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Terim Kapakin KA, Gümüş R, Bolat İ, Kirman EM, İmik A. Effects of experimental wheat and corn gluten on liver tissue in rats: biochemical, histopathological, immunohistochemical and immunofluorescence methods. REVISTA CIENTÍFICA DE LA FACULTAD DE CIENCIAS VETERINARIAS 2024; XXXIV:1-11. [DOI: 10.52973/rcfcv-e34500] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/04/2025]
Abstract
This study was aimed at determining the effects of wheat gluten, corn gluten and soybean meal, incorporated into feed as protein sources, on the hepatic tissue of rats, based on the investigation of histopathological parameters (degeneration, inflammation, biliary hyperplasia and fat droplets), immunohistochemical parameters (transglutaminase, gliadin, IgA, IgG, CD4 and CD8), and the serum levels of hepatic enzymes [(aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH)]. Three groups, referred to as Wheat Group, Group Corn and Group Soybean, were established, and were given high levels of wheat gluten, corn gluten and soybean meal as protein sources in the feed, respectively. The study material comprised forty–eight 20–day–old female Sprague Dawley rats. In the group, which received dietary wheat gluten, the hepatic tissue presented with numerically higher histopathological and immunohistochemical parameters on day 45 of the study, and numerically higher histopathological parameters on day 165 of the study (P>0.05). On day 165 of the study, when compared to Groups Corn and Soybean, Group Wheat displayed a significantly different level of sensitivity to immunohistochemical parameters (transglutaminase, gliadin, IgA, IgG, CD4 and CD8). It was determined that gluten significantly reduced the activity of the liver enzymes LDH and AST. In result, it was ascertained that rats, not carrying the genes HLA–DQ2 and DQ8, when fed on a ration incorporated with a high level of wheat gluten, displayed slightly affected hepatic tissue histopathological parameters and significantly increased immunohistochemical parameters (transglutaminase, gliadin, IgA, IgG, CD4 and CD8).
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Affiliation(s)
- Kübra Asena Terim Kapakin
- Ataturk University, Faculty of Veterinary Medicine, Department of Veterinary Pathology. Erzurum, Türkiye
| | - Recep Gümüş
- Sivas Cumhuriyet University, Faculty of Veterinary Medicine, Department of Animal Nutrition and Nutritional Disorders. Sivas, Türkiye
| | - İsmail Bolat
- Ataturk University, Faculty of Veterinary Medicine, Department of Veterinary Pathology. Erzurum, Türkiye
| | - Esra Manavoğlu Kirman
- Ataturk University, Faculty of Veterinary Medicine, Department of Veterinary Pathology. Erzurum, Türkiye
| | - Aybüke İmik
- Faculty of Veterinary Medicine, Faculty of Health Sciences, Department of Nutrition and Dietetics. Selçuk University, Konya, Türkiye
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Dreyfuss M, Getz B, Lebwohl B, Ramni O, Underberger D, Ber TI, Steinberg-Koch S, Jenudi Y, Gazit S, Patalon T, Chodick G, Shoenfeld Y, Ben-Tov A. A machine learning tool for early identification of celiac disease autoimmunity. Sci Rep 2024; 14:30760. [PMID: 39730479 DOI: 10.1038/s41598-024-80817-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Accepted: 11/21/2024] [Indexed: 12/29/2024] Open
Abstract
Identifying which patients should undergo serologic screening for celiac disease (CD) may help diagnose patients who otherwise often experience diagnostic delays or remain undiagnosed. Using anonymized outpatient data from the electronic medical records of Maccabi Healthcare Services, we developed and evaluated five machine learning models to classify patients as at-risk for CD autoimmunity prior to first documented diagnosis or positive serum tissue transglutaminase (tTG-IgA). A train set of highly seropositive (tTG-IgA > 10X ULN) cases (n = 677) with likely CD and controls (n = 176,293) with no evidence of CD autoimmunity was used for model development. Input features included demographic information and commonly available laboratory results. The models were then evaluated for discriminative ability as measured by AUC on a distinct set of highly seropositive cases (n = 153) and controls (n = 41,087). The highest performing model was XGBoost (AUC = 0.86), followed by logistic regression (AUC = 0.85), random forest (AUC = 0.83), multilayer perceptron (AUC = 0.80) and decision tree (AUC = 0.77). Contributing features for the XGBoost model for classifying a patient as at-risk for undiagnosed CD autoimmunity included signs of anemia, transaminitis and decreased high-density lipoprotein. This model's ability to distinguish cases of incident CD autoimmunity from controls shows promise as a potential clinical tool to identify patients with increased risk of having undiagnosed celiac disease in the community, for serologic screening.
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Affiliation(s)
| | | | - Benjamin Lebwohl
- Celiac Disease Center, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA
| | - Or Ramni
- Predicta Med Analytics Ltd., Ramat Gan, Israel
| | | | - Tahel Ilan Ber
- Predicta Med Analytics Ltd., Ramat Gan, Israel
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- PhaseV, Tel Aviv, Israel
| | | | | | - Sivan Gazit
- Kahn Sagol Maccabi Research & Innovation Center, Maccabi Healthcare Services, Tel Aviv, Israel
| | - Tal Patalon
- Kahn Sagol Maccabi Research & Innovation Center, Maccabi Healthcare Services, Tel Aviv, Israel
| | - Gabriel Chodick
- Kahn Sagol Maccabi Research & Innovation Center, Maccabi Healthcare Services, Tel Aviv, Israel
| | - Yehuda Shoenfeld
- Zabludowicz Center for Autoimmune Diseases, Chaim Sheba Medical Center, Tel Hashomer, Israel
| | - Amir Ben-Tov
- Kahn Sagol Maccabi Research & Innovation Center, Maccabi Healthcare Services, Tel Aviv, Israel
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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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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Ciacci C, De Micco I, Di Stefano M, Mengoli C. Celiac disease in adult patients. PEDIATRIC AND ADULT CELIAC DISEASE 2024:103-123. [DOI: 10.1016/b978-0-443-13359-6.00001-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Hitawala AA, Almomani A, Onwuzo S, Boustany A, Kumar P, Asaad I. Prevalence of autoimmune, cholestatic and nonalcoholic fatty liver disease in celiac disease. Eur J Gastroenterol Hepatol 2023; 35:1030-1036. [PMID: 37395201 DOI: 10.1097/meg.0000000000002599] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/04/2023]
Abstract
BACKGROUND While there is higher prevalence of autoimmune, cholestatic and fatty liver disease in celiac disease (CeD), most data is from small-scale studies. We evaluated the prevalence and risk factors of the same using large cohort data. METHODS A population-based cross-sectional study was conducted using Explorys, a multi-institutional database. Prevalence and risk factors of autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC) and nonalcoholic fatty liver disease (NAFLD) in CeD were assessed. RESULTS Out of 70 352 325 subjects, 136 735 had CeD (0.19%). The prevalence of AIH (0.32%), PBC (0.15%), PSC (0.004%) and NAFLD (0.7%) were high in CeD. After adjusting for age, gender, Caucasian race and anti-tissue transglutaminase antibody (anti-TTG), CeD subjects had higher odds of AIH [adjusted odds ratio (aOR) 7.06, 95% confidence interval (CI) 6.32-7.89] and PBC (aOR 4.16, 95% CI 3.46-5.0). Even after adjusting for CeD, anti-TTG positivity concurred with higher odds of AIH (aOR 4.79, 95% CI 3.88-5.92) and PBC (aOR 9.22, 95% CI 7.03-12.1). After adjusting for age, gender, Caucasian race, diabetes mellitus (DM), obesity, hypothyroidism and metabolic syndrome, there was higher prevalence of NAFLD in CeD, with the aOR in the presence of DM type 1 being 2.1 (95% CI 1.96-2.25), and in the presence of DM type 2 being 2.92 (95% CI 2.72-3.14). CONCLUSION Subjects with CeD are more likely to have AIH, PBC, PSC and NAFLD. AIH and PBC have higher odds in the presence of anti-TTG. The odds of NAFLD in CeD are high regardless of type of DM.
