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Lin M, Huang R, Li W, Peng H, Chen J, Qiu Y, Liu Y, Chen L. Dysbiosis of the gut micro-flora aggravates symptoms and accelerates disease progression in MASLD-IBD Co-morbid mice through host-microbial metabolic imbalance. Arch Biochem Biophys 2025; 769:110441. [PMID: 40320060 DOI: 10.1016/j.abb.2025.110441] [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: 12/12/2024] [Revised: 04/09/2025] [Accepted: 04/26/2025] [Indexed: 05/07/2025]
Abstract
Studies have shown that dysregulation of intestinal microbial structure and co-metabolic imbalance caused by diet and other factors play important role in MASLD and IBD. However, it is unclear how host-microbial interactions differ in the two diseases, and what potential impact they have on accelerating disease progression. Our study aims to find the disease characteristics in MASLD, IBD and their complication from the perspective of host-microbial metabolism. In our study, mouse models of MASLD, IBD, and MASLD-IBD induced by high-fat diet and dextran sulfate sodium. Detecting the pathological changes of colon and liver. Using 16s rRNA to screen out specific micro-flora, and UPLC-MS to monitor the changes of metabolites in feces. The micro-flora-metabolite co-expression network was constructed by Cytoscape software. The result showed that MASLD-IBD mice aggravate intestinal barrier damage, hepatic steatosis and fibrosis, immune inflammation and other pathological changes. In MASLD-IBD mice, the structural change of gut micro-flora is similar to IBD mice, which significantly reduced the abundance of Actinobacteriota, Desulfobacterota while increasing the abundance of Proteobacteria, and the metabolic disorder include nine metabolic pathways, such as tryptophan, bile acids and short-chain fatty acids, is similar to MASLD mice. Their co-expression network indicates that different specific micro-flora are closely related to the metabolic disorder and disease symptoms of MASLD-IBD mice. Analyzing the relationship between intestinal microbial dysregulation and hoetic co-metabolic imbalance is helpful to understand the mechanism of MASLD and IBD comorbidity, which suggesting that combined liver-gut therapy may be a new method for the treatment of MASLD-IBD complication.
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Affiliation(s)
- Minling Lin
- School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, 510006, China
| | - Ruiting Huang
- School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, 510006, China
| | - Wanyu Li
- School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, 510006, China
| | - Hui Peng
- School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, 510006, China
| | - Jun Chen
- School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, 510006, China
| | - Yongyi Qiu
- School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, 510006, China
| | - Yi Liu
- School of Chinese Medicine, Southern Medical University, Guangzhou, 510515, China.
| | - Lei Chen
- School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, 510006, China.
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Janani KV, Saberian P, Patel HB, Keetha NR, Etemadzadeh A, Patel A, Hashemi SM, Amini-Salehi E, Gurram A. Prevalence of metabolic syndrome in patients with inflammatory bowel disease: a meta-analysis on a global scale. JOURNAL OF HEALTH, POPULATION, AND NUTRITION 2025; 44:112. [PMID: 40205601 PMCID: PMC11983980 DOI: 10.1186/s41043-025-00860-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/07/2025] [Accepted: 04/01/2025] [Indexed: 04/11/2025]
Abstract
BACKGROUND Metabolic syndrome (MetS) is a cluster of metabolic abnormalities that increase the risk of cardiovascular diseases (CVD). Patients with inflammatory bowel disease (IBD) may be at higher risk of developing MetS due to chronic inflammation, altered adipokine profiles, and the effects of corticosteroid treatment. However, the prevalence of MetS in IBD patients remains inconsistent across studies. This meta-analysis aims to estimate the prevalence of MetS in IBD patients and compare its occurrence between Crohn's disease (CD) and ulcerative colitis (UC). METHODS A systematic search was conducted across PubMed, Scopus, Embase, and Web of Science from their inception up to January 19, 2025. Eligible observational studies reporting MetS prevalence in IBD patients were included. Meta-analysis was performed using a random-effects model, with heterogeneity assessed via the I² statistic. Comprehensive Meta-Analysis (CMA) software, version 4.0 was used for analysis. RESULTS The pooled prevalence of MetS in IBD patients was 21.8% (95% CI: 14.3-31.6%). The prevalence was higher in UC patients (32.7%, 95% CI: 16.0-55.5%) compared to CD patients (14.1%, 95% CI: 8.6-22.3%). Patients with UC had significantly higher odds of MetS than those with CD (OR = 1.38, 95% CI: 1.03-1.85, P = 0.02). Additionally, IBD patients with MetS were significantly older than those without (MD: 9.89, 95% CI: 5.12-14.67, P < 0.01). CONCLUSION In summary, this meta-analysis reveals a notable prevalence of MetS among patients with IBD, particularly in those with UC, where the prevalence is higher than in CD. The analysis also shows that IBD patients with MetS tend to be older, suggesting age as a contributing factor. These findings underscore the need for routine metabolic screening in IBD care, especially in UC and elderly patients.
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Affiliation(s)
- Khushbu Viresh Janani
- Soundview Medical Associates, Department of Internal Medicine, Hartford Healthcare, 50 Danbury Road, Wilton, CT, 06612, USA
| | - Parsa Saberian
- Cardiovascular Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Hardik B Patel
- Department of Internal Medicine, Yale New Haven Health Bridgeport Hospital, 267 Grant Street, Bridgeport, CT, 06610, USA
| | - Narsimha Rao Keetha
- Ohio Kidney and Hypertension Center, 7255, Old Oak Blvd, Ste C111 Middleburg Hts, Fairview Park, OH, 44130, USA
| | - Ardalan Etemadzadeh
- Cardiovascular Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Anya Patel
- , Nashua High School South 36 Riverside St, Nashua, NH, 03062, USA
| | - Seyyed Mohammad Hashemi
- Cardiovascular Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
| | - Ehsan Amini-Salehi
- Gastrointestinal and Liver Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran.
| | - Anoop Gurram
- Department of Hospital Medicine, Cleveland Clinic, 33300 Cleveland Clinic Blvd, Avon, Ohio, ashua, NH, 44011, 03062, USA
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Aggarwal K, Singh B, Goel A, Agrawal DK, Bansal S, Kanagala SG, Anamika F, Gupta A, Jain R. Complex dichotomous links of nonalcoholic fatty liver disease and inflammatory bowel disease: exploring risks, mechanisms, and management modalities. Intest Res 2024; 22:414-427. [PMID: 38835139 PMCID: PMC11534450 DOI: 10.5217/ir.2024.00001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2023] [Revised: 04/04/2024] [Accepted: 04/15/2024] [Indexed: 06/06/2024] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) has been shown to be linked to inflammatory bowel disease (IBD) due to established risk factors such as obesity, age, and type 2 diabetes in numerous studies. However, alternative research suggests that factors related to IBD, such as disease activity, duration, and drug-induced toxicity, can contribute to NAFLD. Recent research findings suggest IBD relapses are correlated with dysbiosis, mucosal damage, and an increase in cytokines. In contrast, remission periods are characterized by reduced metabolic risk factors. There is a dichotomy evident in the associations between NAFLD and IBD during relapses and remissions. This warrants a nuanced understanding of the diverse influences on disease manifestation and progression. It is possible to provide a holistic approach to care for patients with IBD by emphasizing the interdependence between metabolic and inflammatory disorders.
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Affiliation(s)
- Kanishk Aggarwal
- Department of Medicine, Dayanand Medical College, Ludhiana, India
| | - Bhupinder Singh
- Department of Medicine, Government Medical College Amritsar, Amritsar, India
| | - Abhishek Goel
- Department of Medicine, Cape Fear Valley Medical Center, Fayetteville, NC, USA
| | | | - Sourav Bansal
- Department of Medicine, Government Medical College Amritsar, Amritsar, India
| | | | - Fnu Anamika
- Department of Medicine, University College of Medical Sciences, New Delhi, India
| | | | - Rohit Jain
- Department of Medicine, Penn State Milton S. Hershey Medical Center, Hershey, PA, USA
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4
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Enkler L, Spang A. Functional interplay of lipid droplets and mitochondria. FEBS Lett 2024; 598:1235-1251. [PMID: 38268392 DOI: 10.1002/1873-3468.14809] [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: 10/12/2023] [Revised: 12/12/2023] [Accepted: 01/04/2024] [Indexed: 01/26/2024]
Abstract
Our body stores energy mostly in form of fatty acids (FAs) in lipid droplets (LDs). From there the FAs can be mobilized and transferred to peroxisomes and mitochondria. This transfer is dependent on close opposition of LDs and mitochondria and peroxisomes and happens at membrane contact sites. However, the composition and the dynamics of these contact sites is not well understood, which is in part due to the dependence on the metabolic state of the cell and on the cell- and tissue-type. Here, we summarize the current knowledge on the contacts between lipid droplets and mitochondria both in mammals and in the yeast Saccharomyces cerevisiae, in which various contact sites are well studied. We discuss possible functions of the contact site and their implication in disease.
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Affiliation(s)
| | - Anne Spang
- Biozentrum, University of Basel, Switzerland
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Wei Z, Wang J. Exploration of the core pathway of inflammatory bowel disease complicated with metabolic fatty liver and two-sample Mendelian randomization study of the causal relationships behind the disease. Front Immunol 2024; 15:1375654. [PMID: 38698841 PMCID: PMC11063260 DOI: 10.3389/fimmu.2024.1375654] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2024] [Accepted: 04/05/2024] [Indexed: 05/05/2024] Open
Abstract
Background Inflammatory bowel disease (IBD) is often associated with complex extraintestinal manifestations. The incidence of nonalcoholic fatty liver disease (NAFLD) in IBD populations is increasing yearly. However, the mechanism of interaction between NAFLD and IBD is not clear. Consequently, this study aimed to explore the common genetic characteristics of IBD and NAFLD and identify potential therapeutic targets. Materials and methods Gene chip datasets for IBD and NAFLD were obtained from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was performed to identify modules in those datasets related to IBD and NAFLD. ClueGO was used for biological analysis of the shared genes between IBD and NAFLD. Based on the Human MicroRNA Disease Database (HMDD), microRNAs (miRNAs) common to NAFLD and IBD were obtained. Potential target genes for the miRNAs were predicted using the miRTarbase, miRDB, and TargetScan databases. Two-sample Mendelian randomization (MR) and two-way MR were used to explore the causal relationship between Interleukin-17 (IL-17) and the risk of IBD and NAFLD using data from GWAS retrieved from an open database. Results Through WGCNA, gene modules of interest were identified. GO enrichment analysis using ClueGO suggested that the abnormal secretion of chemokines may be a common pathophysiological feature of IBD and NAFLD, and that the IL-17-related pathway may be a common key pathway for the pathological changes that occur in IBD and NAFLD. The core differentially expressed genes (DEGs) in IBD and NAFLD were identified and included COL1A1, LUM, CCL22, CCL2, THBS2, COL1A2, MMP9, and CXCL8. Another cohort was used for validation. Finally, analysis of the miRNAs identified potential therapeutic targets. The MR results suggested that although there was no causal relationship between IBD and NAFLD, there were causal relationships between IL-17 and IBD and NAFLD. Conclusion We established a comorbid model to explain the potential mechanism of IBD with NAFLD and identified the chemokine-related pathway mediated by cytokine IL-17 as the core pathway in IBD with NAFLD, in which miRNA also plays a role and thus provides potential therapeutic targets.
