RESUMO
The rising global prevalence of inflammatory bowel diseases (IBD), such as Crohn's disease (CD) and ulcerative colitis (UC), underscores the need to examine current and future IBD care costs. Direct healthcare expenses, including ambulatory visits, hospitalizations, and medications, are substantial, averaging $9,000 to $12,000 per person annually in high-income regions. However, these estimates do not fully account for factors such as disease severity, accessibility, and variability in healthcare infrastructure among regions. Indirect costs, predominantly stemming from loss in productivity due to absenteeism, presenteeism, and other intangible costs, further contribute to the financial burden of IBD. Despite efforts to quantify indirect costs, many aspects remain poorly understood, leading to an underestimation of their actual impact. Challenges to achieving cost sustainability include disparities in access, treatment affordability, and the absence of standardized cost-effective care guidelines. Strategies for making IBD care sustainable include early implementation of biologic therapies, focusing on cost-effectiveness in settings with limited resources, and promoting the uptake of biosimilars to reduce direct costs. Multidisciplinary care teams leveraging technology and patient-reported outcomes also hold promise in reducing both direct and indirect costs associated with IBD. Addressing the increasing financial burden of IBD requires a comprehensive approach that tackles disparities, enhances access to cost-effective therapeutics, and promotes collaborative efforts across healthcare systems. Embracing innovative strategies can pave the way for personalized, cost-effective care accessible to all individuals with IBD, ensuring better outcomes and sustainability.
RESUMO
BACKGROUND AND AIMS: There are few studies on the cost-effectiveness of telemedicine for inflammatory bowel diseases (IBD). We assessed the long-term cost-effectiveness of a telemedicine solution (eCare) compared to standard care (sCare), as well as its efficacy according to patient-reported outcomes (PRO). METHODS: Between 2015 and 2020 we conducted a retrospective, register-based study among patients with ulcerative colitis (UC) and Crohn's disease (CD). Direct and indirect healthcare costs over a five-year period were obtained from Danish registers and compared to a control group. Costs were estimated on a yearly basis from one year before, until five years after, inclusion in the trial. Patients were divided into cohorts of those not receiving (cohort 1), and those receiving (cohort 2), biologics. RESULTS: We recruited 574 IBD patients. In cohort 1 (61.5%), average total direct costs and total earnings per patient per year were 14,043 and 307,793 in eCare compared to 16,226 and 252,166 in sCare, respectively. In cohort 2 (38.5%), average total direct costs and total earnings were 73,916 and 215,833 in eCare compared to 41,748 and 203,667 in sCare, respectively. PRO showed increasing quality of life and was higher in cohort 1 than cohort 2. Disease activity among CD patients increased after years 3 and 4 in cohorts 1 and 2, respectively. CONCLUSION: Telemedicine is cost-effective for patients not receiving biologics. However, treatment with biologics is more expensive for patients enrolled in eCare. Careful attention to PRO in eCare improves quality of life and could prolong time to relapse.
RESUMO
BACKGROUND AND AIMS: Intestinal ultrasound has become a crucial tool for assessing inflammation in patients with inflammatory bowel disease, prompting a surge in demand for trained sonographers. While educational programs exist, the length of training needed to reach proficiency in correctly classifying inflammation remains unclear. Our study addresses this gap partly by exploring the learning curves associated with the deliberate practice of sonographic disease assessment, focusing on the key disease activity parameters of bowel wall thickness, bowel wall stratification, color Doppler signal, and inflammatory fat. METHODS: Twenty-one novices and six certified intestinal ultrasound practitioners engaged in an 80-case deliberate practice online training program. A panel of three experts independently graded ultrasound images representing various degrees of disease activity and agreed upon a consensus score. We used statistical analyses, including mixed-effects regression models, to evaluate learning trajectories. Pass/fail thresholds distinguishing novices from certified practitioners were determined through contrasting-groups analyses. RESULTS: Novices showed significant improvement in interpreting bowel wall thickness, surpassing the pass/fail threshold, and reached mastery level by case 80. For color Doppler signal and inflammatory fat, novices surpassed the pass/fail threshold but did not achieve mastery. Novices did not improve in assessing bowel wall stratification. CONCLUSIONS: We found considerable individual and group-level differences in learning curves supporting the concept of competency-based training for assessing bowel wall thickness, color Doppler signal and inflammatory fat. However, despite practice over 80 cases, novices did not improve in their interpretation of bowel wall stratification, suggesting that a different approach is needed for this parameter.