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Affiliation(s)
- Asif Ali Hitawala
- Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio
| | - Ashraf Almomani
- Department of Gastroenterology and Digestive Diseases, Cleveland Clinic Foundation, Weston, Florida
| | - Somtochukwu Onwuzo
- Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio
| | - Antoine Boustany
- Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio
| | - Prabhat Kumar
- Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio
| | - Imad Asaad
- Department of Gastroenterology and Digestive Diseases, Cleveland Clinic Foundation, Cleveland, Ohio, USA
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Di Tommaso N, Santopaolo F, Gasbarrini A, Ponziani FR. The Gut-Vascular Barrier as a New Protagonist in Intestinal and Extraintestinal Diseases. Int J Mol Sci 2023; 24:ijms24021470. [PMID: 36674986 PMCID: PMC9864173 DOI: 10.3390/ijms24021470] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Revised: 01/07/2023] [Accepted: 01/09/2023] [Indexed: 01/15/2023] Open
Abstract
The intestinal barrier, with its multiple layers, is the first line of defense between the outside world and the intestine. Its disruption, resulting in increased intestinal permeability, is a recognized pathogenic factor of intestinal and extra-intestinal diseases. The identification of a gut-vascular barrier (GVB), consisting of a structured endothelium below the epithelial layer, has led to new evidence on the etiology and management of diseases of the gut-liver axis and the gut-brain axis, with recent implications in oncology as well. The gut-brain axis is involved in several neuroinflammatory processes. In particular, the recent description of a choroid plexus vascular barrier regulating brain permeability under conditions of gut inflammation identifies the endothelium as a key regulator in maintaining tissue homeostasis and health.
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Affiliation(s)
- Natalia Di Tommaso
- Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Francesco Santopaolo
- Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Antonio Gasbarrini
- Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Translational Medicine and Surgery Department, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Francesca Romana Ponziani
- Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Translational Medicine and Surgery Department, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
- Correspondence:
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Poddighe D, Dossybayeva K, Abdukhakimova D, Akhmaltdinova L, Ibrayeva A. Celiac Disease and Gallbladder: Pathophysiological Aspects and Clinical Issues. Nutrients 2022; 14:4379. [PMID: 36297063 PMCID: PMC9612360 DOI: 10.3390/nu14204379] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Revised: 10/03/2022] [Accepted: 10/04/2022] [Indexed: 11/27/2022] Open
Abstract
Background: Celiac Disease (CD) is an immune-mediated disorder which primarily affects the small intestine; however, extra-intestinal organs are often affected by the pathological process, too. As regards the digestive system, liver alterations in CD patients have been widely described, which can also extend to the biliary tract. Notably, gallbladder function can be altered in CD patients. In this review, we specifically analyze and summarize the main pathophysiological aspects and clinical evidence of gallbladder dysfunction in CD patients, in order to discuss the potential medical complications and clinical research gaps. In addition to some perturbations of bile composition, CD patients can develop gallbladder dysmotility, which mainly expresses with an impaired emptying during the digestive phase. The main pathophysiological determinant is a perturbation of cholecystokinin secretion by the specific duodenal enteroendocrine cells in response to the appropriate nutrient stimulation in CD patients. This situation appears to be reversible with a gluten-free diet in most cases. Despite this gallbladder impairment, CD patients do not seem to be more predisposed to gallbladder complications, such as calculous and acalculous cholecystitis. However, very few clinical studies have actively investigated these clinical aspects, which may not be completely evidenced so far; alternatively, the substantial improvements in the last two decades regarding CD diagnosis, which have reduced the diagnostic delay (and related dietary treatment), may have lessened the potential clinical consequences of CD-related gallbladder dysfunction. Specific clinical studies focused on these aspects are needed for a better understanding of the clinical implications of gallbladder alterations in CD patients.
