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Gisbert JP, Chaparro M. Common Mistakes in Managing Patients with Inflammatory Bowel Disease. J Clin Med 2024; 13:4795. [PMID: 39200937 PMCID: PMC11355176 DOI: 10.3390/jcm13164795] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Revised: 08/12/2024] [Accepted: 08/13/2024] [Indexed: 09/02/2024] Open
Abstract
Introduction: Errors are very common in medical practice and in particular, in the healthcare of patients with inflammatory bowel disease (IBD); however, most of these can be prevented. Aim: To address common errors in the management of IBD. Methods: Our approach to this problem consists in identifying mistakes frequently observed in clinical practice (according to our experience) in the management of patients with IBD, then reviewing the scientific evidence available on the subject, and finally proposing the most appropriate recommendation for each case. Results: The most common mistakes in the management of IBD include those related to diagnosis and differential diagnosis, prevention, nutrition and diet, treatment with different drugs (mainly 5-aminosalicylates, corticosteroids, thiopurines, and anti-TNF agents), extraintestinal manifestations, anemia, elderly patients, pregnancy, and surgery. Conclusions: Despite the availability of guidelines for both disease management and preventive aspects of IBD care, a considerable variation in clinical practice still remains. In this review, we have identified common mistakes in the management of patients with IBD in clinical practice. There is a clear need for a greater dissemination of clinical practice guidelines among gastroenterologists and for the implementation of ongoing training activities supported by scientific societies. Finally, it is desirable to follow IBD patients in specialized units, which would undoubtedly be associated with higher-quality healthcare and a lower likelihood of errors in managing these patients.
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Affiliation(s)
- Javier P. Gisbert
- Gastroenterology Unit, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), 28006 Madrid, Spain;
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Zhong Z, Xu M, Ge C, Tan J. Exploring shared molecular signatures and regulatory mechanisms in nonalcoholic steatohepatitis and inflammatory bowel disease using integrative bioinformatics analysis. Sci Rep 2024; 14:12085. [PMID: 38802459 PMCID: PMC11130338 DOI: 10.1038/s41598-024-62310-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Accepted: 05/15/2024] [Indexed: 05/29/2024] Open
Abstract
The co-existence of inflammatory bowel disease (IBD) and non-alcoholic steatohepatitis (NASH) has raised interest in identifying shared molecular mechanisms and potential therapeutic targets. However, the relationship between these two diseases remains unclear and effective medical treatments are still lacking. Through the bioinformatics analysis in this study, 116 shared differentially expressed genes (SDEGs) were identified between IBD and NASH datasets. GO and KEGG pathway analyses revealed significant involvement of SDEGs in apoptotic processes, cell death, defense response, cytokine and chemokine activity, and signaling pathways. Furthermore, weighted gene co-expression network analysis (WGCNA) identified five shared signature genes associated specifically with IBD and NASH, they were CXCL9, GIMAP2, ADAMTS5, GRAP, and PRF1. These five genes represented potential diagnostic biomarkers for distinguishing patients with diseases from healthy individuals by using two classifier algorithms and were positively related to autophagy, ferroptosis, angiogenesis, and immune checkpoint factors in the two diseases. Additionally, single-cell analysis of IBD and NASH samples highlighted the expression of regulatory genes in various immune cell subtypes, emphasizing their significance in disease pathogenesis. Our work elucidated the shared signature genes and regulatory mechanisms of IBD and NASH, which could provide new potential therapies for patients with IBD and NASH.
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Affiliation(s)
- Zixuan Zhong
- Chongqing Key Laboratory of Medicinal Resources in the Three Gorges Reservoir Region, School of Biological and Chemical Engineering, Chongqing University of Education, Chongqing, 400067, People's Republic of China.
- Research Center of Brain Intellectual Promotion and Development for Children Aged 0-6 Years, Chongqing University of Education, Chongqing, 400067, People's Republic of China.
| | - Minxuan Xu
- Chongqing Key Laboratory of Medicinal Resources in the Three Gorges Reservoir Region, School of Biological and Chemical Engineering, Chongqing University of Education, Chongqing, 400067, People's Republic of China
- Research Center of Brain Intellectual Promotion and Development for Children Aged 0-6 Years, Chongqing University of Education, Chongqing, 400067, People's Republic of China
- Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400030, People's Republic of China
| | - Chenxu Ge
- Chongqing Key Laboratory of Medicinal Resources in the Three Gorges Reservoir Region, School of Biological and Chemical Engineering, Chongqing University of Education, Chongqing, 400067, People's Republic of China
- Research Center of Brain Intellectual Promotion and Development for Children Aged 0-6 Years, Chongqing University of Education, Chongqing, 400067, People's Republic of China
- Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400030, People's Republic of China
| | - Jun Tan
- Chongqing Key Laboratory of Medicinal Resources in the Three Gorges Reservoir Region, School of Biological and Chemical Engineering, Chongqing University of Education, Chongqing, 400067, People's Republic of China
- Research Center of Brain Intellectual Promotion and Development for Children Aged 0-6 Years, Chongqing University of Education, Chongqing, 400067, People's Republic of China
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van Asseldonk DP, Crouwel F, Seinen ML, Scheffer PG, Veldkamp AI, de Boer NK, Lissenberg-Witte B, Peters GJ, van Bodegraven AA. Exploring the role of oxidative stress and the effect of N-acetylcysteine in thiopurine-induced liver injury in inflammatory bowel disease: A randomized crossover pilot study. Basic Clin Pharmacol Toxicol 2024; 134:507-518. [PMID: 38284479 DOI: 10.1111/bcpt.13978] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Revised: 12/29/2023] [Accepted: 01/01/2024] [Indexed: 01/30/2024]
Abstract
Thiopurine treatment is regularly complicated by drug-induced liver injury. It has been suggested that oxidative stress may play a synergistic role. To assess whether thiopurine-induced liver injury coincides with increased oxidative stress and whether co-administration with N-acetylcysteine is protective, we performed a randomized open label crossover pilot study in inflammatory bowel disease patients with thiopurine-induced increased serum liver tests. The study comprised four stages of 4 weeks. Patients received no additional therapy followed by N-acetylcysteine 1200 mg twice a day, or the other way around, alongside ongoing thiopurine treatment. The third and fourth stages comprised a washout period and thiopurine reintroduction period. Nine patients completed the study, and the addition of N-acetylcysteine decreased myeloperoxidase concentrations (33.6-24.5 pmol/L, p = 0.038). The other biomarkers remained unchanged, including thiopurine metabolites, xanthine oxidase activity, thiopurine S-methyltransferase activity and serum liver enzyme activity tests. Reintroduction of thiopurines led to an increase of F2-isoprostanes (101-157 ng/mmol, p = 0.038), but not of serum liver enzyme activity tests. Results suggests that thiopurines may increase oxidative stress and although the addition of N-acetylcysteine led to a decrease in plasma myeloperoxidase concentrations, it does not protect from thiopurine-induced increase of serum liver tests.
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Affiliation(s)
- Dirk P van Asseldonk
- Department of Gastroenterology and Hepatology, Noordwest Ziekenhuisgroep, Alkmaar, The Netherlands
- Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism Research Institute, Amsterdam University Medical Centers, Location VUMC, Amsterdam, The Netherlands
| | - Femke Crouwel
- Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism Research Institute, Amsterdam University Medical Centers, Location VUMC, Amsterdam, The Netherlands
| | - Margien L Seinen
- Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism Research Institute, Amsterdam University Medical Centers, Location VUMC, Amsterdam, The Netherlands
- Department of Gastroenterology and Hepatology, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands
| | - Peter G Scheffer
- Metabolic Laboratory, Department of Clinical Chemistry, Amsterdam University Medical Centers, Location VUMC, Amsterdam, The Netherlands
| | - Agnes I Veldkamp
- Department of Clinical Pharmacology and Pharmacy, Amsterdam University Medical Centers, Location VUMC, Amsterdam, The Netherlands
| | - Nanne K de Boer
- Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism Research Institute, Amsterdam University Medical Centers, Location VUMC, Amsterdam, The Netherlands
| | - Birgit Lissenberg-Witte
- Department of Epidemiology and Data Science, Amsterdam University Medical Centers, Location VUMC, Amsterdam, The Netherlands
| | - Godefridus J Peters
- Department of Medical Oncology, Amsterdam University Medical Centers, Location VUMC, Amsterdam, The Netherlands
- Department of Biochemistry, Medical University of Gdansk, Gdansk, Poland
| | - Adriaan A van Bodegraven
- Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology Endocrinology Metabolism Research Institute, Amsterdam University Medical Centers, Location VUMC, Amsterdam, The Netherlands
- Department of Gastroenterology, Geriatrics, Internal and Intensive Care Medicine (CO-MIK), Zuyderland Medical Centre, Heerlen-Sittard-Geleen, The Netherlands
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Lai X, Zhou H, Wan Y, Kuang J, Yang Y, Mai L, Chen Y, Liu B. Magnesium isoglycyrrhizinate attenuates nonalcoholic fatty liver disease by strengthening intestinal mucosal barrier. Int Immunopharmacol 2024; 128:111429. [PMID: 38171057 DOI: 10.1016/j.intimp.2023.111429] [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: 07/19/2023] [Revised: 12/11/2023] [Accepted: 12/19/2023] [Indexed: 01/05/2024]
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) has recently risen to the top spot among chronic liver diseases in the world. However, there are no recognized treatments for it. Magnesium isoglycyrrhizate (MgIG) has potential as a NAFLD/NASH therapy. AIMS To investigate the efficacy of MgIG in improving NAFLD/NASH and the possible pathways and mechanisms. METHODS C57bl/6 mice were fed a high-fat diet (HFD) and 1 % dextran sulfate sodium (DSS) for 12 weeks to establish the NAFLD/NASH model. MgIG was administered by gavage during the last 7 weeks. First, the therapeutic effects of MgIG on hepatic steatosis and fibrosis, liver injury, and inflammation in the NAFLD/NASH mice were evaluated. Second, liver oxidative stress and hepatocyte apoptosis were detected. Finally, the effect of MgIG on intestinal permeability and short-chain fatty acid (SCFA) levels in mice's intestinal contents were examined. RESULTS MgIG administration attenuated HFD-induced hepatic steatosis and fibrosis, improved serum biochemical and NAFLD/NASH mice, reduced liver oxidative stress and hepatocyte apoptosis, improved intestinal permeability, and increased fecal SCFA levels in NAFLD/NASH mice. CONCLUSION MgIG protects against HFD-induced NAFLD/NASH through multiple pathways as well as mechanisms and holds promise as a potentially effective treatment for NAFLD/NASH.
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Affiliation(s)
- Xueying Lai
- Department of Gastroenterology, Panyu Central Hospital, Guangzhou, 511400, China
| | - Hong Zhou
- National Clinical Research Center for Kidney Disease, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - Yu Wan
- Department of Gastroenterology, Panyu Central Hospital, Guangzhou, 511400, China
| | - Jiesi Kuang
- Department of Gastroenterology, Panyu Central Hospital, Guangzhou, 511400, China
| | - Yuhui Yang
- Department of Gastroenterology, Panyu Central Hospital, Guangzhou, 511400, China
| | - Limei Mai
- Department of Gastroenterology, Panyu Central Hospital, Guangzhou, 511400, China
| | - Yumei Chen
- Department of Infectious Diseases, Panyu Central Hospital, Guangzhou, 511400, China
| | - Bin Liu
- Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
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Wang W, Gao X, Kang N, Wang C, Li C, Yu H, Zhang X. Shared biomarkers and immune cell infiltration signatures in ulcerative colitis and nonalcoholic steatohepatitis. Sci Rep 2023; 13:18497. [PMID: 37898694 PMCID: PMC10613305 DOI: 10.1038/s41598-023-44853-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2023] [Accepted: 10/12/2023] [Indexed: 10/30/2023] Open
Abstract
The coexistence of ulcerative colitis (UC) and nonalcoholic steatohepatitis (NASH) involves a intricate interplay, though the precise pathophysiological mechanisms remain elusive. To shed light on this, our study endeavors to unravel the shared gene signatures and molecular mechanisms by employing quantitative bioinformatics analysis on a publicly available RNA-sequencing database. Gene expression profiles of UC (GSE87466) and NASH (GSE89632) were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were analyzed using R software. After identifying common DEGs, functional enrichment analysis, protein-protein interaction (PPI) network analysis and module construction were performed to obtain candidate hub genes. GSE47908 for UC and GSE159676 for NASH were selected to validate the obtained candidate genes. A total of 119 common DEGs were found in NASH and UC patients. Functional and pathway analyses emphasized that viral infection, inflammation and immune response were enriched in these two diseases. After module construction and validation, CD2, CD8A, GNLY, IFI44, NKG7 and OAS2 were identified as hub genes. 6 hub genes and their combined prediction scores were found with an impressive accuracy and sensitivity. Functional estimation, gene set enrichment analysis and immune infiltration signature identification showed notable associations of the six hub genes with T cells, natural killer cells and type I interferon levels. In addition, we constructed UC combined with NASH mice model successfully with significantly higher expression of hub genes in both liver and colonic tissues than those in control group. Our study elucidates 6 hub genes of UC and NASH, which may participate in immune, inflammatory and antiviral effects. These findings provide some potential biochemical markers for further exploration of UC coexistence with NASH.
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Affiliation(s)
- Wenxin Wang
- Department of Gastroenterology and Hepatology, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Hebei Clinical Research Center for Digestive Diseases, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China
| | - Xin Gao
- Department of Gastroenterology and Hepatology, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Hebei Clinical Research Center for Digestive Diseases, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China
| | - Ning Kang
- Department of Gastroenterology and Hepatology, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Hebei Clinical Research Center for Digestive Diseases, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China
| | - Chen Wang
- Department of Gastroenterology and Hepatology, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Hebei Clinical Research Center for Digestive Diseases, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China
| | - Chenyang Li
- Department of Gastroenterology and Hepatology, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Hebei Clinical Research Center for Digestive Diseases, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China
| | - Huan Yu
- Department of Gastroenterology and Hepatology, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Hebei Clinical Research Center for Digestive Diseases, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China
| | - Xiaolan Zhang
- Department of Gastroenterology and Hepatology, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Hebei Clinical Research Center for Digestive Diseases, The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, Hebei, China.
