaminasemia, liver cirrhosis, and autoimmune hepatitis. We conducted a systematic review with meta-analyses to determine the pooled prevalence of CeD in patients with cryptogenic cirrhosis, all-cause cirrhosis, cryptogenic hypertransaminasemia, and all-cause hypertransaminasemia. METHODS We searched PubMed and EMBASE up to January 2022. Cross-sectional, case-control, and prospective cohort studies performing serological tests and/or intestinal biopsy for CeD on patients with cryptogenic cirrhosis, all-cause cirrhosis, cryptogenic hypertransaminasemia, and all-cause hypertransaminasemia were included to calculate pooled estimates of seroprevalence and the prevalence of biopsy-confirmed CeD in these 4 groups. RESULTS Of 6,871 articles screened, 20 articles were included finally in 3 meta-analyses for cryptogenic cirrhosis, all-cause cirrhosis, and cryptogenic hypertransaminasemia. For the all-cause hypertransaminasemia group, a qualitative review of 4 studies was conducted instead of a meta-analysis due to significant differences in studies. The pooled prevalence (95% confidence interval) of biopsy-confirmed CeD in cryptogenic cirrhosis was 4.6% (2.2%-7.5%) while the pooled prevalence of biopsy-confirmed CeD in all-cause cirrhosis was 0.8% (0%-3.4%). The pooled prevalence of biopsy-confirmed CeD in cryptogenic hypertransaminasemia was 5.7% (3.2%-8.8%). DISCUSSION Nearly 1 in 20 patients each with cryptogenic cirrhosis and cryptogenic hypertransaminasemia have CeD; hence, they should both be considered high-risk groups for CeD. While the prevalence of CeD in those with all-cause cirrhosis is similar to that in general population, it may be worth screening them for CeD because liver pathology has the potential for reversal in them.
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Affiliation(s)
- Shakira Yoosuf
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, Delhi, India
- Chettinad Hospital and Research Institute, Chennai, Tamilnadu, India
| | - Prashant Singh
- Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan, USA
| | - Ashank Khaitan
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, Delhi, India
| | - Tor A Strand
- Department of Global Public Health, Innlandet Hospital Trust, Lillehammer, Norway
| | - Vineet Ahuja
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, Delhi, India
| | - Govind K Makharia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, Delhi, India
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Salarian L, Khavaran M, Dehghani SM, Mashhadiagha A, Moosavi SA, Rezaeianzadeh S. Extra-intestinal manifestations of Celiac disease in children: their prevalence and association with human leukocyte antigens and pathological and laboratory evaluations. BMC Pediatr 2023; 23:8. [PMID: 36597078 PMCID: PMC9811781 DOI: 10.1186/s12887-022-03826-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2022] [Accepted: 12/28/2022] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Celiac disease (CD) is an autoimmune disease caused by gluten intake. Traditionally CD was believed to be a disease of the gut, although a wide range of extra-intestinal manifestations (EIM) was recognized. The exact prevalence of EIM and the associated risk factors have not been well studied. AIM We aimed to assess the prevalence of EIM in children with CD and their association with human leukocyte antigen (HLA) typing, and pathological and laboratory indices. METHOD We conducted a cross-sectional study on children and adolescents with a definite diagnosis of CD. They were followed in the main Celiac Clinic of Southern Iran. RESULTS We included 204 children who were visited between 2012 and 2017. Nearly 85% of them were positive for HLA-DQ2 and 40.6% for HLA-DQ8. The most prevalent intestinal complaints reported were abdominal pain (42.6%) and chronic constipation (19.1%). Failure-to-thrive (32.7%), iron deficiency anemia (25%), short stature (20.5%), and eczema (18.6%) were the most common EIMs. However, failure-to-thrive and short stature were presented at significantly younger ages, whereas those patients with concomitant type 1 diabetes mellitus (DM) were significantly older. We also found significant relationships between autoimmune thyroid disease and HLA-DQ5, and the presence of headaches with HLA-DQ7. The prevalence of HLA types of DQ2, DQ8, DQ6, and DQ7 significantly varied among different Marsh groups. Patients who were positive for HLA-DQ8, were significantly older, taller, and weightier. No significant association was found between HLA types and any of the gastrointestinal symptoms, anti-tTG and compliance to gluten free diet. Moreover, there were no statistically significant differences detected between the presence of each individual EIM, the level of IgA anti-tTG, sex, and Marsh typing. CONCLUSION This study highlights the presence of EIM in CD and their associated factors. We show the potential role of HLA typing in some EIMs, which may shed light for future studies.
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Affiliation(s)
- Leila Salarian
- grid.412571.40000 0000 8819 4698Department of Pediatric Endocrinology, Shiraz University of Medical Sciences, Shiraz, Iran ,grid.412571.40000 0000 8819 4698Shiraz Neonatal Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mohammad Khavaran
- grid.412571.40000 0000 8819 4698Department of Pediatric Endocrinology, Shiraz University of Medical Sciences, Shiraz, Iran ,grid.412571.40000 0000 8819 4698Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Seyed Mohsen Dehghani
- grid.412571.40000 0000 8819 4698Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Amirali Mashhadiagha
- grid.412571.40000 0000 8819 4698Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran ,grid.412571.40000 0000 8819 4698Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Seyed Ali Moosavi
- grid.412571.40000 0000 8819 4698Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran ,grid.412571.40000 0000 8819 4698Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Shayan Rezaeianzadeh
- grid.412571.40000 0000 8819 4698Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
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Bakhshipour A, Rafaiee R. Spontaneous Latency in Adult Patients with Celiac Disease on a Normal Diet after Gluten-Free Diet: Case Series. Middle East J Dig Dis 2022; 14:354-358. [PMID: 36619275 PMCID: PMC9489428 DOI: 10.34172/mejdd.2022.295] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Accepted: 04/29/2022] [Indexed: 11/06/2022] Open
Abstract
Celiac disease (CeD) is an immune condition induced by the consumption of gluten-containing foods in genetically-predisposed persons. CeD, in addition to digestive disease, is a multisystem disorder. If untreated, it is potentially can be a dangerous disorder and lead to morbidity and even mortality. At present, the only treatment option is a lifelong gluten-free diet (GFD), and all authors recommended this regimen. To the best of our knowledge, there are rare reports of the complete remission of disorder on GFD and reintroduction of a normal diet in affected patients. In this report, we describe five patients with CeD who developed complete remission of clinical symptoms, histopathological changes, and serology on a gluten-containing diet. All patients had CeD based on a positive tissue transglutaminase antibody (TTG IgA) and typical histopathological changes in duodenal biopsy with the complete disappearance of symptoms on the GFD regimen. All patients followed GFD for a mean 4 (±0.54) years. In conclusion, this study has shown that some CeD patients diagnosed in adulthood can recover a normal mucosa after a long period of the gluten-containing diet without relapsing any clinical or biological symptoms of CeD.
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Affiliation(s)
- Alireza Bakhshipour
- Associate Professor, Infectious Diseases and Tropical Medicine Research Center, Research Institute of Cellular and Molecular Science in Infectious Diseases, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Raheleh Rafaiee
- Assistant Professor, Department of Neuroscience, School of Advanced Technologies in Medicine, Mazandaran University of Medical Sciences, Sari, Iran,Corresponding Author: Raheleh Rafaiee, MD, MPH, Ph.D. Department of Neuroscience, School of Advanced Technologies in Medicine, Mazandaran University of Medical Sciences, Sari, Iran Tel:+98 1133543081 Fax:+98 1133285109
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Altay D, Doğan Y. Liver Involvement in Children during the Diagnosis of Celiac Disease: A Single-Center Experience from Turkey. Middle East J Dig Dis 2022; 14:200-206. [PMID: 36619153 PMCID: PMC9489308 DOI: 10.34172/mejdd.2022.273] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Accepted: 05/03/2022] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND: Liver abnormalities in Celiac disease (CD) are common. The aim of this study was to investigate the children with CD who were followed up in our clinic presenting with elevated aminotransferase levels. METHODS: In this study, the data of 419 pediatric patients with CD were retrospectively analyzed, and those with elevated aminotransferase levels during the diagnosis of CD were assessed. RESULTS: Elevation of aminotransferase levels was found in 66 (15.7%) patients among the 419 patients during the diagnosis of CD. The mean age of these patients was 7.33±3.96 years. Liver enzymes were mildly elevated in 63 (95.4%) patients. However, half of the patients with elevated liver enzymes had a 1.25-fold increase in aminotransferase levels. Patients with hypertransaminasemia had higher weight loss and lower folic acid values compared with patients with normal liver enzymes. Patients' liver tests were reverted to normal, except for two patients with chronic liver disease, after 9.27±3.16 months of administering a gluten-free diet. CONCLUSION: Patients with liver involvement should be investigated for CD. Especially, mildly elevation of aminotransferase levels should be taken into account by pediatricians for Celiac hepatitis.