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Affiliation(s)
- Dimitri Poddighe
- Department of Medicine, Nazarbayev University School of Medicine, Nur-Sultan 010000, Kazakhstan
- National Research Center for Maternal and Child Health, Clinical Academic Department of Pediatrics, University Medical Center, Nur-Sultan 010000, Kazakhstan
| | - Kuanysh Dossybayeva
- Department of Medicine, Nazarbayev University School of Medicine, Nur-Sultan 010000, Kazakhstan
| | - Diyora Abdukhakimova
- Department of Medicine, Nazarbayev University School of Medicine, Nur-Sultan 010000, Kazakhstan
| | | | - Aigul Ibrayeva
- National Research Center for Maternal and Child Health, Program of Pediatric Gastroenterology, Clinical Academic Department of Pediatrics, University Medical Center, Nur-Sultan 010000, Kazakhstan
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Regev A, Ben-Tov A, Yerushalmy-Feler A, Weintraub Y, Moran-Lev H, Cohen S, Amir AZ. Elevated liver enzymes of newly diagnosed pediatric celiac patients-a prospective-observational study. Eur J Pediatr 2022; 181:753-762. [PMID: 34586475 DOI: 10.1007/s00431-021-04259-w] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Revised: 09/02/2021] [Accepted: 09/05/2021] [Indexed: 02/07/2023]
Abstract
Celiac disease clinical presentation is constantly changing. We set to determine the prevalence of elevated transaminases in newly diagnosed celiac patients and to evaluate this sub-group of patients for associated clinical and laboratory findings and assess their natural course of disease following therapeutic diet initiation. We conducted a prospective-observational study of all newly diagnosed pediatric celiac patients, between August 2016 and April 2018, in a pediatric gastroenterology clinic. Clinical data, anthropometrics, and blood test results were recorded at diagnosis and at 3, 6, and 12 months, respectively, of follow-up. We compared patients with normal and elevated transaminases at diagnosis. ALT threshold was set at 24 U/l. Of 125 newly diagnosed celiac patients, 31 (24.8%) had elevated ALT at diagnosis; two (1.6%) with over 3 × ULN. Patients with elevated ALT at diagnosis were significantly younger (mean age 5.5 (SD 3.4) vs. 7.3 (SD 3.7) years, p < 0.01) and more commonly presented with diarrhea (32.3% vs. 14.9%, p = 0.03). Eighty percent of patients with elevated ALT levels normalized their ALT within 3 months and all within 1 year. Following gluten-free diet initiation, patients with elevated ALT had similar clinical course, growth, serology normalization rate, and laboratory results, compared to patients with normal ALT over a 1-year follow-up. A single patient was simultaneously co-diagnosed with celiac disease and autoimmune hepatitis.Conclusion: Clinically significant ALT abnormalities are rare among newly diagnosed pediatric celiac patients. Significant elevations failing to normalize on a gluten-free diet should raise concern of a concomitant primary liver disease and warrant further investigations. What is Known: • Elevated liver enzymes may be an extra-intestinal manifestation of celiac disease. • Reported prevalences of ALT elevations among children with a new diagnosis of celiac disease ranges between 5 and 40%. What is New: • ALT elevations are present in 25% of children with a new diagnosis of celiac disease. • Significant elevations (>3 × ULN) are rare (1.6%). • Elevated liver enzymes are associated with earlier age at diagnosis. • The natural history of patients with elevated liver enzymes at diagnosis is comparable to those without.
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Affiliation(s)
- Asaf Regev
- Pediatrics, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. .,Dana-Dwek Children's Hospital, the Tel-Aviv Medical Center, Tel-Aviv University, Tel Aviv, Israel.
| | - Amir Ben-Tov
- The Pediatric Gastroenterology, Hepatology & Nutrition Clinic, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.,Dana-Dwek Children's Hospital, the Tel-Aviv Medical Center, Tel-Aviv University, Tel Aviv, Israel
| | - Anat Yerushalmy-Feler
- The Pediatric Gastroenterology, Hepatology & Nutrition Clinic, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.,Dana-Dwek Children's Hospital, the Tel-Aviv Medical Center, Tel-Aviv University, Tel Aviv, Israel
| | - Yael Weintraub
- The Pediatric Gastroenterology, Hepatology & Nutrition Clinic, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.,Dana-Dwek Children's Hospital, the Tel-Aviv Medical Center, Tel-Aviv University, Tel Aviv, Israel
| | - Hadar Moran-Lev
- The Pediatric Gastroenterology, Hepatology & Nutrition Clinic, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.,Dana-Dwek Children's Hospital, the Tel-Aviv Medical Center, Tel-Aviv University, Tel Aviv, Israel
| | - Shlomi Cohen
- The Pediatric Gastroenterology, Hepatology & Nutrition Clinic, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.,Dana-Dwek Children's Hospital, the Tel-Aviv Medical Center, Tel-Aviv University, Tel Aviv, Israel
| | - Achiya Z Amir
- The Pediatric Gastroenterology, Hepatology & Nutrition Clinic, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. .,Dana-Dwek Children's Hospital, the Tel-Aviv Medical Center, Tel-Aviv University, Tel Aviv, Israel.
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9
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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: 552] [Impact Index Per Article: 110.4] [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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Nicoletti A, Ponziani FR, Biolato M, Valenza V, Marrone G, Sganga G, Gasbarrini A, Miele L, Grieco A. Intestinal permeability in the pathogenesis of liver damage: From non-alcoholic fatty liver disease to liver transplantation. World J Gastroenterol 2019; 25:4814-4834. [PMID: 31543676 PMCID: PMC6737313 DOI: 10.3748/wjg.v25.i33.4814] [Citation(s) in RCA: 108] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2019] [Revised: 07/04/2019] [Accepted: 07/19/2019] [Indexed: 02/06/2023] Open
Abstract
The intimate connection and the strict mutual cooperation between the gut and the liver realizes a functional entity called gut-liver axis. The integrity of intestinal barrier is crucial for the maintenance of liver homeostasis. In this mutual relationship, the liver acts as a second firewall towards potentially harmful substances translocated from the gut, and is, in turn, is implicated in the regulation of the barrier. Increasing evidence has highlighted the relevance of increased intestinal permeability and consequent bacterial translocation in the development of liver damage. In particular, in patients with non-alcoholic fatty liver disease recent hypotheses are considering intestinal permeability impairment, diet and gut dysbiosis as the primary pathogenic trigger. In advanced liver disease, intestinal permeability is enhanced by portal hypertension. The clinical consequence is an increased bacterial translocation that further worsens liver damage. Furthermore, this pathogenic mechanism is implicated in most of liver cirrhosis complications, such as spontaneous bacterial peritonitis, hepatorenal syndrome, portal vein thrombosis, hepatic encephalopathy, and hepatocellular carcinoma. After liver transplantation, the decrease in portal pressure should determine beneficial effects on the gut-liver axis, although are incompletely understood data on the modifications of the intestinal permeability and gut microbiota composition are still lacking. How the modulation of the intestinal permeability could prevent the initiation and progression of liver disease is still an uncovered area, which deserves further attention.