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Rodriguez-Duque JC, Calleja JL, Iruzubieta P, Hernández-Conde M, Rivas-Rivas C, Vera MI, Garcia MJ, Pascual M, Castro B, García-Blanco A, García-Nieto E, Olmo SCD, Cagigal ML, Lopez-Montejo L, Fernández-Lamas T, Rasines L, Fortea JI, Vaque JP, Frias Y, Rivero M, Arias-Loste MT, Crespo J. Increased risk of MAFLD and Liver Fibrosis in Inflammatory Bowel Disease Independent of Classic Metabolic Risk Factors. Clin Gastroenterol Hepatol 2023; 21:406-414.e7. [PMID: 35124272 DOI: 10.1016/j.cgh.2022.01.039] [Citation(s) in RCA: 35] [Impact Index Per Article: 17.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Revised: 01/17/2022] [Accepted: 01/19/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS There is conflicting evidence regarding the prevalence of and risk factors for metabolic-associated fatty liver disease (MAFLD) in patients with inflammatory bowel disease (IBD). We aimed to determine MAFLD prevalence and risk factors in IBD patients. METHODS Cross-sectional, case-control study included all consecutive IBD patients treated at 2 different university hospitals. Controls were subjects randomly selected from the general population and matched by age, sex, type 2 diabetes status, and body mass index in a 1:2 ratio. MAFLD was confirmed by controlled attenuation parameter. Liver biopsies were collected when MAFLD with significant liver fibrosis was suspected. In addition, age- and fibrosis stage-paired non-IBD patients with biopsy-proven MAFLD served as a secondary control group. RESULTS Eight hundred thirty-one IBD patients and 1718 controls were included. The prevalence of MAFLD and advanced liver fibrosis (transient elastography ≥9.7 kPa) was 42.00% and 9.50%, respectively, in IBD patients and 32.77% and 2.31%, respectively, in the general population (P < .001). A diagnosis of IBD was an independent predictor of MAFLD (adjusted odds ratio, 1.99; P < .001) and an independent risk factor for advanced liver fibrosis (adjusted odds ratio, 5.55; P < .001). Liver biopsies were obtained from 40 IBD patients; MAFLD was confirmed in all cases, and fibrosis of any degree was confirmed in 25 of 40 cases (62.5%). Body mass index and type 2 diabetes prevalence were significantly lower in IBD-MAFLD patients than in severity-paired patients with biopsy-proven MAFLD. CONCLUSIONS MAFLD and liver fibrosis are particularly prevalent in IBD patients, regardless of the influence of classic metabolic risk factors.
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Affiliation(s)
- Juan Carlos Rodriguez-Duque
- Gastroenterology and Hepatology Department, University Hospital Marqués de Valdecilla, Santander, Spain; Group of Clinical and Translational Research in Digestive Diseases Infection, Immunity and Digestive Pathology Group, Research Institute Marqués de Valdecilla (IDIVAL), Santander, Spain
| | - José Luis Calleja
- Gastroenterology and Hepatology Department, University Hospital Puerta de Hierro-Majadahonda, Madrid, Spain
| | - Paula Iruzubieta
- Gastroenterology and Hepatology Department, University Hospital Marqués de Valdecilla, Santander, Spain; Group of Clinical and Translational Research in Digestive Diseases Infection, Immunity and Digestive Pathology Group, Research Institute Marqués de Valdecilla (IDIVAL), Santander, Spain
| | - Marta Hernández-Conde
- Gastroenterology and Hepatology Department, University Hospital Puerta de Hierro-Majadahonda, Madrid, Spain
| | - Coral Rivas-Rivas
- Gastroenterology and Hepatology Department, University Hospital Marqués de Valdecilla, Santander, Spain; Group of Clinical and Translational Research in Digestive Diseases Infection, Immunity and Digestive Pathology Group, Research Institute Marqués de Valdecilla (IDIVAL), Santander, Spain
| | - María Isabel Vera
- Gastroenterology and Hepatology Department, University Hospital Puerta de Hierro-Majadahonda, Madrid, Spain
| | - Maria Jose Garcia
- Gastroenterology and Hepatology Department, University Hospital Marqués de Valdecilla, Santander, Spain; Group of Clinical and Translational Research in Digestive Diseases Infection, Immunity and Digestive Pathology Group, Research Institute Marqués de Valdecilla (IDIVAL), Santander, Spain
| | - Marta Pascual
- Gastroenterology and Hepatology Department, University Hospital Marqués de Valdecilla, Santander, Spain; Group of Clinical and Translational Research in Digestive Diseases Infection, Immunity and Digestive Pathology Group, Research Institute Marqués de Valdecilla (IDIVAL), Santander, Spain
| | - Beatriz Castro
- Gastroenterology and Hepatology Department, University Hospital Marqués de Valdecilla, Santander, Spain; Group of Clinical and Translational Research in Digestive Diseases Infection, Immunity and Digestive Pathology Group, Research Institute Marqués de Valdecilla (IDIVAL), Santander, Spain
| | - Agustín García-Blanco
- Group of Clinical and Translational Research in Digestive Diseases Infection, Immunity and Digestive Pathology Group, Research Institute Marqués de Valdecilla (IDIVAL), Santander, Spain
| | - Enrique García-Nieto
- Group of Clinical and Translational Research in Digestive Diseases Infection, Immunity and Digestive Pathology Group, Research Institute Marqués de Valdecilla (IDIVAL), Santander, Spain
| | - Soraya Curiel-Del Olmo
- Group of Clinical and Translational Research in Digestive Diseases Infection, Immunity and Digestive Pathology Group, Research Institute Marqués de Valdecilla (IDIVAL), Santander, Spain
| | - María Luisa Cagigal
- Pathology Department, University Hospital Marqués de Valdecilla, Santander, Spain
| | - Lorena Lopez-Montejo
- Group of Clinical and Translational Research in Digestive Diseases Infection, Immunity and Digestive Pathology Group, Research Institute Marqués de Valdecilla (IDIVAL), Santander, Spain
| | - Tatiana Fernández-Lamas
- Group of Clinical and Translational Research in Digestive Diseases Infection, Immunity and Digestive Pathology Group, Research Institute Marqués de Valdecilla (IDIVAL), Santander, Spain
| | - Laura Rasines
- Group of Clinical and Translational Research in Digestive Diseases Infection, Immunity and Digestive Pathology Group, Research Institute Marqués de Valdecilla (IDIVAL), Santander, Spain
| | - José Ignacio Fortea
- Gastroenterology and Hepatology Department, University Hospital Marqués de Valdecilla, Santander, Spain; Group of Clinical and Translational Research in Digestive Diseases Infection, Immunity and Digestive Pathology Group, Research Institute Marqués de Valdecilla (IDIVAL), Santander, Spain
| | - José Pedro Vaque
- Group of Clinical and Translational Research in Digestive Diseases Infection, Immunity and Digestive Pathology Group, Research Institute Marqués de Valdecilla (IDIVAL), Santander, Spain; Molecular Biology Department, University of Cantabria, Santander, Spain
| | - Yza Frias
- Gastroenterology and Hepatology Department, University Hospital Puerta de Hierro-Majadahonda, Madrid, Spain
| | - Montserrat Rivero
- Gastroenterology and Hepatology Department, University Hospital Marqués de Valdecilla, Santander, Spain; Group of Clinical and Translational Research in Digestive Diseases Infection, Immunity and Digestive Pathology Group, Research Institute Marqués de Valdecilla (IDIVAL), Santander, Spain
| | - María Teresa Arias-Loste
- Gastroenterology and Hepatology Department, University Hospital Marqués de Valdecilla, Santander, Spain; Group of Clinical and Translational Research in Digestive Diseases Infection, Immunity and Digestive Pathology Group, Research Institute Marqués de Valdecilla (IDIVAL), Santander, Spain.
| | - Javier Crespo
- Gastroenterology and Hepatology Department, University Hospital Marqués de Valdecilla, Santander, Spain; Group of Clinical and Translational Research in Digestive Diseases Infection, Immunity and Digestive Pathology Group, Research Institute Marqués de Valdecilla (IDIVAL), Santander, Spain.
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Little R, Kamath BM, Ricciuto A. Liver Disease in Pediatric Inflammatory Bowel Disease. PEDIATRIC INFLAMMATORY BOWEL DISEASE 2023:129-149. [DOI: 10.1007/978-3-031-14744-9_11] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Cheng Y, McLean R, Sewell JL, Huang C, Khalili M. Inflammatory bowel disease type influences development of elevated liver enzymes. JGH Open 2022; 6:846-853. [PMID: 36514498 PMCID: PMC9730719 DOI: 10.1002/jgh3.12831] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Revised: 09/15/2022] [Accepted: 10/08/2022] [Indexed: 11/06/2022]
Abstract
Background and Aim Up to a third of patients with inflammatory bowel disease (IBD) have elevated liver enzymes (ELE). We evaluated the incidence, predictors, and outcomes associated with ELE in a diverse and vulnerable IBD cohort. Methods We retrospectively evaluated 336 IBD patients receiving care at the San Francisco safety net gastroenterology clinics between June 1996 and December 2019. Baseline characteristics were captured at first visit, then patients were followed until last clinic activity or death. Testing and etiology, pattern of ELE defined as transient (<1 month) or persistent (≥1 month), were assessed. Multivariate modeling evaluated predictors of ELE at baseline, new ELE at follow-up, and pattern of ELE. Results Baseline median age was 40.3 years, 62% male, 46% White (13% Black, 19% Asian, and 18% Latino), and 59% had ulcerative colitis (UC). Among those without known liver disease (n = 14), 51.6% (166 of 322; 52 at baseline, 114 during follow-up) had ELE. In multivariate logistic regression, 5-aminosalicylic acid use (odds ratio [OR] 2.2, 95% confidence interval [CI]: 1.07-4.4, P = 0.03) and higher body mass index (OR 1.08, 95% CI: 1.02-1.14, P = 0.01) were associated with baseline ELE. In multivariate Cox regression, UC (vs. Crohn's disease [CD]) had a 34% lower risk of developing new ELE during follow-up (hazard ratio [HR] 0.66, 95% CI: 0.46-0.95, P = 0.02). Mortality rate was higher for patients with ELE (0% normal vs 2.3% transient ELE vs 6.5% persistent ELE, P < 0.001). Conclusion ELE is prevalent in IBD, especially in CD, and associated with higher rates of mortality. Identification and management of ELE particularly when persistent are important to IBD outcomes.
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Affiliation(s)
- Yao‐Wen Cheng
- Department of Medicine, Division of GastroenterologyUniversity of California San FranciscoSan FranciscoCaliforniaUSA
| | - Richard McLean
- Department of Medicine, Division of GastroenterologyUniversity of California San FranciscoSan FranciscoCaliforniaUSA
| | - Justin L Sewell
- Department of Medicine, Division of GastroenterologyUniversity of California San FranciscoSan FranciscoCaliforniaUSA
| | - Chiung‐Yu Huang
- Department of Epidemiology and BiostatisticsUniversity of California San FranciscoSan FranciscoCaliforniaUSA
| | - Mandana Khalili
- Department of Medicine, Division of GastroenterologyUniversity of California San FranciscoSan FranciscoCaliforniaUSA
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Eberhardy AC, Heinrich NA, McFadden RA, Reiter LV. Prevalence of hepatotoxicity and myelosuppression with alternate day use of azathioprine and glucocorticoids for treatment of dermatological conditions in dogs. Vet Dermatol 2022; 33:503-508. [PMID: 36000613 DOI: 10.1111/vde.13115] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Revised: 05/08/2022] [Accepted: 06/01/2022] [Indexed: 11/29/2022]
Abstract
BACKGROUND The use of azathioprine (AZA) in dogs is limited by the potential for hepatotoxicity and myelosuppression. HYPOTHESIS/OBJECTIVES To determine the prevalence of AZA-associated hepatotoxicity in dogs with dermatological conditions receiving alternate-day AZA. The hypothesis was that dogs receiving AZA every other day (EOD) would have a lower prevalence of hepatotoxicity compared to published data for dogs receiving daily AZA. A secondary aim was to determine the prevalence of AZA-associated myelosuppression over the same time period and population. ANIMALS Forty-one client-owned dogs with dermatological conditions treated with AZA EOD and glucocorticoids with clinical and haematological follow-up available for a minimum of two months of AZA therapy. METHODS Retrospective analysis of data from April 1994 to July 2020. Hepatotoxicity was defined as elevation of alanine aminotransferase (ALT) at least twofold above the reference range. RESULTS Azathioprine-associated hepatotoxicity was observed in two of 41 dogs (4.9%), with onset at 18 and 40 days, respectively. One dog receiving AZA at 1.9 mg/kg EOD had a fourfold increase in ALT. The other dog (AZA dose 2.3 mg/kg EOD) had a 30-fold increase in ALT. Azathioprine was not associated with thrombocytopenia, anaemia or neutropenia in any dogs. Lymphopenia developed in one dog (2.4%) with onset at 105 days. CONCLUSIONS AND CLINICAL RELEVANCE Alternate-day AZA administration with tapering glucocorticoids was well-tolerated in dogs with dermatological conditions.
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Affiliation(s)
| | | | | | - Lisa V Reiter
- McKeever Dermatology Clinics, Eden Prairie, Minnesota, USA
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10
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Núñez F P, Castro F, Mezzano G, Quera R, Diaz D, Castro L. Hepatobiliary manifestations in inflammatory bowel disease: A practical approach. World J Hepatol 2022; 14:319-337. [PMID: 35317174 PMCID: PMC8891676 DOI: 10.4254/wjh.v14.i2.319] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Revised: 09/10/2021] [Accepted: 01/26/2022] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel diseases (IBD) are associated with various hepatobiliary disorders. They can occur at any moment in the course of the disease or associated with the treatment. The prevalence of liver dysfunction can reach up to 50% in different studies. Nonalcoholic fatty liver disease is considered the most common hepatobiliary complication in IBD, while primary sclerosing cholangitis is the most specific. Management of hepatic manifestations in IBD involves a multidisciplinary approach that includes a high index of suspicion and joint management with hepatologists. The medical confrontation with abnormal liver tests must include an exhaustive study to determine if these patterns can be related to IBD, associated diseases or to the therapies used.