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Affiliation(s)
| | - Jiangbin Wang
- Department of Digestive, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
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Shen Z, Zhang M, Liu Y, Ge C, Lu Y, Shen H, Zhu L. Prevalence of metabolic syndrome in patients with inflammatory bowel disease: a systematic review and meta-analysis. BMJ Open 2024; 14:e074659. [PMID: 38453206 PMCID: PMC10921521 DOI: 10.1136/bmjopen-2023-074659] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2023] [Accepted: 02/12/2024] [Indexed: 03/09/2024] Open
Abstract
OBJECTIVES Patients with inflammatory bowel disease (IBD) may experience comorbidities involving metabolic syndrome (MetS). However, this association remains controversial. Our objective was to estimate the prevalence of MetS in patients with IBD and assess whether MetS is more strongly associated with ulcerative colitis (UC) or Crohn's disease (CD). DESIGN Systematic review and meta-analysis. DATA SOURCES PubMed, Cochrane Library, Web of Science, EMBASE and MEDLINE were searched from their inception to July 2022. ELIGIBILITY CRITERIA Observational studies reporting data regarding the rate of comorbid MetS among patients with IBD and published in English. DATA EXTRACTION AND SYNTHESIS The Preferred Reporting Items for Systematic Reviews and Meta-Analyses and the Meta-analysis of Observational Studies in Epidemiology reporting guidelines were followed. Pooled prevalence, ORs and 95% CIs were calculated using random-effects models. The Newcastle-Ottawa Scale and the Agency for Healthcare Research and Quality checklist were used. Heterogeneity, sensitivity and stratified analyses were performed using R (V.4.2.1). RESULTS 11 eligible studies involving 2501 patients were included. Of these studies, four reported MetS prevalence separately by IBD phenotype, and only one contained a non-IBD comparison group. Overall, the methodological quality of the included studies was moderate. The pooled prevalence of MetS in IBD was 19.4% (95% CI 15.1% to 23.8%), with a moderate heterogeneity (I2=51.8%, Cochrane Q statistic=12.4, p=0.053). Stratified analyses demonstrated that the aggregate estimate of comorbid MetS was significantly higher in UC than in CD (38.2% vs 13.6%, χ2=4.88, p=0.03). We found a positive association between MetS and UC compared with CD (OR=2.11, 95% CI 1.19 to 3.74, p=0.01). Additionally, four studies identified that higher age was a risk factor associated with the development of MetS. CONCLUSIONS MetS is not rare in IBD, especially in UC. However, longitudinal studies are needed to further clarify the relationship between IBD and MetS. PROSPERO REGISTRATION NUMBER CRD42022346340.
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Affiliation(s)
- Zhaofeng Shen
- Department of Science and Technology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Mengyuan Zhang
- Department of Gastroenterology, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Yijing Liu
- Department of Gastroenterology, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Changchang Ge
- Department of Gastroenterology, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Yi Lu
- Department of Gastroenterology, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Hong Shen
- Department of Gastroenterology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Lei Zhu
- Department of Gastroenterology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
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7
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Gupta A, Vuyyuru SK, Kante B, Kumar P, Farooqui M, Ranjan MK, Singh N, Mundhra SK, Madan D, Golla R, Singh N, Makharia G, Kedia S, Ahuja V. "Prevalence, Predictors, and Impact of Hepatic Steatosis in Patients With Ulcerative Colitis: A Prospective Observational Cohort Study". J Clin Exp Hepatol 2024; 14:101293. [PMID: 38076443 PMCID: PMC10709497 DOI: 10.1016/j.jceh.2023.10.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Accepted: 10/10/2023] [Indexed: 09/27/2024] Open
Abstract
BACKGROUND AND AIMS There are no prospective studies evaluating effect of non-alcoholic fatty liver disease (NAFLD) in patients with ulcerative colitis (UC). This prospective observational study assessed the prevalence of NAFLD, its predictors, and its effect on long-term outcomes in UC. METHODS Consecutive UC patients underwent transient elastography, body composition analysis, bone densitometry, anthropometry, and baseline demographic and subjective global assessment. NAFLD was diagnosed by controlled attenuation parameter of >260 dB/m. To evaluate predictors and outcomes, patients of UC with NAFLD (n = 29) were compared with age- and sex-matched patients of UC without NAFLD (n = 27). RESULTS Among 107 patients of UC (mean age-29 ± 10.6 years; males = 56%, median disease duration-48 [interquartile range: 24-84] months, left sided/pancolitis = 84%), 27% (n = 29) had NAFLD. Patients with body mass index (BMI) > 23 kg/m2 had higher proportion of NAFLD than with normal or low BMI (54.7% [23/42] vs 10% [5/50] vs 6.7% [1/15]). Patients with NAFLD had high BMI (P < 0.001), waist circumference, and fat mass (P < 0.001) but similar fat-free mass (P = 0.798) compared to patients without NAFLD. There was no difference in immunosuppressant and cumulative steroid exposure between two groups. Dietary parameters including daily energy, protein, fat, and carbohydrate intake were similar between the two groups. On multivariate analysis, high BMI was found to be predictive and low socioeconomic status as a protective factor of NAFLD. On long-term follow-up of three years, there was no difference in steroid, or biologic requirement, disease-related hospitalization, or composite of all three outcomes between two groups. CONCLUSION The prevalence of NAFLD was found in nearly a quarter of patients of UC and was affected by metabolic parameters rather than disease activity.
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Affiliation(s)
- Arti Gupta
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Sudheer K. Vuyyuru
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Bhaskar Kante
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Peeyush Kumar
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Mariyam Farooqui
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Mukesh K. Ranjan
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Neha Singh
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Sandeep K. Mundhra
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Divya Madan
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Rithvik Golla
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Namrata Singh
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Govind Makharia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Saurabh Kedia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Vineet Ahuja
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
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Martínez-Domínguez SJ, García-Mateo S, Gargallo-Puyuelo CJ, Gallego Llera B, Refaie E, Callau P, Mendi C, Baptista PM, Hernández Ainsa M, Arroyo-Villarino MT, López de la Cruz J, Martínez-García J, Alfambra E, Simón Marco MÁ, Ampuero J, Gomollón F. Crohn´s disease is an independent risk factor for liver fibrosis in patients with inflammatory bowel disease and non-alcoholic fatty liver disease. Eur J Intern Med 2024; 120:99-106. [PMID: 37872034 DOI: 10.1016/j.ejim.2023.10.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Revised: 10/09/2023] [Accepted: 10/13/2023] [Indexed: 10/25/2023]
Abstract
BACKGROUND AND AIMS Controversial data have been reported regarding the prevalence of Non-Alcoholic Fatty Liver Disease (NAFLD) in Inflammatory Bowel Disease (IBD) population and IBD-related risk factors. The aim of the study was to assess the prevalence and risk factors associated with NAFLD and liver fibrosis in IBD participants compared with non-IBD controls. METHODS Cross-sectional, case-control study including 741 IBD cases and 170 non-IBD controls, matched by sex and age. All participants underwent liver ultrasound, transient elastography and laboratory tests. A logistic regression multivariable analysis was performed adjusting for classic metabolic risk factors and history of systemic steroid use. RESULTS The prevalence of NAFLD and significant liver fibrosis was 45 % and 10 % in IBD group, and 40 % and 2.9 % in non-IBD group (p = 0.255 and 0.062, respectively). Longer IBD duration (aOR 1.02 95% CI (1.001-1.04)) and older age at IBD diagnosis (aOR 1.02 95 % CI (1.001-1.04)) were independent risk factors for NAFLD in IBD group. Crohn´s Disease was an independent risk factor for significant liver fibrosis in participants with IBD and NAFLD (aOR 3.97 95 % CI (1.78-8.96)). NAFLD occurred at lower BMI levels in IBD group with NAFLD compared to non-IBD group with NAFLD (aOR 0.92 95 % CI (0.87-0.98)). CONCLUSIONS Although we found no differences in the prevalence of NAFLD and liver fibrosis between IBD group and non-IBD group, our findings suggest that liver fibrosis progression should be closely monitored in patients with concomitant CD and NAFLD, more in particular in those with long standing active disease.