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Affiliation(s)
- Alberto Nicoletti
- Fondazione Policlinico Universitario A Gemelli IRCCS, Rome 00168, Italy
- Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Francesca Romana Ponziani
- Fondazione Policlinico Universitario A Gemelli IRCCS, Rome 00168, Italy
- Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Marco Biolato
- Fondazione Policlinico Universitario A Gemelli IRCCS, Rome 00168, Italy
- Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Venanzio Valenza
- Fondazione Policlinico Universitario A Gemelli IRCCS, Rome 00168, Italy
- Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Giuseppe Marrone
- Fondazione Policlinico Universitario A Gemelli IRCCS, Rome 00168, Italy
- Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Gabriele Sganga
- Fondazione Policlinico Universitario A Gemelli IRCCS, Rome 00168, Italy
- Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Antonio Gasbarrini
- Fondazione Policlinico Universitario A Gemelli IRCCS, Rome 00168, Italy
- Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Luca Miele
- Fondazione Policlinico Universitario A Gemelli IRCCS, Rome 00168, Italy
- Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Antonio Grieco
- Fondazione Policlinico Universitario A Gemelli IRCCS, Rome 00168, Italy
- Università Cattolica del Sacro Cuore, Rome 00168, Italy
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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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12
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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: 396] [Impact Index Per Article: 66.0] [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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Floreani A, De Martin S, Secchi MF, Cazzagon N. Extrahepatic autoimmunity in autoimmune liver disease. Eur J Intern Med 2019; 59:1-7. [PMID: 30360943 DOI: 10.1016/j.ejim.2018.10.014] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2018] [Accepted: 10/16/2018] [Indexed: 02/07/2023]
Abstract
The most important autoimmune liver disease include: autoimmune hepatitis, primary biliary cholangitis and primary sclerosing cholangitis. In general, about one in three patients with an autoimmune liver disease have a concomitant extrahepatic autoimmune disease, which may include rheumatological, endocrinological, gastrointestinal, pulmonary or dermatological conditions. The pathogenesis of these conditions includes the production of both innate and adaptive immune responses targeting cholangiocytes as well as different extrahepatic tissues. In this sense, extrahepatic autoimmunity represent a continuous spectrum of autoimmunity involving liver and extrahepatic tissues. This review aims to focus the clinical and pathophysiological aspects of extrahepatic autoimmunity associated to autoimmune liver diseases.
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Affiliation(s)
- Annarosa Floreani
- Dept of Surgery, Oncology and Gastroenterology, University of Padova, Via Giustiniani, 2, 35128, Italy.
| | - Sara De Martin
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy
| | - Maria Francesca Secchi
- Dept of Surgery, Oncology and Gastroenterology, University of Padova, Via Giustiniani, 2, 35128, Italy
| | - Nora Cazzagon
- Dept of Surgery, Oncology and Gastroenterology, University of Padova, Via Giustiniani, 2, 35128, Italy
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14
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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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15
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Parzanese I, Qehajaj D, Patrinicola F, Aralica M, Chiriva-Internati M, Stifter S, Elli L, Grizzi F. Celiac disease: From pathophysiology to treatment. World J Gastrointest Pathophysiol 2017; 8:27-38. [PMID: 28573065 PMCID: PMC5437500 DOI: 10.4291/wjgp.v8.i2.27] [Citation(s) in RCA: 157] [Impact Index Per Article: 19.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2016] [Revised: 03/08/2017] [Accepted: 03/23/2017] [Indexed: 02/06/2023] Open
Abstract
Celiac disease, also known as "celiac sprue", is a chronic inflammatory disorder of the small intestine, produced by the ingestion of dietary gluten products in susceptible people. It is a multifactorial disease, including genetic and environmental factors. Environmental trigger is represented by gluten while the genetic predisposition has been identified in the major histocompatibility complex region. Celiac disease is not a rare disorder like previously thought, with a global prevalence around 1%. The reason of its under-recognition is mainly referable to the fact that about half of affected people do not have the classic gastrointestinal symptoms, but they present nonspecific manifestations of nutritional deficiency or have no symptoms at all. Here we review the most recent data concerning epidemiology, pathogenesis, clinical presentation, available diagnostic tests and therapeutic management of celiac disease.
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16
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Prevalence and associated factors of abnormal liver values in children with celiac disease. Dig Liver Dis 2016; 48:1023-9. [PMID: 27338852 DOI: 10.1016/j.dld.2016.05.022] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2016] [Revised: 05/23/2016] [Accepted: 05/24/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND The prevalence and factors associated with transaminasemia in celiac disease are poorly known. AIMS To investigate these issues in paediatric celiac patients and controls. METHODS Alanine aminotransferase (ALT) was studied in 150 children with untreated celiac disease, 161 disease controls and 500 population-based controls. The association between ALT and clinical and histological variables and the effect of a gluten-free diet were investigated in celiac patients. RESULTS ALT was >30U/l: celiac disease 14.7%, ulcerative colitis 37.2%, Crohn's disease 16.7%, reflux disease 16.2%, functional gastrointestinal symptoms 8.9%, and controls 3.6%. Factors associated with increased ALT were poor growth (45.5% vs 24.2%, P=0.039) and severe villous atrophy (median 23.0U/l vs partial atrophy 19.0U/l, P=0.008), but not age, sex, body-mass index, type or severity of symptoms and co-morbidities. ALT had a moderate correlation with endomysial (r=0.334, P<0.001) and transglutaminase antibodies (r=0.264, P=0.002) and ferritin (r=-0.225, P=0.03), but not with other laboratory values. On gluten-free diet median ALT decreased from 22.0U/l to 18.0U/l (P=0.002) and 80% of the high values normalized. CONCLUSION Increased ALT is associated with more advanced serological and histological celiac disease. Adherence to a gluten-free diet appears to result in normalization or reduction of ALT levels.
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17
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Snyder J, Butzner JD, DeFelice AR, Fasano A, Guandalini S, Liu E, Newton KP. Evidence-Informed Expert Recommendations for the Management of Celiac Disease in Children. Pediatrics 2016; 138:peds.2015-3147. [PMID: 27565547 DOI: 10.1542/peds.2015-3147] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/23/2016] [Indexed: 12/11/2022] Open
Abstract
Although the need for effective long-term follow-up for patients with celiac disease (CD) has been recognized by many expert groups, published practice guidelines have not provided a clear approach for the optimal management of these patients. In an attempt to provide a thoughtful and practical approach for managing these patients, a group of experts in pediatric CD performed a critical review of the available literature in 6 categories associated with CD to develop a set of best practices by using evidence-based data and expert opinion. The 6 categories included the following: bone health, hematologic issues, endocrine problems, liver disease, nutritional issues, and testing. Evidence was assessed by using standardized criteria for evaluating the quality of the data, grade of evidence, and strength of conclusions. Over 600 publications were reviewed, and 172 were chosen for inclusion. The thorough review of the results demonstrated that the quality of the data available was often insufficient to provide unequivocal best practices. However, using the available data and the clinical experience of the panel, a practical framework for the management of children with CD was created. These recommendations were developed by our expert panel and do not necessarily reflect the policy of the American Academy of Pediatrics. The potential usefulness of these best practices is underscored by the fact that consensus, measured by the outcome of anonymous voting, was reached by the panel for 24 of the 25 questions. We hope that these best practices may be useful to the pediatric gastroenterology and larger general pediatric communities.