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Affiliation(s)
- Paulina Núñez F
- Universidad de los Andes,Inflammatory Bowel Disease Program, Digestive Disease Center, Santiago 7600976, RM, Chile
- Inflammatory Bowel Disease Program, Hospital San Juan de Dios, Universidad de Chile, Santiago 7701230, RM, Chile
| | - Fabiola Castro
- Universidad de los Andes,Hepatology Program, Digestive Disease Center, Santiago 7600976, RM, Chile
| | - Gabriel Mezzano
- Universidad de los Andes,Hepatology Program, Digestive Disease Center, Santiago 7600976, RM, Chile
- Department of Gastroenterology, Hospital del Salvador/Universidad de Chile, Santiago 7600976, RM, Chile
| | - Rodrigo Quera
- Universidad de los Andes,Inflammatory Bowel Disease Program, Digestive Disease Center, Santiago 7600976, RM, Chile
| | - Diego Diaz
- Medicine, Universidad de los Andes, Santiago 770976, RM, Chile
| | - Lorena Castro
- Universidad de los Andes,Hepatology Program, Digestive Disease Center, Santiago 7600976, RM, Chile
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11
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Singh A, Mahajan R, Kedia S, Dutta AK, Anand A, Bernstein CN, Desai D, Pai CG, Makharia G, Tevethia HV, Mak JWY, Kaur K, Peddi K, Ranjan MK, Arkkila P, Kochhar R, Banerjee R, Sinha SK, Ng SC, Hanauer S, Verma S, Dutta U, Midha V, Mehta V, Ahuja V, Sood A. Use of thiopurines in inflammatory bowel disease: an update. Intest Res 2022; 20:11-30. [PMID: 33845546 PMCID: PMC8831775 DOI: 10.5217/ir.2020.00155] [Citation(s) in RCA: 60] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Revised: 02/19/2021] [Accepted: 03/01/2021] [Indexed: 12/11/2022] Open
Abstract
Inflammatory bowel disease (IBD), once considered a disease of the Western hemisphere, has emerged as a global disease. As the disease prevalence is on a steady rise, management of IBD has come under the spotlight. 5-Aminosalicylates, corticosteroids, immunosuppressive agents and biologics are the backbone of treatment of IBD. With the advent of biologics and small molecules, the need for surgery and hospitalization has decreased. However, economic viability and acceptability is an important determinant of local prescription patterns. Nearly one-third of the patients in West receive biologics as the first/initial therapy. The scenario is different in developing countries where biologics are used only in a small proportion of patients with IBD. Increased risk of reactivation of tuberculosis and high cost of the therapy are limitations to their use. Thiopurines hence become critical for optimal management of patients with IBD in these regions. However, approximately one-third of patients are intolerant or develop adverse effects with their use. This has led to suboptimal use of thiopurines in clinical practice. This review article discusses the clinical aspects of thiopurine use in patients with IBD with the aim of optimizing their use to full therapeutic potential.
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Affiliation(s)
- Arshdeep Singh
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, India
| | - Ramit Mahajan
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, India
| | - Saurabh Kedia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Amit Kumar Dutta
- Department of Gastroenterology, Christian Medical College, Vellore, India
| | - Abhinav Anand
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Charles N. Bernstein
- University of Manitoba IBD Clinical and Research Centre, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada
| | - Devendra Desai
- P. D. Hinduja Hospital and Medical Research Centre, Mumbai, India
| | - C. Ganesh Pai
- Department of Gastroenterology, Kasturba Medical College, Manipal, India
| | - Govind Makharia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | | | - Joyce WY Mak
- Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Kirandeep Kaur
- Department of Pharmacology, Dayanand Medical College and Hospital, Ludhiana, India
| | - Kiran Peddi
- Citizens Centre for Digestive Disorders, Hyderabad, India
| | - Mukesh Kumar Ranjan
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Perttu Arkkila
- Department of Gastroenterology, Helsinki University Central Hospital, Helsinki, Finland
| | - Rakesh Kochhar
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Rupa Banerjee
- Asian Institute of Gastroenterology Hyderabad, Hyderabad, India
| | - Saroj Kant Sinha
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Siew Chien Ng
- Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong
| | - Stephen Hanauer
- Department of Medicine, Northwestern University, Chicago, IL, USA
| | - Suhang Verma
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Usha Dutta
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Vandana Midha
- Department of Internal Medicine, Dayanand Medical College, Ludhiana, India
| | - Varun Mehta
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, India
| | - Vineet Ahuja
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Ajit Sood
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, India
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12
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Gaspar R, Branco CC, Macedo G. Liver manifestations and complications in inflammatory bowel disease: A review. World J Hepatol 2021; 13:1956-1967. [PMID: 35070000 PMCID: PMC8727205 DOI: 10.4254/wjh.v13.i12.1956] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 05/27/2021] [Accepted: 11/15/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatobiliary manifestations are common in inflammatory bowel disease (IBD), with 30% of patients presenting abnormal liver tests and 5% developing chronic liver disease. They range from asymptomatic elevated liver tests to life-threatening disease and usually follow an independent course from IBD. The pathogenesis of liver manifestations or complications and IBD can be closely related by sharing a common auto-immune background (in primary sclerosing cholangitis, IgG4-related cholangitis, and autoimmune hepatitis), intestinal inflammation (in portal vein thrombosis and granulomatous hepatitis), metabolic impairment (in non-alcoholic fatty liver disease or cholelithiasis), or drug toxicity (in drug induced liver injury or hepatitis B virus infection reactivation). Their evaluation should prompt a full diagnostic workup to identify and readily treat all complications, improving management and outcome.
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Affiliation(s)
- Rui Gaspar
- Department of Gastroenterology and Hepatology, Centro Hospitalar de São João, Porto 4200, Portugal
| | - Catarina Castelo Branco
- Internal Medicine Department, Centro Hospitalar e Universitário do Porto, Porto 4200, Portugal
| | - Guilherme Macedo
- Department of Gastroenterology and Hepatology, Centro Hospitalar de São João, Porto 4200, Portugal
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13
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Losurdo G, Brescia IV, Lillo C, Mezzapesa M, Barone M, Principi M, Ierardi E, Di Leo A, Rendina M. Liver involvement in inflammatory bowel disease: What should the clinician know? World J Hepatol 2021; 13:1534-1551. [PMID: 34904028 PMCID: PMC8637677 DOI: 10.4254/wjh.v13.i11.1534] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 05/06/2021] [Accepted: 10/11/2021] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel disease (IBD) may show a wide range of extraintestinal manifestations. In this context, liver involvement is a focal point for both an adequate management of the disease and its prognosis, due to possible serious comorbidity. The association between IBD and primary sclerosing cholangitis is the most known example. This association is relevant because it implies an increased risk of both colorectal cancer and cholangiocarcinoma. Additionally, drugs such as thiopurines or biologic agents can cause drug-induced liver damage; therefore, this event should be considered when planning IBD treatment. Additionally, particular consideration should be given to the evidence that IBD patients may have concomitant chronic viral hepatitis, such as hepatitis B and hepatitis C. Chronic immunosuppressive regimens may cause a hepatitis flare or reactivation of a healthy carrier state, therefore careful monitoring of these patients is necessary. Finally, the spread of obesity has involved even IBD patients, thus increasing the risk of non-alcoholic fatty liver disease, which has already proven to be more common in IBD patients than in the non-IBD population. This phenomenon is considered an emerging issue, as it will become the leading cause of liver cirrhosis.
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Affiliation(s)
- Giuseppe Losurdo
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy.
| | - Irene Vita Brescia
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
| | - Chiara Lillo
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
| | - Martino Mezzapesa
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
| | - Michele Barone
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
| | - Mariabeatrice Principi
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
| | - Enzo Ierardi
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
| | - Alfredo Di Leo
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
| | - Maria Rendina
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
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14
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Shen B, Wang J, Guo Y, Gu T, Shen Z, Zhou C, Li B, Xu X, Li F, Zhang Q, Cai X, Dong H, Lu L. Dextran Sulfate Sodium Salt-Induced Colitis Aggravates Gut Microbiota Dysbiosis and Liver Injury in Mice With Non-alcoholic Steatohepatitis. Front Microbiol 2021; 12:756299. [PMID: 34795650 PMCID: PMC8593467 DOI: 10.3389/fmicb.2021.756299] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Accepted: 09/30/2021] [Indexed: 12/15/2022] Open
Abstract
Objective: Inflammatory bowel disease (IBD) is characterized by gut microbiota dysbiosis, which is also frequently observed in patients with non-alcoholic fatty liver disease. Whether gut microbiota dysbiosis in IBD patients promotes the development of non-alcoholic steatohepatitis (NASH) remains unclear. We aimed to explore the role of gut microbiota dysbiosis in the development of NASH in mice with dextran sulfate sodium salt (DSS) induced colitis. Design: Dextran sulfate sodium salt was used to induce colitis, and high fat (HF), in combination with a high-fructose diet, was used to induce NASH in C57BL/6J male mice. Mice were treated with (1%) DSS to induce colitis in cycles, and each cycle consisted of 7 days of DSS administration followed by a 10-day interval. The cycles were repeated throughout the experimental period of 19 weeks. Pathological alterations in colitis and NASH were validated by hematoxylin and eosin (H&E), oil red O, Sirius red staining, and immunofluorescence. Gut microbiota was examined by 16S rRNA sequencing, and gene expression profiles of hepatic non-parenchymal cells (NPCs) were detected by RNA sequencing. Results: Dextran sulfate sodium salt administration enhanced the disruption of the gut-vascular barrier and aggravated hepatic inflammation and fibrosis in mice with NASH. DSS-induced colitis was accompanied by gut microbiota dysbiosis, characterized by alteration in the core microbiota composition. Compared with the HF group, the abundance of p_Proteobacteria and g_Bacteroides increased, while that of f_S24-7 decreased in the DSS + HF mice. Specifically, gut microbiota dysbiosis was characterized by enrichment of lipopolysaccharide producing bacteria and decreased abundance of short-chain fatty acid-producing bacteria. Gene expression analysis of liver NPCs indicated that compared with the HF group, genes related to both inflammatory response and angiocrine signaling were altered in the DSS + HF group. The expression levels of inflammation-related and vascular development genes correlated significantly with the abundance of p_Proteobacteria, g_Bacteroides, or f_S24-7 in the gut microbiota, implying that gut microbiota dysbiosis induced by DSS might aggravate hepatic inflammation and fibrosis by altering the gene expression in NPCs. Conclusion: Dextran sulfate sodium salt-induced colitis may promote the progression of liver inflammation and fibrosis by inducing microbiota dysbiosis, which triggers an inflammatory response and disrupts angiocrine signaling in liver NPCs. The abundance of gut microbiota was associated with expression levels of inflammation-related genes in liver NPCs and may serve as a potential marker for the progression of NASH.
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Affiliation(s)
- Bo Shen
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Junjun Wang
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yuecheng Guo
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Tianyi Gu
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhenyang Shen
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Cui Zhou
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Binghang Li
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xianjun Xu
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Fei Li
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qidi Zhang
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaobo Cai
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Hui Dong
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Lungen Lu
- Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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15
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Voss J, Schneider CV, Kleinjans M, Bruns T, Trautwein C, Strnad P. Hepatobiliary phenotype of individuals with chronic intestinal disorders. Sci Rep 2021; 11:19954. [PMID: 34620902 PMCID: PMC8497585 DOI: 10.1038/s41598-021-98843-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Accepted: 09/03/2021] [Indexed: 02/06/2023] Open
Abstract
Despite the known functional relationship between the gut and the liver, the clinical consequences of this circuit remain unclear. We assessed the hepatobiliary phenotype of cohorts with celiac disease (CeD), Crohn´s disease (CD) and ulcerative colitis (UC). Baseline liver function tests and the frequency of hepatobiliary diseases were analyzed in 2377 CeD, 1738 CD, 3684 UC subjects and 488,941 controls from the population-based UK Biobank cohort. In this cohort study associations were adjusted for age, sex, BMI, diabetes, and alcohol consumption. Compared to controls, cohorts with CeD, but not CD/UC displayed higher AST/ALT values. Subjects with CD/UC but not CeD had increased GGT levels. Elevated ALP and cholelithiasis were significantly more common in all intestinal disorders. Non-alcoholic steatohepatitis and hepatocellular carcinoma (HCC) were enriched in CeD and CD (NASH: taOR = 4.9 [2.2-11.0] in CeD, aOR = 4.2 [1.7-10.3] in CD, HCC: aOR = 4.8 [1.8-13.0] in CeD, aOR = 5.9 [2.2-16.1] in CD), while cholangitis was more common in the CD/UC cohorts (aOR = 11.7 [9.1-15.0] in UC, aOR = 3.5 [1.8-6.8] in CD). Chronic hepatitis, autoimmune hepatitis (AIH) and cirrhosis were more prevalent in all intestinal disorders. In UC/CD, a history of intestinal surgery was associated with elevated liver enzymes and increased occurrence of gallstones (UC: aOR = 2.9 [2.1-4.1], CD: 1.7 [1.2-2.3]). Our data demonstrate that different intestinal disorders predispose to distinct hepatobiliary phenotypes. An increased occurrence of liver cirrhosis, NASH, AIH and HCC and the impact of surgery warrant further exploration.
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Affiliation(s)
- Jessica Voss
- Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Germany
| | - Carolin V Schneider
- Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Germany
| | - Moritz Kleinjans
- Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Germany
| | - Tony Bruns
- Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Germany
| | - Christian Trautwein
- Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Germany
| | - Pavel Strnad
- Medical Clinic III, Gastroenterology, Metabolic Diseases and Intensive Care, University Hospital RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Germany.
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16
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Wang Y, Liu Y. Gut-liver-axis: Barrier function of liver sinusoidal endothelial cell. J Gastroenterol Hepatol 2021; 36:2706-2714. [PMID: 33811372 DOI: 10.1111/jgh.15512] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Revised: 03/02/2021] [Accepted: 03/27/2021] [Indexed: 12/15/2022]
Abstract
Liver diseases are associated with the leaky gut via the gut-liver-axis. Previous studies have paid much attention to the effect of gut barrier damage. Notably, clinical observations and basic research reveal that the gut barrier damage seldom leads to liver injury independently but aggravates pre-existing liver diseases such as non-alcoholic fatty liver disease and drug-induced liver injury. These evidences suggest that there is a hepatic barrier in the gut-liver-axis, protecting the liver against gut-derived pathogenic factors. However, it has never been investigated which type of liver cell plays the role of hepatic barrier. Under physiological conditions, liver sinusoidal endothelial cell (LSEC) can take up and eliminate virus, bacteriophage, microbial products, and metabolic wastes. LSEC also keeps the homeostasis of liver immune environment via tolerance-inducing and anti-inflammatory functions. In contrast, under pathological conditions, the clearance function of LSEC is impaired, and LSEC turns into a pro-inflammatory pattern. Given its anatomical position and physiological functions, LSEC is proposed as the hepatic barrier in the gut-liver-axis. In this review, we aim to further understand the role of LSEC as the hepatic barrier. Future studies are warranted to seek effective treatments to improve LSEC health, which appears to be a promising approach to prevent gut-derived liver injury.
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Affiliation(s)
- Yang Wang
- Department of Gastroenterology, Peking University People's Hospital, Beijing, China.,Clinical Center of Immune-Mediated Digestive Diseases, Peking University People's Hospital, Beijing, China
| | - Yulan Liu
- Department of Gastroenterology, Peking University People's Hospital, Beijing, China.,Clinical Center of Immune-Mediated Digestive Diseases, Peking University People's Hospital, Beijing, China
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17
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Gibiino G, Sartini A, Gitto S, Binda C, Sbrancia M, Coluccio C, Sambri V, Fabbri C. The Other Side of Malnutrition in Inflammatory Bowel Disease (IBD): Non-Alcoholic Fatty Liver Disease. Nutrients 2021; 13:2772. [PMID: 34444932 PMCID: PMC8398715 DOI: 10.3390/nu13082772] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Revised: 08/09/2021] [Accepted: 08/11/2021] [Indexed: 12/26/2022] Open
Abstract
Steatohepatitis and hepatobiliary manifestations constitute some of the most common extra-intestinal manifestations of Inflammatory Bowel Disease (IBD). On the other hand, non-alcoholic fatty liver disease (NAFLD) affects around 25% of the world's population and is attracting ever more attention in liver transplant programs. To outline the specific pathways linking these two conditions is a pressing task for 21st-century researchers. We are accustomed to expecting the occurrence of fatty liver disease in obese people, but current evidence suggests that there are several different pathways also occurring in underweight patients. Genetic factors, inflammatory signals and microbiota are key players that could help in understanding the entire pathogenesis of NAFLD, with the aim of defining the multiple expressions of malnutrition. In the current review, we summarize the most recent literature regarding the epidemiology, pathogenesis and future directions for the management of NAFLD in patients affected by IBD.