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Affiliation(s)
- Derya Altay
- Assistant Professor, Erciyes University, Faculty of Medicine, Department of Pediatric Gastroenterology, Hepatology and Nutrition, Kayseri, Turkey,Corresponding Author: Derya Altay, MD Erciyes University, Faculty of Medicine, Department of Pediatric Gastroenterology, Hepatology and Nutrition, Kayseri, Turkey, 23119 Tel: + 90 352 207 66 66 Fax: + 90 352 437 58 25
| | - Yaşar Doğan
- Professor, Fırat University, Faculty of Medicine, Department of Pediatric Gastroenterology, Hepatology and Nutrition, Elazığ, Turkey
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Raiteri A, Granito A, Giamperoli A, Catenaro T, Negrini G, Tovoli F. Current guidelines for the management of celiac disease: A systematic review with comparative analysis. World J Gastroenterol 2022; 28:154-175. [PMID: 35125825 PMCID: PMC8793016 DOI: 10.3748/wjg.v28.i1.154] [Citation(s) in RCA: 64] [Impact Index Per Article: 21.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Revised: 08/08/2021] [Accepted: 12/25/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Wheat and other gluten-containing grains are widely consumed, providing approximately 50% of the caloric intake in both industrialised and developing countries. The widespread diffusion of gluten-containing diets has rapidly led to a sharp increase in celiac disease prevalence. This condition was thought to be very rare outside Europe and relatively ignored by health professionals and the global media. However, in recent years, the discovery of important diagnostic and pathogenic milestones has led to the emergence of celiac disease (CD) from obscurity to global prominence. These modifications have prompted experts worldwide to identify effective strategies for the diagnosis and follow-up of CD. Different scientific societies, mainly from Europe and America, have proposed guidelines based on CD's most recent evidence. AIM To identify the most recent scientific guidelines on CD, aiming to find and critically analyse the main differences. METHODS We performed a database search on PubMed selecting papers published between January 2010 and January 2021 in the English language. PubMed was lastly accessed on 1 March 2021. RESULTS We distinguished guidelines from 7 different scientific societies whose reputation is worldwide recognized and representative of the clinical practice in different geographical regions. Differences were noted in the possibility of a no-biopsy diagnosis, HLA testing, follow-up protocols, and procedures. CONCLUSION We found a relatively high concordance between the guidelines for CD. Important modifications have occurred in the last years, especially about the possibility of a no-biopsy diagnosis in children. Other modifications are expected in the next future and will probably involve the extension of the non-invasive diagnosis to the adult population and the follow-up modalities.
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Affiliation(s)
- Alberto Raiteri
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy
| | - Alessandro Granito
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy
| | - Alice Giamperoli
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy
| | - Teresa Catenaro
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy
| | - Giulia Negrini
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy
| | - Francesco Tovoli
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy
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9
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Villavicencio Kim J, Wu GY. Celiac Disease and Elevated Liver Enzymes: A Review. J Clin Transl Hepatol 2021; 9:116-124. [PMID: 33604262 PMCID: PMC7868701 DOI: 10.14218/jcth.2020.00089] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2020] [Revised: 11/08/2020] [Accepted: 11/17/2020] [Indexed: 02/06/2023] Open
Abstract
Aminotransferases are commonly found to be elevated in patients with celiac disease in association with two different types of liver dysfunction: cryptogenic liver disorders and autoimmune disorders. The purpose of this review is to discuss the mechanisms by which aminotransferases become elevated in celiac disease, clinical manifestations, and response to gluten-free diet. Many studies have shown that celiac patients with cryptogenic liver disease have normalization in aminotransferases, intestinal histologic improvement and serologic resolution after 6-12 months of strict gluten-free diet. In patients with an underlying autoimmune liver disease, simultaneous treatment for both conditions resulted in normalized elevated aminotransferases. The literature suggests that intestinal permeability may be at least one of the mechanisms by which liver damage occurs. Patients with celiac disease should have liver enzymes routinely checked and treated with a strict gluten-free diet if found to be abnormal. Lack of improvement in patients who have strictly adhered to gluten-free diet should prompt further workup for other causes of liver disease.
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Affiliation(s)
- Jaimy Villavicencio Kim
- Department of Medicine, University of Connecticut Health Center, Farmington, CT, USA
- Correspondence to: Jaimy Villavicencio Kim, Department of Medicine, University of Connecticut Health Center, 263 Farmington Ave, Farmington, CT 06032, USA. Tel: +1-860-899-8739, E-mail:
| | - George Y. Wu
- Division of GastroenterologyHepatology, University of Connecticut Health Center, Farmington, CT, USA
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10
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Tarar ZI, Zafar MU, Farooq U, Basar O, Tahan V, Daglilar E. The Progression of Celiac Disease, Diagnostic Modalities, and Treatment Options. J Investig Med High Impact Case Rep 2021; 9:23247096211053702. [PMID: 34693776 PMCID: PMC8767653 DOI: 10.1177/23247096211053702] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Revised: 09/20/2021] [Accepted: 09/28/2021] [Indexed: 01/15/2023] Open
Abstract
Celiac disease (CD) is an autoimmune disorder that affects genetically predisposed individuals who are sensitive to gluten and related proteins. It affects children and adults with increasing prevalence in the older age groups. Both adaptive and innate immune responses play role in CD pathogenesis which results in damage of lamina propria and deposition of intraepithelial lymphocytes. There are other proposed mechanisms of CD pathogenesis like gastrointestinal infections, intestinal microbiota, and early introduction of gluten. The diagnosis of CD is based on clinical symptoms and serological testing, though a majority of cases are asymptomatic, and small intestinal biopsies are required to confirm the diagnosis. Celiac disease is generally associated with other autoimmune diseases, and it is advisable to test these patients for diseases like type 1 diabetes mellitus, Addison's disease, thyroid diseases, inflammatory bowel disease, and autoimmune hepatitis. The patient with a new diagnosis of CD requires close follow-up after starting treatment to see symptom improvement and check dietary compliance. A newly diagnosed patient is advised to follow with a dietitian to better understand the dietary restrictions as about 20% of patients stay symptomatic even after starting treatment due to noncompliance or poor understanding of diet restrictions. The most effective treatment for CD is a gluten-free diet, but work on non-dietary therapy is in process and few medications are in the clinical trial phase.
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Affiliation(s)
| | | | - Umer Farooq
- Loyola Medicine/MacNeal Hospital, Berwyn, IL, USA
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11
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Yanny B, Grewal JK, Vaswani VK. Celiac Disease and the Liver. DIAGNOSIS AND MANAGEMENT OF GLUTEN-ASSOCIATED DISORDERS 2021:27-40. [DOI: 10.1007/978-3-030-56722-4_3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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12
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Mack CL, Adams D, Assis DN, Kerkar N, Manns MP, Mayo MJ, Vierling JM, Alsawas M, Murad MH, Czaja AJ. Diagnosis and Management of Autoimmune Hepatitis in Adults and Children: 2019 Practice Guidance and Guidelines From the American Association for the Study of Liver Diseases. Hepatology 2020; 72:671-722. [PMID: 31863477 DOI: 10.1002/hep.31065] [Citation(s) in RCA: 546] [Impact Index Per Article: 109.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2019] [Accepted: 11/25/2019] [Indexed: 02/06/2023]
Affiliation(s)
- Cara L Mack
- Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO
| | - David Adams
- Centre for Liver Research, University of Birmingham, Birmingham, UK
| | - David N Assis
- Department of Internal Medicine, Yale School of Medicine, New Haven, CT
| | - Nanda Kerkar
- Golisano Children's Hospital at Strong, University of Rochester Medical Center, New York, NY
| | - Michael P Manns
- Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Marlyn J Mayo
- Division of Digestive and Liver Diseases, University of Texas SW Medical Center, Dallas, TX
| | - John M Vierling
- Medicine and Surgery, Baylor College of Medicine, Houston, TX
| | | | - Mohammad H Murad
- Mayo Knowledge and Encounter Research Unit, Mayo Clinic College of Medicine, Rochester, MN
| | - Albert J Czaja
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN
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13
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Stickel F, Wartenberg M, Bouzourene H, Ortner MA, Rogler G. Recurrent Fever and Failure to Thrive in an 11-Year-Old Boy. Case Rep Gastroenterol 2019; 13:350-356. [PMID: 31607835 PMCID: PMC6787408 DOI: 10.1159/000502604] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2019] [Accepted: 08/09/2019] [Indexed: 12/03/2022] Open
Abstract
Recurrent fever is frequent among children and mostly associated with viral infections inoculated via social contacts with others of the same age. Rarely, severe conditions such as hematological malignancies, pediatric rheumatoid diseases, chronic infections, or inherited recurrent fever syndromes are causative. Herein, we present the case of an 11-year-old boy with frequently recurring high-fever episodes since early childhood, failure to thrive, and iron deficiency who was found to have classical celiac disease (CD) with highly elevated tissue transglutaminase and anti-gliadin antibodies and marked duodenal villous atrophy. Upon implementation of a gluten-free diet, the boy ceased to have fevers, antibodies decreased markedly, his iron status improved, and he significantly gained weight. Although infrequent, recurrent fever should be included into the polymorphic clinical picture of CD, and the threshold of testing for diagnostic antibodies should be low in such patients.
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Affiliation(s)
- Felix Stickel
- Hepatology Unit, Klinik Beau-Site, Hirslanden Bern, Bern, Switzerland.,Department of Gastroenterology and Hepatology, University Hospital of Zurich, Zurich, Switzerland
| | | | | | - Maria Anna Ortner
- Department of Gastroenterology and Hepatology, University Hospital of Zurich, Zurich, Switzerland
| | - Gerhard Rogler
- Department of Gastroenterology and Hepatology, University Hospital of Zurich, Zurich, Switzerland
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14
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El-Shaheed AA, El-Arab AE, El-Kassas GM, El Wakeel MA, Abou-Zekri M, Anwar M. An Innovative Effective Nutritional Therapy for Vitamin D Deficiency in Children with Celiac Disease. BIOMEDICAL & PHARMACOLOGY JOURNAL 2019; 12:1481-1490. [DOI: 10.13005/bpj/1778] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/02/2023]
Abstract
Children with celiac disease (CD) are susceptible to reduced bone mineral density (BMD). Our target is to assess the severity of vitamin D deficiency in CD children on a gluten-free diet (GFD), and to evaluate the effectiveness of adding an innovative GF meal, on the clinical and bone biochemical indices of CD patients. 50 CD children who were diagnosed and followed up at Pediatric gastroenterology clinic, Specialized pediatric hospital, Cairo University; by serology and biopsy of the duodenum were included in this prospective study. CD children were on GFD for at least one year. As a control group, 40 healthy children were enrolled. Thorough clinical examination, anthropometric assessment, a complete history and 24 hours dietary recall were done for all the participants in this work. We introduced our innovative GF meal to CD patients twice/day, for 3 consecutive months. Venous blood samples were withdrawn from patients at the study beginning and after 3 months for detection of serum vitamin D, calcium, phosphorous and alkaline phosphatase levels. The anthropometric measurements, serum vitamin D, and calcium were markedly decreased in CD children than that of controls. In CD patients, a significant increase in anthropometric parameters, vitamin D and calcium were found. While there was a significant decline of serum alkaline phosphatase, and a slight decrease in serum phosphorus at the study end. The innovative gluten-free prepared meal confirmed to be of high nutritional value in the management of vitamin D deficiency and improvement of bone indices in CD patient.