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Affiliation(s)
- John Snyder
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Children's National Health Systems, Washington, District of Columbia;
| | - J Decker Butzner
- Division of Paediatric Gastroenterology, Hepatology and Nutrition, University of Calgary, Calgary, Alberta, Canada
| | - Amy R DeFelice
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, New York-Presbyterian Hospital, Columbia University, New York, New York
| | - Alessio Fasano
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Massachusetts General Hospital for Children, Boston, Massachusetts
| | - Stefano Guandalini
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, University of Chicago Medical Center, Chicago, Illinois
| | - Edwin Liu
- Digestive Health Institute, Children's Hospital Colorado, Aurora, Colorado; and
| | - Kimberly P Newton
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Rady Children's Hospital and University of California San Diego School of Medicine, San Diego, California
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Abstract
OBJECTIVES The aim of the present study was to determine the proportion of pediatric patients with celiac disease (CD) who had transaminases obtained at diagnosis and to determine the proportion with hypertransaminasemia. METHODS Data from newly diagnosed patients with CD at Nationwide Children's Hospital from February 2007 to March 2014 were retrospectively reviewed. Alanine transaminase (ALT) and aspartate transaminase (AST) values at diagnosis and after initiation of a gluten-free diet (GFD) were assessed. RESULTS Of 388 patients (mean age 10.1 ± 4.4 years, 235 girls), 185 (47.7%) had transaminases obtained at the time of diagnosis. Twenty-eight of one hundred eighty-five (15.1%) had an elevated ALT and/or AST level with an average ALT 2.52 × upper limit of normal (ULN) and AST 1.87 × ULN. Those with hypertransaminasemia were younger than those with normal levels (6.31 ± 4.75 vs 11.00 ± 4.28 years, P < 0.0001). Sex, symptoms at diagnosis, and weight, height, and body mass index z scores were not predictive of elevated transaminases. Of the 21 patients with hypertransaminasemia at diagnosis who had repeat laboratory test results after starting the GFD, 15 (71.4%) normalized whereas 6 (28.6%) remained elevated. CONCLUSIONS There is variation in practice among pediatric gastroenterologists in the assessment of transaminases in children with CD. Hypertransaminasemia is present at diagnosis in a significant proportion of children with CD although at a lower frequency than previously reported. Younger patients are more likely to have an elevation in transaminases. Abnormal transaminases normalize in the majority of patients within 1 year after initiation of a GFD.
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19
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Czaja AJ. Diagnosis and Management of Autoimmune Hepatitis: Current Status and Future Directions. Gut Liver 2016; 10:177-203. [PMID: 26934884 PMCID: PMC4780448 DOI: 10.5009/gnl15352] [Citation(s) in RCA: 101] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2015] [Accepted: 11/04/2015] [Indexed: 02/06/2023] Open
Abstract
Autoimmune hepatitis is characterized by autoantibodies, hypergammaglobulinemia, and interface hepatitis on histological examination. The features lack diagnostic specificity, and other diseases that may resemble autoimmune hepatitis must be excluded. The clinical presentation may be acute, acute severe (fulminant), or asymptomatic; conventional autoantibodies may be absent; centrilobular necrosis and bile duct changes may be present; and the disease may occur after liver transplantation or with features that suggest overlapping disorders. The diagnostic criteria have been codified, and diagnostic scoring systems can support clinical judgment. Nonstandard autoantibodies, including antibodies to actin, α-actinin, soluble liver antigen, perinuclear antineutrophil antigen, asialoglycoprotein receptor, and liver cytosol type 1, are tools that can support the diagnosis, especially in patients with atypical features. Prednisone or prednisolone in combination with azathioprine is the preferred treatment, and strategies using these medications in various doses can ameliorate treatment failure, incomplete response, drug intolerance, and relapse after drug withdrawal. Budesonide, mycophenolate mofetil, and calcineurin inhibitors can be considered in selected patients as frontline or salvage therapies. Molecular (recombinant proteins and monoclonal antibodies), cellular (adoptive transfer and antigenic manipulation), and pharmacological (antioxidants, antifibrotics, and antiapoptotic agents) interventions constitute future directions in management. The evolving knowledge of the pathogenic pathways and the advances in technology promise new management algorithms.
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Affiliation(s)
- Albert J. Czaja
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN,
USA
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20
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Frankos V, Najeeullah R, Morgan J. Critical Evaluation for Alternative Causes of Drug Induced and Herbal Induced (DILI/HILI) Hepatotoxicity. Health (London) 2016. [DOI: 10.4236/health.2016.89084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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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: 41] [Impact Index Per Article: 4.1] [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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22
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Massironi S, Branchi F, Rossi RE, Fraquelli M, Elli L, Bardella MT, Cavalcoli F, Conte D. Hepatic hemangioma in celiac patients: data from a large consecutive series. Gastroenterol Res Pract 2015; 2015:749235. [PMID: 25649925 PMCID: PMC4306374 DOI: 10.1155/2015/749235] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2014] [Accepted: 12/24/2014] [Indexed: 02/05/2023] Open
Abstract
Background and Aims. Hepatic hemangioma (HH) has a widely ranging prevalence. The etiology is unclear; however, associations with autoimmune disorders have been described. We aimed at evaluating the prevalence of HH in celiac disease. Methods. Ninety-seven consecutive patients with celiac disease (18 M, 79 F, median age 41, and range 17-84 years) underwent liver ultrasound between January 2011 and 2012. The findings were compared with those of 1352 nonceliac patients (581 M, 771 F, median age 50, and range 16-94 years), without liver disease or previously detected HH, who underwent US in the same period. Results. Ultrasonographic findings consistent with HH were observed in 14 celiac patients (14.4%), a prevalence significantly higher than in controls (69 cases, 5.1%) (P = 0.0006). Subgroup analysis showed that, among women, the prevalence of HH was 16.4% in the celiac disease group (13/79) compared with 5.9% in controls (46/771) (P = 0.002). In celiac setting, HH had a median diameter of 1.3 cm and presented as a single lesion in 12 cases (86%). Conclusions. Our findings are consistent with a significantly higher prevalence of HH in celiac patients. Although mechanisms underlying this association remain unclear, autoimmune and metabolic processes, as well as alterations of gut-liver axis equilibrium, could play a role.