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Affiliation(s)
- Samuel J Martínez-Domínguez
- Department of Gastroenterology, Lozano Blesa University Hospital, Zaragoza 50009, Spain; Aragón Health Research Institute (IIS Aragón), Zaragoza 50009, Spain; School of Medicine, University of Zaragoza, Zaragoza 50009, Spain.
| | - Sandra García-Mateo
- Department of Gastroenterology, Lozano Blesa University Hospital, Zaragoza 50009, Spain; Aragón Health Research Institute (IIS Aragón), Zaragoza 50009, Spain; School of Medicine, University of Zaragoza, Zaragoza 50009, Spain
| | - Carla J Gargallo-Puyuelo
- Department of Gastroenterology, Lozano Blesa University Hospital, Zaragoza 50009, Spain; Aragón Health Research Institute (IIS Aragón), Zaragoza 50009, Spain; School of Medicine, University of Zaragoza, Zaragoza 50009, Spain
| | | | - Engy Refaie
- Scuola di Specializzazione in Chirurgia Generale, Università degli Studi di Pavia Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Pilar Callau
- Primary care center "Delicias Sur", Zaragoza 50009, Spain
| | - Carolina Mendi
- Primary care center "Universitas", Zaragoza 50017, Spain
| | - Pedro M Baptista
- Aragón Health Research Institute (IIS Aragón), Zaragoza 50009, Spain; Biomedical Engineering Department Universidad Carlos III de Madrid, Madrid, Spain; Fundación ARAID (Fundación Agencia Aragonesa para la Investigación y el Desarrollo), Zaragoza 50018, Spain; CIBER Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid 28029, Spain
| | - María Hernández Ainsa
- Department of Gastroenterology, Lozano Blesa University Hospital, Zaragoza 50009, Spain; Aragón Health Research Institute (IIS Aragón), Zaragoza 50009, Spain
| | - María Teresa Arroyo-Villarino
- Department of Gastroenterology, Lozano Blesa University Hospital, Zaragoza 50009, Spain; Aragón Health Research Institute (IIS Aragón), Zaragoza 50009, Spain; School of Medicine, University of Zaragoza, Zaragoza 50009, Spain
| | - Julia López de la Cruz
- Department of Gastroenterology, Lozano Blesa University Hospital, Zaragoza 50009, Spain; Aragón Health Research Institute (IIS Aragón), Zaragoza 50009, Spain
| | - Javier Martínez-García
- Aragón Health Research Institute (IIS Aragón), Zaragoza 50009, Spain; School of Medicine, University of Zaragoza, Zaragoza 50009, Spain
| | - Erika Alfambra
- Aragón Health Research Institute (IIS Aragón), Zaragoza 50009, Spain
| | - Miguel Ángel Simón Marco
- Department of Gastroenterology, Lozano Blesa University Hospital, Zaragoza 50009, Spain; Aragón Health Research Institute (IIS Aragón), Zaragoza 50009, Spain; School of Medicine, University of Zaragoza, Zaragoza 50009, Spain
| | - Javier Ampuero
- Unit for the Clinical Management of Digestive Diseases, Virgen del Rocío University Hospital, Spain; Department of Medicine, University of Sevilla, Spain; Institute of Biomedicine of Sevilla, Spain; CIBER Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid 28029, Spain
| | - Fernando Gomollón
- Department of Gastroenterology, Lozano Blesa University Hospital, Zaragoza 50009, Spain; Aragón Health Research Institute (IIS Aragón), Zaragoza 50009, Spain; School of Medicine, University of Zaragoza, Zaragoza 50009, Spain; CIBER Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid 28029, Spain
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9
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Martínez-Domínguez SJ, García-Mateo S, Laredo V, Gargallo-Puyuelo CJ, Gallego Llera B, López de la Cruz J, Gomollón F. Liver Fibrosis in Non-Alcoholic Fatty Liver Disease and Progression to Hepatocellular Carcinoma in Patients with Inflammatory Bowel Disease: A Systematic Review. Cancers (Basel) 2023; 15:3367. [PMID: 37444477 DOI: 10.3390/cancers15133367] [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: 06/06/2023] [Accepted: 06/19/2023] [Indexed: 07/15/2023] Open
Abstract
The aim of the systematic review is to assess the prevalence and risk factors of liver fibrosis in patients with Inflammatory Bowel Disease (IBD) and Non-Alcoholic Fatty Liver Disease (NAFLD) and to discuss the role of liver fibrosis in the progression to hepatocellular carcinoma (HCC). We performed a structured search in PubMed, Web of Science, Embase, and Scopus up to 3 March 2023 to identify observational studies reporting liver fibrosis in patients with NAFLD and IBD. Quality of studies was assessed using the Newcastle-Ottawa Scale (NOS) score. A total of 23 studies met our inclusion criteria, including 629,781 patients. A total of 10 cross-sectional, 3 case-control, and 10 cohort studies were included. Fourteen studies had a NOS score ≥ 7 points. NAFLD was diagnosed in 2162/6332 (34.1%) IBD participants. However, NAFLD diagnosis was established in 924/2962 (31.2%) healthy individuals without IBD. Advanced liver fibrosis was found in 116 (11.6%) of 992 IBD patients with NAFLD. Most studies found an association between NAFLD and classic cardiovascular risk factors such as older age, male sex, higher BMI, diabetes, hypertension and dyslipidemia. In addition, metabolic syndrome features were also associated with an increased risk of significant and advanced liver fibrosis. Although no strong association between NAFLD and IBD therapy was reported, some studies associated NAFLD with IBD diagnosis, Crohn's Disease, a complicated course of IBD, disease activity, and IBD duration. Advanced liver fibrosis was also associated with Crohn's disease in several studies. In conclusion, NAFLD and advanced liver fibrosis are prevalent and clinically relevant extraintestinal manifestations, so its diagnosis and potential progression to HCC should be carefully considered in daily clinical practice.
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Affiliation(s)
- Samuel J Martínez-Domínguez
- Department of Gastroenterology, Lozano Blesa University Hospital, 50009 Zaragoza, Spain
- Aragón Health Research Institute (IIS Aragón), 50009 Zaragoza, Spain
- School of Medicine, University of Zaragoza, 50009 Zaragoza, Spain
| | - Sandra García-Mateo
- Department of Gastroenterology, Lozano Blesa University Hospital, 50009 Zaragoza, Spain
- Aragón Health Research Institute (IIS Aragón), 50009 Zaragoza, Spain
- School of Medicine, University of Zaragoza, 50009 Zaragoza, Spain
| | - Viviana Laredo
- Department of Gastroenterology, Lozano Blesa University Hospital, 50009 Zaragoza, Spain
- Aragón Health Research Institute (IIS Aragón), 50009 Zaragoza, Spain
- School of Medicine, University of Zaragoza, 50009 Zaragoza, Spain
| | - Carla J Gargallo-Puyuelo
- Department of Gastroenterology, Lozano Blesa University Hospital, 50009 Zaragoza, Spain
- Aragón Health Research Institute (IIS Aragón), 50009 Zaragoza, Spain
- School of Medicine, University of Zaragoza, 50009 Zaragoza, Spain
| | | | - Julia López de la Cruz
- Department of Gastroenterology, Lozano Blesa University Hospital, 50009 Zaragoza, Spain
- Aragón Health Research Institute (IIS Aragón), 50009 Zaragoza, Spain
- School of Medicine, University of Zaragoza, 50009 Zaragoza, Spain
| | - Fernando Gomollón
- Department of Gastroenterology, Lozano Blesa University Hospital, 50009 Zaragoza, Spain
- Aragón Health Research Institute (IIS Aragón), 50009 Zaragoza, Spain
- School of Medicine, University of Zaragoza, 50009 Zaragoza, Spain
- CIBER for Liver and Digestive Diseases (CIBERehd), 28029 Madrid, Spain
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10
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Jarmakiewicz-Czaja S, Gruszecka J, Filip R. What Do NAFLD, Liver Fibrosis, and Inflammatory Bowel Disease Have in Common? Review of the Current Literature. Metabolites 2023; 13:metabo13030378. [PMID: 36984818 PMCID: PMC10051776 DOI: 10.3390/metabo13030378] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Revised: 02/22/2023] [Accepted: 02/27/2023] [Indexed: 03/08/2023] Open
Abstract
Liver disease is one of the most common extraintestinal manifestations of inflammatory bowel disease (IBD). Often the course of liver disease is associated with an exacerbation of the underlying disease (Crohn’s Disease/Ulcerative Colitis). Nonalcoholic steatohepatitis encompasses a wide spectrum of liver damage. The most common form is nonalcoholic fatty liver disease (NAFLD) (75–80%), and the less common but more dangerous form is nonalcoholic steatohepatitis (NASH). NAFLD is now the most common cause of chronic liver disease in developed countries and the leading indication for liver transplantation in the United States. Genetic, demographic, clinical, and environmental factors can play a role in the pathogenesis of NAFLD. The increasing prevalence of NAFLD is associated with a widespread obesity epidemic, metabolic complications, including hypertension, type 2 diabetes, and dyslipidaemia. Some of the most common manifestations of IBD are liver, biliary tract, and gallbladder diseases. The liver fibrosis process has a complex pathophysiology and is often dependent on exogenous factors such as the treatment used and endogenous factors such as the gut microbiome. However, the factors that link IBD and liver fibrosis are not yet clear. The main purpose of the review is to try to find links between IBD and selected liver diseases and to identify knowledge gaps that will inform further research.
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Affiliation(s)
| | - Jolanta Gruszecka
- Institute of Health Sciences, Medical College of Rzeszow University, 35-959 Rzeszow, Poland
- Department of Clinical Microbiology, Clinical Hospital No. 2, 35-959 Rzeszow, Poland
| | - Rafał Filip
- Institute of Medicine, Medical College of Rzeszow University, 35-959 Rzeszow, Poland
- Department of Gastroenterology with IBD Unit, Clinical Hospital No. 2, 35-959 Rzeszow, Poland
- Correspondence:
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11
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Cassotta M, Cianciosi D, De Giuseppe R, Navarro-Hortal MD, Armas Diaz Y, Forbes-Hernández TY, Pifarre KT, Pascual Barrera AE, Grosso G, Xiao J, Battino M, Giampieri F. Possible role of nutrition in the prevention of inflammatory bowel disease-related colorectal cancer: A focus on human studies. Nutrition 2023; 110:111980. [PMID: 36965240 DOI: 10.1016/j.nut.2023.111980] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 01/10/2023] [Accepted: 01/22/2023] [Indexed: 02/05/2023]
Abstract
Patients with inflammatory bowel disease (IBD) are at substantially high risk for colorectal cancer (CRC). IBD-associated CRC accounts for roughly 10% to 15% of the annual mortality in patients with IBD. IBD-related CRC also affects younger patients compared with sporadic CRC, with a 5-y survival rate of 50%. Regardless of medical therapies, the persistent inflammatory state characterizing IBD raises the risk for precancerous changes and CRC, with additional input from several elements, including genetic and environmental risk factors, IBD-associated comorbidities, intestinal barrier dysfunction, and gut microbiota modifications. It is well known that nutritional habits and dietary bioactive compounds can influence IBD-associated inflammation, microbiome abundance and composition, oxidative stress balance, and gut permeability. Additionally, in recent years, results from broad epidemiologic and experimental studies have associated certain foods or nutritional patterns with the risk for colorectal neoplasia. The present study aimed to review the possible role of nutrition in preventing IBD-related CRC, focusing specifically on human studies. It emerges that nutritional interventions based on healthy, nutrient-dense dietary patterns characterized by a high intake of fiber, vegetables, fruit, ω-3 polyunsaturated fatty acids, and a low amount of animal proteins, processed foods, and alcohol, combined with probiotic supplementation have the potential of reducing IBD-activity and preventing the risk of IBD-related CRC through different mechanisms, suggesting that targeted nutritional interventions may represent a novel promising approach for the prevention and management of IBD-associated CRC.