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Affiliation(s)
- Giulia Gibiino
- Gastroenterology and Digestive Endoscopy Unit, Ospedale Morgagni-Pierantoni, AUSL Romagna, 47121 Forlì, Italy; (A.S.); (C.B.); (M.S.); (C.C.); (C.F.)
- Gastroenterology and Digestive Endoscopy Unit, Ospedale M.Bufalini, AUSL Romagna, 47521 Cesena, Italy
| | - Alessandro Sartini
- Gastroenterology and Digestive Endoscopy Unit, Ospedale Morgagni-Pierantoni, AUSL Romagna, 47121 Forlì, Italy; (A.S.); (C.B.); (M.S.); (C.C.); (C.F.)
- Gastroenterology and Digestive Endoscopy Unit, Ospedale M.Bufalini, AUSL Romagna, 47521 Cesena, Italy
| | - Stefano Gitto
- Department of Experimental and Clinical Medicine, University of Florence, 50100 Florence, Italy;
| | - Cecilia Binda
- Gastroenterology and Digestive Endoscopy Unit, Ospedale Morgagni-Pierantoni, AUSL Romagna, 47121 Forlì, Italy; (A.S.); (C.B.); (M.S.); (C.C.); (C.F.)
- Gastroenterology and Digestive Endoscopy Unit, Ospedale M.Bufalini, AUSL Romagna, 47521 Cesena, Italy
| | - Monica Sbrancia
- Gastroenterology and Digestive Endoscopy Unit, Ospedale Morgagni-Pierantoni, AUSL Romagna, 47121 Forlì, Italy; (A.S.); (C.B.); (M.S.); (C.C.); (C.F.)
- Gastroenterology and Digestive Endoscopy Unit, Ospedale M.Bufalini, AUSL Romagna, 47521 Cesena, Italy
| | - Chiara Coluccio
- Gastroenterology and Digestive Endoscopy Unit, Ospedale Morgagni-Pierantoni, AUSL Romagna, 47121 Forlì, Italy; (A.S.); (C.B.); (M.S.); (C.C.); (C.F.)
- Gastroenterology and Digestive Endoscopy Unit, Ospedale M.Bufalini, AUSL Romagna, 47521 Cesena, Italy
| | - Vittorio Sambri
- Unit of Microbiology, The Great Romagna Hub Laboratory, 47522 Pievesestina, Italy;
- Unit of Microbiology, DIMES, University of Bologna, 40125 Bologna, Italy
| | - Carlo Fabbri
- Gastroenterology and Digestive Endoscopy Unit, Ospedale Morgagni-Pierantoni, AUSL Romagna, 47121 Forlì, Italy; (A.S.); (C.B.); (M.S.); (C.C.); (C.F.)
- Gastroenterology and Digestive Endoscopy Unit, Ospedale M.Bufalini, AUSL Romagna, 47521 Cesena, Italy
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18
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Wang Y, Zhang Y, Liu Y, Xu J, Liu Y. Gut-Liver Axis: Liver Sinusoidal Endothelial Cells Function as the Hepatic Barrier in Colitis-Induced Liver Injury. Front Cell Dev Biol 2021; 9:702890. [PMID: 34336855 PMCID: PMC8322652 DOI: 10.3389/fcell.2021.702890] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Accepted: 06/22/2021] [Indexed: 12/12/2022] Open
Abstract
Background Based on the gut–liver axis theory, a leaky gut can aggravate liver injury. However, clinical studies suggest that although gut mucosa damage is commonly observed in inflammatory bowel disease (IBD), it seldom leads to severe liver injury. We hypothesize that there is a hepatic barrier in the gut–liver axis, which protects the liver against gut-derived invasive factors. Methods Colitis was induced by dextran sulfate sodium (DSS) in eight different liver injury models in Sprague–Dawley rats. Liver sinusoidal endothelial cell (LSEC) injury was evaluated by a scanning and transmission electron microscope. Neutrophils were depleted by injection of anti-rat polymorphonuclear serum. Two pneumonia models were also induced to investigate the mechanism of neutrophil recruitment and activation. LSECs isolated from rat liver were used to investigate the effect on neutrophil recruitment and activation. Results Among eight liver injury models, DSS colitis had no effect on liver injury in three models with normal LSECs. In the other five models with LSEC rupture, liver injury was significantly exacerbated by colitis, and increased hepatic neutrophil accumulation was observed. When neutrophils were depleted, colitis-induced liver injury was significantly attenuated. In pneumonia, liver injury, and colitis models, the level of CXCL1 correlated with the recruitment of neutrophils in different tissues, while DSS colitis and LSEC injury synergistically contributed to increased CXCL1 expression in the liver. In colitis-induced liver injury, neutrophils were activated in the liver. Injured LSECs showed both structural and functional changes, with significantly increased expression of CXCL1 and TNF-α under the stimulation of lipopolysaccharide (LPS). The combination of gut-derived LPS and LSEC-derived TNF-α led to the activation of neutrophils, characterized by enhanced production of reactive oxygen species, pro-inflammatory cytokines, and the formation of neutrophil extracellular traps. Conclusion LSECs constitute a vitally important barrier in the gut–liver axis, defending the liver against colitis-induced injury. When LSECs are damaged, they can turn into a pro-inflammatory pattern under the stimulation of LPS. LSEC injury and colitis-derived LPS synergistically contribute to the recruitment and activation of hepatic neutrophils. Neutrophils play a pivotal role as a downstream effector in colitis-induced liver injury.
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Affiliation(s)
- Yang Wang
- Department of Gastroenterology, Peking University People's Hospital, Beijing, China.,Clinical Center of Immune-Mediated Digestive Diseases, Peking University People's Hospital, Beijing, China
| | - Yifan Zhang
- Department of Gastroenterology, Peking University People's Hospital, Beijing, China.,Clinical Center of Immune-Mediated Digestive Diseases, Peking University People's Hospital, Beijing, China
| | - Yun Liu
- Department of Gastroenterology, Peking University People's Hospital, Beijing, China.,Clinical Center of Immune-Mediated Digestive Diseases, Peking University People's Hospital, Beijing, China
| | - Jun Xu
- Department of Gastroenterology, Peking University People's Hospital, Beijing, China.,Clinical Center of Immune-Mediated Digestive Diseases, Peking University People's Hospital, Beijing, China.,Institute of Clinical Molecular Biology & Central Laboratory, Peking University People's Hospital, Beijing, China
| | - Yulan Liu
- Department of Gastroenterology, Peking University People's Hospital, Beijing, China.,Clinical Center of Immune-Mediated Digestive Diseases, Peking University People's Hospital, Beijing, China
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19
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Park I, Jung J, Lee S, Park K, Ryu JW, Son MY, Cho HS, Kim DS. Characterization of terminal-ileal and colonic Crohn's disease in treatment-naïve paediatric patients based on transcriptomic profile using logistic regression. J Transl Med 2021; 19:250. [PMID: 34098982 PMCID: PMC8185924 DOI: 10.1186/s12967-021-02909-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Accepted: 05/24/2021] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Inflammatory bowel disease (IBD) is a chronic and idiopathic inflammatory disorder of the gastrointestinal tract and comprises ulcerative colitis (UC) and Crohn's disease (CD). Crohn's disease can affect any part of the gastrointestinal tract, but mainly the terminal ileum and colon. In the present study, we aimed to characterize terminal-ileal CD (ICD) and colonic CD (CCD) at the molecular level, which might enable a more optimized approach for the clinical care and scientific research of CD. METHODS We analyzed differentially expressed genes in samples from 23 treatment-naïve paediatric patients with CD and 25 non-IBD controls, and compared the data with previously published RNA-Seq data using multi-statistical tests and confidence intervals. We implemented functional profiling and proposed statistical methods for feature selection using a logistic regression model to identify genes that are highly associated in ICD or CCD. We also validated our final candidate genes in independent paediatric and adult cohorts. RESULTS We identified 550 genes specifically expressed in patients with CD compared with those in healthy controls (p < 0.05). Among these DEGs, 240 from patients with CCD were mainly involved in mitochondrial dysfunction, whereas 310 from patients with ICD were enriched in the ileum functions such as digestion, absorption, and metabolism. To choose the most effective gene set, we selected the most powerful genes (p-value ≤ 0.05, accuracy ≥ 0.8, and AUC ≥ 0.8) using logistic regression. Consequently, 33 genes were identified as useful for discriminating CD location; the accuracy and AUC were 0.86 and 0.83, respectively. We then validated the 33 genes with data from another independent paediatric cohort (accuracy = 0.93, AUC = 0.92) and adult cohort (accuracy = 0.88, AUC = 0.72). CONCLUSIONS In summary, we identified DEGs that are specifically expressed in CCD and ICD compared with those in healthy controls and patients with UC. Based on the feature selection analysis, 33 genes were identified as useful for discriminating CCD and ICD with high accuracy and AUC, for not only paediatric patients but also independent cohorts. We propose that our approach and the final gene set are useful for the molecular classification of patients with CD, and it could be beneficial in treatments based on disease location.
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Affiliation(s)
- Ilkyu Park
- Department of Bioinformatics, KRIBB School of Bioscience, Korea University of Science and Technology (UST), 217 Gajeong-ro, Yuseong-gu, Daejeon, Korea.,Department of Environmental Disease Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon, 34141, Korea
| | - Jaeeun Jung
- Department of Environmental Disease Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon, 34141, Korea
| | - Sugi Lee
- Department of Bioinformatics, KRIBB School of Bioscience, Korea University of Science and Technology (UST), 217 Gajeong-ro, Yuseong-gu, Daejeon, Korea.,Department of Environmental Disease Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon, 34141, Korea
| | - Kunhyang Park
- Department of Core Facility Management Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon, Korea
| | - Jea-Woon Ryu
- Department of Rare Disease Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon, Korea
| | - Mi-Young Son
- Department of Stem Cell Convergence Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon, Korea.
| | - Hyun-Soo Cho
- Department of Stem Cell Convergence Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon, Korea.
| | - Dae-Soo Kim
- Department of Bioinformatics, KRIBB School of Bioscience, Korea University of Science and Technology (UST), 217 Gajeong-ro, Yuseong-gu, Daejeon, Korea. .,Department of Environmental Disease Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-gu, Daejeon, 34141, Korea.
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20
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Kreijne JE, de Vries AC, de Veer RC, Bouma G, Dijkstra G, Voskuil MD, West R, van Moorsel SAW, de Jong DJ, de Boer NK, van der Woude CJ. Limited added value of laboratory monitoring in thiopurine maintenance monotherapy in inflammatory bowel disease patients. Aliment Pharmacol Ther 2020; 51:1353-1364. [PMID: 32342997 DOI: 10.1111/apt.15734] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2019] [Revised: 08/13/2019] [Accepted: 03/25/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND To timely detect myelotoxicity and hepatotoxicity, laboratory monitoring at 3-month intervals is advised throughout thiopurine maintenance treatment for IBD. However, reported incidence rates of myelotoxicity and hepatotoxicity in maintenance treatment are low. AIM To assess incidence rates and clinical consequences of myelotoxicity and hepatotoxicity in thiopurine maintenance therapy after at least 1 year of thiopurine treatment. METHODS Retrospective analysis of therapy adjustment for laboratory toxicity in adult IBD patients after 12 consecutive months of azathioprine (AZA) or mercaptopurine monotherapy (ie baseline) between 2000 and 2016. Incidence rates of laboratory toxicity (ie myelotoxicity [leucocyte count <4.0 × 10e9/L, and/or platelet count <150 × 10e9/L] and/or hepatotoxicity (gamma-glutamyltransferase [GGT], alkaline phosphatase [AP], ALT and/or AST above ULN, excluding isolated increased AST/AP]) and associated diagnostic procedures and complications were assessed. RESULTS In total, 12,391 laboratory assessments were performed on 1132 patients (56% female, AZA 74%) during 3.3 years of median follow-up. Median monitoring frequency was 3.1 assessments/treatment year. Only 83/12,391 (0.7%) assessments resulted in therapy adjustment, dose reduction in 46 patients, cessation in 28 and allopurinol initiation in nine; risk of therapy adjustment was 1.9% per treatment year. Incidence rates of myelotoxicity were 7.1% (5.1% mild/1.8% moderate/0.1% severe) and hepatotoxicity 5.1% (3.8% mild/1.1% moderate/0.2% severe) per treatment year. Treatment-related complications with concurrent laboratory toxicity occurred in 12 patients (1.1%) and would not have been prevented by monitoring. CONCLUSION Severe laboratory toxicity is uncommon after 1 year of thiopurine monotherapy at 4-month monitoring intervals. Therapy adjustments are rare after detection of laboratory toxicity. After 1 year of thiopurine monotherapy, laboratory monitoring may be lowered to less than a 4-month interval.
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Affiliation(s)
- Joany E Kreijne
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Annemarie C de Vries
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Rozanne C de Veer
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
| | - Gerd Bouma
- Department of Gastroenterology and Hepatology, Amsterdam UMC, Vrije Universiteit Amsterdam, AG&M Research Institute, Amsterdam, The Netherlands
| | - Gerard Dijkstra
- Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
| | - Michiel D Voskuil
- Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
| | - Rachel West
- Department of Gastroenterology and Hepatology, Franciscus Gasthuis & Vlietland, Rotterdam, The Netherlands
| | - Sofia A W van Moorsel
- Department of Pharmacology, Zuyderland Medical Center, Heerlen-Sittard-Geleen, The Netherlands
| | - Dirk J de Jong
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Nanne K de Boer
- Department of Gastroenterology and Hepatology, Amsterdam UMC, Vrije Universiteit Amsterdam, AG&M Research Institute, Amsterdam, The Netherlands
| | - C Janneke van der Woude
- Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
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21
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Zou ZY, Shen B, Fan JG. Systematic Review With Meta-analysis: Epidemiology of Nonalcoholic Fatty Liver Disease in Patients With Inflammatory Bowel Disease. Inflamm Bowel Dis 2019; 25:1764-1772. [PMID: 30918952 DOI: 10.1093/ibd/izz043] [Citation(s) in RCA: 52] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is increasingly identified in patients with inflammatory bowel disease (IBD), but there are few systematic reviews and meta-analyses of the studies of NAFLD in IBD patients. METHODS MEDLINE, Web of Science, Cochrane Library, and Scopus were searched (until August 2018) to identify observational studies that reported the prevalence and risk factors for NAFLD in IBD patients. Pooled prevalence, odds ratios (OR), mean difference (MD), and 95% confidence intervals (95% CI) were calculated. Study quality was assessed using the modified Newcastle-Ottawa scale. RESULTS Of the 662 citations evaluated, 19 studies (including 5620 subjects) reported the prevalence of NAFLD in IBD population and were included for the analysis. The overall pooled prevalence was 27.5% (95% CI, 20.7%-34.2%). The prevalence was higher in older patients (MD = 8.22; 95% CI, 6.22-10.22), type 2 diabetes (OR = 3.85; 95% CI, 2.49-5.95), hypertension (OR = 3.18; 95% CI, 2.36-4.28), obesity (OR = 2.79; 95% CI, 1.73-4.50), insulin resistance (OR = 6.66; 95% CI, 1.28-34.77), metabolic syndrome (OR = 4.96; 95% CI, 3.05-8.05), chronic kidney disease (OR = 4.83; 95% CI, 1.79-13.04), methotrexate use (OR = 1.76; 95% CI, 1.02-3.06), surgery for IBD (OR = 1.28; 95% CI, 1.02-1.62), and longer duration of IBD (MD = 5.60; 95% CI, 2.24-8.97). CONCLUSIONS We found that NAFLD was not uncommon in the IBD population. Older age, metabolic risk factors, methotrexate use, prior surgery, and longer duration of IBD are predictors for the presence of NAFLD in IBD. Screening of NAFLD might be recommended among IBD patients with the aforementioned factors.