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Affiliation(s)
- Sara Massironi
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 28, 20122 Milan, Italy
| | - Federica Branchi
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 28, 20122 Milan, Italy
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Via Francesco Sforza 35, 20122 Milan, Italy
| | - Roberta Elisa Rossi
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 28, 20122 Milan, Italy
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Via Francesco Sforza 35, 20122 Milan, Italy
| | - Mirella Fraquelli
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 28, 20122 Milan, Italy
| | - Luca Elli
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 28, 20122 Milan, Italy
| | - Maria Teresa Bardella
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 28, 20122 Milan, Italy
| | - Federica Cavalcoli
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 28, 20122 Milan, Italy
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Via Francesco Sforza 35, 20122 Milan, Italy
| | - Dario Conte
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 28, 20122 Milan, Italy
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Via Francesco Sforza 35, 20122 Milan, Italy
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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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25
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Trivedi PJ, Adams DH. Mucosal immunity in liver autoimmunity: A comprehensive review. J Autoimmun 2013; 46:97-111. [DOI: 10.1016/j.jaut.2013.06.013] [Citation(s) in RCA: 72] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2013] [Accepted: 06/19/2013] [Indexed: 12/14/2022]
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26
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Abstract
Celiac disease (CD) is an autoimmune condition affecting the small intestine, triggered by the ingestion of gluten, the protein fraction of wheat, barley, and rye. There is a strong linkage between CD and HLA-DQ2 and HLA-DQ8 haplotypes. Multiple case reports and small series suggest concordance between CD and other autoimmune disorders. This paper provides a brief overview of the pathogenesis of CD and reviews the literature regarding associations between CD and other autoimmune diseases, including the potential effects of gluten-free diet therapy on the prevention or amelioration of associated diseases.
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Affiliation(s)
- Jolanda M Denham
- Nationwide Children's Hospital, The Ohio State University School of Medicine, 700 Children's Drive, Columbus, OH 43205, USA.
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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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Volta U, Caio G, Tovoli F, De Giorgio R. Gut-liver axis: an immune link between celiac disease and primary biliary cirrhosis. Expert Rev Gastroenterol Hepatol 2013; 7:253-261. [PMID: 23445234 DOI: 10.1586/egh.13.5] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
The association between celiac disease and primary biliary cirrhosis is well established. The breakdown of gut-liver axis equilibrium plays a central role in the development of immune disorders involving the small bowel and liver. In celiac disease, immunologically active molecules generated from the cross-linking between tissue transglutaminase and food/bacterial antigens reach the liver through the portal circulation owing to the increased intestinal permeability. A molecular mimicry between bacterial antigens and the pyruvate dehydrogenase E2 component, recognized by antimitochondrial autoantibodies, may have a role in primary biliary cirrhosis pathogenesis. An aberrant intestinal T lymphocyte homing to the liver may contribute to trigger immune hepatic damage. Both celiac disease and primary biliary cirrhosis share several features, including a higher prevalence in females, autoimmune comorbidities and specific autoantibodies. Reciprocal screening for both diseases is recommended, as an early diagnosis with the appropriate treatment can improve the outcome of these patients.
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Affiliation(s)
- Umberto Volta
- Department of Medical & Surgical Sciences, St. Orsola-Malpighi Hospital, University of Bologna, Italy.
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29
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Abenavoli L, Milic N, De Lorenzo A, Luzza F. A pathogenetic link between non-alcoholic fatty liver disease and celiac disease. Endocrine 2013; 43:65-7. [PMID: 22740094 DOI: 10.1007/s12020-012-9731-y] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2012] [Accepted: 06/13/2012] [Indexed: 02/08/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) has recently been recognized as the leading cause of the abnormalities in the liver function tests in the Western countries. Celiac disease (CD) is a permanent immunological intolerance to gluten proteins in genetically predisposed individuals. CD has been reported in 4-13 % of the cases with steatohepatitis, although the pathogenesis of the liver steatosis in CD patients is unclear. Based on the literature data, it can be concluded that the inclusion of serological markers of CD should be a part of the general workup in the patients with steatosis when other causes of the liver disease are excluded and in the patients with NAFLD when metabolic risk factors are not evident.
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Affiliation(s)
- Ludovico Abenavoli
- Department of Health Sciences, University "Magna Græcia", Viale Europa, 88100, Catanzaro, Italy.
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Drastich P, Honsová E, Lodererová A, Jarešová M, Pekáriková A, Hoffmanová I, Tučková L, Tlaskalová-Hogenová H, Špičák J, Sánchez D. Celiac disease markers in patients with liver diseases: A single center large scale screening study. World J Gastroenterol 2012; 18:6255-6262. [PMID: 23180946 PMCID: PMC3501774 DOI: 10.3748/wjg.v18.i43.6255] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To study the coincidence of celiac disease, we tested its serological markers in patients with various liver diseases.
METHODS: Large-scale screening of serum antibodies against tissue transglutaminase (tTG), and deamidated gliadin using enzyme-linked immunosorbent assay and serum antibodies against endomysium using immunohistochemistry, in patients with various liver diseases (n = 962) and patients who underwent liver transplantation (OLTx, n = 523) was performed. The expression of tTG in liver tissue samples of patients simultaneously suffering from celiac disease and from various liver diseases using immunohistochemistry was carried out. The final diagnosis of celiac disease was confirmed by histological analysis of small-intestinal biopsy.
RESULTS: We found that 29 of 962 patients (3%) with liver diseases and 5 of 523 patients (0.8%) who underwent OLTx were seropositive for IgA and IgG anti-tTG antibodies. However, celiac disease was biopsy-diagnosed in 16 patients: 4 with autoimmune hepatitis type I, 3 with Wilson's disease, 3 with celiac hepatitis, 2 with primary sclerosing cholangitis, 1 with primary biliary cirrhosis, 1 with Budd-Chiari syndrome, 1 with toxic hepatitis, and 1 with non-alcoholic steatohepatitis. Unexpectedly, the highest prevalence of celiac disease was found in patients with Wilson's disease (9.7%), with which it is only rarely associated. On the other hand, no OLTx patients were diagnosed with celiac disease in our study. A pilot study of the expression of tTG in liver tissue using immunohistochemistry documented the overexpression of this molecule in endothelial cells and periportal hepatocytes of patients simultaneously suffering from celiac disease and toxic hepatitis, primary sclerosing cholangitis or autoimmune hepatitis type I.
CONCLUSION: We suggest that screening for celiac disease may be beneficial not only in patients with associated liver diseases, but also in patients with Wilson's disease.