RESUMO
BACKGROUND AND AIMS: The natural history of Crohn's disease leading to intestinal failure is not well characterised. This study aims to describe the clinical course of Crohn's disease preceding intestinal failure and compare disease course and burden between Crohn's disease patients with and without intestinal failure. METHODS: Patients with Crohn's disease complicated by intestinal failure from Rigshospitalet, Copenhagen (n=182) and a nationwide Danish Crohn's disease cohort without intestinal failure (n=22,845) were included. Using nationwide registries in Denmark, disease course was determined from hospitalisations, surgeries and outpatient medications, and disease burden was determined from employment and mortality data. RESULTS: The 10-year cumulative incidence of intestinal failure following Crohn's disease diagnosis declined from 2.7% prior to 1980 to 0.2% after 2000. Compared to Crohn's disease patients without intestinal failure, those with intestinal failure experienced significantly longer duration of severe disease (50 vs. 19 years per 100 patient-years, p<0.01), secondary to greater corticosteroid use (71% vs. 60%, p=0.02), inpatient contacts (98% vs. 55%, p<0.01), and abdominal surgeries (99% vs. 48%, p<0.01). However, exposure to biologics was not different between the two groups (20.4% vs. 21%, p=0.95), and duration on biologics was shorter in Crohn's disease patients with intestinal failure (2,068 vs. 4,126 days per 100 patient-years, p=0.02). Standard mortality ratio in Crohn's disease patients with intestinal failure was 3.66 [97.5% CI 2.79,4.72]. CONCLUSION: Patients with Crohn's disease complicated by intestinal failure experienced a more persistently severe preceding course of Crohn's disease but were not more likely to be treated with biological therapy.
RESUMO
BACKGROUND: Paediatric-onset and elderly-onset inflammatory bowel disease (IBD) present unique treatment challenges. AIMS: We investigated treatment patterns following a first and second course of systemic steroids in paediatric- and elderly-onset IBD and compared them to adult-onset IBD. METHODS: All patients diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) between 2000 and 2018 were identified through the Danish healthcare registries. Patients were divided into groups based on their age at diagnosis. Kaplan-Meier plots were prepared for medications and surgeries after diagnosis and after the first and second courses of systemic steroids. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using multivariate Cox regression analysis for steroid-sparing medications. RESULTS: 1851 CD (13%) and 1687 (6%) UC patients were paediatric-onset, while 2952 (20%) CD and 5812 (23%) UC patients were elderly-onset. Paediatric-onset more frequently received immunomodulators [CD: HR: 1.64, CI: 1.52-1.77, UC: HR: 2.29, CI: 2.02-2.61] and biologics [CD: HR: 1.43, CI: 1.25-1.65, UC: HR: 1.27, CI: 0.99-1.64], while elderly-onset less frequently received immunomodulators [CD: HR: 0.39, CI: 0.35-0.44, UC: HR: 0.58, CI: 0.50-0.67] and biologics [CD: HR: 0.19, CI: 0.14-0.25, UC: HR: 0.36, CI: 0.27-0.48] compared to adult-onset age groups. After two courses of systemic steroids, elderly-onset still received less steroid-sparing medications. High frailty was associated with lower usage of medications for elderly-onset. CONCLUSION: There are significant differences in the use of steroid-sparing medication between age of onset, even after two courses with systemic steroids. High frailty could account for some of these differences in elderly-onset IBD.
Assuntos
Colite Ulcerativa , Doença de Crohn , Humanos , Dinamarca , Masculino , Feminino , Adolescente , Adulto , Idoso , Criança , Pessoa de Meia-Idade , Doença de Crohn/tratamento farmacológico , Adulto Jovem , Colite Ulcerativa/tratamento farmacológico , Fatores Etários , Estudos de Coortes , Idade de Início , Sistema de Registros , Esteroides/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Agentes de Imunomodulação/uso terapêutico , Pré-Escolar , Resultado do TratamentoRESUMO
This article is the second in a series of two publications on the European Crohn's and Colitis Organisation [ECCO] evidence-based consensus on the management of Crohn's disease. The first article covers medical management; the present article addresses surgical management, including preoperative aspects and drug management before surgery. It also provides technical advice for a variety of common clinical situations. Both articles together represent the evidence-based recommendations of the ECCO for Crohn's disease and an update of prior ECCO guidelines.