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Affiliation(s)
| | - Aly Ezz El-Arab
- Food Science and Nutrition Department, National Research Center, Cairo, Egypt
| | | | | | - Maha Abou-Zekri
- Consultant of Pediatric gastroenterology, specialized pediatric hospital, Cairo University, Egypt
| | - Mona Anwar
- Department of pharmacology, college of pharmacy, Aljouf University, Sakaka, Kingdom of Saudi Arabia
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15
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Caio G, Volta U, Sapone A, Leffler DA, De Giorgio R, Catassi C, Fasano A. Celiac disease: a comprehensive current review. BMC Med 2019; 17:142. [PMID: 31331324 PMCID: PMC6647104 DOI: 10.1186/s12916-019-1380-z] [Citation(s) in RCA: 545] [Impact Index Per Article: 90.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Accepted: 06/27/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Celiac disease remains a challenging condition because of a steady increase in knowledge tackling its pathophysiology, diagnosis, management, and possible therapeutic options. MAIN BODY A major milestone in the history of celiac disease was the identification of tissue transglutaminase as the autoantigen, thereby confirming the autoimmune nature of this disorder. A genetic background (HLA-DQ2/DQ8 positivity and non-HLA genes) is a mandatory determinant of the development of the disease, which occurs with the contribution of environmental factors (e.g., viral infections and dysbiosis of gut microbiota). Its prevalence in the general population is of approximately 1%, with female predominance. The disease can occur at any age, with a variety of symptoms/manifestations. This multifaceted clinical presentation leads to several phenotypes, i.e., gastrointestinal, extraintestinal, subclinical, potential, seronegative, non-responsive, and refractory. Although small intestinal biopsy remains the diagnostic 'gold standard', highly sensitive and specific serological tests, such as tissue transglutaminase, endomysial and deamidated gliadin peptide antibodies, have become gradually more important in the diagnostic work-up of celiac disease. Currently, the only treatment for celiac disease is a life-long, strict gluten-free diet leading to improvement in quality of life, ameliorating symptoms, and preventing the occurrence of refractory celiac disease, ulcerative jejunoileitis, and small intestinal adenocarcinoma and lymphoma. CONCLUSIONS The present review is timely and provides a thorough appraisal of various aspects characterizing celiac disease. Remaining challenges include obtaining a better understanding of still-unclear phenotypes such as slow-responsive, potential (minimal lesions) and seronegative celiac disease. The identification of alternative or complementary treatments to the gluten-free diet brings hope for patients unavoidably burdened by diet restrictions.
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Affiliation(s)
- Giacomo Caio
- Department of Medical Sciences, University of Ferrara, Via Aldo Moro 8, Cona, 44124 Ferrara, Italy
- Center for Celiac Research and Treatment, Massachusetts General Hospital, Boston, MA 02114 USA
| | - Umberto Volta
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy
| | - Anna Sapone
- Center for Celiac Research and Treatment, Massachusetts General Hospital, Boston, MA 02114 USA
- Takeda Pharmaceuticals International Co, Cambridge, MA 02139 USA
| | - Daniel A. Leffler
- Takeda Pharmaceuticals International Co, Cambridge, MA 02139 USA
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA 02115 USA
| | - Roberto De Giorgio
- Department of Medical Sciences, University of Ferrara, Via Aldo Moro 8, Cona, 44124 Ferrara, Italy
| | - Carlo Catassi
- Center for Celiac Research and Treatment, Massachusetts General Hospital, Boston, MA 02114 USA
- Department of Pediatrics, Center for Celiac Research, Università Politecnica delle Marche, 60121 Ancona, Italy
| | - Alessio Fasano
- Center for Celiac Research and Treatment, Massachusetts General Hospital, Boston, MA 02114 USA
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16
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Abstract
Celiac disease is a multisystem disorder. Celiac hepatitis characterized by gluten-responsive mild elevation of transaminases is the more common liver manifestation of celiac disease. Celiac disease may also be associated or coexist with other chronic liver disorders. Shared genetic risk and increased intestinal permeability have been suggested to be the most relevant events in the pathogenesis of liver injury in celiac disease. The aim of this article is to review the full spectrum of liver disorders in patients with celiac disease.
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Affiliation(s)
- Alberto Rubio-Tapia
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905
| | - Joseph A. Murray
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905
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17
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Hujoel IA, Reilly NR, Rubio-Tapia A. Celiac Disease: Clinical Features and Diagnosis. Gastroenterol Clin North Am 2019; 48:19-37. [PMID: 30711209 DOI: 10.1016/j.gtc.2018.09.001] [Citation(s) in RCA: 52] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The presentation in celiac disease is shifting from the classical malabsorptive presentation to more nonclassical presentations, requiring clinicians to maintain a high level of suspicion for the disease and to be aware of the possible extraintestinal manifestations. The diagnosis of celiac disease is guided by initial screening with serology, followed by confirmation with an upper endoscopy and small intestinal biopsy. In some pediatric cases, biopsy may be avoided.
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Affiliation(s)
- Isabel A Hujoel
- Division of Gastroenterology and Hepatology, Mayo Clinic, 200 1st Street Southwest, Rochester, MN 55905, USA
| | - Norelle R Reilly
- Division of Pediatric Gastroenterology, Columbia University Medicine Center, 630 West 168th Street, PH-17, New York, NY 10032, USA
| | - Alberto Rubio-Tapia
- Division of Gastroenterology and Hepatology, Mayo Clinic, 200 1st Street Southwest, Rochester, MN 55905, USA.
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18
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Popp A, Mäki M. Gluten-Induced Extra-Intestinal Manifestations in Potential Celiac Disease-Celiac Trait. Nutrients 2019; 11:nu11020320. [PMID: 30717318 PMCID: PMC6412544 DOI: 10.3390/nu11020320] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2018] [Revised: 01/28/2019] [Accepted: 01/29/2019] [Indexed: 12/24/2022] Open
Abstract
Celiac disease patients may suffer from a number of extra-intestinal diseases related to long-term gluten ingestion. The diagnosis of celiac disease is based on the presence of a manifest small intestinal mucosal lesion. Individuals with a normal biopsy but an increased risk of developing celiac disease are referred to as potential celiac disease patients. However, these patients are not treated. This review highlights that patients with normal biopsies may suffer from the same extra-intestinal gluten-induced complications before the disease manifests at the intestinal level. We discuss diagnostic markers revealing true potential celiac disease. The evidence-based medical literature shows that these potential patients, who are “excluded” for celiac disease would in fact benefit from gluten-free diets. The question is why wait for an end-stage disease to occur when it can be prevented? We utilize research on dermatitis herpetiformis, which is a model disease in which a gluten-induced entity erupts in the skin irrespective of the state of the small intestinal mucosal morphology. Furthermore, gluten ataxia can be categorized as its own entity. The other extra-intestinal manifestations occurring in celiac disease are also found at the latent disease stage. Consequently, patients with celiac traits should be identified and treated.
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Affiliation(s)
- Alina Popp
- University of Medicine and Pharmacy "Carol Davila" and National Institute for Mother and Child Health "Alessandrescu-Rusescu", Bucharest 020395, Romania.
- Faculty of Medicine and Health Technology, Tampere University and Tampere University Hospital, 33520 Tampere, Finland.
| | - Markku Mäki
- Faculty of Medicine and Health Technology, Tampere University and Tampere University Hospital, 33520 Tampere, Finland.
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19
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Abstract
Coeliac disease (CD) develops in genetically susceptible individuals who, in response to unclear environmental triggers, develop an immune response triggered by gluten ingestion. It is now recognised as a global disease affecting about 0.7% of the world's population. The clinical presentation ranges from malabsorption to asymptomatic individuals diagnosed by screening high-risk groups. Diagnosis requires the demonstration of small intestinal villous atrophy in the presence of circulating coeliac auto-antibodies and/or an unequivocal response to a gluten-free diet (GFD). Recent guidelines suggest that, in a subset of children, duodenal biopsies can be avoided in the presence of strict symptomatic and serological criteria. While the majority of patients respond to a GFD, up to 20% of patients with CD have persistent or recurrent symptoms. There are several aetiologies for residual or new symptoms in a patient with CD on a GFD, with inadvertent exposure to gluten being the most common. Following a GFD can be challenging for patients with CD and understanding the barriers/challenges faced by patients in maintaining a GFD is crucial for compliance. Abbreviations: AGA: anti-gliadin antibodies; Anti-DGP-ab: anti-deamidated gliadin peptide antibodies; Anti-tTG-ab: anti-tissue transglutaminase antibodies; ATD: auto-immune thyroid disorders; BMD: bone mineral density; CD: coeliac disease; DH: dermatitis herpetiformis; EMA: anti-endomysial antibodies; FDR: first-degree relatives; GFD: gluten-free diet; HbA1c: haemoglobin A1c; HLA: human leucocyte antigen; IBS: irritable bowel syndrome; LMIC: low- and middle-income countries; NPV: negative predictive value; NRCD: non-responsive coeliac disease; POCT: point-of-care tests; SDR: second-degree relatives; SIBO: small intestinal bacterial overgrowth; T1DM: type 1 diabetes mellitus; ULN: upper limit of normal.