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Affiliation(s)
- Zi-Yuan Zou
- Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- The First Clinical School, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Bo Shen
- Center for Inflammatory Bowel Disease, Department of Gastroenterology, Hepatology, and Nutrition, Cleveland Clinic, Cleveland, Ohio, USA
| | - Jian-Gao Fan
- Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Key Lab of Pediatric Gastroenterology and Nutrition, Shanghai, China
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22
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Velázquez KT, Enos RT, Bader JE, Sougiannis AT, Carson MS, Chatzistamou I, Carson JA, Nagarkatti PS, Nagarkatti M, Murphy EA. Prolonged high-fat-diet feeding promotes non-alcoholic fatty liver disease and alters gut microbiota in mice. World J Hepatol 2019; 11:619-637. [PMID: 31528245 PMCID: PMC6717713 DOI: 10.4254/wjh.v11.i8.619] [Citation(s) in RCA: 125] [Impact Index Per Article: 20.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2019] [Revised: 07/05/2019] [Accepted: 07/16/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) has become an epidemic largely due to the worldwide increase in obesity. While lifestyle modifications and pharmacotherapies have been used to alleviate NAFLD, successful treatment options are limited. One of the main barriers to finding safe and effective drugs for long-term use in NAFLD is the fast initiation and progression of disease in the available preclinical models. Therefore, we are in need of preclinical models that (1) mimic the human manifestation of NAFLD and (2) have a longer progression time to allow for the design of superior treatments.
AIM To characterize a model of prolonged high-fat diet (HFD) feeding for investigation of the long-term progression of NAFLD.
METHODS In this study, we utilized prolonged HFD feeding to examine NAFLD features in C57BL/6 male mice. We fed mice with a HFD (60% fat, 20% protein, and 20% carbohydrate) for 80 wk to promote obesity (Old-HFD group, n = 18). A low-fat diet (LFD) (14% fat, 32% protein, and 54% carbohydrate) was administered for the same duration to age-matched mice (Old-LFD group, n = 15). An additional group of mice was maintained on the LFD (Young-LFD, n = 20) for a shorter duration (6 wk) to distinguish between age-dependent and age-independent effects. Liver, colon, adipose tissue, and feces were collected for histological and molecular assessments.
RESULTS Prolonged HFD feeding led to obesity and insulin resistance. Histological analysis in the liver of HFD mice demonstrated steatosis, cell injury, portal and lobular inflammation and fibrosis. In addition, molecular analysis for markers of endoplasmic reticulum stress established that the liver tissue of HFD mice have increased phosphorylated Jnk and CHOP. Lastly, we evaluated the gut microbial composition of Old-LFD and Old-HFD. We observed that prolonged HFD feeding in mice increased the relative abundance of the Firmicutes phylum. At the genus level, we observed a significant increase in the abundance of Adercreutzia, Coprococcus, Dorea, and Ruminococcus and decreased relative abundance of Turicibacter and Anaeroplasma in HFD mice.
CONCLUSION Overall, these data suggest that chronic HFD consumption in mice can mimic pathophysiological and some microbial events observed in NAFLD patients.
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Affiliation(s)
- Kandy T Velázquez
- Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC 29209, United States
| | - Reilly T Enos
- Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC 29209, United States
| | - Jackie E Bader
- Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC 29209, United States
| | - Alexander T Sougiannis
- Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC 29209, United States
| | - Meredith S Carson
- Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC 29209, United States
| | - Ioulia Chatzistamou
- Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC 29209, United States
| | - James A Carson
- Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC 29209, United States
- College of Health Professions, University of Tennessee Health Sciences Center, Memphis, TN 38163, United States
| | - Prakash S Nagarkatti
- Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC 29209, United States
| | - Mitzi Nagarkatti
- Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC 29209, United States
| | - E Angela Murphy
- Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC 29209, United States
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23
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Arieira C, Monteiro S, Xavier S, Dias de Castro F, Magalhães J, Moreira MJ, Marinho C, Cotter J. Hepatic steatosis and patients with inflammatory bowel disease: when transient elastography makes the difference. Eur J Gastroenterol Hepatol 2019; 31:998-1003. [PMID: 30839437 DOI: 10.1097/meg.0000000000001319] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Recent studies suggest an increased prevalence of hepatic steatosis (HS) in patients with inflammatory bowel disease (IBD). Features such as chronic inflammation, previous surgeries, drug-induced hepatotoxicity, malnutrition, and intestinal dysbiosis seem to be involved in its pathogenesis. AIMS The aim of this study was to assess the frequency of HS in patients with IBD quantified by controlled attenuation parameter (CAP) and by clinical-analytical scores: Hepatic Steatosis Index (HSI) and Fatty Liver Index (FLI). The secondary aim was to investigate risk factors associated with HS in patients with IBD. PATIENTS AND METHODS A cross-sectional study was carried out including consecutive outpatients observed in our department between January and March 2017. HS was defined as HSI of at least 36 or FLI of at least 60 or CAP of greater than 248. RESULTS A total of 161 patients were included, with a mean age of 40.6±12.8 years. There were 86 (53.4%) female patients. Overall, 62.7% had Crohn's disease and 37.1% had ulcerative colitis. Moreover, 73 (45.3%) patients had CAP greater than 248, 27 (16.8%) had FLI greater than 60, and 46 (28.6%) had HSI greater than 36.We found that patients with CAP of greater than 248 were more frequently obese (28.8 vs. 0.0% P<0.001), male (57.5 vs. 37.5% P=0.011), and presented more frequently with metabolic syndrome (23.9 vs. 4.5% P <0.001). With regard to IBD factors, patients with HS had a higher frequency of previous surgeries (31.5 vs. 12.5% P=0.003). In multivariate analysis, only male sex [odds ratio: 5.7 (95% confidence interval: 2.0-15.9); P=0.001] and previous surgeries [odds ratio: 5.9 (95% confidence interval: 1.5-22.9); P=0.011] were independent risk factors of HS. CONCLUSION In our cohort, the frequency of HS varied between 16.8 and 45.3% defined by noninvasive methods. We found that male sex and previous history of surgery were the independent risk factors of HS when quantified by transient elastography.
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Affiliation(s)
- Cátia Arieira
- Department of Gastroenterology, Hospital da Senhora da Oliveira
- School of Medicine, Life and Health Sciences Research Institute, University of Minho
- ICVS/3B's, PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Sara Monteiro
- Department of Gastroenterology, Hospital da Senhora da Oliveira
- School of Medicine, Life and Health Sciences Research Institute, University of Minho
- ICVS/3B's, PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Sofia Xavier
- Department of Gastroenterology, Hospital da Senhora da Oliveira
- School of Medicine, Life and Health Sciences Research Institute, University of Minho
- ICVS/3B's, PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Francisca Dias de Castro
- Department of Gastroenterology, Hospital da Senhora da Oliveira
- School of Medicine, Life and Health Sciences Research Institute, University of Minho
- ICVS/3B's, PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Joana Magalhães
- Department of Gastroenterology, Hospital da Senhora da Oliveira
- School of Medicine, Life and Health Sciences Research Institute, University of Minho
- ICVS/3B's, PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Maria J Moreira
- Department of Gastroenterology, Hospital da Senhora da Oliveira
- School of Medicine, Life and Health Sciences Research Institute, University of Minho
- ICVS/3B's, PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Carla Marinho
- Department of Gastroenterology, Hospital da Senhora da Oliveira
- School of Medicine, Life and Health Sciences Research Institute, University of Minho
- ICVS/3B's, PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - José Cotter
- Department of Gastroenterology, Hospital da Senhora da Oliveira
- School of Medicine, Life and Health Sciences Research Institute, University of Minho
- ICVS/3B's, PT Government Associate Laboratory, Braga/Guimarães, Portugal
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Prevalence of fatty liver disease in patients with inflammatory bowel disease: a transient elastography study on the basis of a controlled attenuation parameter. MARMARA MEDICAL JOURNAL 2019. [DOI: 10.5472/marumj.570907] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
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25
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Seo KI, Kang SB. [Hepatobiliary Manifestation of Inflammatory Bowel Disease]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2019; 73:248-259. [PMID: 31132831 DOI: 10.4166/kjg.2019.73.5.248] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/03/2019] [Revised: 05/05/2019] [Accepted: 05/12/2019] [Indexed: 12/13/2022]
Abstract
The hepatobiliary system is one of the most common sites of extraintestinal manifestation in patients with inflammatory bowel disease (IBD). The progression of IBD can lead to a primary hepatobiliary manifestation and can occur secondary to multiple drugs or accompanying viral infections. Primary sclerosing cholangitis is the representative hepatobiliary manifestation of IBD, particularly in ulcerative colitis. Although most agents used in the treatment of IBD are potentially hepatotoxic, the risk of serious hepatitis or liver failure is low. The prevalence of HBV and HCV in IBD is similar to the general population, but the clinical concern is HBV reactivation associated with immunosuppressive therapy. Patients undergoing cytotoxic chemotherapy or immunosuppressive therapy with a moderate to high risk of HBV reactivation require prophylactic antiviral therapy. On the other hand, HCV has little risk of reactivation. Patients with IBD are more likely to have nonalcoholic fatty liver disease than the general population and tend to occur at younger ages. IBD and cholelithiasis are closely related, especially in Crohn's disease.
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Affiliation(s)
- Kwang Il Seo
- Department of Internal Medicine, Kosin University College of Medicine, Busan, Korea
| | - Sang-Bum Kang
- Division of Gastroenterology, Department of Internal Medicine, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Daejeon, Korea
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Abstract
Hepatobiliary disorders are commonly encountered in patients with inflammatory bowel disease (IBD). Although primary sclerosing cholangitis is the stereotypical hepatobiliary disorder associated with IBD, other diseases, including autoimmune hepatitis and nonalcoholic fatty liver disease, also are encountered in this population. Several agents used for treatment of IBD may cause drug-induced liver injury, although severe hepatotoxicity occurs infrequently. Furthermore, reactivation of hepatitis B virus infection may occur in patients with IBD treated with systemic corticosteroids and biologic agents.
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Affiliation(s)
- Mahmoud Mahfouz
- Department of Internal Medicine, Mount Sinai Medical Center, 4300 Alton Road, Suite 301, Miami Beach, FL 33140, USA
| | - Paul Martin
- Division of Gastroenterology and Hepatology, University of Miami Miller School of Medicine, 1120 Northwest 14 Street #1115, Miami, FL 33136, USA.
| | - Andres F Carrion
- Division of Gastroenterology and Hepatology, University of Miami Miller School of Medicine, 1120 Northwest 14 Street #1115, Miami, FL 33136, USA
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27
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Suárez Ferrer C, González-Lama Y, González-Partida I, Calvo Moya M, Vera Mendoza I, Matallana Royo V, Arevalo Serrano J, Abreu Garcia L. Usefulness of Thiopurine Monotherapy for Crohn's Disease in the Era of Biologics: A Long-Term Single-Center Experience. Dig Dis Sci 2019; 64:875-879. [PMID: 30542812 DOI: 10.1007/s10620-018-5381-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2017] [Accepted: 11/14/2018] [Indexed: 12/23/2022]
Abstract
BACKGROUND Thiopurines are classically used in Crohn's disease (CD). Treatment fails in a proportion of patients either due to adverse events (AE) or lack of efficacy. Increasing use of anti-TNFα biologic drugs may have had impact on thiopurines usage. AIM To evaluate the evolving use of azathioprine (AZA) monotherapy in the era of biologics. METHODS The study retrospectively analyzed clinical records of all CD patients who started treatment with AZA monotherapy at our center since 1990. Dates of starting AZA and treatment failure (TF) were collected. We defined AZA TF if it was withdrawn due to lack of efficacy or AE, or biologics were added. RESULTS A total of 383 patients were included: 46.5% were males and mean age was 31 (range 17-84) years. Median follow-up was 43 (range 0.2-289) months. Overall, 147 patients (38%) experienced TF. Median cumulative survival time of AZA was 126 (95% CI 105-147) months. Proportion of patients with AZA TF increased along time: 7 patients in 1990-1995 (4.7% of all TF); 8 in 1996-2000 (5.4%); 22 in 2001-2005(15%); 41 in 2006-2010 (28%); 69 in 2011-2014 (47%) (p = 0.04). 7%, 21%, 4%, 45%, and 33.3% of patients moved to biologics in each period, respectively (χ2 = 13.07; p < 0.05). Seventy-four patients (18.4%) stopped AZA due to AE, and 73(19%) due to lack of efficacy. Regarding AZA indication, prevention of postoperative recurrence obtained better results than steroid dependency (p = 0.001); perianal fistulizing CD predicted poorer outcomes (p = 0.002). CONCLUSION An important proportion of CD patients under AZA monotherapy experienced TF in our experience. Although AZA monotherapy remains useful for CD in the era of biologics, current clinical practice is shifting to anti-TNFα biologic drugs in an increasing proportion of patients.
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Affiliation(s)
- Cristina Suárez Ferrer
- IBD Unit, Digestive Department, Puerta de Hierro University Hospital, Majadahonda, Madrid, Spain
| | - Yago González-Lama
- IBD Unit, Digestive Department, Puerta de Hierro University Hospital, Majadahonda, Madrid, Spain
| | - Irene González-Partida
- IBD Unit, Digestive Department, Puerta de Hierro University Hospital, Majadahonda, Madrid, Spain
| | - Marta Calvo Moya
- IBD Unit, Digestive Department, Puerta de Hierro University Hospital, Majadahonda, Madrid, Spain
| | - Isabel Vera Mendoza
- IBD Unit, Digestive Department, Puerta de Hierro University Hospital, Majadahonda, Madrid, Spain
| | - Virginia Matallana Royo
- IBD Unit, Digestive Department, Puerta de Hierro University Hospital, Majadahonda, Madrid, Spain
| | - Juan Arevalo Serrano
- Internal Medicine Department, Principe de Asturias University Hospital, Alcalá de Henares, Madrid, Spain
| | - Luis Abreu Garcia
- IBD Unit, Digestive Department, Puerta de Hierro University Hospital, Majadahonda, Madrid, Spain.