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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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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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Mounajjed T, Oxentenko A, Shmidt E, Smyrk T. The liver in celiac disease: clinical manifestations, histologic features, and response to gluten-free diet in 30 patients. Am J Clin Pathol 2011; 136:128-37. [PMID: 21685040 DOI: 10.1309/ajcpdomy5ri5tpmn] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
Descriptive reports of liver histologic features in celiac disease (CD) are sparse, and the effect of a gluten-free diet (GFD) on the course of liver injury is poorly understood. We reviewed liver biopsy specimens in 30 patients with CD and performed immunostains for IgG, IgG4, IgM, and IgA. Subsequent liver biochemical tests and compliance with the GFD were recorded. Of the patients, 19 had autoimmune-mediated liver disease (AILD; autoimmune hepatitis, 9; primary sclerosing cholangitis, 7; and primary biliary cirrhosis, 3). The remaining 11 patients had cryptogenic hepatitis (5), hepatitis C (2), steatohepatitis (2), sarcoidosis (1), and T-cell lymphoma (1). The liver disease diagnosis preceded the CD diagnosis in all groups except steatohepatitis. Although 82% of patients without AILD had symptomatic CD, only 26% of patients with AILD had such symptoms. The pathology of the specific liver disease was not atypical in histologic features or IgG/IgM ratios. While GFD improved cryptogenic hepatitis, it did not seem to affect AILD. We propose that AILD and cryptogenic hepatitis in patients with CD represent distinct clinical, histologic, and immunohistochemical entities rather than 2 ends of a spectrum of liver injury.
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Abstract
Numerous complications can occur in celiac disease, nutritional (growth failure in children, malnutrition, vitamin deficiencies), hematologic (anaemia), bone disease (osteoporosis, fracture), gynaecologic (hypo fertility), cardiovascular (coronaropathy, venous thrombosis), neurological (peripheral neuropathy), hepatic (cytolysis, cirrhosis). Celiac disease is associated with an increased risk of autoimmune diseases (type 1 diabetes, thyroiditis), and cancer (upper digestive tract, hepatocellular carcinoma, lymphoma). The main digestive complications are microscopic colitis and refractory sprue, which are resistant to gluten-free diet. It can be associated with a monoclonal proliferation of intraepithelial lymphocytes (type 2 refractory sprue), which may be considered as a cryptic lymphoma and can lead to invasive T lymphoma, which occurs in one celiac patient in 1000. Gluten-free diet protects from the occurrence of most complications and correct the over-mortality related to these complications.
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Colecchia A, Di Biase AR, Scaioli E, Festi D. Coeliac disease and autoimmune hepatitis: Gluten-free diet can influence liver disease outcome. Dig Liver Dis 2011; 43:247. [PMID: 21145795 DOI: 10.1016/j.dld.2010.09.011] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2010] [Accepted: 09/30/2010] [Indexed: 12/11/2022]
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Samarasena JB, Hu KQ. Hepatobiliary manifestations of gastrointestinal and nutritional disorders. Clin Liver Dis 2011; 15:89-110. [PMID: 21111995 DOI: 10.1016/j.cld.2010.09.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Hepatobiliary manifestations of gastrointestinal and nutritional disorders can occur as part of the clinical spectrum of the underlying disease or as a consequence of the treatment of the disease. This article reviews aspects of pathogenesis, diagnosis, and management of hepatobiliary manifestations associated with a selection of gastrointestinal and nutritional disorders including inflammatory bowel disease, celiac disease, Whipple's disease, and parenteral nutrition associated disorders.
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Affiliation(s)
- Jason B Samarasena
- Division of Gastroenterology, University of California Irvine Medical Center, 101 The City Drive, City Tower, Suite 400, Zot 4092, Orange, CA 92868, USA
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Prasad KK, Debi U, Sinha SK, Nain CK, Singh K. Hepatobiliary disorders in celiac disease: an update. Int J Hepatol 2011; 2011:438184. [PMID: 21994857 PMCID: PMC3170807 DOI: 10.4061/2011/438184] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2010] [Revised: 09/02/2010] [Accepted: 10/06/2010] [Indexed: 12/30/2022] Open
Abstract
This communication reviews recent literature and summarizes hepatobiliary abnormalities that may complicate the clinical course of celiac disease. A wide spectrum of hepatobiliary diseases has been described, including asymptomatic elevations of liver enzyme levels, nonspecific hepatitis, nonalcoholic fatty liver disease, and autoimmune and cholestatic liver disease. Moreover, in the majority of patients, liver enzyme levels will normalize on a gluten-free diet. In addition, celiac disease may be associated with rare hepatic complications, such as hepatic T-cell lymphoma. Because many celiac patients do not have overt gastrointestinal symptoms, a high index of suspicion is required. Simple methods of detecting celiac disease such as serum antibody tests help in the early identification of the disease, thus preventing serious complications of the disorder. The IgG DGP antibody test and IgA tTG antibody test used in combination are an excellent screening test for suspected cases of celiac disease.
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Affiliation(s)
- Kaushal K. Prasad
- Department of Superspeciality of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India,Division of GE Histopathology, Department of Superspeciality of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India,*Kaushal K. Prasad:
| | - Uma Debi
- Department of Radiodiagnosis, Government Medical College & Hospital, Sector 32, Chandigarh 160030, India
| | - Saroj K. Sinha
- Department of Superspeciality of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India
| | - Chander K. Nain
- Department of Superspeciality of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India
| | - Kartar Singh
- Department of Superspeciality of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India
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Tovoli F, De Giorgio R, Caio G, Grasso V, Frisoni C, Serra M, Caputo C, Stanghellini V, Bolondi L, Corinaldesi R, Volta U. Autoimmune Hepatitis and Celiac Disease: Case Report Showing an Entero-Hepatic Link. Case Rep Gastroenterol 2010; 4:469-475. [PMID: 21103207 PMCID: PMC2988861 DOI: 10.1159/000321992] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Celiac disease is an autoimmune disorder primarily targeting the small bowel, although extraintestinal extensions have been reported. The autoimmune processes can affect the liver with manifestations such as primary biliary cirrhosis and autoimmune hepatitis. We describe a 61-year-old woman with celiac disease and an increased levels of aminotransferases. The persistence of increased levels of aminotransferases after 1 year of gluten-free diet and the positivity for an anti-nuclear and anti-double-strand DNA antibodies led to a misdiagnosis of systemic lupus erythematosus-related hepatitis. Based on these findings the patient was placed on steroids, which after a few months were stopped because of the onset of diabetes mellitus. Soon after steroid withdrawal, the patient had a marked increase in aminotransferases and γ-globulins, and a liver biopsy revealed chronic active hepatitis. A course of three months of steroids and azathioprine normalized both biochemical and clinical parameters. Currently the patient is symptom-free and doing well. In conclusion, a hypertransaminasemia persisting after a gluten-free diet should be interpreted as a sign of coexisting autoimmune liver disease. Any autoantibody positivity (in this case to ANA and anti-dsDNA) should be carefully considered in order to avoid misdiagnosis delaying appropriate clinical management.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | - Umberto Volta
- Department of Clinical Medicine and Department of Digestive Diseases and Internal Medicine, Sant'Orsola-Malpighi Hospital, Università Alma Mater Studiorum di Bologna, Bologna, Italy
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39
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Abstract
Different hepatic and biliary tract disorders may occur with celiac disease. Some have been hypothesized to share genetic or immunopathogenetic factors, such as primary biliary cirrhosis, primary sclerosing cholangitis, and autoimmune hepatitis. Other hepatic changes in celiac disease may occur with malnutrition resulting from impaired nutrient absorption, including hepatic steatosis. In addition, celiac disease may be associated with rare hepatic complications, such as hepatic T-cell lymphoma.