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Affiliation(s)
- Manuela Cassotta
- Research Group on Food, Nutritional Biochemistry and Health, Universidad Europea del Atlántico, Santander, Spain
| | - Danila Cianciosi
- Department of Clinical Sciences, Faculty of Medicine, Polytechnic University of Marche, Ancona, Italy
| | - Rachele De Giuseppe
- Laboratory of Dietetics and Clinical Nutrition, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, Pavia, Italy; NBFC, National Biodiversity Future Center, Palermo 90133, Italy
| | - Maria Dolores Navarro-Hortal
- Biomedical Research Centre, Institute of Nutrition and Food Technology "José Mataix Verdú," Department of Physiology, Faculty of Pharmacy, University of Granada, Armilla, Granada, Spain
| | - Yasmany Armas Diaz
- Department of Clinical Sciences, Faculty of Medicine, Polytechnic University of Marche, Ancona, Italy
| | - Tamara Yuliett Forbes-Hernández
- Biomedical Research Centre, Institute of Nutrition and Food Technology "José Mataix Verdú," Department of Physiology, Faculty of Pharmacy, University of Granada, Armilla, Granada, Spain
| | - Kilian Tutusaus Pifarre
- Research Group on Food, Nutritional Biochemistry and Health, Universidad Europea del Atlántico, Santander, Spain; Project Department, Universidade Internacional do Cuanza, Cuito, Bié, Angola
| | - Alina Eugenia Pascual Barrera
- Research Group on Food, Nutritional Biochemistry and Health, Universidad Europea del Atlántico, Santander, Spain; Department of Project Management, Universidad Internacional Iberoamericana, Campeche, Mexico
| | - Giuseppe Grosso
- Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
| | - Jianbo Xiao
- Nutrition and Bromatology Group, Department of Analytical Chemistry and Food Science, Faculty of Food Science and Technology, Universidade de Vigo - Ourense Campus, Ourense, Spain
| | - Maurizio Battino
- Research Group on Food, Nutritional Biochemistry and Health, Universidad Europea del Atlántico, Santander, Spain; Department of Clinical Sciences, Faculty of Medicine, Polytechnic University of Marche, Ancona, Italy; International Joint Research Laboratory of Intelligent Agriculture and Agri-products Processing, Jiangsu University, Zhenjiang, China
| | - Francesca Giampieri
- Research Group on Food, Nutritional Biochemistry and Health, Universidad Europea del Atlántico, Santander, Spain.
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12
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Papaefthymiou A, Potamianos S, Goulas A, Doulberis M, Kountouras J, Polyzos SA. Inflammatory Bowel Disease-associated Fatty Liver Disease: the Potential Effect of Biologic Agents. J Crohns Colitis 2022; 16:852-862. [PMID: 34972203 DOI: 10.1093/ecco-jcc/jjab212] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2021] [Revised: 09/02/2021] [Accepted: 11/19/2021] [Indexed: 01/16/2023]
Abstract
Inflammatory bowel diseases [IBD] exhibit intestinal and systemic manifestations. Nonalcoholic fatty liver disease [NAFLD] is a common co-existing condition, possibly contributing to the cardio-metabolic burden and overall morbidity. Εmerging therapeutic choices of biologic agents have modified the clinical course of IBD; however, their impact on IBD-associated NAFLD has not been extensively evaluated. The prevalence of NAFLD varies among IBD patients, but it appears higher than in the general population in the majority of quality studies. In terms of pathogenetic and risk factors of NAFLD, they may vary with IBD activity. Dysbiosis, mucosal damage, and cytokine release have been implicated in the pathogenesis during the relapses, whereas metabolic risk factors seem to play a dominant role during the remissions of IBD. Considering biologics, although quality data are scarce, agents suppressing tumour necrosis factor may offer potential benefits in IBD-associated NAFLD, whereas anti-integrins do not appear to confer any therapeutic advantage. In conclusion, IBD-associated NAFLD possibly follows two different patterns, one manifested during the relapses and one during the remissions of IBD. Some, but not all, biologics may benefit NAFLD in patients with IBD. Further mechanistic and prospective cohort studies are warranted to illuminate the effects of various biologics on NAFLD.
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Affiliation(s)
- Apostolis Papaefthymiou
- Department of Gastroenterology, University Hospital of Larisa, Larisa, Thessaly, Greece.,First Laboratory of Pharmacology, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece
| | - Spyros Potamianos
- Department of Gastroenterology, University Hospital of Larisa, Larisa, Thessaly, Greece
| | - Antonis Goulas
- First Laboratory of Pharmacology, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece
| | - Michael Doulberis
- First Laboratory of Pharmacology, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece.,Division of Gastroenterology and Hepatology, Medical University Department, Kantonsspital Aarau, Aarau, Switzerland
| | - Jannis Kountouras
- Second Medical Clinic, Ippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece
| | - Stergios A Polyzos
- First Laboratory of Pharmacology, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece
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13
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Chen L, Fan Z, Sun X, Qiu W, Chen Y, Zhou J, Lv G. Mendelian Randomization Rules Out Causation Between Inflammatory Bowel Disease and Non-Alcoholic Fatty Liver Disease. Front Pharmacol 2022; 13:891410. [PMID: 35662732 PMCID: PMC9161361 DOI: 10.3389/fphar.2022.891410] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Accepted: 04/05/2022] [Indexed: 11/30/2022] Open
Abstract
Background: Inflammatory bowel disease (IBD) and non-alcoholic fatty liver disease (NAFLD) usually co-exist clinically. However, whether such association is causal is still unknown. Methods: Genetic variants were extracted as instrumental variables from the largest genome-wide association study (GWAS) of IBD, Crohn’s disease (CD) and ulcerative colitis (UC) with 25,042 cases and 34,915 controls (GWAS p-value < 5 × 10−8). Information of genetic variants in NAFLD was extracted from a GWAS with 1,483 cases and 17,781controls. Also, liver fat content (LFC) was included as the outcome. Then, a bi-direction Mendelian randomization (MR) was carried out to appraise the causal relationship between NAFLD on IBD. Besides, a multivariable MR (MVMR) design was carried to adjust for body mass index (BMI) and type 2 diabetes (T2D) as well. Results: Generally, IBD might not affect the risk of NAFLD (OR = 0.994 [0.970, 1.019]), together with its subtypes including UC and CD. However, genetically-elevated risk of IBD might cause liver fat accumulation (beta = 0.019, p-value = 0.016) while turning insignificant at Bonferroni correction. Besides, no causal effect of NAFLD on IBD was observed (OR = 0.968 [0.928, 1.009]), together with UC and CD. Also, genetically-elevated LFC could not impact IBD, UC and CD either. The MR CAUSE analysis supported these null associations and MVMR analysis also supported such null associations even after adjusting for BMI and T2D. Conclusion: This MR study ruled out the causal relationship between IBD and NAFLD, suggesting therapeutics targeting NAFLD might not work for IBD and vice versa.
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14
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Glucocorticosteroids and the Risk of NAFLD in Inflammatory Bowel Disease. Can J Gastroenterol Hepatol 2022; 2022:4344905. [PMID: 35600209 PMCID: PMC9117063 DOI: 10.1155/2022/4344905] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Accepted: 04/13/2022] [Indexed: 02/08/2023] Open
Abstract
Each year, the incidence of nonalcoholic fatty liver (NAFLD) disease increases. NAFLD is a chronic disease. One of the most common causes of NAFLD is an inadequate lifestyle, which is characterized by a lack or low physical activity and eating highly processed foods rich in saturated fat and salt and containing low amount of fiber. Moreover, disturbances in intestinal microbiome and the use of certain drugs may predispose to NAFLD. NAFLD is an increasingly described disease in patients with inflammatory bowel disease (IBD). Recent data also indicate a frequent coexistence of metabolic syndrome in this group of patients. Certain groups of drugs also increase the risk of developing inflammation, liver fibrosis, and cirrhosis. Particularly important in the development of NAFLD are steroids, which are used in the treatment of many diseases, for example, IBD. NAFLD is one of the most frequent parenteral manifestations of the disease in IBD patients. However, there is still insufficient information on what dose and exposure time of selected types of steroids may lead to the development of NAFLD. It is necessary to conduct further research in this direction. Therefore, patients with IBD should be constantly monitored for risk factors for the development of NAFLD.
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15
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van Lingen E, Tushuizen ME, Steenhuis MEJ, van Deynen T, Martens J, Morales DDI, van der Meulen-de Jong AE, Molendijk I, van der Marel S, Maljaars PWJ. Disease activity in inflammatory bowel disease patients is associated with increased liver fat content and liver fibrosis during follow-up. Int J Colorectal Dis 2022; 37:349-356. [PMID: 34791524 DOI: 10.1007/s00384-021-04065-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/05/2021] [Indexed: 02/04/2023]
Abstract
PURPOSE Liver steatosis is a frequently reported condition in patients with inflammatory bowel disease (IBD). Different factors, both metabolic and IBD-associated, are believed to contribute to the pathogenesis. The aim of our study was to calculate the prevalence of liver steatosis and fibrosis in IBD patients and to evaluate which factors influence changes in steatosis and fibrosis during follow-up. METHODS From June 2017 to February 2018, demographic and biochemical data was collected at baseline and after 6-12 months. Measured by transient elastography (FibroScan), liver steatosis was defined as Controlled Attenuation Parameter (CAP) ≥248 and fibrosis as liver stiffness value (Emed) ≥7.3 kPa. IBD disease activity was defined as C-reactive protein (CRP) ≥10 mg/l and/or fecal calprotectin (FCP) ≥150 μg/g. Univariate and multivariate regression analysis was performed; a p-value of ≤0.05 was considered significant. RESULTS Eighty-two out of 112 patients were seen for follow-up; 56% were male. The mean age was 43 ± 16.0 years, and mean BMI was 25.1 ± 4.7 kg/m2. The prevalence of liver steatosis was 40% and of fibrosis was 20%. At baseline, 26 patients (32%) had an active episode of IBD. Using a multivariate analysis, disease activity at baseline was associated with an increase in liver steatosis (B = 37, 95% CI 4.31-69.35, p = 0.027) and liver fibrosis (B = 1.2, 95% CI 0.27-2.14, p = 0.016) during follow-up. CONCLUSIONS This study confirms the relatively high prevalence of liver steatosis and fibrosis in IBD patients. We demonstrate that active IBD at baseline is associated with both an increase in liver steatosis and fibrosis during follow-up.