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Predication of post-operative outcome of colectomy in ulcerative colitis patients using Model of End-Stage Liver Disease Score. Int J Colorectal Dis 2018; 33:1763-1772. [PMID: 30220056 DOI: 10.1007/s00384-018-3147-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/14/2018] [Indexed: 02/04/2023]
Abstract
PURPOSE Model of End-Stage Liver Disease (MELD) score was developed to predict mortality in patients with liver disease. The aim of this study was to investigate the relationship between preoperative MELD score and 30-day surgical outcomes using the American College of Surgeons National Surgical Quality Improvement Program. METHODS Patients with ulcerative colitis (UC) (ICD: 556.X) who underwent colectomy were identified from NSQIP 2005 to 2013. The primary outcomes were bleeding complications, and overall morbidity and mortality. RESULTS A total of 7534 UC patients undergoing colectomy were identified. Patients with a higher MELD score had a longer hospital stay; more bleeding; and cardiac, respiratory, renal, thromboembolic, and septic complications as well as mortality. Patients were stratified into 4 groups by MELD score: < 7, 7-11, 12-15, and > 15 and a stratified multivariate analysis was done. Patients with a MELD score 12-15 (odds ratio [OR] 1.9, 95% confidence interval [CI] 1.1-1.3) and MELD > 15 (OR 2.6, 95%CI 1.5-4.7) were at significant risk for bleeding complication. Apart from the MELD score, the presence of ascites (OR 2.5, 95%CI 1.2-5.1) or varices (OR 1.0, 95%CI 1.01-1.03) was also significantly associated with post-operative bleeding complication. MELD 12-15 and MELD > 15 were also found to be risk factors for overall morbidity (OR 5.3, 95%CI 1.8-15.7; OR 10.3, 95%CI 3.6-29.7, respectively) and mortality (OR 3.3, 95%CI 1.3-8.4; OR 5.9, 95%CI 2.4-14.6, respectively). CONCLUSION UC patients with a higher MELD score were associated with a higher post-colectomy morbidity and mortality. MELD score > 11 was an independent indicator for post-operative bleeding, and overall complications and mortality.
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Effects of inflammatory bowel disease treatment on the risk of nonalcoholic fatty liver disease: a meta-analysis. Eur J Gastroenterol Hepatol 2018; 30:854-860. [PMID: 29697458 DOI: 10.1097/meg.0000000000001144] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Epidemiological studies have demonstrated an association between inflammatory bowel disease (IBD) and an increased risk for the development of nonalcoholic fatty liver disease (NAFLD). However, the risk of NAFLD in IBD patients who receive different medical treatments including glucocorticoids, immunomodulators, and tumor necrosis factor-α inhibitors remains unclear. We aimed to assess whether the use of certain IBD medications is associated with the development of NAFLD. MATERIALS AND METHODS A systematic review was carried out in Medline, Embase, and Cochrane databases from inception through October 2017 to identify studies that assessed the association between the use of IBD medications and the risk of developing NAFLD. Effect estimates from the individual study were derived and combined using random-effect, generic inverse variance method of DerSimonian and Laird. RESULTS Seven observational studies with a total of 1610 patients were enrolled. There was no significant association between the use of IBD medications and the incidence of NAFLD. The pooled odds ratios of NAFLD in patients who use biological agents, immunomodulators, methotrexate, and steroids were 0.85 [95% confidence interval (CI): 0.49-1.46], 1.19 (95% CI: 0.70-2.01), 3.62 (95% CI: 0.48-27.39), and 1.24 (95% CI: 0.85-1.82), respectively. Egger's regression asymmetry test was performed and showed no publication bias. CONCLUSION Our study demonstrates no significant association between medications used in the treatment of IBD and the risk of developing NAFLD. The findings of our study suggest a complex, multifactorial relationship between IBD and the development of NAFLD beyond the scope of current pharmacological intervention.
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Principi M, Iannone A, Losurdo G, Mangia M, Shahini E, Albano F, Rizzi SF, La Fortezza RF, Lovero R, Contaldo A, Barone M, Leandro G, Ierardi E, Di Leo A. Nonalcoholic Fatty Liver Disease in Inflammatory Bowel Disease: Prevalence and Risk Factors. Inflamm Bowel Dis 2018; 24:1589-1596. [PMID: 29688336 DOI: 10.1093/ibd/izy051] [Citation(s) in RCA: 53] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is common in inflammatory bowel diseases (IBD). Herein, NAFLD prevalence and risk factors in a large IBD cohort were evaluated and compared to that of a non-IBD sample. METHODS Crohn's disease/ulcerative colitis outpatients referred to IBD service of our Gastroenterology Unit were enrolled. Subjects affected by functional and motor gastrointestinal disorders, in whom IBD was ruled out, referred to general outpatient service in the same area, were considered as nonIBD group. Exclusion criteria were based on previous diagnosis of nonNAFLD chronic liver diseases and secondary causes of fat liver overload. Characteristics of IBD and liver status were collected. Risk factors for metabolic syndrome were analyzed. Ultrasonographic presence and degree of steatosis were assessed. Data were examined by univariate and multivariate analyses. RESULTS For this study 465 IBD and 189 non-IBD subjects were consecutively enrolled. NAFLD was found in 28.0% and 20.1% in IBD and non-IBD subjects, respectively (P = 0.04). IBD patients with NAFLD were younger than non-IBD ones. There was no significant difference in steatosis grade and association between NAFLD and IBD behavior, extension, activity, and drugs. In the IBD group, multivariate analysis demonstrated that NAFLD was independently associated to metabolic syndrome (OR=2.24, 95%CI 1.77-28.81), diabetes (OR=1.71, 95%CI 1.43-12.25), fasting blood glucose (OR=1.36, 95%CI 1.13-1.68), and abdominal circumference (OR=1.68, 95%CI 1.15-14.52). CONCLUSIONS NAFLD is more common and occurs at a younger age in IBD than in nonIBD subjects. However, further investigation is required to ascertain possible NAFLD pathogenic IBD-related factors other than conventional/metabolic ones. 10.1093/ibd/izy051_video1izy051.video15774874877001.
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Affiliation(s)
- Mariabeatrice Principi
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, AOU Policlinico, University of Bari, Italy
| | - Andrea Iannone
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, AOU Policlinico, University of Bari, Italy
| | - Giuseppe Losurdo
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, AOU Policlinico, University of Bari, Italy
| | - Michela Mangia
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, AOU Policlinico, University of Bari, Italy
| | - Endrit Shahini
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, AOU Policlinico, University of Bari, Italy
| | - Francesca Albano
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, AOU Policlinico, University of Bari, Italy
| | - Salvatore Fabio Rizzi
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, AOU Policlinico, University of Bari, Italy
| | - Rosa Federica La Fortezza
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, AOU Policlinico, University of Bari, Italy
| | - Rosa Lovero
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, AOU Policlinico, University of Bari, Italy
| | - Antonella Contaldo
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, AOU Policlinico, University of Bari, Italy
| | - Michele Barone
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, AOU Policlinico, University of Bari, Italy
| | - Gioacchino Leandro
- National Institute of Gastroenterology, "S De Bellis" Research Hospital, Castellana Grotte, Italy
| | - Enzo Ierardi
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, AOU Policlinico, University of Bari, Italy
| | - Alfredo Di Leo
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, AOU Policlinico, University of Bari, Italy
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Abstract
Anemia is a frequent complication of many inflammatory disorders, including inflammatory bowel disease. Although the pathogenesis of this problem is multifactorial, a key component is the abnormal elevation of the hormone hepcidin, the central regulator of systemic iron homeostasis. Investigations over the last decade have resulted in important insights into the role of hepcidin in iron metabolism and the mechanisms that lead to hepcidin dysregulation in the context of inflammation. These insights provide the foundation for novel strategies to prevent and treat the anemia associated with inflammatory diseases.
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Affiliation(s)
- Smriti Verma
- Mucosal Immunology and Biology Research Center, Department of Pediatrics, Massachusetts General Hospital and Harvard Medical School, Building 114, 16th Street, Charlestown, Boston, MA 02129, USA.
| | - Bobby J Cherayil
- Mucosal Immunology and Biology Research Center, Department of Pediatrics, Massachusetts General Hospital and Harvard Medical School, Building 114, 16th Street, Charlestown, Boston, MA 02129, USA.
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Sagami S, Ueno Y, Tanaka S, Fujita A, Hayashi R, Oka S, Hyogo H, Chayama K. Significance of non-alcoholic fatty liver disease in Crohn's disease: A retrospective cohort study. Hepatol Res 2017; 47:872-881. [PMID: 27737498 DOI: 10.1111/hepr.12828] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2016] [Revised: 09/19/2016] [Accepted: 10/08/2016] [Indexed: 02/08/2023]
Abstract
AIM The prevalence of non-alcoholic fatty liver disease (NAFLD) and Crohn's disease (CD) is increasing. The aim of our study was to evaluate the prevalence of NAFLD in patients with CD, as well as to investigate the effect of NAFLD on the disease course of CD. METHODS Our retrospective cohort study included 303 patients who underwent abdominal ultrasound for CD and NAFLD diagnosis at our center between November 2008 and October 2014. Serum C-reactive protein (CRP) level and rate of remission, defined by a score <150 on the Crohn's Disease Activity Index, were compared between CD patients with and without NAFLD, using multivariate logistic regression. The effect of NAFLD on the surgery-free interval was evaluated using Cox proportional hazards models, adjusted for potential demographic confounders. RESULTS Non-alcoholic fatty liver disease was diagnosed in 66 (21.8%) patients in our study cohort and was associated with lower CRP levels (0.58 vs. 2.18 mg/dL, P < 0.0001) and a higher rate of remission (75.9% vs. 53.7%, P = 0.0024). Non-alcoholic fatty liver disease was identified as an independent predictor of a negative CRP level (<0.3 mg/dL; odds ratio, 1.85; 95% confidence interval, 1.03-3.37) and higher rate of remission (odds ratio, 2.57; 95% confidence interval, 1.21-5.80). Non-alcoholic fatty liver disease was associated with longer surgery-free interval (log-rank test, P = 0.0035), with NAFLD identified as a positive predictor of surgery-free interval (P = 0.0014). CONCLUSIONS Non-alcoholic fatty liver disease may offer a protective effect in patients with CD and could be used as a prognostic marker in patients with CD.
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Affiliation(s)
- Shintaro Sagami
- Department of Medicine and Molecular Science, Hiroshima University, Hiroshima, Japan
| | - Yoshitaka Ueno
- Department of Endoscopy, Hiroshima University Hospital, Hiroshima, Japan
| | - Shinji Tanaka
- Department of Endoscopy, Hiroshima University Hospital, Hiroshima, Japan
| | - Akira Fujita
- Department of Medicine and Molecular Science, Hiroshima University, Hiroshima, Japan
| | - Ryohei Hayashi
- Department of Endoscopy, Hiroshima University Hospital, Hiroshima, Japan
| | - Shiro Oka
- Department of Endoscopy, Hiroshima University Hospital, Hiroshima, Japan
| | - Hideyuki Hyogo
- Department of Gastroenterology, Hiroshima General Hospital, Hiroshima, Japan
| | - Kazuaki Chayama
- Department of Medicine and Molecular Science, Hiroshima University, Hiroshima, Japan
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Abstract
INTRODUCTION Ulcerative colitis (UC) is a chronic inflammatory bowel disease with a relapsing-remitting course that determines significant morbidity and can associate with local complications and/or extra-intestinal manifestations. Pharmacological therapies are often required for a lifetime with possible risks of toxicity and side effects. Areas covered: Non-biological therapies (i.e. aminosalicylates, corticosteroids and immunosuppressive drugs) are widely used in UC patients for controlling the active phases of the disease and maintaining remission. Expert Opinion: Aminosalycilates have a good safety profile with a low risk of idiosyncrasic reactions. In contrast, the use of corticosteroids and immunosuppressive drugs can associate with unacceptable side effects, some of which are potentially life threatening. Mechanisms underlying the development of these side effects are not fully understood and strategies aimed to prevent them have not yet been standardized. However, clinicians should monitor the patients during therapy to recognize the adverse events at an early stage of the occurrence. New drugs that selectively target molecules involved in the amplification of the ongoing mucosal inflammation are currently under investigation. Preliminary data indicate that such compounds have better overall safety and tolerability than corticosteroids and immunosuppressive drugs.
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Affiliation(s)
- Edoardo Troncone
- a Department of Systems Medicine , University of Rome "Tor Vergata" , Rome , Italy
| | - Giovanni Monteleone
- a Department of Systems Medicine , University of Rome "Tor Vergata" , Rome , Italy
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Epidemiology and Risk Factors of Nonalcoholic Fatty Liver Disease Among Patients with Inflammatory Bowel Disease. Inflamm Bowel Dis 2017; 23:998-1003. [PMID: 28511199 DOI: 10.1097/mib.0000000000001085] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) has been increasingly identified in patients with inflammatory bowel disease (IBD). We aimed to determine risk factors of NAFLD in patients with IBD. METHODS We examined 3 groups of patients: IBD + NAFLD, IBD only, and NAFLD only. Data on demographics, body mass index, duration of IBD, type of medication use, laboratory data, and metabolic risk factors were collected. RESULTS A total of 168 patients between the ages 19 and 82 were evaluated, 56 patients in each group. Patients with IBD + NAFLD were significantly older than IBD only patients 45.0 (±14.1) versus 35.0 (±13), P = 0.007, and their mean body mass index was higher 30.4 (±10.2) versus 25.6 (±6.4); P = 0.002. IBD + NAFLD patients in comparison with IBD only patients had significantly longer duration of IBD (20 [±12.2] versus 10 [±7.7], P = 0.004), had an increased risk of diabetes (16% versus 2%, P = 0.01), and obesity (40% versus 20%, P = 0.02). There were no differences in the mean age or the mean body mass index (32.6 versus 30.4, P = 0.07) between patients with IBD + NAFLD and NAFLD only. More patients were obese in the NAFLD only group compared with the IBD + NAFLD group (59% versus 40%, P = 0.03), had hypertension (55% versus 33%, P = 0.02), hyperlipidemia (53% versus 17.5%, P = 0.0001), and diabetes (40% versus 16%, P = 0.0001). CONCLUSIONS IBD patients with NAFLD had longer disease duration of IBD and developed NAFLD with fewer metabolic risk factors than patients with NAFLD only. These findings suggest that there may be other factors that contribute to the development of NAFLD in the IBD population.