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Affiliation(s)
- Jeremy R Glissen Brown
- a Division of Gastroenterology and Hepatology , Beth Israel Deaconess Medical Center , Boston , Massachusetts , USA
| | - Prashant Singh
- a Division of Gastroenterology and Hepatology , Beth Israel Deaconess Medical Center , Boston , Massachusetts , USA
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20
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Plauth M, Bernal W, Dasarathy S, Merli M, Plank LD, Schütz T, Bischoff SC. ESPEN guideline on clinical nutrition in liver disease. Clin Nutr 2019; 38:485-521. [PMID: 30712783 DOI: 10.1016/j.clnu.2018.12.022] [Citation(s) in RCA: 392] [Impact Index Per Article: 65.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2018] [Accepted: 12/18/2018] [Indexed: 02/06/2023]
Abstract
This update of evidence-based guidelines (GL) aims to translate current evidence and expert opinion into recommendations for multidisciplinary teams responsible for the optimal nutritional and metabolic management of adult patients with liver disease. The GL was commissioned and financially supported by ESPEN. Members of the guideline group were selected by ESPEN. We searched for meta-analyses, systematic reviews and single clinical trials based on clinical questions according to the PICO format. The evidence was evaluated and used to develop clinical recommendations implementing the SIGN method. A total of 85 recommendations were made for the nutritional and metabolic management of patients with acute liver failure, severe alcoholic steatohepatitis, non-alcoholic fatty liver disease, liver cirrhosis, liver surgery and transplantation as well as nutrition associated liver injury distinct from fatty liver disease. The recommendations are preceded by statements covering current knowledge of the underlying pathophysiology and pathobiochemistry as well as pertinent methods for the assessment of nutritional status and body composition.
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Affiliation(s)
- Mathias Plauth
- Department of Internal Medicine, Municipal Hospital of Dessau, Dessau, Germany.
| | - William Bernal
- Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Srinivasan Dasarathy
- Division of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH, USA
| | - Manuela Merli
- Gastroenterology and Hepatology Unit, Sapienza University of Rome, Rome, Italy
| | - Lindsay D Plank
- Department of Surgery, University of Auckland, Auckland, New Zealand
| | - Tatjana Schütz
- IFB Adiposity Diseases, Leipzig University Medical Centre, Leipzig, Germany
| | - Stephan C Bischoff
- Department for Clinical Nutrition, University of Hohenheim, Stuttgart, Germany
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21
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Schranz M, Lucà MG, D’Antiga L, Fagiuoli S. The Liver in Systemic Illness. PEDIATRIC HEPATOLOGY AND LIVER TRANSPLANTATION 2019:361-396. [DOI: 10.1007/978-3-319-96400-3_22] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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22
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Hoffmanová I, Sánchez D, Tučková L, Tlaskalová-Hogenová H. Celiac Disease and Liver Disorders: From Putative Pathogenesis to Clinical Implications. Nutrients 2018; 10:nu10070892. [PMID: 30002342 PMCID: PMC6073476 DOI: 10.3390/nu10070892] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2018] [Revised: 07/04/2018] [Accepted: 07/10/2018] [Indexed: 12/12/2022] Open
Abstract
Immunologically mediated liver diseases belong to the common extraintestinal manifestations of celiac disease. We have reviewed the current literature that addresses the association between celiac disease and liver disorders. We searched relevant articles on MEDLINE/PubMed up to 15 June 2018. The objective of the article is to provide a comprehensive and up-to-date review on the latest hypotheses explaining the pathogenetic relationship between celiac disease and liver injury. Besides the involvement of gut–liver axis, tissue transglutaminase antibodies, and impairment of intestinal barrier, we integrate the latest achievements made in elucidation of the role of gut microbiota in celiac disease and liver disorders, that has not yet been sufficiently discussed in the literature in this context. The further objective is to provide a complete clinical overview on the types of liver diseases frequently found in celiac disease. In conclusion, the review highlights the clinical implication, recommend a rational approach for managing elevated transaminases in celiac patients, and underscore the importance of screening for celiac disease in patients with associated liver disease.
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Affiliation(s)
- Iva Hoffmanová
- Centre for Research on Nutrition, Metabolism and Diabetes, Third Faculty of Medicine, Charles University, Ruska 87, 100 00 Prague, Czech Republic.
- Second Department of Internal Medicine, Third Faculty of Medicine, Charles University, Ruska 87, 100 00 Prague, Czech Republic.
| | - Daniel Sánchez
- Laboratory of Cellular and Molecular Immunology, Institute of Microbiology of the Czech Academy of Sciences, v.v.i., Videnska 1083, 142 20 Prague, Czech Republic.
| | - Ludmila Tučková
- Laboratory of Cellular and Molecular Immunology, Institute of Microbiology of the Czech Academy of Sciences, v.v.i., Videnska 1083, 142 20 Prague, Czech Republic.
| | - Helena Tlaskalová-Hogenová
- Laboratory of Cellular and Molecular Immunology, Institute of Microbiology of the Czech Academy of Sciences, v.v.i., Videnska 1083, 142 20 Prague, Czech Republic.
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23
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Joshi A, Falodia S, Kumar N, Gupta P, Khatri PC. Prevalence of celiac disease among pediatric patients with cryptogenic cirrhosis and effect of gluten-free-diet. Indian J Gastroenterol 2018; 37:243-247. [PMID: 29948993 DOI: 10.1007/s12664-018-0857-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2018] [Accepted: 05/17/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND Liver involvement in celiac disease (CD) is classified into autoimmune and cryptogenic. The association between CD and autoimmune liver diseases like autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis is well-established; however, the data on patients with cryptogenic cirrhosis, particularly from India, are scanty. So we did this study to find the prevalence of CD in patients with cryptogenic cirrhosis. METHODS This was a prospective observational study, involving children of less than 18 years old attending Pediatric and Gastroenterology clinic with a diagnosis of cryptogenic cirrhosis. The patients were evaluated for CD and divided into two groups: chronic liver disease (CLD) with CD, and CLD without CD. Both the groups were followed up for 6 months. CLD with CD group was treated with gluten-free-diet (GFD) and CLD without CD group was followed up without any specific intervention except standard care of CLD. RESULTS Out of 84 patients, 11 (13.1%) were diagnosed as CLD with CD. There was an improvement in hemoglobin levels, liver function tests, and Child-Pugh score after initiation of GFD in CLD with CD group. CONCLUSION The prevalence of CD in cryptogenic cirrhosis was 13.1%. Screening for CD is recommended for cryptogenic cirrhosis. Hepatic functions improve with a GFD in CD patients with cirrhosis.
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Affiliation(s)
- Ashish Joshi
- Department of Gastroenterology, Sardar Patel Medical College, Bikaner, 334 001, India
| | - Sushil Falodia
- Department of Gastroenterology, Sardar Patel Medical College, Bikaner, 334 001, India
| | - Naveen Kumar
- Department of General Medicine, Sardar Patel Medical College, Bikaner, 334 001, India.
| | - Pawan Gupta
- Department of Pediatrics, Sardar Patel Medical College, Bikaner, 334 001, India
| | - P C Khatri
- Department of Pediatrics, Sardar Patel Medical College, Bikaner, 334 001, India
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24
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Vatansever S, Paköz ZB, Ünsal B. Primer biliyer sirozda çölyak hastalığı birlikteliği. EGE TIP DERGISI 2018. [DOI: 10.19161/etd.455438] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
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Malakouti M, Kataria A, Ali SK, Schenker S. Elevated Liver Enzymes in Asymptomatic Patients - What Should I Do? J Clin Transl Hepatol 2017; 5:394-403. [PMID: 29226106 PMCID: PMC5719197 DOI: 10.14218/jcth.2017.00027] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2017] [Revised: 06/22/2017] [Accepted: 07/12/2017] [Indexed: 12/14/2022] Open
Abstract
Elevated liver enzymes are a common scenario encountered by physicians in clinical practice. For many physicians, however, evaluation of such a problem in patients presenting with no symptoms can be challenging. Evidence supporting a standardized approach to evaluation is lacking. Although alterations of liver enzymes could be a normal physiological phenomenon in certain cases, it may also reflect potential liver injury in others, necessitating its further assessment and management. In this article, we provide a guide to primary care clinicians to interpret abnormal elevation of liver enzymes in asymptomatic patients using a step-wise algorithm. Adopting a schematic approach that classifies enzyme alterations on the basis of pattern (hepatocellular, cholestatic and isolated hyperbilirubinemia), we review an approach to abnormal alteration of liver enzymes within each section, the most common causes of enzyme alteration, and suggest initial investigations.
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Affiliation(s)
- Mazyar Malakouti
- Division of Gastroenterology and Nutrition, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
- *Correspondence to: Archish Kataria, Department of Internal Medicine, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, MC 7878, San Antonio, TX 78229, USA. Tel: +1-210-665-7038, Fax: +1-210-567-4856, E-mail: ; Mazyar Malakouti, Division of Gastroenterology and Nutrition, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, MC 7878, San Antonio, TX 78229, USA. Tel: +1-204-803-2523, Fax: +1-210-567-4856, E-mail:
| | - Archish Kataria
- Department of Internal Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
- *Correspondence to: Archish Kataria, Department of Internal Medicine, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, MC 7878, San Antonio, TX 78229, USA. Tel: +1-210-665-7038, Fax: +1-210-567-4856, E-mail: ; Mazyar Malakouti, Division of Gastroenterology and Nutrition, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, MC 7878, San Antonio, TX 78229, USA. Tel: +1-204-803-2523, Fax: +1-210-567-4856, E-mail:
| | - Sayed K. Ali
- Department of Internal Medicine, University of Central Florida, College of Medicine, Orlando, FL, USA
| | - Steven Schenker
- Division of Gastroenterology and Nutrition, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
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Pavlovic M, Berenji K, Bukurov M. Screening of celiac disease in Down syndrome - Old and new dilemmas. World J Clin Cases 2017; 5:264-269. [PMID: 28798921 PMCID: PMC5535317 DOI: 10.12998/wjcc.v5.i7.264] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2017] [Revised: 04/28/2017] [Accepted: 05/03/2017] [Indexed: 02/06/2023] Open
Abstract
Celiac disease (CD) is a common and well defined autoimmune disorder caused by gliadin and related proteins of wheat, rye, and barley. Epidemiologic studies confirmed that CD is highly associated with other autoimmune diseases and with Down syndrome (DS). The symptomatic form of CD in patients with DS is more frequent than asymptomatic forms. However, growth impairment, anemia, intermittent diarrhea, and constipation are symptoms and signs typically of children with DS without CD. Late identification of the disease can lead to various complications, sometimes even very severe. Therefore, systematic screening for CD is essential in the management of children and adolescents with DS. Many medical organizations recommend screening in this group of patients. However, current policy statements vary in their recommendations for screening and there is still a need for establishing uniform diagnostic criteria.
