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1.
Disease Prognostic Biomarkers in Inflammatory Bowel Diseases-A Reality Check.
Zilbauer, M, Heuschkel, R
Journal of Crohn's & colitis. 2022;(1):162-165
Abstract
Inflammatory bowel diseases [IBD] such as Crohn's disease [CD] and ulcerative colitis [UC] are complex conditions presenting with a wide range of phenotypes. Given major variation in disease severity and outcomes as well as response to existing therapies, a personalised treatment approach stands the chance of improving the overall disease outcome as well as minimising potentially harmful side effects. However, disease activity or distribution at the point of diagnosis are poor predictors of future disease outcome. Hence, the urgent need to develop biomarkers that could either predict the overall disease course [i.e., disease prognostic biomarkers] or the response to individual therapies [i.e., disease predictive biomarkers]. Despite the widely accepted need for such biomarkers to improve the management of IBD patients, their development has proven to be challenging for a number of reasons. Based on our own experience in this field, we perform a reality check on existing evidence, discuss main challenges, and outline future perspectives.
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2.
Incidence and Prevalence of Inflammatory Bowel Disease across Asia.
Park, J, Cheon, JH
Yonsei medical journal. 2021;(2):99-108
Abstract
Inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), are chronic inflammatory disorders of the gastrointestinal tract caused by interactions between genetic, environmental, immunological, and microbial factors. While the incidence and prevalence of IBD in Asian populations were relatively lower than those in Western countries, they appear to be gradually increasing. A Westernized diet, high socioeconomic status, improvement of hygiene, and development of vaccination could affect the increases in IBD incidence and prevalence in Asian countries. This review describes the latest trends in the incidence and prevalence of IBD in Asia. Studying the epidemiology of IBD in Asia may unravel the etiopathogenesis of and risk factors for IBD.
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3.
IFIH1 loss-of-function variants contribute to very early-onset inflammatory bowel disease.
Cananzi, M, Wohler, E, Marzollo, A, Colavito, D, You, J, Jing, H, Bresolin, S, Gaio, P, Martin, R, Mescoli, C, et al
Human genetics. 2021;(9):1299-1312
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Abstract
Genetic defects of innate immunity impairing intestinal bacterial sensing are linked to the development of Inflammatory Bowel Disease (IBD). Although much evidence supports a role of the intestinal virome in gut homeostasis, most studies focus on intestinal viral composition rather than on host intestinal viral sensitivity. To demonstrate the association between the development of Very Early Onset IBD (VEOIBD) and variants in the IFIH1 gene which encodes MDA5, a key cytosolic sensor for viral nucleic acids. Whole exome sequencing (WES) was performed in two independent cohorts of children with VEOIBD enrolled in Italy (n = 18) and USA (n = 24). Luciferase reporter assays were employed to assess MDA5 activity. An enrichment analysis was performed on IFIH1 comparing 42 VEOIBD probands with 1527 unrelated individuals without gastrointestinal or immunological issues. We identified rare, likely loss-of-function (LoF), IFIH1 variants in eight patients with VEOIBD from a combined cohort of 42 children. One subject, carrying a homozygous truncating variant resulting in complete LoF, experienced neonatal-onset, pan-gastrointestinal, IBD-like enteropathy plus multiple infectious episodes. The remaining seven subjects, affected by VEOIBD without immunodeficiency, were carriers of one LoF variant in IFIH1. Among these, two patients also carried a second hypomorphic variant, with partial function apparent when MDA5 was weakly stimulated. Furthermore, IFIH1 variants were significantly enriched in children with VEOIBD as compared to controls (p = 0.007). Complete and partial MDA5 deficiency is associated with VEOIBD with variable penetrance and expressivity, suggesting a role for impaired intestinal viral sensing in IBD pathogenesis.
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4.
Biologics and pregnancy: a clinician's guide to the management of IBD in pregnant women.
Guerrero Vinsard, D, Kane, SV
Expert review of gastroenterology & hepatology. 2021;(6):633-641
Abstract
Introduction: Women with inflammatory bowel disease (IBD) endorse a tremendous amount of concern about medication exposure during pregnancy and their effects on the fetus. Medical providers caring for this patient population should be well informed and feel comfortable counseling their patients for the best pregnancy outcome possible.Areas covered: It is of particular importance to understand the implications of use of biologics in preconception, pregnancy, and postpartum timeframes. Herein, we aim to inform the clinician about the impact of uncontrolled inflammation during pregnancy, the mechanisms of biologic transport through the placenta, the effects of biologics in maternal and neonatal outcomes, and additional postpartum considerations such as breastfeeding and vaccination safety.Expert opinion: The groundwork already set by previous research in terms of safety of biologic therapy during pregnancy has been reassuring. With the advent of more mechanisms of action but similar protein structure, i.e. they are IgG1 antibodies; the authors anticipate the recommendation of continuation of therapy throughout pregnancy will be sustained.