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Tran-Minh ML, Sousa P, Maillet M, Allez M, Gornet JM. Hepatic complications induced by immunosuppressants and biologics in inflammatory bowel disease. World J Hepatol 2017; 9:613-626. [PMID: 28539989 PMCID: PMC5424291 DOI: 10.4254/wjh.v9.i13.613] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2017] [Revised: 04/01/2017] [Accepted: 04/24/2017] [Indexed: 02/06/2023] Open
Abstract
The incidence of inflammatory bowel diseases (IBD) is rising worldwide. The therapeutic options for IBD are expanding, and the number of drugs with new targets will rapidly increase in coming years. A rapid step-up approach with close monitoring of intestinal inflammation is extensively used. The fear of side effects represents one the most limiting factor of their use. Despite a widespread use for years, drug induced liver injury (DILI) management remains a challenging situation with Azathioprine and Methotrexate. DILI seems less frequent with anti-tumor necrosis factor agents and new biologic therapies. The aim of this review is to report incidence, physiopathology and practical guidelines in case of DILI occurrence with the armamentarium of old and new drugs in the field of IBD.
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Hepatic Issues and Complications Associated With Inflammatory Bowel Disease: A Clinical Report From the NASPGHAN Inflammatory Bowel Disease and Hepatology Committees. J Pediatr Gastroenterol Nutr 2017; 64:639-652. [PMID: 27984347 DOI: 10.1097/mpg.0000000000001492] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Hepatobiliary disorders are common in patients with inflammatory bowel disease (IBD), and persistent abnormal liver function tests are found in approximately 20% to 30% of individuals with IBD. In most cases, the cause of these elevations will fall into 1 of 3 main categories. They can be as a result of extraintestinal manifestations of the disease process, related to medication toxicity, or the result of an underlying primary hepatic disorder unrelated to IBD. This latter possibility is beyond the scope of this review article, but does need to be considered in anyone with elevated liver function tests. This review is provided as a clinical summary of some of the major hepatic issues that may occur in patients with IBD.
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Restellini S, Chazouillères O, Frossard JL. Hepatic manifestations of inflammatory bowel diseases. Liver Int 2017; 37:475-489. [PMID: 27712010 DOI: 10.1111/liv.13265] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2016] [Accepted: 09/27/2016] [Indexed: 12/18/2022]
Abstract
Inflammatory bowel diseases are associated with various hepatobiliary disorders, reported both in Crohn's disease and ulcerative colitis. They may occur at any moment in the natural course of the disease. The prevalence of liver dysfunction rises from 3% to 50% accordingly to definitions used in different studies. Fatty liver is considered as the most common hepatobiliary complication in inflammatory bowel diseases while primary sclerosing cholangitis is the most specific one. Less frequently, inflammatory bowel diseases-associated hepatobiliary disorders include: autoimmune hepatitis/ primary sclerosing cholangitis overlap syndrome, IgG4-associated cholangiopathy, primary biliary cholangitis, hepatic amyloidosis, granulomatous hepatitis, cholelithiasis, portal vein thrombosis and liver abscess. The spectrum of these manifestations varies according to the type of inflammatory bowel diseases. Treatments of inflammatory bowel diseases may cause liver toxicity, although incidence of serious complications remains low. However, early diagnosis of drug-induced liver injury is of major importance as it affects future clinical management. When facing abnormal liver tests, clinicians should undertake a full diagnostic work-up in order to determine whether the hepatic abnormalities are related to the inflammatory bowel diseases or not. Management of hepatic manifestations in inflammatory bowel diseases usually involves both hepatologists and gastroenterologists because of the complexity of some situations.
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Affiliation(s)
- Sophie Restellini
- Service de Gastroentérologie et Hépatologie, Hôpitaux Universitaires de Genève, Genève, Suisse
| | - Olivier Chazouillères
- Division d'Hépatologie, Centre de Référence des Maladies Inflammatoires des Voies Biliaires, et Université de Sorbonne, UPMC Univ Paris 06, UMR_S 938, CDR Saint-Antoine, AP-HP, Hôpital Saint-Antoine, Paris, France
| | - Jean-Louis Frossard
- Service de Gastroentérologie et Hépatologie, Hôpitaux Universitaires de Genève, Genève, Suisse
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Barlow JJ, Hawthorne AB. Crohn's disease for the general physician: management. Br J Hosp Med (Lond) 2017; 78:77-81. [PMID: 28165796 DOI: 10.12968/hmed.2017.78.2.77] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Crohn's disease presents to general physicians in a variety of ways. The previous article outlined clinical features and initial investigations, and this article covers management of Crohn's disease, including monitoring and drug toxicity.
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Affiliation(s)
- J J Barlow
- Gastroenterology Specialist Trainee, Department of Gastroenterology, University Hospital of Wales, Cardiff
| | - A B Hawthorne
- Consultant Physician and Gastroenterologist, Department of Gastroenterology, University Hospital of Wales, Cardiff CF14 4XW
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Abstract
OBJECTIVE The objective of the study was to define the clinical, biochemical, and histologic features of liver injury from thiopurines. BACKGROUND Azathioprine (Aza) and 6-mercaptopurine (6-MP) can cause liver injury, but no large series exist. METHODS Clinical and laboratory data and 6-month outcomes of patients with thiopurine hepatotoxicity from the Drug-Induced Liver Injury Network Prospective Study were analyzed. RESULTS Twenty-two patients were identified, 12 due to Aza and 10 due to 6-MP, with a median age of 55 years; the majority were female (68%). Inflammatory bowel disease was the indication in 55%, and the median thiopurine dose was 150 (range, 25 to 300) mg daily. The median latency to onset was 75 (range, 3 to 2584) days. Injury first arose after a dose escalation in 59% of patients, the median latency after dose increase being 44 (range, 3 to 254) days. At onset, the median alanine aminotransferase level was 210 U/L, alkaline phosphatase was 151 U/L, and bilirubin was 7.4 mg/dL (peak, 13.4 mg/dL). There were no major differences between Aza and 6-MP cases, but anicteric cases typically had nonspecific symptoms and a hepatocellular pattern of enzyme elevations, whereas icteric cases experienced cholestatic hepatitis with modest enzyme elevations in a mixed pattern. One patient with preexisting cirrhosis required liver transplantation; all others resolved clinically. One patient still had moderate alkaline phosphatase elevations 2 years after onset. CONCLUSIONS Nearly three-quarters of patients with thiopurine-induced liver injury present with self-limited, cholestatic hepatitis, typically within 3 months of starting or a dose increase. The prognosis is favorable except in patients with preexisting cirrhosis.
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Barendregt J, de Jong M, Haans JJ, van Hoek B, Hardwick J, Veenendaal R, van der Meulen A, Srivastava N, Stuyt R, Maljaars J. Liver test abnormalities predict complicated disease behaviour in patients with newly diagnosed Crohn's disease. Int J Colorectal Dis 2017; 32:459-467. [PMID: 27900523 PMCID: PMC5355514 DOI: 10.1007/s00384-016-2706-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/10/2016] [Indexed: 02/04/2023]
Abstract
BACKGROUNDS In coeliac disease, the prevalence of liver test abnormalities (LTAs) is higher in patients with more severe mucosal inflammation. In Crohn's disease, prognosis is related to the severity of mucosal inflammation. AIM The aim of this study was to investigate whether the presence of LTA predicts the occurrence of complicated disease behaviour in newly diagnosed Crohn's disease. METHODS A retrospective cohort study was performed in patients newly diagnosed with Crohn's disease between 2002 and 2011. The complicated disease was defined as the occurrence of stricturing and/or perforating disease. LTAs were defined as a value of any of alkaline phosphatase (AP), gamma-glutamyl transpeptidase (GGT), aspartate aminotransferase (AST), or alanine aminotransferase (ALT) over the upper limit of normal. RESULTS Three hundred eighty-three patients were included, of whom 34.1% had LTA. LTAs were mostly mild (less than two times the upper limit of normal). During the 5-year follow-up, 33.1% of patients in the group with LTA developed complicated disease behaviour compared to 14.6% in patients without LTA (p < 0.001). The presence of LTA was identified as a risk factor for complicated disease behaviour (HR 2.6, 95% confidence interval (CI) 1.5-4.2, p < 0.0001). CONCLUSIONS In newly diagnosed Crohn's disease, the presence of LTA was an independent risk factor for the development of complicated disease behaviour.
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Affiliation(s)
- Jessika Barendregt
- 0000000089452978grid.10419.3dDepartment of Gastroenterology-Hepatology, Leiden University Medical Centre, Leiden, The Netherlands
| | - Myrthe de Jong
- 0000000089452978grid.10419.3dDepartment of Gastroenterology-Hepatology, Leiden University Medical Centre, Leiden, The Netherlands
| | - Jeoffrey J. Haans
- grid.412966.eDepartment of Gastroenterology-Hepatology, Maastricht University Medical Centre, Maastricht, The Netherlands
| | - Bart van Hoek
- 0000000089452978grid.10419.3dDepartment of Gastroenterology-Hepatology, Leiden University Medical Centre, Leiden, The Netherlands
| | - James Hardwick
- 0000000089452978grid.10419.3dDepartment of Gastroenterology-Hepatology, Leiden University Medical Centre, Leiden, The Netherlands
| | - Roeland Veenendaal
- 0000000089452978grid.10419.3dDepartment of Gastroenterology-Hepatology, Leiden University Medical Centre, Leiden, The Netherlands
| | - Andrea van der Meulen
- 0000000089452978grid.10419.3dDepartment of Gastroenterology-Hepatology, Leiden University Medical Centre, Leiden, The Netherlands
| | - Nidhi Srivastava
- Department of Gastroenterology-Hepatology, Haaglanden Medical Centre, The Hague, The Netherlands
| | - Rogier Stuyt
- 0000 0004 0568 6689grid.413591.bDepartment of Gastroenterology-Hepatology, Haga Hospital, The Hague, The Netherlands
| | - Jeroen Maljaars
- 0000000089452978grid.10419.3dDepartment of Gastroenterology-Hepatology, Leiden University Medical Centre, Leiden, The Netherlands
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Meijer B, Simsek M, Blokzijl H, de Man RA, Coenraad MJ, Dijkstra G, van Nieuwkerk CM, Mulder CJ, de Boer NK. Nodular regenerative hyperplasia rarely leads to liver transplantation: A 20-year cohort study in all Dutch liver transplant units. United European Gastroenterol J 2016; 5:658-667. [PMID: 28815029 DOI: 10.1177/2050640616680550] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2016] [Accepted: 10/18/2016] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Nodular regenerative hyperplasia is an uncommon liver condition associated with several autoimmune disorders and drugs. The clinical symptoms of nodular regenerative hyperplasia vary from asymptomatic to severe complications of portal hypertension (nodular regenerative hyperplasia-syndrome). OBJECTIVE The purpose of this study was to identify the prognosis and optimal management, as well as the role of liver transplantation, in nodular regenerative hyperplasia. METHODS The pathology databases of all three Dutch liver transplant units were retrospectively scrutinised for explanted livers diagnosed with nodular regenerative hyperplasia or without clear diagnosis. Pre- and post-transplantation clinical, biochemical, radiological and histological information was obtained from electronic and paper records. RESULTS In total, 1886 patients received a liver transplant. In 255 patients, nodular regenerative hyperplasia could not be excluded. After detailed chart review, the native livers of 11 patients (0.6%) (82% male, median age: 44 years) displayed nodular regenerative hyperplasia. Seven patients (64%) had underlying disorders or drug exposure which possibly caused nodular regenerative hyperplasia. Laboratory and imaging abnormalities were present in all patients but did not contribute to the diagnosis of nodular regenerative hyperplasia. Five-year survival was 73% (median follow-up: four years, range: 2-248 months). CONCLUSION Nodular regenerative hyperplasia is a rare finding in patients, predominantly young males, transplanted for end-stage liver disease with unknown aetiology. Nonetheless, liver transplantation may have an important role in end-stage nodular regenerative hyperplasia-syndrome.
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Affiliation(s)
- Berrie Meijer
- Department of Gastroenterology and Hepatology, VU University Medical Center Amsterdam, The Netherlands
| | - Melek Simsek
- Department of Gastroenterology and Hepatology, VU University Medical Center Amsterdam, The Netherlands
| | - Hans Blokzijl
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, The Netherlands
| | - Robert A de Man
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Minneke J Coenraad
- Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands
| | - Gerard Dijkstra
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, The Netherlands
| | - Carin Mj van Nieuwkerk
- Department of Gastroenterology and Hepatology, VU University Medical Center Amsterdam, The Netherlands
| | - Chris Jj Mulder
- Department of Gastroenterology and Hepatology, VU University Medical Center Amsterdam, The Netherlands
| | - Nanne Kh de Boer
- Department of Gastroenterology and Hepatology, VU University Medical Center Amsterdam, The Netherlands
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Chao CY, Battat R, Al Khoury A, Restellini S, Sebastiani G, Bessissow T. Co-existence of non-alcoholic fatty liver disease and inflammatory bowel disease: A review article. World J Gastroenterol 2016; 22:7727-7734. [PMID: 27678354 PMCID: PMC5016371 DOI: 10.3748/wjg.v22.i34.7727] [Citation(s) in RCA: 68] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2016] [Revised: 06/19/2016] [Accepted: 08/01/2016] [Indexed: 02/06/2023] Open
Abstract
Emerging data have highlighted the co-existence of non-alcoholic fatty liver disease (NAFLD) and inflammatory bowel disease; both of which are increasingly prevalent disorders with significant complications and impact on future health burden. Cross-section observational studies have shown widely variable prevalence rates of co-existing disease, largely due to differences in disease definition and diagnostic tools utilised in the studies. Age, obesity, insulin resistance and other metabolic conditions are common risks factors in observational studies. However, other studies have also suggested a more dominant role of inflammatory bowel disease related factors such as disease activity, duration, steroid use and prior surgical intervention, in the development of NAFLD. This suggests a potentially more complex pathogenesis and relationship between the two diseases which may be contributed by factors including altered intestinal permeability, gut dysbiosis and chronic inflammatory response. Commonly used immunomodulation agents pose potential hepatic toxicity, however no definitive evidence exist linking them to the development of hepatic steatosis, nor are there any data on the impact of therapy and prognosis in patient with co-existent diseases. Further studies are required to assess the impact and establish appropriate screening and management strategies in order to allow early identification, intervention and improve patient outcomes.