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Ghozzi M, Ben Salem MA, Mbarki F, Jmaa A, Baccouch A, Sakly N, Ben Jazia E, Ghedira I. Screening for celiac disease, by endomysial antibodies, in patients with unexplained hypertransaminasaemia. Scand J Clin Lab Invest 2017. [PMID: 28632434 DOI: 10.1080/00365513.2017.1338746] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
OBJECTIVE To do a serological screening for celiac disease in patients with unexplained liver cytolysis. MATERIALS AND METHODS Fifty-six patients with liver cytolysis without known aetiology were studied. Endomysial antibodies were determined by indirect immunofluorescence on human umbilical cord. Two thousand and five hundred blood donors served as control group. For statistical analysis, we used Chi-square or Fisher's exact test. RESULTS The frequency of IgA endomysial antibodies in our patients was significantly higher than in the control group (8.92% vs. 0.28%, p < .001). In female, endomysial antibodies were significantly more frequent in patients than in healthy subjects (12.12% vs. 0.4%; p < .001). In male, endomysial antibodies were significantly more frequent in patients than in healthy subjects (4.34% vs. 0.22%; p = .006). The frequency of positive EMA in female patients was higher than in male, but the difference was not statistically significant (12.12% vs. 4.43%; p = .6). Two patients were non-compliant with the gluten-free diet. One patient was out of touch. For the two other patients, transaminase levels reverted to normal level within six months of strict gluten withdrawal. CONCLUSIONS A screening for celiac disease should be included within the diagnosis protocol of liver cytolysis.
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Affiliation(s)
- Mariam Ghozzi
- a Department of Immunology , Farhat Hached University Hospital , Sousse , Tunisia.,b Research Unit (03/UR/07-02), Faculty of Pharmacy , Monastir University , Tunisia
| | | | - Fatma Mbarki
- a Department of Immunology , Farhat Hached University Hospital , Sousse , Tunisia
| | - Ali Jmaa
- c Department of Gastroenterology , Sahloul University Hospital , Sousse , Tunisia
| | - Azza Baccouch
- d Department of Gastroenterology , Ibn El Jazzar Hospital , Kairouan , Tunisia
| | - Nabil Sakly
- e Department of Immunology , Fattouma Bourguiba University Hospital , Monastir , Tunisia
| | - Elhem Ben Jazia
- f Department of Gastroenterology , Farhat Hached University Hospital , Sousse , Tunisia
| | - Ibtissem Ghedira
- a Department of Immunology , Farhat Hached University Hospital , Sousse , Tunisia.,b Research Unit (03/UR/07-02), Faculty of Pharmacy , Monastir University , Tunisia
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Choung RS, Murray JA. Reply. Gastroenterology 2017; 152:1244-1245. [PMID: 28268094 DOI: 10.1053/j.gastro.2017.03.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/02/2022]
Affiliation(s)
- Rok Seon Choung
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Joseph A Murray
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
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Abstract
Celiac disease is an autoimmune disorder induced by gluten in genetically susceptible individuals. It can result in intraintestinal and extraintestinal manifestations of disease including diarrhea, weight loss, anemia, osteoporosis, or lymphoma. Diagnosis of celiac disease is made through initial serologic testing and then confirmed by histopathologic examination of duodenal biopsies. Generally celiac disease is a benign disorder with a good prognosis in those who adhere to a gluten-free diet. However, in refractory disease, complications may develop that warrant additional testing with more advanced radiologic and endoscopic methods. This article reviews the current strategy to diagnose celiac disease and the newer modalities to assess for associated complications.
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Affiliation(s)
- Sarah Shannahan
- Division of Internal Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Daniel A Leffler
- Division of Gastroenterology, The Celiac Center, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215, USA.
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Shim YY, Olivia CM, Liu J, Boonen R, Shen J, Reaney MJT. Secoisolariciresinol Diglucoside and Cyanogenic Glycosides in Gluten-free Bread Fortified with Flaxseed Meal. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2016; 64:9551-9558. [PMID: 27998066 DOI: 10.1021/acs.jafc.6b03962] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/06/2023]
Abstract
Flaxseed (Linum usitatissimum L.) meal contains cyanogenic glycosides (CGs) and the lignan secoisolariciresinol diglucoside (1). Gluten-free (GF) doughs and baked goods were produced with added flaxseed meal (20%, w/w) then 1, and CGs were determined in fortified flour, dough, and bread with storage (0, 1, 2, and 4 weeks) at different temperatures (-18, 4, and 22-23 °C). 1 was present in flour, dough, and GF bread after baking. 1 was stable with extensive storage (up to 4 weeks) and was not affected by storage temperature. CGs in flaxseed meal and fortified GF samples were analyzed by 1H NMR of the cyanohydrins. Linamarin and/or linustatin were the primary CGs in both flaxseed meal and fortified flour. CGs decreased with storage in dough fortified with flaxseed meal or GF bread after baking. GF bakery food products fortified with flaxseed meal had reduced CGs but remained a good source of dietary 1.
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Affiliation(s)
- Youn Young Shim
- Prairie Tide Chemicals Inc. , 102 Melville Street, Saskatoon, Saskatchewan S7J 0R1, Canada
- Department of Plant Sciences, University of Saskatchewan , 51 Campus Drive, Saskatoon, Saskatchewan S7N 5A8, Canada
- Guangdong Saskatchewan Oilseed Joint Laboratory, Department of Food Science and Engineering, Jinan University , Guangzhou, Guangdong 510632, China
| | - Clara M Olivia
- Prairie Tide Chemicals Inc. , 102 Melville Street, Saskatoon, Saskatchewan S7J 0R1, Canada
| | - Jun Liu
- Department of Plant Sciences, University of Saskatchewan , 51 Campus Drive, Saskatoon, Saskatchewan S7N 5A8, Canada
| | - Rineke Boonen
- Prairie Tide Chemicals Inc. , 102 Melville Street, Saskatoon, Saskatchewan S7J 0R1, Canada
- Food Technology Agrobiotechnology Nutrition and Health Science, Wageningen University , Droevendaalsesteeg 4, Wageningen 6708 PB, Netherlands
| | - Jianheng Shen
- Department of Plant Sciences, University of Saskatchewan , 51 Campus Drive, Saskatoon, Saskatchewan S7N 5A8, Canada
| | - Martin J T Reaney
- Prairie Tide Chemicals Inc. , 102 Melville Street, Saskatoon, Saskatchewan S7J 0R1, Canada
- Department of Plant Sciences, University of Saskatchewan , 51 Campus Drive, Saskatoon, Saskatchewan S7N 5A8, Canada
- Guangdong Saskatchewan Oilseed Joint Laboratory, Department of Food Science and Engineering, Jinan University , Guangzhou, Guangdong 510632, China
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Marciano F, Savoia M, Vajro P. Celiac disease-related hepatic injury: Insights into associated conditions and underlying pathomechanisms. Dig Liver Dis 2016; 48:112-119. [PMID: 26711682 DOI: 10.1016/j.dld.2015.11.013] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2015] [Revised: 11/11/2015] [Accepted: 11/17/2015] [Indexed: 12/11/2022]
Abstract
BACKGROUND Celiac disease (CD) is the most common autoimmune enteropathy. Clinical manifestations may range from a typical malabsorption syndrome to several apparently unrelated extra-intestinal symptoms. AIM Here we specifically focus on the spectrum of CD-related liver disorders and the underlying pathomechanisms. METHODS A computer-based search up to August 2015 was completed using appropriate keywords. References from selected papers were also reviewed and used if relevant. RESULTS An unexplained hypertransaminasemia with nonspecific histologic hepatic changes is the most common hepatic presentation. CD however can coexist with a number of liver disorders such as Autoimmune Hepatitis, Autoimmune Cholangitis, Primary Biliary Cirrhosis and Primary Sclerosing Cholangitis requiring a specific treatment in addition to gluten-free diet. CD has also been associated with Viral Hepatitis, Fatty Liver, Non-Alcoholic Steatohepatitis and some severe cryptogenic hepatopaties in the liver transplantation list. Pathomechanisms underlying hepatic injury in CD are multiple, appear still not completely defined and may probably co-occur. CONCLUSIONS An ever-increasing number of CD-related liver injuries exist, probably representing a continuum of a same disorder where genetic predisposition, timing, and duration of previous gluten exposure might influence the reversibility of liver damage. Evidences, although not conclusive, support therefore testing for CD also in cryptogenic hepatobiliary conditions where the relationship with CD has not yet been fully investigated.