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Affiliation(s)
- E van Lingen
- Department of Gastroenterology and Hepatology, Leiden University Medical Center (LUMC), Leiden, The Netherlands.
| | - M E Tushuizen
- Department of Gastroenterology and Hepatology, Leiden University Medical Center (LUMC), Leiden, The Netherlands
| | - M E J Steenhuis
- Department of Gastroenterology and Hepatology, Leiden University Medical Center (LUMC), Leiden, The Netherlands
| | - T van Deynen
- Department of Gastroenterology and Hepatology, Leiden University Medical Center (LUMC), Leiden, The Netherlands
| | - J Martens
- Department of Gastroenterology and Hepatology, Leiden University Medical Center (LUMC), Leiden, The Netherlands
| | - D Diaz-Infante Morales
- Department of Gastroenterology and Hepatology, Leiden University Medical Center (LUMC), Leiden, The Netherlands
| | - A E van der Meulen-de Jong
- Department of Gastroenterology and Hepatology, Leiden University Medical Center (LUMC), Leiden, The Netherlands
| | - I Molendijk
- Department of Gastroenterology and Hepatology, Leiden University Medical Center (LUMC), Leiden, The Netherlands
| | - S van der Marel
- Department of Gastroenterology and Hepatology, Haaglanden Medical Center (HMC), The Hague, The Netherlands
| | - P W J Maljaars
- Department of Gastroenterology and Hepatology, Leiden University Medical Center (LUMC), Leiden, The Netherlands
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16
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Perez-Carreras M, Casis-Herce B, Rivera R, Fernandez I, Martinez-Montiel P, Villena V. Non-alcoholic fatty liver disease in patients with intestinal, pulmonary or skin diseases: Inflammatory cross-talk that needs a multidisciplinary approach. World J Gastroenterol 2021; 27:7113-7124. [PMID: 34887631 PMCID: PMC8613653 DOI: 10.3748/wjg.v27.i41.7113] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Revised: 07/04/2021] [Accepted: 09/16/2021] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is currently considered the most common cause of liver disease. Its prevalence is increasing in parallel with the obesity and type 2 diabetes mellitus (DM2) epidemics in developed countries. Several recent studies have suggested that NAFLD may be the hepatic manifestation of a systemic inflammatory metabolic disease that also affects other organs, such as intestine, lungs, skin and vascular endothelium. It appears that local and systemic proinflammatory/anti-inflammatory cytokine imbalance, together with insulin resistance and changes in the intestinal microbiota, are pathogenic mechanisms shared by NAFLD and other comorbidities. NAFLD is more common in patients with extrahepatic diseases such as inflammatory bowel disease (IBD), obstructive syndrome apnea (OSA) and psoriasis than in the general population. Furthermore, there is evidence that this association has a negative impact on the severity of liver lesions. Specific risk characteristics for NAFLD have been identified in populations with IBD (i.e. age, obesity, DM2, previous bowel surgery, IBD evolution time, methotrexate treatment), OSA (i.e. obesity, DM2, OSA severity, increased transaminases) and psoriasis (i.e. age, metabolic factors, severe psoriasis, arthropathy, elevated transaminases, methotrexate treatment). These specific phenotypes might be used by gastroenterologists, pneumologists and dermatologists to create screening algorithms for NAFLD. Such algorithms should include non-invasive markers of fibrosis used in NAFLD to select subjects for referral to the hepatologist. Prospective, controlled studies in NAFLD patients with extrahepatic comorbidities are required to demonstrate a causal relationship and also that appropriate multidisciplinary management improves these patients’ prognosis and survival.
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Affiliation(s)
- Mercedes Perez-Carreras
- Gastroenterology and Hepatology Unit, 12 de Octubre Universitary Hospital, Madrid 28041, Spain
- Faculty of Medicine, Complutense University, Madrid 28040, Spain
| | - Begoña Casis-Herce
- Gastroenterology and Hepatology Unit, 12 de Octubre Universitary Hospital, Madrid 28041, Spain
- Faculty of Medicine, Complutense University, Madrid 28040, Spain
| | - Raquel Rivera
- Faculty of Medicine, Complutense University, Madrid 28040, Spain
- Dermatology Department, 12 de Octubre Universitary Hospital, Madrid 28041, Spain
| | - Inmaculada Fernandez
- Gastroenterology and Hepatology Unit, 12 de Octubre Universitary Hospital, Madrid 28041, Spain
- Faculty of Medicine, Complutense University, Madrid 28040, Spain
| | - Pilar Martinez-Montiel
- Gastroenterology and Hepatology Unit, 12 de Octubre Universitary Hospital, Madrid 28041, Spain
- Faculty of Medicine, Complutense University, Madrid 28040, Spain
| | - Victoria Villena
- Faculty of Medicine, Complutense University, Madrid 28040, Spain
- Pneumology Service, 12 de Octubre Universitary Hospital, Madrid 28041, Spain
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17
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Ritaccio G, Stoleru G, Abutaleb A, Cross RK, Shetty K, Sakiani S, Wong U. Nonalcoholic Fatty Liver Disease Is Common in IBD Patients However Progression to Hepatic Fibrosis by Noninvasive Markers Is Rare. Dig Dis Sci 2021; 66:3186-3191. [PMID: 32894439 PMCID: PMC7936981 DOI: 10.1007/s10620-020-06588-6] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2020] [Accepted: 08/26/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder in western countries and an increasing cause of end-stage liver disease and hepatocellular carcinoma. NAFLD is known to coexist in patients with inflammatory bowel disease (IBD). This study aims to examine the prevalence of NAFLD, as well as trends in NAFLD-associated fibrosis, in a well-characterized IBD cohort utilizing a validated noninvasive test. METHODS We conducted a single-center retrospective chart review of patients at a large academic IBD center between 2007 and 2017. Patients with IBD and concurrent hepatic steatosis were identified. Charts were reviewed for baseline characteristics and laboratory data in order to calculate and trend NAFLD progression over time by a noninvasive marker, the NAFLD fibrosis score (NFS). RESULTS Of 207 patients with IBD and concurrent NAFLD, NFS was able to be calculated for 138 patients at index diagnosis. A subsequent NFS was able to be calculated at 5-year follow-up for 56 patients. Over 5 years, 9 patients (16%) had worsening in NFS category, 4 patients (7%) had improvement in NFS category, and the remaining 43 patients (77%) stayed within their index NFS category. CONCLUSIONS IBD patients with NAFLD tend to have stable liver disease over 4-6 years, and the risk of liver disease progression is low. This is the first study to document the progression of NAFLD by noninvasive testing over time.
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Affiliation(s)
- Gabrielle Ritaccio
- Department of Medicine, University of Maryland Medical Center, Baltimore, MD, USA
| | - Gianna Stoleru
- Department of Medicine, University of Maryland Medical Center, Baltimore, MD, USA
| | - Ameer Abutaleb
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Maryland School of Medicine, 685 West Baltimore Street, #8-00, Baltimore, MD, 21201, USA
| | - Raymond K Cross
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Maryland School of Medicine, 685 West Baltimore Street, #8-00, Baltimore, MD, 21201, USA
| | - Kirti Shetty
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Maryland School of Medicine, 685 West Baltimore Street, #8-00, Baltimore, MD, 21201, USA
| | - Sasan Sakiani
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Maryland School of Medicine, 685 West Baltimore Street, #8-00, Baltimore, MD, 21201, USA
| | - Uni Wong
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Maryland School of Medicine, 685 West Baltimore Street, #8-00, Baltimore, MD, 21201, USA.
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18
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Arrested Development: Slow Progression of Fibrosis in Patients with NAFLD and IBD. Dig Dis Sci 2021; 66:2853-2854. [PMID: 33089485 DOI: 10.1007/s10620-020-06672-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/09/2020] [Indexed: 12/09/2022]
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19
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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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20
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Hoffmann P, Jung V, Behnisch R, Gauss A. Prevalence and risk factors of nonalcoholic fatty liver disease in patients with inflammatory bowel diseases: A cross-sectional and longitudinal analysis. World J Gastroenterol 2020; 26:7367-7381. [PMID: 33362390 PMCID: PMC7739163 DOI: 10.3748/wjg.v26.i46.7367] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Revised: 11/03/2020] [Accepted: 11/21/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is common in the German population, with an even higher prevalence in inflammatory bowel disease patients.
AIM To investigate the risk factors for NAFLD in inflammatory bowel disease patients.
METHODS This monocentric retrospective study with a cross-sectional and a longitudinal part included 694 patients. Inclusion criteria were diagnosed inflammatory bowel disease, age ≥ 18 years, availability of at least one abdominal ultrasound. Patients with infectious or suspected alcoholic fatty liver disease were excluded. NAFLD was defined by increased echogenicity at liver ultrasound. Demographic characteristics, disease activity and medications were analyzed as potential risk factors. Parameters influencing the course of NAFLD were identified by a generalized linear mixed model.
RESULTS Forty-eight percent of Crohn’s disease (CD) patients and 44% of ulcerative colitis patients suffered from NAFLD. Its occurrence was associated with greater age, hypertension and body mass index (BMI) in both groups, and with higher disease activity and dyslipidemia in CD. 2467 ultrasound results were included in the longitudinal analysis. Risk factors for NAFLD were age, BMI, higher disease activity, bowel resection(s), endoscopic activity and azathioprine use in CD; and BMI and endoscopic activity in ulcerative colitis.
CONCLUSION NAFLD was highly prevalent in this cohort of German inflammatory bowel disease patients. Its risk increased mainly with rising age and BMI. This analysis provides a rationale for non-invasive liver screening in inflammatory bowel disease patients.
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Affiliation(s)
- Peter Hoffmann
- Department of Gastroenterology and Hepatology, University Hospital Heidelberg, Heidelberg 69120, Germany
| | - Victoria Jung
- Department of Gastroenterology and Hepatology, University Hospital Heidelberg, Heidelberg 69120, Germany
| | - Rouven Behnisch
- Institute of Medical Biometry and Informatics, University Hospital Heidelberg, Heidelberg 69120, Germany
| | - Annika Gauss
- Department of Gastroenterology and Hepatology, University Hospital Heidelberg, Heidelberg 69120, Germany
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21
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Abstract
Non-alcoholic fatty liver disease is a highly prevalent medical condition, characterized by intrahepatic fat accumulation which may eventually lead to hepatic inflammation, cell death and reactive fibrosis. Obesity and metabolic disturbances constitute significant contributors to liver steatosis pathogenesis, however, there is a growing awareness that fatty liver may emerge even in normal weight or metabolically healthy individuals. In recent years, advanced imaging techniques have revealed that liver steatosis is quite common in inflammatory bowel disease patients, suggesting that intestinal inflammation and disturbances of the liver-gut axis may also play a key role in non-alcoholic fatty liver disease pathophysiology. The current review focuses on the co-occurrence of the two disorders, integrating research findings on epidemiology, clinical characteristics and common pathophysiological processes. The study of liver steatosis in inflammatory bowel disease patients may provide useful insights on the complex links between dietary fat intake, metabolic dysregulation, gut physiology and intrahepatic cellular mechanisms underlying liver inflammation and damage.