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Incidence and Predictors of Nonalcoholic Fatty Liver Disease by Serum Biomarkers in Patients with Inflammatory Bowel Disease. Inflamm Bowel Dis 2016; 22:1937-44. [PMID: 27379445 DOI: 10.1097/mib.0000000000000832] [Citation(s) in RCA: 74] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Patients with inflammatory bowel disease (IBD) are at high risk for non-alcoholic fatty liver disease (NAFLD). Longitudinal data on incident NAFLD are lacking. We employed non-invasive methods to study incidence and predictors of NAFLD. METHODS This was a retrospective study of IBD patients without known liver disease followed at IBD clinic of McGill University. NAFLD was defined as Hepatic Steatosis Index (HSI) ≥36 and absence of alcohol intake. Advanced liver fibrosis was diagnosed by FIB-4 ≥2.67. Active IBD was defined as partial Mayo score ≥3 for ulcerative colitis, Harvey Bradshaw Index ≥ 5 or flare during follow-up. Kaplan-Meier and Cox regression analyses were used to investigate incidence and predictors of NAFLD development. RESULTS Three hundred twenty-one consecutive patients (median age 33.7 yr, 47% males) were observed for a median of 3.2 years (interquartile range 1.5-6). Over 1181.2 persons-year (PY), 108 (33.6%) patients developed NAFLD, accounting for an incidence rate of 9.1/100 PY (95% confidence interval [CI], 7.4-10.9). 7 (2.2%) patients developed advanced liver fibrosis, accounting for an incidence rate of 0.5/100 PY (95% CI, 0.2-1.1). Development of NAFLD was predicted by disease activity (adjusted hazard ratio [aHR] = 1.58; 95% CI, 1.08-2.33, P = 0.02), disease duration (aHR = 1.12; 95% CI, 1.03-1.23, P = 0.01), and prior surgery for IBD (aHR = 1.34; 95% CI, 1.04-1.74, P = 0.02). CONCLUSIONS NAFLD is a frequent comorbidity in patients with IBD. These patients can also develop advanced liver fibrosis. Disease activity, duration of IBD and prior surgery are predictors of NAFLD development. This should represent one more incentive to achieve and maintain early clinical remission. Further prospective studies are of interest.
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Chen JH, Andrews JM, Kariyawasam V, Moran N, Gounder P, Collins G, Walsh AJ, Connor S, Lee TWT, Koh CE, Chang J, Paramsothy S, Tattersall S, Lemberg DA, Radford-Smith G, Lawrance IC, McLachlan A, Moore GT, Corte C, Katelaris P, Leong RW. Review article: acute severe ulcerative colitis - evidence-based consensus statements. Aliment Pharmacol Ther 2016; 44:127-144. [PMID: 27226344 DOI: 10.1111/apt.13670] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2015] [Revised: 12/18/2015] [Accepted: 04/27/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND Acute severe ulcerative colitis (ASUC) is a potentially life-threatening complication of ulcerative colitis. AIM To develop consensus statements based on a systematic review of the literature of the management of ASUC to improve patient outcome. METHODS Following a literature review, the Delphi method was used to develop the consensus statements. A steering committee, based in Australia, generated the statements of interest. Three rounds of anonymous voting were carried out to achieve the final results. Acceptance of statements was pre-determined by ≥80% votes in 'complete agreement' or 'agreement with minor reservation'. RESULTS Key recommendations include that patients with ASUC should be: hospitalised, undergo unprepared flexible sigmoidoscopy to assess severity and to exclude cytomegalovirus colitis, and be provided with venous thromboembolism prophylaxis and intravenous hydrocortisone 100 mg three or four times daily with close monitoring by a multidisciplinary team. Rescue therapy such as infliximab or ciclosporin should be started if insufficient response by day 3, and colectomy considered if no response to 7 days of rescue therapy or earlier if deterioration. With such an approach, it is expected that colectomy rate during admission will be below 30% and mortality less than 1% in specialist centres. CONCLUSION These evidenced-based consensus statements on acute severe ulcerative colitis, developed by a multidisciplinary group, provide up-to-date best practice recommendations that improve and harmonise management as well as provide auditable quality assessments.
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Affiliation(s)
- J-H Chen
- Concord Hospital, Sydney, NSW, Australia
| | - J M Andrews
- Royal Adelaide Hospital, Adelaide, SA, Australia
| | | | - N Moran
- Concord Hospital, Sydney, NSW, Australia
| | - P Gounder
- Concord Hospital, Sydney, NSW, Australia
| | - G Collins
- Concord Hospital, Sydney, NSW, Australia
| | - A J Walsh
- St. Vincent Hospital, Sydney, NSW, Australia
| | - S Connor
- Liverpool Hospital, Sydney, NSW, Australia
| | - T W T Lee
- Wollongong Hospital, Wollongong, NSW, Australia
| | - C E Koh
- Royal Prince Alfred Hospital, Sydney, NSW, Australia
| | - J Chang
- Concord Hospital, Sydney, NSW, Australia
| | | | - S Tattersall
- Royal North Shore Hospital, Sydney, NSW, Australia
| | - D A Lemberg
- Sydney Children's Hospital, Sydney, NSW, Australia
| | - G Radford-Smith
- Royal Brisbane and Women's Hospital, Brisbane, Qld, Australia
| | - I C Lawrance
- Saint John of God Hospital, Perth, WA, Australia
| | | | - G T Moore
- Monash Medical Centre, Melbourne, Vic., Australia
| | - C Corte
- Concord Hospital, Sydney, NSW, Australia
| | | | - R W Leong
- Concord Hospital, Sydney, NSW, Australia
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Abstract
Awareness of the extraintestinal manifestations of Crohn disease is increasing in dermatology and gastroenterology, with enhanced identification of entities that range from granulomatous diseases recapitulating the underlying inflammatory bowel disease to reactive conditions and associated dermatoses. In this review, the underlying etiopathology of Crohn disease is discussed, and how this mirrors certain skin manifestations that present in a subset of patients is explored. The array of extraintestinal manifestations that do not share a similar pathology, but which are often seen in association with inflammatory bowel disease, is also discussed. Treatment and pathogenetic mechanisms, where available, are discussed.
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Affiliation(s)
- Joshua W Hagen
- Department of Dermatology, University of Pittsburgh Medical Center, Medical Arts Building, 3708 Fifth Avenue, 5th Floor, Pittsburgh, PA 15213, USA
| | - Jason M Swoger
- Department of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh Medical Center, 200 Lothrop street, C-Wing, Mezzanine, Pittsburgh, PA 15213, USA
| | - Lisa M Grandinetti
- Department of Dermatology, University of Pittsburgh Medical Center, Medical Arts Building, 3708 Fifth Avenue, 5th Floor, Pittsburgh, PA 15213, USA.
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Walker AM, Zhou X, Ananthakrishnan AN, Weiss LS, Shen R, Sobel RE, Bate A, Reynolds RF. Computer-assisted expert case definition in electronic health records. Int J Med Inform 2016; 86:62-70. [DOI: 10.1016/j.ijmedinf.2015.10.005] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2015] [Revised: 10/13/2015] [Accepted: 10/15/2015] [Indexed: 12/21/2022]
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PNPLA3 148M Carriers with Inflammatory Bowel Diseases Have Higher Susceptibility to Hepatic Steatosis and Higher Liver Enzymes. Inflamm Bowel Dis 2016; 22:134-40. [PMID: 26355465 PMCID: PMC4894778 DOI: 10.1097/mib.0000000000000569] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Inflammatory bowel diseases (IBD) are characterized by chronic relapsing inflammation of the gastrointestinal tract and encompass Crohn's disease and ulcerative colitis. IBD are often associated with extraintestinal manifestations affecting multiple organs including the liver. Increased levels of serum aminotransferases, possibly related to nonalcoholic fatty liver disease, constitute one of the most frequently described IBD-related liver diseases. The PNPLA3 I148M substitution is a major common genetic determinant of hepatic fat content and progression to chronic liver disease. The aim of this study was to investigate whether carriers of PNPLA3 148M allele with IBD have higher risk of liver steatosis and increase in transaminases levels. METHODS The PNPLA3 I148M (rs738409) genotype was performed by Taqman assays in 158 individuals from Southern Italy (namely, Catanzaro cohort) and in 207 individuals from Northern Italy (namely, Milan cohort) with a definite diagnosis of IBD. Demographic and clinical data and also alanine transaminase levels were collected for both cohorts. The Catanzaro cohort underwent liver evaluation by sonography and liver stiffness and controlled attenuation parameter measurements by transient elastography. RESULTS Here, we show for the first time that carriers of the PNPLA3 148M allele with IBD have a greater risk of hepatic steatosis (odds ratio, 2.9, and confidence interval, 1.1-7.8), higher controlled attenuation parameter values (P = 0.029), and increased circulating alanine transaminase (P = 0.035) in the Catanzaro cohort. We further confirm the higher alanine transaminase levels in the Milan cohort (P < 0.001). CONCLUSIONS Our results show that PNPLA3 148M carriers with IBD have higher susceptibility to hepatic steatosis and liver damage.
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Valentino PL, Feldman BM, Walters TD, Griffiths AM, Ling SC, Pullenayegum EM, Kamath BM. Abnormal Liver Biochemistry Is Common in Pediatric Inflammatory Bowel Disease: Prevalence and Associations. Inflamm Bowel Dis 2015; 21:2848-56. [PMID: 26273817 DOI: 10.1097/mib.0000000000000558] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Liver enzymes (LEs) abnormalities associated with pediatric inflammatory bowel diseases (IBD) are understudied. We undertook to describe the development and associations of abnormal LEs in pediatric IBD. METHODS We ascertained a cohort of 300 children with IBD and collected retrospective data. A Kaplan-Meier analysis determined the time to development of different thresholds of abnormal LEs. Associations between clinical variables and the development of abnormal LEs were determined. RESULTS The probability of developing the first episode of abnormal LEs above the upper limit of normal (ULN) within 150 months was 58.1% (16.3% by 1 mo post-IBD diagnosis). There was a 6% prevalence of primary sclerosing cholangitis (PSC) or autoimmune sclerosing cholangitis (ASC) in this cohort. Of those diagnosed with PSC/ASC, 93% had persistent LE elevations at a threshold of >2× ULN, while those without PSC/ASC had a 4% probability of this abnormality. Elevated gamma glutamyltranspeptidase levels of 252 U/L had a 99% sensitivity and 71% specificity for PSC/ASC in IBD. After exclusion of patients with PSC/ASC, corticosteroids, antibiotics, and exclusive enteral nutrition demonstrated strongly positive associations with the first development of abnormal LEs >ULN (hazard ratio 2.1 [95% confidence interval, 1.3-3.3], hazard ratio 5.6 [95% confidence interval, 3.6-8.9], hazard ratio 4.2 [95% confidence interval, 1.6-11.3], respectively). CONCLUSIONS Abnormal LEs are common in pediatric IBD and occur early. PSC/ASC is associated with persistently high LEs and gamma glutamyltranspeptidase levels >252 U/L. Children with IBD are at risk of elevated LEs if they require medications other than 5-ASA to induce IBD remission.
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Affiliation(s)
- Pamela L Valentino
- *Division of Gastroenterology, Hepatology, and Nutrition, The University of Toronto, ON, Canada; †Department of Pediatrics, The University of Toronto, Toronto, ON, Canada; ‡Institute of Health Policy, Management and Evaluation, The University of Toronto, Toronto, ON, Canada; §Child Health Evaluative Sciences, Hospital for Sick Children and The University of Toronto, Toronto, ON, Canada; and ‖Division of Rheumatology, The University of Toronto, Toronto, ON, Canada
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Liver steatosis is a risk factor for hepatotoxicity in patients with inflammatory bowel disease under immunosuppressive treatment. Eur J Gastroenterol Hepatol 2015; 27:698-704. [PMID: 25923946 DOI: 10.1097/meg.0000000000000350] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
OBJECTIVE In inflammatory bowel disease (IBD), hepatic disorders are frequently due to nonalcoholic fatty liver disease and drug-induced hepatotoxicity. Immunosuppressive treatment is known to exert hepatotoxic side effects by a still unknown mode. The relevance of liver steatosis for the development of drug-related hepatotoxicity in IBD is unknown. METHODS The charts of 259 patients with IBD under immunosuppression with either azathioprine, 6-mercaptopurine, or methotrexate were reviewed. The prevalence of liver steatosis was assessed by means of ultrasound reports. Aspartate transaminase and alanine transaminase above the normal range were used to indicate liver abnormalities. RESULTS Liver steatosis on the basis of ultrasound criteria was observed in 73 patients (28.2%). In patients with liver steatosis, the presence of elevated liver enzymes (ELE) was found to be significantly more prevalent (28.8 vs. 14.5%, P=0.0095). The finding of liver steatosis was associated with higher age (44.1 vs. 34.5 years, P<0.0001) and body weight (BMI 26.7 vs. 23.4 kg/m, P<0.0001). Development of ELE under immunosuppression was seen in 50 patients (19.3%). Of the patients who developed ELE, 44.0% (vs. 24.4%, P=0.0095) showed liver steatosis. Logistic regression analysis revealed that male individuals showed an increased likelihood of developing ELE associated with steatosis (P=0.0118, odds ratio=3.93) and that patients who received steroids less often developed ELE in association with liver steatosis (P=0.0414, odds ratio=0.31). CONCLUSION This study suggests that fatty liver represents a risk factor for hepatotoxicity in patients with IBD under immunosuppressive treatment and should be routinely considered in treatment strategies.
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Incidence, pattern, and etiology of elevated liver enzymes in pediatric inflammatory bowel disease. J Pediatr Gastroenterol Nutr 2015; 60:592-7. [PMID: 25493346 DOI: 10.1097/mpg.0000000000000672] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Patients with inflammatory bowel disease (IBD) often develop elevated liver enzymes (ELE), which are frequently a benign, transient finding, but may be related to treatment or IBD-associated liver diseases. Distinguishing benign from pathologic ELE is crucial for focused diagnostic and therapeutic interventions. We sought to characterize the incidence, character, chronicity, degree, and etiology of ELE in children with IBD. METHODS Institutional review board-approved retrospective review of all of the patients with IBD (2-21 years) seen between October 2009 and October 2012 with >9 months of follow-up were included in the study. We examined body mass index, disease activity, extent, phenotype, concurrent medications, and character, chronicity, degree of enzyme elevation, and final diagnosis. RESULTS A total of 219 of 514 patients with IBD had ≥1 episode of ELE. Five patients were excluded for preexisting liver disease, leaving 214 patients (Crohn disease [CD]: 14.8 ± 3.5 years, 46% girls; ulcerative colitis [UC]: 14.4 ± 4.2 years, 37% girls). One hundred forty-eight patients (69%) had a hepatic, 17 (8%) cholestatic, and 49 (23%) mixed character of ELE. There were no significant differences in character, chronicity, or degree of ELE between CD and UC (P = 0.71, P = 0.58, P > 0.33). Of the 128 patients with sufficient data to determine chronicity, 98 (77%) had transient elevations, (CD: n = 66, 75% and UC: n = 32, 80%). Episodes of ELE were idiopathic in 87% of patients with IBD. A final diagnosis of idiopathic ELE was associated with a lower degree of ELE elevation (P < 0.0001). CONCLUSIONS Pediatric patients with IBD commonly experience transient, idiopathic ELE. Our findings suggest that higher degrees of ELE, specifically alanine aminotransferase, are associated with an etiology that requires more extensive evaluation.
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