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5.
Multifaceted pathogenesis of liver steatosis in inflammatory bowel disease: a systematic review.
Spagnuolo, R, Abenavoli, L, Corea, A, Larussa, T, Mancina, RM, Cosco, C, Luzza, F, Doldo, P
European review for medical and pharmacological sciences. 2021;(18):5818-5825
Abstract
OBJECTIVE Non-Alcoholic Fatty Liver Disease (NAFLD), as a hepatic manifestation of metabolic syndrome (MET)-related obesity, insulin resistance, dyslipidemia, and hypertension, is the main cause of chronic liver disease. Inflammatory Bowel Diseases (IBD), (Crohn's Disease (CD) and Ulcerative Colitis (UC)), are often associated with extraintestinal manifestations. Of these, NAFLD is one of the most frequently reported. To highlight the etiopathogenesis of NAFLD in IBD, we performed a systematic review emphasizing the relationship between NAFLD genetic alterations, metabolic syndrome, and drugs. MATERIALS AND METHODS According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement (PRISMA) criteria, we performed a systematic literature search on PubMed, Google Scholar, and Web of Science for literature updated from 2010 to 1 March 2021. Inclusion criteria for studies were observational design and Randomized Controlled Trials (RCTs); written in English; primary research only; based on adult patients, and human research only. RESULTS We identified nine studies on the link between NAFLD and IBD. Among these, two described the genetic predisposition to NAFLD of patients with IBD. Four reported an association between MetS and NAFLD in IBD patients. Regarding medications, none of four studies included, detected a relationship between NAFLD onset and IBD treatment (corticosteroids, immunomodulators, methotrexate, or biologics). However, a retrospective study showed a protective effect of anti-TNF alpha therapies against altered liver enzymes. CONCLUSIONS In this interplay between genetic, metabolic, drug, and inflammatory factors, the underlying pathogenic mechanisms behind NAFLD in IBD are still far from clear. Further studies are needed to better clarify the role of individual components influencing the development of NAFLD in IBD.
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6.
The Other Side of Malnutrition in Inflammatory Bowel Disease (IBD): Non-Alcoholic Fatty Liver Disease.
Gibiino, G, Sartini, A, Gitto, S, Binda, C, Sbrancia, M, Coluccio, C, Sambri, V, Fabbri, C
Nutrients. 2021;(8)
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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7.
Diet and Nutrition in Pediatric Inflammatory Bowel Diseases.
Cucinotta, U, Romano, C, Dipasquale, V
Nutrients. 2021;(2)
Abstract
Both genetic and environmental factors are involved in the onset of inflammatory bowel disease (IBD). In particular, diet composition is suspected to significantly contribute to IBD risk. In recent years, major interest has raised about the role of nutrition in disease pathogenesis and course, and many studies have shown a clear link between diet composition and intestinal permeability impairment. Moreover, many IBD-related factors, such as poor dietary intake, nutrients loss and drugs interact with nutritional status, thus paving the way for the development of many therapeutic strategies in which nutrition represents the cornerstone, either as first-line therapy or as reversing nutritional deficiencies and malnutrition in IBD patients. Exclusive enteral nutrition (EEN) is the most rigorously supported dietary intervention for the treatment of Crohn's Disease (CD), but is burdened by a low tolerability, especially in pediatric patients. Promising alternative regimens are represented by Crohn's Disease Exclusion Diet (CDED), and other elimination diets, whose use is gradually spreading. The aim of the current paper is to provide a comprehensive and updated overview on the latest evidence about the role of nutrition and diet in pediatric IBD, focusing on the different nutritional interventions available for the management of the disease.
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8.
What Links an Increased Cardiovascular Risk and Inflammatory Bowel Disease? A Narrative Review.