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22
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23
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Szilagyi A. Relationship(s) between obesity and inflammatory bowel diseases: possible intertwined pathogenic mechanisms. Clin J Gastroenterol 2019; 13:139-152. [PMID: 31452062 PMCID: PMC7101293 DOI: 10.1007/s12328-019-01037-y] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2019] [Accepted: 08/15/2019] [Indexed: 12/17/2022]
Abstract
The inflammatory bowel diseases, Crohn's and ulcerative colitis have increased in incidence and prevalence from the mid-eighteen to the late nineteen centuries. From then to the current twenty-first century there has been a more rapid expansion of these disease to areas previously experiencing low rates. This latter expansion coincides with the current obesity pandemic which also began toward the end of the last century. Although the two diseases have radically different frequencies, there are interesting links between them. Four areas link the diseases. On an epidemiological level, IBD tends to follow a north-south gradient raising the importance of vitamin D in protection. Obesity has very weak relationship with latitude, but both diseases follow adult lactase distributions colliding in this plane. Is it possible that obesity (a low vitamin D condition with questionable response to supplements) reduces effects in IBD? On a pathogenic level, pro-inflammatory processes mark both IBD and obesity. The similarity raises the question of whether obesity could facilitate the development of IBD. Features of the metabolic syndrome occur in both, with or without obesity in IBD. The fourth interaction between the two diseases is the apparent effect of obesity on the course of IBD. There are suggestions that obesity may reduce the efficacy of biologic agents. Yet there is some suggestion also that obesity may reduce the need for hospitalization and surgery. The apparent co-expansion of both obesity and IBD suggests similar environmental changes may be involved in the promotion of both.
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Affiliation(s)
- Andrew Szilagyi
- Division of Gastroenterology, Department of Medicine, Jewish General Hospital, McGill University Medical School, 3755 Cote St Catherine Rd, Room E110, Montreal, QC, H3T 1E2, Canada.
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24
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Likhitsup A, Dundulis J, Ansari S, Patibandla S, Hutton C, Kennedy K, Helzberg JH, Chhabra R. High prevalence of non-alcoholic fatty liver disease in patients with inflammatory bowel disease receiving anti-tumor necrosis factor therapy. Ann Gastroenterol 2019; 32:463-468. [PMID: 31474792 PMCID: PMC6686093 DOI: 10.20524/aog.2019.0405] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2019] [Accepted: 06/25/2019] [Indexed: 02/07/2023] Open
Abstract
Background: Non-alcoholic fatty liver disease (NAFLD) is common in patients with inflammatory bowel disease (IBD). This study evaluated the prevalence of NAFLD and the associated risk factors among IBD patients who received anti-tumor necrosis factor (TNF) therapy. Methods: Adult IBD patients receiving anti-TNF therapy (infliximab, adalimumab, certolizumab, golimumab) were enrolled. Hepatic steatosis was assessed by abdominal ultrasound. Patients with a history of excessive alcohol or recent steroid use were excluded. Univariate and multivariate analysis were performed. Results: Eighty patients, 55% male, mean age 42±15 years, were enrolled. The sonographic prevalence of NAFLD was 54% (43/80), significantly higher than the general prevalence in the US adult population (30%) (P<0.0001). NAFLD patients had a significantly higher proportion of males, as well as greater body weight and body mass index, compared to non-NAFLD. The Crohns disease activity index (CDAI) was significantly higher among patients with NAFLD. Multivariate analysis demonstrated that a higher CDAI was independently associated with NAFLD, with an odds ratio of 1.6 (95% confidence interval 1.05-2.44; P=0.03). Conclusions: The presence of IBD is strongly associated with NAFLD. We identified a high prevalence of NAFLD among IBD patients receiving anti-TNF. CDAI was independently associated with hepatic steatosis. Further studies are still needed to evaluate the pathophysiology of NAFLD development and disease progression among IBD populations.
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Affiliation(s)
- Alisa Likhitsup
- University of Missouri Kansas City (Alisa Likhitsup, Jason Dundulis, Shaya Ansari, Sruthi Patibandla, John H. Helzberg, Rajiv Chhabra).,Saint Luke's Hospital of Kansas City (Alisa Likhitsup, Jason Dundulis, Shaya Ansari, John H. Helzberg, Rajiv Chhabra)
| | - Jason Dundulis
- University of Missouri Kansas City (Alisa Likhitsup, Jason Dundulis, Shaya Ansari, Sruthi Patibandla, John H. Helzberg, Rajiv Chhabra).,Saint Luke's Hospital of Kansas City (Alisa Likhitsup, Jason Dundulis, Shaya Ansari, John H. Helzberg, Rajiv Chhabra)
| | - Shaya Ansari
- University of Missouri Kansas City (Alisa Likhitsup, Jason Dundulis, Shaya Ansari, Sruthi Patibandla, John H. Helzberg, Rajiv Chhabra).,Saint Luke's Hospital of Kansas City (Alisa Likhitsup, Jason Dundulis, Shaya Ansari, John H. Helzberg, Rajiv Chhabra)
| | - Sruthi Patibandla
- University of Missouri Kansas City (Alisa Likhitsup, Jason Dundulis, Shaya Ansari, Sruthi Patibandla, John H. Helzberg, Rajiv Chhabra)
| | - Colleen Hutton
- Mid-America Heart Institute St. Luke's Health System (Colleen Hutton, Kevin Kennedy), Kansas City, MO, USA
| | - Kevin Kennedy
- Mid-America Heart Institute St. Luke's Health System (Colleen Hutton, Kevin Kennedy), Kansas City, MO, USA
| | - John H Helzberg
- University of Missouri Kansas City (Alisa Likhitsup, Jason Dundulis, Shaya Ansari, Sruthi Patibandla, John H. Helzberg, Rajiv Chhabra).,Saint Luke's Hospital of Kansas City (Alisa Likhitsup, Jason Dundulis, Shaya Ansari, John H. Helzberg, Rajiv Chhabra)
| | - Rajiv Chhabra
- University of Missouri Kansas City (Alisa Likhitsup, Jason Dundulis, Shaya Ansari, Sruthi Patibandla, John H. Helzberg, Rajiv Chhabra).,Saint Luke's Hospital of Kansas City (Alisa Likhitsup, Jason Dundulis, Shaya Ansari, John H. Helzberg, Rajiv Chhabra)
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25
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Likhitsup A, Dundulis J, Ansari S, El-Halawany H, Michelson R, Hutton C, Kennedy K, Helzberg JH, Chhabra R. Prevalence of non-alcoholic fatty liver disease on computed tomography in patients with inflammatory bowel disease visiting an emergency department. Ann Gastroenterol 2019; 32:283-286. [PMID: 31040626 PMCID: PMC6479650 DOI: 10.20524/aog.2019.0371] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2019] [Accepted: 02/01/2019] [Indexed: 12/13/2022] Open
Abstract
Background Non-alcoholic fatty liver disease (NAFLD) is common in patients with inflammatory bowel disease (IBD). The purpose of this study was to further examine the prevalence of NAFLD in IBD patients. Methods We retrospectively reviewed the medical records of IBD patients who visited the emergency department because of abdominal pain between January 2009 and December 2014. These were compared with a group of 70 controls without IBD, matched for age and body mass index (BMI). Computed tomography data were analyzed for the presence or absence of hepatic steatosis. Patient with recent steroid or excessive alcohol use were excluded. Univariate and multivariate analyses were performed. Results NAFLD prevalence was 44% (31/70) in the IBD group vs. 16% (11/70) in controls (P<0.001). There was no significant difference between the 2 groups in age, sex distribution, BMI, presence of diabetes, or levels of serum transaminases, serum albumin or platelets. In multivariate analysis, the presence of IBD was independently associated with NAFLD (odds ratio 4.53, 95% confidence interval 2.00-10.26; P=0.002). Conclusions The presence of IBD is strongly and independently associated with NAFLD. Systemic inflammation and alteration of the intestinal microbiome have been proposed as mechanisms, but further studies are needed to better elucidate the pathophysiology.