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Affiliation(s)
- Hugh James Freeman
- Department of Medicine (Gastroenterology), University of British Columbia, Vancouver, British Columbia, Canada
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40
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Dinler G, Atalay E, Kalayci AG. Celiac disease in 87 children with typical and atypical symptoms in Black Sea region of Turkey. World J Pediatr 2009; 5:282-6. [PMID: 19911143 DOI: 10.1007/s12519-009-0053-y] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2008] [Accepted: 03/10/2009] [Indexed: 12/31/2022]
Abstract
BACKGROUND Celiac disease presents with a spectrum of clinical disorders. The variety of clinical presentations largely depends on age and extraintestinal findings. This study aimed to determine typical and atypical cases according to presenting symptoms and to evaluate their biochemical and pathological parameters. METHODS Eighty-seven patients with celiac disease in our unit between 2000 and 2007 were reviewed. Their diagnosis was made by serological and histological examination. The patients were divided into two groups according to their typical or atypical symptoms. RESULTS The mean age of the patients at diagnosis was 8.2 years (range, 1-18 years), but patients presenting with typical symptoms were younger than those presenting with atypical symptoms. The patients in the two groups did not differ significantly in sex, weight and height Z scores except age. Diarrhea (96.3%), abdominal distention (65.4%) and failure to thrive (60%) were the most common clinical presentations in the typical group, and short stature (62.5%) and anemia (31.2%) were the most common in the atypical group. Total/subtotal villous atrophy was significantly higher in the typical group than in the atypical group. CONCLUSIONS Many children with celiac disease show an atypical form. The understanding of presentations of celiac disease may prevent delayed diagnosis. Celiac disease should be specially investigated in patients with recurrent iron deficiency anemia, short stature and autoimmune disorders.
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Affiliation(s)
- Gönül Dinler
- Unit of Pediatric Gastroenterology Hepatology and Nutrition, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey.
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Abstract
Celiac sprue (CS) is a gluten-sensitive enteropathy with many autoimmune features. CS involves multiple organs through immune and nonimmune processes, and is frequently associated with other autoimmune disorders. This article reviews the co-occurrence of CS with autoimmune disorders of the cutaneous, nervous, endocrine, musculoskeletal, gastrointestinal and cardiovascular systems. The types of autoimmune disorders associated with CS and the prevalence of CS in other autoimmune disorders are also discussed. A brief review of the literature on the potential mechanisms behind these associations and the therapeutic effects of a gluten-free diet for autoimmune comorbidities in CS is also provided.
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Affiliation(s)
- Shadi Rashtak
- Division of Medicine, Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Eric V Marietta
- Division of Medicine, Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
- Department of Dermatology, Mayo Clinic, Rochester, MN, USA
- Department of Immunology, Mayo Clinic, Rochester, MN, USA
| | - Joseph A Murray
- Department of Medicine, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, 200 First Street, SW, Rochester, MN 55905, USA, Tel.: +1 507 284 2631, Fax: +1 507 266 9081,
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Silano M, Volta U, Vincentini O, De Vincenzi M. Clinical features of chronic C virus hepatitis in patients with celiac disease. Eur J Clin Microbiol Infect Dis 2009; 28:1267-9. [PMID: 19529964 DOI: 10.1007/s10096-009-0769-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2009] [Accepted: 06/01/2009] [Indexed: 02/07/2023]
Affiliation(s)
- M Silano
- Division of Food Science, Human Nutrition and Health, Istituto Superiore di Sanità, Viale Regina Elena 299, Roma, 00161, Italy.
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43
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Abstract
A complex interplay of liver, bile ducts, and the gut critically determines functioning of these organs in health and disease. Biochemical and physiological aspects of their interaction and the role of inflammatory cells, cytokines, bile acids, visceral hormones, neuropeptides and other messengers in the pathogenesis of model immune-mediated hepatobiliary disorders are discussed in the actual issue of Clinical Reviews in Allergy and Immunology. Potential molecular targets for future therapeutic approaches are also addressed.
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Affiliation(s)
- Ulrich Beuers
- Department of Gastroenterology and Hepatology, G4-213 Academic Medical Center, University of Amsterdam, P.O. Box 22700, 1100 DE, Amsterdam, The Netherlands.
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Wakim-Fleming J, Zein NN, Bennett A, Lopez R, Santisi J, Carey WD. Histological abnormalities of the small bowel mucosa in cirrhosis and portal hypertension. World J Gastroenterol 2008; 14:6370-5. [PMID: 19009654 PMCID: PMC2766120 DOI: 10.3748/wjg.14.6370] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To study the small bowel (SB) mucosa on biopsy in cirrhotic patients with portal hypertension and in non-cirrhotic controls and grade findings according to the Marsh criteria.
METHODS: We prospectively enrolled 51 consecutive patients undergoing an upper endoscopy for their routine medical care. Twenty five patients with cirrhosis and portal hypertension were compared to 26 controls. We obtained coeliac serology and multiple upper small bowel biopsies on all 51 patients. A GI pathologist interpreted biopsies and graded findings according to the Marsh criteria. We assessed equivalence in Marsh grade between cirrhotic and non-cirrhotic controls using the Mann-Whitney test for equivalence.
RESULTS: Gender, ethnicity and age were similar between both groups. Marsh grades were equivalent between the groups. Grade of 0 was present in 96% and grade of 1 was present in 4% of both groups and there was no villus atrophy or decrease in villus/crypt ratio in patients with portal hypertension.
CONCLUSION: This study provides evidence for the lack of villus atrophy in patients with cirrhosis and portal hypertension, and supports the continuous reliance on the Marsh criteria when the diagnosis of coeliac disease is to be made in the presence of cirrhosis.
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