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MESH Headings
- Autoimmune Diseases/epidemiology
- Autoimmune Diseases/immunology
- Celiac Disease/epidemiology
- Celiac Disease/immunology
- Cholangitis/epidemiology
- Cholangitis/immunology
- Cholangitis, Sclerosing/epidemiology
- Cholangitis, Sclerosing/immunology
- Comorbidity
- Hepatitis, Autoimmune/epidemiology
- Hepatitis, Autoimmune/immunology
- Hepatitis, Viral, Human/epidemiology
- Hepatitis, Viral, Human/immunology
- Humans
- Liver Cirrhosis, Biliary/epidemiology
- Liver Cirrhosis, Biliary/immunology
- Liver Diseases/enzymology
- Liver Diseases/epidemiology
- Liver Diseases/immunology
- Non-alcoholic Fatty Liver Disease/epidemiology
- Non-alcoholic Fatty Liver Disease/immunology
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Affiliation(s)
- Francesca Marciano
- Department of Molecular Medicine and Medical Biotechnology, University of Naples "Federico II", Naples, Italy.
| | - Marcella Savoia
- Department of Molecular Medicine and Medical Biotechnology, University of Naples "Federico II", Naples, Italy.
| | - Pietro Vajro
- Department of Medicine and Surgery, Pediatrics Section, University of Salerno, Baronissi, Italy; ELFID, University of Naples "Federico II", Naples, Italy.
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Abstract
Celiac disease is a multisystem immune based disorder that is triggered by the ingestion of gluten in genetically susceptible individuals. The prevalence of celiac disease has risen in recent decades and is currently about 1% in most Western populations. The reason for this rise is unknown, although environmental factors related to the hygiene hypothesis are suspected. The pathophysiology of celiac disease involves both the innate and adaptive immune response to dietary gluten. Clinical features are diverse and include gastrointestinal symptoms, metabolic bone disease, infertility, and many other manifestations. Although a gluten-free diet is effective in most patients, this diet can be burdensome and can limit quality of life; consequently, non-dietary therapies are at various stages of development. This review also covers non-celiac gluten sensitivity. The pathophysiology of this clinical phenotype is poorly understood, but it is a cause of increasing interest in gluten-free diets in the general population.
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Affiliation(s)
- Benjamin Lebwohl
- Celiac Disease Center, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA Department of Medical Epidemiology and Biostatistics, Karolinska University Hospital and Karolinska Institute, Stockholm, Sweden
| | - Jonas F Ludvigsson
- Department of Medical Epidemiology and Biostatistics, Karolinska University Hospital and Karolinska Institute, Stockholm, Sweden Department of Pediatrics, Örebro University Hospital, Sweden
| | - Peter H R Green
- Celiac Disease Center, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
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Abstract
Coeliac disease is a common disorder that can arise at any age and typically presents with a broad spectrum of symptoms. The disease is thought to be underdiagnosed, in part owing to the fact that coeliac disease is often characterized by associated conditions and extraintestinal manifestations that can misdirect and impede diagnosis. Some of these manifestations are direct consequences of autoimmunity, such as dermatitis herpetiformis or gluten ataxia, whereas others are indirectly related to inflammation and/or malabsorption including anaemia, osteoporosis, short stature and delayed puberty. Any organ from the central nervous system to joints, liver or teeth can be affected. In some cases, extraintestinal symptoms are the only clinical manifestations of coeliac disease or occur in conjunction with diarrhoea and malabsorptive symptoms. An increased awareness among medical practitioners of the variety of extraintestinal manifestations of coeliac disease is essential to improve diagnosis and treatment.
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Affiliation(s)
- Daniel A Leffler
- The Celiac Centre at Beth Israel Deaconess Medical Centre, 330 Brookline Avenue, Boston, MA 02215, USA
| | - Peter H R Green
- Celiac Disease Centre at Columbia University, 180 Fort Washington Avenue, HP 934, New York, NY 10032, USA
| | - Alessio Fasano
- Centre for Celiac Research, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA
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Rathi S, Dhiman RK. Hepatobiliary Quiz (Answers)-15 (2015). J Clin Exp Hepatol 2015; 5:269-71. [PMID: 26628847 PMCID: PMC4632104 DOI: 10.1016/j.jceh.2015.08.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Affiliation(s)
| | - Radha K. Dhiman
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India
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Castillo NE, Vanga RR, Theethira TG, Rubio-Tapia A, Murray JA, Villafuerte J, Bonder A, Mukherjee R, Hansen J, Dennis M, Kelly CP, Leffler DA. Prevalence of abnormal liver function tests in celiac disease and the effect of a gluten-free diet in the US population. Am J Gastroenterol 2015; 110:1216-22. [PMID: 26150087 DOI: 10.1038/ajg.2015.192] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2015] [Accepted: 05/24/2015] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Guidelines recommend routine screening of liver function tests (LFTs) in patients diagnosed with celiac disease (CD). However, little is known about the prevalence of liver disorders in CD outside of Europe. Our aims were to estimate the prevalence of LFT abnormalities in CD and to evaluate the effect of a gluten-free diet (GFD) on LFTs. METHODS Adult patients with biopsy-proven CD were identified from a prospectively maintained database and matched with healthy controls. LFT levels for women and men were defined as abnormal based on the Third National Health and Nutrition Examination Survey (NHANES III) criteria. Data on demographics, coexisting liver diseases, and laboratory work-ups including aspartate transaminase (AST) and alanine transaminase (ALT) values at the time of diagnosis and on a GFD were recorded. Subsequently, data from this cohort were compared with data from 7,789 individuals participating in the National Health and Nutrition Examination Survey, 2009-2010. Univariate logistic regression, Wilcoxon signed-ranks, Student's t-test, χ(2), and Fischer's exact test were used for statistical analysis. RESULTS In 463 CD patients with ALT or AST levels at the time of CD diagnosis, 40.6% had elevated LFTs compared with 24.2% of treated CD patients (P<0.001) and 16.6% of matched controls (P<0.001). Similarly, 36.7% of CD patients on the NHANES database had abnormal ALT values compared with 19.3% of non-celiac patients (P=0.03). Approximately, 78.6% of CD patients with elevated LFTs at diagnosis normalized LFTs on a GFD after a mean duration of 1.5±1.5 years. CONCLUSIONS Forty percent of individuals will have elevated LFTs at CD diagnosis; however, the majority will normalize with standard CD therapy. LFTs should be checked in all patients with CD and coexisting liver disorder should be considered in patients whose LFTs have not improved within a year on a GFD.
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Affiliation(s)
- Natalia E Castillo
- 1] Celiac Center, Department of Medicine and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA [2] Joint first authors
| | - Rohini R Vanga
- 1] Department of Medicine and Division of Gastroenterology, Baylor College of Medicine, Houston, Texas, USA [2] Joint first authors
| | - Thimmaiah G Theethira
- Celiac Center, Department of Medicine and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Alberto Rubio-Tapia
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Joseph A Murray
- Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA
| | - Javier Villafuerte
- Department of Internal Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Alan Bonder
- Liver Center, Department of Medicine and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Rupa Mukherjee
- Celiac Center, Department of Medicine and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Joshua Hansen
- Celiac Center, Department of Medicine and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Melinda Dennis
- Celiac Center, Department of Medicine and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Ciaran P Kelly
- Celiac Center, Department of Medicine and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Daniel A Leffler
- Celiac Center, Department of Medicine and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
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Anania C, De Luca E, De Castro G, Chiesa C, Pacifico L. Liver involvement in pediatric celiac disease. World J Gastroenterol 2015; 21:5813-5822. [PMID: 26019445 PMCID: PMC4438015 DOI: 10.3748/wjg.v21.i19.5813] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2015] [Revised: 02/27/2015] [Accepted: 04/17/2015] [Indexed: 02/06/2023] Open
Abstract
Celiac disease (CD) is an intestinal inflammatory disease that manifests in genetically susceptible individuals when exposed to dietary gluten. It is a common chronic disorder, with a prevalence of 1% in Europe and North America. Although the disease primarily affects the gut, the clinical spectrum of CD is remarkably varied, and the disease can affect many extraintestinal organs and systems, including the liver. The hepatic dysfunction presenting in CD ranges from asymptomatic liver enzyme elevations or nonspecific reactive hepatitis (cryptogenic liver disorders), to chronic liver disease. In this article, we review the clinical presentations and possible mechanisms of CD-related liver injury to identify strategies for the diagnosis and treatment of these disorders in childhood.
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Das P, Makharia GK. Gut-liver axis and disease infidelity: a subject worth exploring. Indian J Gastroenterol 2014; 33:503-506. [PMID: 25274296 DOI: 10.1007/s12664-014-0503-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2014] [Accepted: 09/01/2014] [Indexed: 02/04/2023]
Affiliation(s)
- Prasenjit Das
- Department of Pathology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110 029, India
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38
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Abstract
Hepatic involvement is often encountered in gastrointestinal (GI) diseases, in part because of the close anatomic and physiologic relations between the liver and GI tract. Drainage of the mesenteric blood supply to the portal vein permits absorbed and/or translocated nutrients, toxins, bacterial elements, cytokines, and immunocytes to gain hepatic access. Liver problems in digestive disorders may range from nonspecific hepatocellular enzyme elevations to significant pathologic processes that may progress to end-stage liver disease. Hepatobiliary manifestations of primary GI diseases in childhood and adolescence are not uncommon and include several well-described associations, such as sclerosing cholangitis with inflammatory bowel disease. Liver damage may also result from the effects of drugs used to treat GI diseases, for example, the hepatotoxicity of immunomodulatory therapies. This review highlights the important features of the hepatic and biliary abnormalities associated with 3 common pediatric GI conditions: inflammatory bowel disease, celiac disease, and cystic fibrosis.