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Affiliation(s)
- Alisa Likhitsup
- Department of Gastroenterology and Hepatology, University of Missouri Kansas City (Alisa Likhitsup, Jason Dundulis, Hani El-Halawany, Randal Michelson, John H. Helzberg, Rajiv Chhabra).,Department of Gastroenterology and Hepatology, Saint Luke's Hospital of Kansas City (Alisa Likhitsup, John H. Helzberg, Rajiv Chhabra)
| | - Jason Dundulis
- Department of Gastroenterology and Hepatology, University of Missouri Kansas City (Alisa Likhitsup, Jason Dundulis, Hani El-Halawany, Randal Michelson, John H. Helzberg, Rajiv Chhabra)
| | - Shaya Ansari
- Department of Radiology, University of Missouri Kansas City (Shaya Ansari)
| | - Hani El-Halawany
- Department of Gastroenterology and Hepatology, University of Missouri Kansas City (Alisa Likhitsup, Jason Dundulis, Hani El-Halawany, Randal Michelson, John H. Helzberg, Rajiv Chhabra)
| | - Randal Michelson
- Department of Gastroenterology and Hepatology, University of Missouri Kansas City (Alisa Likhitsup, Jason Dundulis, Hani El-Halawany, Randal Michelson, John H. Helzberg, Rajiv Chhabra)
| | - Colleen Hutton
- Department of Clinical Research, Mid-America Heart Institute St. Luke's Health System (Colleen Hutton)
| | - Kevin Kennedy
- Department of Biostatistics, Mid-America Heart Institute St. Luke's Health System (Kevin Kennedy), Kansas City, MO, USA
| | - John H Helzberg
- Department of Gastroenterology and Hepatology, University of Missouri Kansas City (Alisa Likhitsup, Jason Dundulis, Hani El-Halawany, Randal Michelson, John H. Helzberg, Rajiv Chhabra).,Department of Gastroenterology and Hepatology, Saint Luke's Hospital of Kansas City (Alisa Likhitsup, John H. Helzberg, Rajiv Chhabra)
| | - Rajiv Chhabra
- Department of Gastroenterology and Hepatology, University of Missouri Kansas City (Alisa Likhitsup, Jason Dundulis, Hani El-Halawany, Randal Michelson, John H. Helzberg, Rajiv Chhabra).,Department of Gastroenterology and Hepatology, Saint Luke's Hospital of Kansas City (Alisa Likhitsup, John H. Helzberg, Rajiv Chhabra)
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26
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Adams LC, Lübbe F, Bressem K, Wagner M, Hamm B, Makowski MR. Non-alcoholic fatty liver disease in underweight patients with inflammatory bowel disease: A case-control study. PLoS One 2018; 13:e0206450. [PMID: 30427909 PMCID: PMC6241122 DOI: 10.1371/journal.pone.0206450] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2018] [Accepted: 10/13/2018] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) was shown to also occur in lean and underweight patients. So far, the prevalence of NAFLD in underweight individuals with and without inflammatory bowel disease (IBD) is insufficiently enlightened. In this cross-sectional age, gender and disease-matched case-control study, underweight patients (BMI<18.5 kg/m2) with inflammatory bowel disease (IBD), who underwent abdominal MRI at 1.5 T/3 T with fat-saturated fast-spin-echo imaging from 10/2005-07/2018 were analysed (control-to-case-ratio 1:1, n = 130). All patients were additionally investigated for duration, history of surgery, medical treatment, laboratory values, liver and spleen diameters. On MRI, liver fat was quantified by two observers based on the relative signal loss on T2-weighted fast spin-echo MR images with fat saturation compared to images without fat saturation. The prevalence of NAFLD/liver steatosis, defined as a measured intrahepatic fat content of at least 5%, was significantly higher in underweight IBD patients than in normal weight patients (87.6% versus 21.5%, p<0.001). Compared to the cases, the liver fat content of the controls was reduced by -0.19 units on average (-19%; 95%Cl: -0.20; -0.14). Similar results were obtained for the subgroup of non-IBD individuals (n = 12; -0.25 units on average (-25%); 95%Cl: -0.35; -0.14). Patients with extremely low body weight (BMI <17.5 kg/m2) showed the highest liver fat content (+0.15 units on average (+15%) compared to underweight patients with a BMI of 17.5-18.5 kg/m2 (p<0.05)). Furthermore, underweight patients showed slightly increased liver enzymes and liver diameters. There were no indications of significant differences in disease duration, type of medications or surgery between cases and controls and also, there were no significant differences between observers or field strengths (p>0.05). The prevalence of liver steatosis was higher among underweight IBD and non-IBD patients compared to normal weight controls. Also, underweight patients showed slightly increased liver enzymes and liver diameters, hinting at initial metabolic disturbances.
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Grants
- Deutsche Forschungsgemeinschaft
- BIH/Charité – Universitätsmedizin Berlin (DE)
- BH has received research grants for the Department of Radiology, Charité – Universitätsmedizin Berlin from the following companies: 1. Abbott, 2. Actelion Pharmaceuticals, 3. Bayer Schering Pharma, 4. Bayer Vital, 5. BRACCO Group, 6. Bristol-Myers Squibb, 7. Charite research organisation GmbH, 8. Deutsche Krebshilfe, 9. Dt. Stiftung für Herzforschung, 10. Essex Pharma, 11. EU Programmes, 12. Fibrex Medical Inc., 13. Focused Ultrasound Surgery Foundation, 14. Fraunhofer Gesellschaft, 15. Guerbet, 16. INC Research, 17. lnSightec Ud., 18. IPSEN Pharma, 19. Kendlel MorphoSys AG, 20. Lilly GmbH, 21. Lundbeck GmbH, 22. MeVis Medical Solutions AG, 23. Nexus Oncology, 24. Novartis, 25. Parexel Clinical Research Organisation Service, 26. Perceptive, 27. Pfizer GmbH, 28. Philipps, 29. Sanofis-Aventis S.A, 30. Siemens, 31. Spectranetics GmbH, 32. Terumo Medical Corporation, 33. TNS Healthcare GMbH, 34. Toshiba, 35. UCB Pharma, 36. Wyeth Pharma, 37. Zukunftsfond Berlin (TSB), 38. Amgen, 39. AO Foundation, 40. BARD, 41. BBraun, 42. Boehring Ingelheimer, 43. Brainsgate, 44. PPD (Clinical Research Organisation), 45. CELLACT Pharma, 46. Celgene, 47. CeloNova BioSciences, 48. Covance, 49. DC Deviees, Ine. USA, 50. Ganymed, 51. Gilead Sciences, 52. Glaxo Smith Kline, 53. ICON (Clinical Research Organisation), 54. Jansen, 55. LUX Bioseienees, 56. MedPass, 57. Merek, 58. Mologen, 59. Nuvisan, 60. Pluristem, 61. Quintiles, 62. Roehe, 63. Sehumaeher GmbH (Sponsoring eines Workshops), 64. Seattle Geneties, 65. Symphogen, 66. TauRx Therapeuties Ud., 67. Accovion, 68. AIO: Arbeitsgemeinschaft Internistische Onkologie, 69. ASR Advanced sleep research, 70. Astellas, 71. Theradex, 72. Galena Biopharma, 73. Chiltern, 74. PRAint, 75. lnspiremd, 76. Medronic, 77. Respicardia, 78. Silena Therapeutics, 79. Spectrum Pharmaceuticals, 80. St. Jude., 81. TEVA, 82. Theorem, 83. Abbvie, 84. Aesculap, 85. Biotronik, 86. Inventivhealth, 87. ISA Therapeutics, 88. LYSARC, 89. MSD, 90. novocure, 91. Ockham oncology, 92. Premier-research, 93. Psi-cro, 94. Tetec-ag, 94. Tetec-ag, 95. Winicker-norimed, 96. Achaogen Inc, 97. ADIR, 98. AstraZenaca AB, 99. Demira Inc, 100.Euroscreen S.A., 101. Galmed Research and Development Ltd., 102. GETNE, 103. Guidant Europe NV, 104. Holaira Inc., 105. Immunomedics Inc., 106. Innate Pharma, 107. Isis Pharmaceuticals Inc, 108. Kantar Health GmbH, 109. MedImmune Inc, 110. Medpace Germany GmbH (CRO), 111. Merrimack Pharmaceuticals Inc, 112. Millenium Pharmaceuticals Inc, 113. Orion Corporation Orion Pharma, 114. Pharmacyclics Inc, 115. PIQUR Therapeutics Ltd, 116. Pulmonx International Sárl, 117. Servier (CRO), 118. SGS Life Science Services (CRO), 119. Treshold Pharmaceuticals Inc.
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Affiliation(s)
- Lisa C. Adams
- Department of Radiology, Charité, Berlin, Germany
- * E-mail:
| | - Falk Lübbe
- Department of Radiology, Charité, Berlin, Germany
| | - Keno Bressem
- Department of Radiology, Charité, Berlin, Germany
| | | | - Bernd Hamm
- Department of Radiology, Charité, Berlin, Germany
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27
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Simon TG, Van Der Sloot KWJ, Chin SB, Joshi AD, Lochhead P, Ananthakrishnan AN, Xavier R, Chung RT, Khalili H. IRGM Gene Variants Modify the Relationship Between Visceral Adipose Tissue and NAFLD in Patients With Crohn's Disease. Inflamm Bowel Dis 2018; 24:2247-2257. [PMID: 29788077 PMCID: PMC6230523 DOI: 10.1093/ibd/izy128] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2017] [Indexed: 02/06/2023]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized comorbidity in Crohn's disease (CD), but the mechanisms are poorly understood. Autophagy is a highly conserved process regulating innate immunity that contributes to CD susceptibility. Emerging data suggest that variants in the autophagy-governing IRGM gene may contribute to the accumulation of visceral adipose tissue (VAT) and hepatic fat. Our objective was to characterize the relationship between VAT, IRGM gene variants, and NAFLD risk in patients with CD. METHODS We included all CD patients in the Prospective Registry in Inflammatory Bowel Disease Study at Massachusetts General Hospital (PRISM) without history of alcohol abuse or liver disease. Hepatic fat was quantified by liver attenuation (LA) on computed tomography, with NAFLD defined by the validated liver:spleen (L:S) ratio. NAFLD severity was estimated by the FIB-4 Index and alanine aminotransferase (ALT). Using logistic regression modeling, we examined the relationship between VAT, autophagy gene variants, and NAFLD risk. RESULTS Among 462 patients, 52% had NAFLD. Increasing VAT quartile was associated with reduced LA (mean change, -7.43; 95% confidence interval [CI], -10.05 to -4.81; Ptrend < 0.0001). In the fully adjusted model, patients in the highest VAT quartile had a 2.2-fold increased NAFLD risk (95% CI, 1.21 to 4.14; Ptrend = 0.032) and a 4.2-fold increased risk of ALT>upper limit of normal (ULN) (95% CI, 1.19 to 14.76; Ptrend = 0.017). The relationship between VAT and NAFLD was modified by IRGM variants rs4958847 and rs13361189 (Pinteraction = 0.005 and Pinteraction < 0.001, respectively). CONCLUSIONS In a large CD cohort, VAT was directly associated with prevalent NAFLD, and this relationship was augmented by functionally annotated IRGM variants associated with impaired autophagy.