Łykowska-Szuber, L, Rychter, AM, Dudek, M, Ratajczak, AE, Szymczak-Tomczak, A, Zawada, A, Eder, P, Lesiak, M, Dobrowolska, A, Krela-Kaźmierczak, I
Nutrients. 2021;(8)
Abstract
Several studies have shown increased rates of cardiovascular disease (CVD) in patients suffering from inflammatory bowel disease (IBD), particularly in cases of early atherosclerosis and myocardial infarction. IBD most frequently begins at an early age, patients usually present normal weight and remain under constant care of a physician, as well as of a nutritionist. Therefore, the classical risk factors of CVD are not reflected in the higher prevalence of CVD in the IBD population. Still, both groups are characterised by chronic inflammation and display similar physiopathological mechanisms. In the course of IBD, increased concentrations of pro-inflammatory cytokines, such as C-reactive protein (CRP) and homocysteine, may lead to endothelial dysfunctions and the development of CVD. Furthermore, gut microbiota dysbiosis in patients with IBD also constitutes a risk factor for an increased susceptibility to cardiovascular disease and atherosclerosis. Additionally, diet is an essential factor affecting both positively and negatively the course of the aforementioned diseases, whereas several dietary patterns may also influence the association between IBD and CVD. Thus, it is essential to investigate the factors responsible for the increased cardiovascular (CV) risk in this group of patients. Our paper attempts to review the role of potential inflammatory and nutritional factors, as well as intestinal dysbiosis and pharmacotherapy, in the increased risk of CVD in IBD patients.
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9.
TNF Inhibitors and Risk of Malignancy in Patients with Inflammatory Bowel Diseases: A Systematic Review.
Muller, M, D'Amico, F, Bonovas, S, Danese, S, Peyrin-Biroulet, L
Journal of Crohn's & colitis. 2021;(5):840-859
Abstract
BACKGROUND AND AIMS The association between tumour necrosis factor inhibitors [TNFi] and malignancy in patients with inflammatory bowel disease [IBD] is not well understood. Our aim was to systematically evaluate the impact of TNFi use on risk of malignancy in IBD patients in daily clinical practice. METHODS We searched Pubmed, Embase and Scopus until March 1, 2020 for observational cohort studies on adult IBD patients reporting malignancy occurrence and TNFi use. RESULTS Twenty-eight studies [20 retrospective and eight prospective] were included, involving 298 717 IBD patients. Mean age at inclusion ranged from 28 to >65 years. Mean follow-up varied from 7 to 80 months. Infliximab was the most frequently used TNFi [13/28 studies, 46.4%], followed by adalimumab [3/28, 10.7%], while both infliximab and adalimumab were evaluated in five studies [17.8%]. In total, 692 malignancies were diagnosed in IBD patients treated with TNFi, accounting for an overall occurrence of 1.0%. The most frequent malignancies were non-melanoma skin cancers [123/692, 17.8%], digestive malignancies [120/692, 17.3%] and haematological malignancies [106/692, 15.3%]. The association between TNFi and malignancy was evaluated in 11 studies [39.3%]: no significant association was found in ten studies, while an increased risk of lymphoma in patients exposed to TNFi was reported in one study. CONCLUSION TNFi treatment is not associated with an increased risk of malignancy in IBD patients in real-life settings. Further large studies are needed to assess the prognosis of patients exposed to TNFi and risk of recurrence or new cancers in subjects with personal malignancy history.
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10.
Sarcopenia in Inflammatory Bowel Disease: A Narrative Overview.
Dhaliwal, A, Quinlan, JI, Overthrow, K, Greig, C, Lord, JM, Armstrong, MJ, Cooper, SC
Nutrients. 2021;(2)
Abstract
Malnutrition is a common condition encountered in patients with inflammatory bowel disease (IBD) and is often associated with sarcopenia (the reduction of muscle mass and strength) which is an ever-growing consideration in chronic diseases. Recent data suggest the prevalence of sarcopenia is 52% and 37% in Crohn's disease and ulcerative colitis, respectively, however it is challenging to fully appreciate the prevalence of sarcopenia in IBD. Sarcopenia is an important consideration in the management of IBD, including the impact on quality of life, prognostication, and treatment such as surgical interventions, biologics and immunomodulators. There is evolving research in many chronic inflammatory states, such as chronic liver disease and rheumatoid arthritis, whereby interventions have begun to be developed to counteract sarcopenia. The purpose of this review is to evaluate the current literature regarding the impact of sarcopenia in the management of IBD, from mechanistic drivers through to assessment and management.