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Affiliation(s)
- Hanh D Vo
- Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital at Downstate, SUNY-Downstate Medical Center, Brooklyn, NY
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Wakim-Fleming J, Pagadala MR, McCullough AJ, Lopez R, Bennett AE, Barnes DS, Carey WD. Prevalence of celiac disease in cirrhosis and outcome of cirrhosis on a gluten free diet: a prospective study. J Hepatol 2014; 61:558-63. [PMID: 24842303 DOI: 10.1016/j.jhep.2014.05.020] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2013] [Revised: 04/17/2014] [Accepted: 05/07/2014] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Current consensus suggests CD to be a multi-systemic disease that could affect any organ system including the liver. It remains under-diagnosed in the US and its prevalence and management in cirrhotic patients has not been studied. Our aim was (1) to estimate the prevalence of CD in cirrhosis, (2) to characterize cirrhotic patients with abnormal celiac serology and normal small bowel biopsy and (3) to evaluate the effect of a GFD on the liver. METHODS A total of 204 consecutive patients with biopsy proven cirrhosis scheduled for an upper endoscopy (EGD) to assess and treat gastro-esophageal varices (GEV) at the Cleveland Clinic between 5/1/2008 and 5/30/2010 were enrolled in the study and followed for 2 years. RESULTS CD affects 2.5% of cirrhotic patients and more than twice the prevalence in the general population. Abnormal EMA >1/10 and high hTTG levels >20 IU can be used to diagnose CD in cirrhosis. Sensitivities and specificities are 100% for EMA and 80% and 94% for hTTG, respectively. After a GFD, patients with CD showed a return to normal levels of their celiac serology, small bowel biopsy and liver enzyme abnormalities. CONCLUSIONS CD is at least twice more common in cirrhotic patients than in the general population and GFD improves liver tests. CD can occur coincidentally with other liver disorders and screening may be warranted during the evaluation of patients with cirrhosis. Abnormal EMA and high hTTG levels can be used to diagnose CD in cirrhosis.
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Affiliation(s)
- Jamile Wakim-Fleming
- Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH, United States.
| | - Mangesh R Pagadala
- Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH, United States
| | - Arthur J McCullough
- Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH, United States
| | - Rocio Lopez
- Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, United States
| | - Ana E Bennett
- Anatomic Pathology, Cleveland Clinic, Cleveland, OH, United States
| | - David S Barnes
- Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH, United States
| | - William D Carey
- Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH, United States
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40
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Rostami-Nejad M, Haldane T, AlDulaimi D, Alavian SM, Zali MR, Rostami K. The role of celiac disease in severity of liver disorders and effect of a gluten free diet on diseases improvement. HEPATITIS MONTHLY 2013; 13:e11893. [PMID: 24348636 PMCID: PMC3842525 DOI: 10.5812/hepatmon.11893] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/01/2013] [Revised: 09/21/2013] [Accepted: 09/25/2013] [Indexed: 02/07/2023]
Abstract
CONTEXT Celiac disease (CD) is defined as a permanent intolerance to ingested gluten. The intolerance to gluten results in immune-mediated damage of small intestine mucosa manifested by villous atrophy and crypt hyperplasia. These abnormalities resolve with initiationa gluten-free diet. EVIDENCE ACQUISITION PubMed, Ovid, and Google were searched for full text articles published between 1963 and 2012. The associated keywords were used, and papers described particularly the impact of celiac disease on severity of liver disorder were identified. RESULTS Recently evidence has emerged revealingthat celiac disease not only is associated with small intestine abnormalities and malabsorption, but is also a multisystem disorder affecting other systems outside gastrointestinal tract, including musculo-skeletal, cardiovascular and nervous systems. Some correlations have been assumed between celiac and liver diseases. In particular, celiac disease is associated with changes in liver biochemistry and linked to alter the prognosis of other disorders. This review will concentrate on the effect of celiac disease and gluten-free diets on the severity of liver disorders. CONCLUSIONS Although GFD effect on the progression of CD associated liver diseases is not well defined, it seems that GFD improves liver function tests in patients with a hypertransaminasemia.
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Affiliation(s)
- Mohammad Rostami-Nejad
- Department of Celiac Disease, Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran
| | - Thea Haldane
- Department of Gastroenterology, Alexandra Hospital, Worcestershire, UK
| | - David AlDulaimi
- Department of Gastroenterology, Alexandra Hospital, Worcestershire, UK
| | - Seyed Moayed Alavian
- Baqiyatallah Research Center for Gastroenterology and Liver Diseases, Baqiyatallah University of Medical Sciences, Tehran, IR Iran
- Middle East Liver Disease Center, Tehran, IR Iran
| | - Mohammad Reza Zali
- Department of Celiac Disease, Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran
| | - Kamran Rostami
- Department of Gastroenterology, Darent Valley Hospital, Darenth Wood Road, Dartford, UK
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Casella G, Antonelli E, Di Bella C, Villanacci V, Fanini L, Baldini V, Bassotti G. Prevalence and causes of abnormal liver function in patients with coeliac disease. Liver Int 2013; 33:1128-1131. [PMID: 23601438 DOI: 10.1111/liv.12178] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2012] [Revised: 12/12/2012] [Accepted: 03/23/2013] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS Coeliac disease patients frequently display mild elevation of liver enzymes and this abnormality usually normalizes after gluten-free diet. To investigate the cause and prevalence of altered liver function tests in coeliac patients, basally and after 1 year of gluten-free diet. PATIENTS AND METHODS Data from 245 untreated CD patients (196 women and 49 men, age range 15-80 years) were retrospectively analysed and the liver function tests before and after diet, as well as associated liver pathologies, were assessed. RESULTS Overall, 43/245 (17.5%) patients had elevated values of one or both aminotransferases; the elevation was mild (<5 times the upper reference limit) in 41 (95%) and marked (>10 times the upper reference limit) in the remaining 2 (5%) patients. After 1 year of gluten-free diet, aminotransferase levels normalized in all but four patients with HCV infection or primary biliary cirrhosis. CONCLUSIONS In coeliac patients, hypertransaminaseaemia at diagnosis and the lack of normalization of liver enzymes after 12 months of diet suggest coexisting liver disease. In such instance, further evaluation is recommended to exclude the liver disease. Early recognition and treatment of coeliac disease in patients affected by liver disease are important to improve the liver function and prevent complications.
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Lauret E, Rodrigo L. Celiac disease and autoimmune-associated conditions. BIOMED RESEARCH INTERNATIONAL 2013; 2013:127589. [PMID: 23984314 PMCID: PMC3741914 DOI: 10.1155/2013/127589] [Citation(s) in RCA: 112] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/10/2013] [Accepted: 06/20/2013] [Indexed: 02/06/2023]
Abstract
Celiac disease (CD) is frequently accompanied by a variety of extradigestive manifestations, thus making it a systemic disease rather than a disease limited to the gastrointestinal tract. This is primarily explained by the fact that CD belongs to the group of autoimmune diseases. The only one with a known etiology is related to a permanent intolerance to gluten. Remarkable breakthroughs have been achieved in the last decades, due to a greater interest in the diagnosis of atypical and asymptomatic patients, which are more frequent in adults. The known presence of several associated diseases provides guidance in the search of oligosymptomatic cases as well as studies performed in relatives of patients with CD. The causes for the onset and manifestation of associated diseases are diverse; some share a similar genetic base, like type 1 diabetes mellitus (T1D); others share pathogenic mechanisms, and yet, others are of unknown nature. General practitioners and other specialists must remember that CD may debut with extraintestinal manifestations, and associated illnesses may appear both at the time of diagnosis and throughout the evolution of the disease. The implementation of a gluten-free diet (GFD) improves the overall clinical course and influences the evolution of the associated diseases. In some cases, such as iron deficiency anemia, the GFD contributes to its disappearance. In other disorders, like T1D, this allows a better control of the disease. In several other complications and/or associated diseases, an adequate adherence to a GFD may slow down their evolution, especially if implemented during an early stage.
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Affiliation(s)
- Eugenia Lauret
- Gastroenterology Unit, Central University Hospital of Asturias (HUCA), Celestino Villamil, 33006 Oviedo, Principality of Asturias, Spain
| | - Luis Rodrigo
- Gastroenterology Unit, Central University Hospital of Asturias (HUCA), Celestino Villamil, 33006 Oviedo, Principality of Asturias, Spain
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43
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Dubois S, Simon J, Veyssier-Belot C, Schiller D. [Unexplained paresthesias in a 28-year-old woman]. Rev Med Interne 2012; 33:597-9. [PMID: 22981464 DOI: 10.1016/j.revmed.2012.07.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2012] [Accepted: 07/06/2012] [Indexed: 11/29/2022]
Affiliation(s)
- S Dubois
- Service de Médecine Interne, Centre Hospitalier de Poissy-St-Germain-en-Laye, 10, rue du Champ-Gaillard, 78360 Poissy, France
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Atypical celiac disease: from recognizing to managing. Gastroenterol Res Pract 2012; 2012:637187. [PMID: 22811701 PMCID: PMC3395124 DOI: 10.1155/2012/637187] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2012] [Accepted: 05/08/2012] [Indexed: 12/23/2022] Open
Abstract
The nonclassic clinical presentation of celiac disease (CD) becomes increasingly common in physician's daily practice, which requires an awareness of its many clinical faces with atypical, silent, and latent forms. Besides the common genetic background (HLA DQ2/DQ8) of the disease, other non-HLA genes are now notably reported with a probable association to atypical forms. The availability of high-sensitive and specific serologic tests such as antitissue transglutuminase, antiendomysium, and more recent antideamidated, gliadin peptide antibodies permits to efficiently uncover a large portion of the submerged CD iceberg, including individuals having conditions associated with a high risk of developing CD (type 1 diabetes, autoimmune diseases, Down syndrome, family history of CD, etc.), biologic abnormalities (iron deficiency anemia, abnormal transaminase levels, etc.), and extraintestinal symptoms (short stature, neuropsychiatric disorders, alopecia, dental enamel hypoplasia, recurrent aphtous stomatitis, etc.). Despite the therapeutic alternatives currently in developing, the strict adherence to a GFD remains the only effective and safe therapy for CD.