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Affiliation(s)
- Tracey G Simon
- Liver Center, Massachusetts General Hospital, Boston, Massachusetts,Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts,Harvard Medical School, Boston, Massachusetts
| | - Kimberley W J Van Der Sloot
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts,Department of Epidemiology, University Medical Center Groningen, Groningen, the Netherlands
| | - Samantha B Chin
- Liver Center, Massachusetts General Hospital, Boston, Massachusetts,Harvard Medical School, Boston, Massachusetts
| | - Amit D Joshi
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts,Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, Massachusetts,Harvard Medical School, Boston, Massachusetts
| | - Paul Lochhead
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts,Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, Massachusetts,Harvard Medical School, Boston, Massachusetts
| | - Ashwin N Ananthakrishnan
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts,Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, Massachusetts,Harvard Medical School, Boston, Massachusetts
| | - Ramnik Xavier
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts,Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, Massachusetts,Harvard Medical School, Boston, Massachusetts
| | - Raymond T Chung
- Liver Center, Massachusetts General Hospital, Boston, Massachusetts,Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts,Harvard Medical School, Boston, Massachusetts
| | - Hamed Khalili
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts,Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, Massachusetts,Harvard Medical School, Boston, Massachusetts,Clinical Epidemiology Unit, Karolinska Institutet, Stockholm Sweden,Address correspondence to: Hamed Khalili, MD, MPH, Massachusetts General Hospital, Crohn’s and Colitis Center, 165 Cambridge Street, 9th Floor, Boston, MA 02114 ()
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28
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Koch LK, Yeh MM. Nonalcoholic fatty liver disease (NAFLD): Diagnosis, pitfalls, and staging. Ann Diagn Pathol 2018; 37:83-90. [PMID: 30312882 DOI: 10.1016/j.anndiagpath.2018.09.009] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2018] [Accepted: 09/25/2018] [Indexed: 02/07/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is increasingly prevalent and strongly associated with obesity, diabetes and the metabolic syndrome, not only in the Western societies, but also in most regions of the world in the 21st century. The spectrum of its histopathology ranges from steatosis to nonalcoholic steatohepatitis (NASH), with risk for progressive fibrosis that may lead to cirrhosis and hepatocellular carcinoma (HCC). Benign and malignant liver tumors have also been more frequently reported with the increasing prevalence of obesity and diabetes. This review addresses the pathology of NAFLD and NASH, and their diagnostic features, diagnostic pitfalls, grading and staging, and clinical correlation.
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Affiliation(s)
- Lisa K Koch
- Department of Pathology, University of Washington School of Medicine, Seattle, WA 98195, United States of America
| | - Matthew M Yeh
- Department of Pathology, University of Washington School of Medicine, Seattle, WA 98195, United States of America; Department of Medicine, University of Washington School of Medicine, Seattle, WA 98195, United States of America.
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29
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Hegarty R, Deheragoda M, Fitzpatrick E, Dhawan A. Paediatric fatty liver disease (PeFLD): All is not NAFLD - Pathophysiological insights and approach to management. J Hepatol 2018; 68:1286-1299. [PMID: 29471012 DOI: 10.1016/j.jhep.2018.02.006] [Citation(s) in RCA: 52] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2017] [Revised: 02/11/2018] [Accepted: 02/13/2018] [Indexed: 12/14/2022]
Abstract
The recognition of a pattern of steatotic liver injury where histology mimicked alcoholic liver disease, but alcohol consumption was denied, led to the identification of non-alcoholic fatty liver disease (NAFLD). Non-alcoholic fatty liver disease has since become the most common chronic liver disease in adults owing to the global epidemic of obesity. However, in paediatrics, the term NAFLD seems incongruous: alcohol consumption is largely not a factor and inherited metabolic disorders can mimic or co-exist with a diagnosis of NAFLD. The term paediatric fatty liver disease may be more appropriate. In this article, we summarise the known causes of steatosis in children according to their typical, clinical presentation: i) acute liver failure; ii) neonatal or infantile jaundice; iii) hepatomegaly, splenomegaly or hepatosplenomegaly; iv) developmental delay/psychomotor retardation and perhaps most commonly; v) the asymptomatic child with incidental discovery of abnormal liver enzymes. We offer this model as a means to provide pathophysiological insights and an approach to management of the ever more complex subject of fatty liver.
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Affiliation(s)
- Robert Hegarty
- Paediatric Liver, GI and Nutrition Centre and Mowatlabs, King's College Hospital, London, United Kingdom
| | - Maesha Deheragoda
- Liver Histopathology, Institute of Liver Studies, King's College Hospital, London, United Kingdom
| | - Emer Fitzpatrick
- Paediatric Liver, GI and Nutrition Centre and Mowatlabs, King's College Hospital, London, United Kingdom
| | - Anil Dhawan
- Paediatric Liver, GI and Nutrition Centre and Mowatlabs, King's College Hospital, London, United Kingdom.
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30
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Sartini A, Gitto S, Bianchini M, Verga MC, Di Girolamo M, Bertani A, Del Buono M, Schepis F, Lei B, De Maria N, Villa E. Non-alcoholic fatty liver disease phenotypes in patients with inflammatory bowel disease. Cell Death Dis 2018; 9:87. [PMID: 29367619 PMCID: PMC5833704 DOI: 10.1038/s41419-017-0124-2] [Citation(s) in RCA: 59] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2017] [Revised: 09/07/2017] [Accepted: 09/13/2017] [Indexed: 02/07/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) can be detected in up to 33.6% of inflammatory bowel disease (IBD) patients, often in absence of metabolic risk factors. Nevertheless, most of previous studies on such issue were conducted within the IBD population only. The primary aim of this study was to compare clinical and metabolic features of NAFLD in patients with and without IBD (w/o IBD) and to identify specific NAFLD phenotypes within the IBD population. Among 223 NAFLD patients, 78 patients with IBD were younger compared to 145 without (w/o) IBD, were less likely to have altered liver enzymes, had lower mean body weight, smaller waist circumference and lower body mass index (BMI); at the same time, MetS was more prevalent among patients w/o IBD (56.6 vs. 23.1%, p < 0.001). Within IBD population, patients with severe IBD showed more often severe steatosis (S3) at ultrasound (US) (32.1 vs. 16.6%, p = 0.01), compared to mild-to-moderate disease. Independent risk factors for S3 US steatosis in IBD patients at the multivariate logistic regression analysis were: more than 1 IBD relapse per year during disease history (OR 17.3, 95% CI 3.6-84), surgery for IBD (OR 15.1, 95% CI 3.1-73.7) and more extensive intestinal involvement (OR 19.4, 95% CI 3.4-110.9); the ongoing anti-Tumor Necrosis Factor alpha (antiTNFα) therapy was the only independent factor which protect toward the presence of altered liver enzymes (OR 0.15, 95% CI 0-0.8, p = 0.02). In conclusion, NAFLD in IBD patients is different from that in patients w/o IBD, who seem to develop different NAFLD phenotypes according to intestinal disease clinical course. More severe IBD seem to predict the presence of more severe steatosis. Therapy with antiTNFα antibodies could prevent alteration of liver enzymes in such population.
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Affiliation(s)
- Alessandro Sartini
- Department of Internal Medicine, Gastroenterology Unit, University of Modena and Reggio Emilia, Modena, Italy
| | - Stefano Gitto
- Department of Internal Medicine, Gastroenterology Unit, University of Modena and Reggio Emilia, Modena, Italy
| | - Marcello Bianchini
- Department of Internal Medicine, Gastroenterology Unit, University of Modena and Reggio Emilia, Modena, Italy
| | - Maria Chiara Verga
- Department of Internal Medicine, Gastroenterology Unit, University of Modena and Reggio Emilia, Modena, Italy
| | - Maria Di Girolamo
- Department of Internal Medicine, Gastroenterology Unit, University of Modena and Reggio Emilia, Modena, Italy
| | - Angela Bertani
- Department of Internal Medicine, Gastroenterology Unit, University of Modena and Reggio Emilia, Modena, Italy
| | - Mariagrazia Del Buono
- Department of Internal Medicine, Gastroenterology Unit, University of Modena and Reggio Emilia, Modena, Italy
| | - Filippo Schepis
- Department of Internal Medicine, Gastroenterology Unit, University of Modena and Reggio Emilia, Modena, Italy
| | - Barbara Lei
- Department of Internal Medicine, Gastroenterology Unit, University of Modena and Reggio Emilia, Modena, Italy
| | - Nicola De Maria
- Department of Internal Medicine, Gastroenterology Unit, University of Modena and Reggio Emilia, Modena, Italy
| | - Erica Villa
- Department of Internal Medicine, Gastroenterology Unit, University of Modena and Reggio Emilia, Modena, Italy.
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Evaluation of interleukin-6 and its soluble receptor components sIL-6R and sgp130 as markers of inflammation in inflammatory bowel diseases. Int J Colorectal Dis 2018; 33:927-936. [PMID: 29748708 PMCID: PMC6002455 DOI: 10.1007/s00384-018-3069-8] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/29/2018] [Indexed: 02/07/2023]
Abstract
PURPOSE Interleukin-6 (IL-6) production and signalling are increased in the inflamed mucosa in inflammatory bowel diseases (IBD). As published serum levels of IL-6 and its soluble receptors sIL-6R and sgp130 in IBD are from small cohorts and partly contradictory, we systematically evaluated IL-6, sIL-6R and sgp130 levels as markers of disease activity in Crohn's disease (CD) and ulcerative colitis (UC). METHODS Consecutive adult outpatients with confirmed CD or UC were included, and their disease activity and medication were monitored. Serum from 212 CD patients (815 measurements) and 166 UC patients (514 measurements) was analysed, and 100 age-matched healthy blood donors were used as controls. RESULTS IL-6 serum levels were significantly elevated in active versus inactive CD and UC, also compared with healthy controls. However, only a fraction of IBD patients showed increased serum IL-6. IL-6 levels ranged up to 32.7 ng/mL in active CD (> 5000-fold higher than in controls), but also up to 6.9 ng/mL in inactive CD. Increases in active UC (up to 195 pg/mL) and inactive UC (up to 27 pg/mL) were less pronounced. Associations between IL-6 serum levels and C-reactive protein concentrations as well as leukocyte and thrombocyte counts were observed. Median sIL-6R and sgp130 levels were only increased by up to 15%, which was considered of no diagnostic significance. CONCLUSIONS Only a minority of IBD patients shows elevated IL-6 serum levels. However, in these patients, IL-6 is strongly associated with disease activity. Its soluble receptors sIL-6R and sgp130 do not appear useful as biomarkers in IBD.
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Does Metabolic Syndrome and Not the Inflammatory Load Predict Nonalcoholic Fatty Liver Disease Severity in Inflammatory Bowel Disease Patients? Dig Dis Sci 2017; 62:2604-2606. [PMID: 28676901 DOI: 10.1007/s10620-017-4665-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2017] [Accepted: 06/23/2017] [Indexed: 12/12/2022]
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Affiliation(s)
- Jill K J Gaidos
- McGuire VA Medical Center, GI/Hepatology Service (111-N), Virginia Commonwealth University, 1201 Broad Rock Boulevard, Richmond, VA, 23249, USA
| | - Michael Fuchs
- McGuire VA Medical Center, GI/Hepatology Service (111-N), Virginia Commonwealth University, 1201 Broad Rock Boulevard, Richmond, VA, 23249, USA.
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