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Massironi S, Rossi RE, Fraquelli M, Bardella MT, Elli L, Maggioni M, Della Valle S, Spampatti MP, Colombo M, Conte D. Transient elastography in patients with celiac disease: a noninvasive method to detect liver involvement associated with celiac disease. Scand J Gastroenterol 2012; 47:640-648. [PMID: 22512436 DOI: 10.3109/00365521.2012.679683] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Liver involvement in celiac disease (CD) is clinically relevant and could require specific treatment in addition to gluten-free diet (GFD). Transient elastography (TE), a noninvasive tool for assessing liver stiffness (LS), has widely been reported as an accurate surrogate marker of liver fibrosis. AIMS To prospectively identify celiac patients with liver involvement by TE and to assess the effect of GFD. MATERIAL AND METHODS Ninety-five histologically confirmed CD patients (24 newly diagnosed) were consecutively evaluated by TE and compared with 146 patients with chronic hepatitis C (HCV) and 54 healthy subjects. RESULTS LS ranged between 2.8 and 6.7 kPa (median 4.9) in healthy subjects, defining 6.9 kPa as the upper reference limit (2 SD above the mean levels). TE was above 6.9 kPa in 10 (10.5%) CD patients. Median TE values resulted significantly higher in CD patients with hypertransaminasemia than those without [6.1 vs. 4.2 kPa (p < 0.01)]. Among the 24 newly diagnosed patients with CD, median TE values declined from 4.4 to 4 kPa, after 6 months of GFD, resulting below 6.9 kPa in 100% of the patients. CONCLUSIONS A subset of CD patients with hypertransaminasemia showed liver involvement by TE. Accordingly, based on its accuracy in predicting liver fibrosis, TE could be used to identify those CD patients suitable for liver biopsy.
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Affiliation(s)
- Sara Massironi
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Gastroenterology Unit 2, Milan, Italy.
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Abstract
Autoimmune hepatitis has a variable clinical phenotype, and the absence of conventional autoantibodies does not preclude its diagnosis or need for treatment. The goals of this review are to describe the frequency and nature of autoantibody-negative autoimmune hepatitis, indicate its outcome after corticosteroid treatment, and increase awareness of the diagnosis in patients with unexplained acute and chronic hepatitis. The frequency of presumed autoantibody-negative autoimmune hepatitis in patients with acute and acute severe presentations is ≤7%, and its frequency in patients with chronic presentations is 1-34%. Patients with acute presentations can have normal serum γ-globulin levels, centrilobular zone 3 necrosis, and low pre-treatment international diagnostic scores. Liver tissue examination is essential for the diagnosis, and hepatic steatosis can be a co-morbid feature. The comprehensive international scoring system can support but never override the clinical diagnosis pre-treatment, and non-standard serological markers should be sought if the clinical diagnosis is uncertain or the diagnostic score is low. A 3-month treatment trial with corticosteroids should be considered in all patients, regardless of the serological findings, and improvements have occurred in 67-87% of cases. Autoantibody-negative autoimmune hepatitis may be associated with an autoantibody outside the conventional battery; it may have a signature autoantibody that is still undiscovered, or its characteristic autoantibodies may have been suppressed or have a delayed expression. The pathogenic mechanisms are presumed to be identical to those of classical disease. Autoantibody-negative autoimmune hepatitis is an infrequent but treatable disease that must be considered in unexplained acute and chronic hepatitis.
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Affiliation(s)
- Albert J Czaja
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, 200 First Street S.W., Rochester, MN 55905, USA.
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47
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Saleem A, Connor HJO, Regan PO. Adult coeliac disease in Ireland: a case series. Ir J Med Sci 2011; 181:225-9. [PMID: 22203320 DOI: 10.1007/s11845-011-0788-z] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2011] [Accepted: 12/15/2011] [Indexed: 12/19/2022]
Abstract
BACKGROUND The clinical spectrum of adult coeliac disease (ACD) is varied with limited Irish data. AIMS AND OBJECTIVES The aim of this study was to analyse the presenting symptoms, associated conditions and complications in a consecutive series of patients with ACD. METHODS Data were obtained from database on patients with ACD between 1988 and 2004. RESULTS One hundred and six patients (69F:37M, mean age: 46, range: 23-95 years) were included. The modes of presentation were diarrhoea in 44 patients (45%), weight loss in 41 (42%), anaemia in 37 (38%), abdominal pain in 15 (15%), fatigue in 8 (8%), hypocalcaemia in 4 (4%) and steatorrhoea in 4 (4%). Associated conditions included thyroid disorders in 7 patients (7%), bipolar affective disorder in 4 (4%), major depression in 3 (3%), rheumatoid disease in 3 (3%), inflammatory bowel disease in 4 (4%) and type I diabetes mellitus in 2 (2%). Malignancy emerged as a major complication in 15 patients (15%) CONCLUSION The presenting features of ACD are diverse and associated with high risk of malignancy.
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Affiliation(s)
- A Saleem
- Faculty of Health Sciences, Trinity College, University of Dublin, Dublin, Ireland.
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Czaja AJ. Cryptogenic chronic hepatitis and its changing guise in adults. Dig Dis Sci 2011; 56:3421-38. [PMID: 21647651 DOI: 10.1007/s10620-011-1769-9] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2011] [Accepted: 05/20/2011] [Indexed: 12/11/2022]
Abstract
Cryptogenic chronic hepatitis is a disease that is unexplained by conventional clinical, laboratory and histological findings, and it can progress to cirrhosis, develop hepatocellular carcinoma, and require liver transplantation. The goals of this review are to describe the changing phenotype of cryptogenic chronic hepatitis in adults, develop a diagnostic algorithm appropriate to current practice, and suggest treatment options. The frequency of cryptogenic hepatitis is estimated at 5.4%. Cryptogenic cirrhosis is diagnosed in 5-30% of patients with cirrhosis, and it is present in 3-14% of adults awaiting liver transplantation. Nonalcoholic fatty liver disease has been implicated in 21-63% of patients, and autoimmune hepatitis is a likely diagnosis in 10-54% of individuals. Viral infections, hereditary liver diseases, celiac disease, and unsuspected alcohol or drug-induced liver injury are recognized infrequently in the current cryptogenic population. Manifestations of the metabolic syndrome heighten the suspicion of nonalcoholic fatty liver disease, and the absence of hepatic steatosis does not discount this possibility. The diagnostic scoring system of the International Autoimmune Hepatitis Group can support the diagnosis of autoimmune hepatitis in some patients. Certain genetic mutations may have disease-specificity, and they suggest that some patients may have an independent and uncharacterized disease. Corticosteroid therapy is effective in patients with autoimmune features, and life-style changes and specific therapies for manifestations of the metabolic syndrome are appropriate for all obese patients. The 1- and 5-year survivals after liver transplantation have ranged from 72-85% to 58-73%, respectively.
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Affiliation(s)
- Albert J Czaja
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, 200 First Street S.W., Rochester, MN 55905, USA.
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Gluten-sensitive hypertransaminasemia in celiac disease: an infrequent and often subclinical finding. Am J Gastroenterol 2011; 106:1689-96. [PMID: 21502996 DOI: 10.1038/ajg.2011.134] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
OBJECTIVES Earlier studies suggest that 40-50% of untreated celiac disease patients have elevated transaminase levels. Celiac disease can also be the underlying reason for unexplained hypertransaminasemia or even liver failure. We investigated the prevalence and gluten dependency of hypertransaminasemia in celiac patients also diagnosed with minor or atypical symptoms. METHODS In the cross-sectional study, serum aspartate (AST) and alanine (ALT) transaminase levels were measured in 313 untreated and 339 treated adult celiac patients and 237 non-celiac controls. In the prospective part, transaminase levels were investigated in 130 celiac patients at diagnosis and after 1 year on a gluten-free diet and in 25 treated celiac patients in clinical remission before and after gluten challenge. RESULTS The proportion of subjects with elevated serum AST values in the untreated celiac disease group (11%) did not differ significantly from that in the treated celiac disease (8%) or non-celiac control groups (9%) (P=0.587). Although the serum transaminase values were within normal range in the majority of untreated patients, initially normal liver enzyme levels decreased significantly on a gluten-free diet. In treated celiac disease, gluten challenge led to mild and transient hypertransaminasemia. CONCLUSIONS In our area, where the prevalence of celiac disease is high, hypertransaminasemia is less frequent in untreated celiac disease patients than previously reported. The regular screening of transaminases in celiac disease needs to be re-evaluated. Although the liver enzyme levels were within the reference values in the majority of celiac patients, an obvious gluten dependence of transaminase levels was observed even in these subjects.
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Kochhar R, Dutta U, Miglani A, Bhagat S, Poornachandra KS, Vaiphei K, Nain CK, Singh K. Celiac disease suspected at endoscopy in patients with chronic liver disease. Indian J Gastroenterol 2011; 30:166-9. [PMID: 21847607 DOI: 10.1007/s12664-011-0106-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2009] [Accepted: 06/21/2011] [Indexed: 02/04/2023]
Abstract
Endoscopic findings of celiac disease have high specificity and sensitivity. We evaluated records of 137 consecutive patients who had endotherapy for variceal hemorrhage, and who had features of celiac disease at endoscopy; patients who had such markers at endoscopy had undergone duodenal histology and serology. Thirty-one patients had changes of portal hypertensive vasculopathy in the duodenum, 8 had scalloping, and 6 had mosaic pattern; 3 patients also had decreased fold height or sparse folds in the descending duodenum. Six of these 8 patients had positive serology and histology suggestive of celiac disease. Endoscopic evaluation resulted in diagnosis of CD in 4.37% patients of chronic liver disease undergoing endotherapy.
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Affiliation(s)
- Rakesh Kochhar
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
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