RESUMO
BACKGROUND: Increased mortality rates have been found in patients suffering from inflammatory bowel disease (IBD). The Faroe Islands have the highest occurrence of IBD, mainly ulcerative colitis (UC). This study investigated mortality of patients with IBD compared with the general Faroese population. METHODS: All patients diagnosed with IBD from 1966-2020 were included, as well as population mortality data. All-cause and cause-specific mortality in the IBD cohort was compared with the population by standardized incidence ratios (SIRs). Risk factors for death within the cohort were assessed by hazard ratios (HRs) using Cox regression. RESULTS: Overall mortality was not increased in patients with Crohn's disease (CD; SIR 0.9; 95% confidence interval [CI], 0.56-1.35) or UC (SIR 1.0; 95% CI, 0.83-1.25). However, patients with UC had an elevated risk of dying from digestive diseases (SIR 4.3; 95% CI, 2.16-7.74). Patients with IBD had lower risk of death of cardiovascular diseases compared with the background population (SIR 0.7; 95% CI, 0.50-0.93). Risk factors for mortality included male gender, age at diagnosis, and use of steroids. Protective factors were use of 5-aminosalicylic acid (5-ASA), thiopurines, and biological treatment. CONCLUSIONS: No increased risk of all-cause mortality in patients with CD or UC was found in this nationwide study compared with the entire Faroese population over more than 5 decades. The risk of death due to digestive diseases was, however, increased in patients with UC, while mortality risk of cardiovascular diseases was lower in patients with IBD.
Increased mortality exists in IBD patients. The Faroe Islands have the highest occurrence in the world, though mortality risk in Faroese patients compared with the population is unknown. No increased overall risk was found, while mortality risk of digestive diseases was elevated.
RESUMO
BACKGROUND: Understanding disease burden is imperative for improving inflammatory bowel disease (IBD) management. This real-world survey investigated residual disease burden and treatment satisfaction among European patients with moderate-to-severe ulcerative colitis (UC) and Crohn's disease (CD). METHODS: The Adelphi Real World IBD Disease Specific Programme was a multinational, cross-sectional survey with retrospective collection of patient- and physician-reported data on disease burden and management. Between October 2020 and March 2021, participating gastroenterologists recruited their next 7 (UC) and 8 (CD) eligible patients and reported demographics and clinical characteristics. Patients completed symptom, health-related quality of life (HRQoL), and treatment satisfaction questionnaires. Data were adjusted for confounding variables and compared between patients in remission (clinical remission, endoscopic remission, or both) and not in remission. RESULTS: Overall, 1040 patients (UC, nâ =â 502; CD, nâ =â 538) were included. Although most patients were in remission (UC, 66.1%; CD, 69.5%), most still reported symptoms (UC, 63.7%; CD, 74.1%), including flatulence, fatigue/tiredness, and abdominal pain/distension. In UC, there were no significant differences in the likelihood of experiencing 7 of 23 symptoms between patients in remission and not in remission. In CD, there was no significant difference in 19 of 23 symptoms between patients in remission and not in remission. Several symptoms were significantly associated with reduced HRQoL. HRQoL was significantly better among patients in remission than not in remission. CONCLUSIONS: Patients with IBD, both in remission and not in remission, experience residual symptoms that impair HRQoL. Comprehensive endpoints, incorporating HRQoL and patients' perspectives, and improved treatments are needed to address residual disease and patients' needs.
This real-world study investigated the residual burden of inflammatory bowel disease on European patients. We found that patientsincluding those in remissionexperience significant symptomatic burden and impaired quality of life, highlighting gaps in current therapeutics and patients' unmet needs.
RESUMO
Improved biomarkers are needed for pediatric inflammatory bowel disease. Here we identify a diagnostic lipidomic signature for pediatric inflammatory bowel disease by analyzing blood samples from a discovery cohort of incident treatment-naïve pediatric patients and validating findings in an independent inception cohort. The lipidomic signature comprising of only lactosyl ceramide (d18:1/16:0) and phosphatidylcholine (18:0p/22:6) improves the diagnostic prediction compared with high-sensitivity C-reactive protein. Adding high-sensitivity C-reactive protein to the signature does not improve its performance. In patients providing a stool sample, the diagnostic performance of the lipidomic signature and fecal calprotectin, a marker of gastrointestinal inflammation, does not substantially differ. Upon investigation in a third pediatric cohort, the findings of increased lactosyl ceramide (d18:1/16:0) and decreased phosphatidylcholine (18:0p/22:6) absolute concentrations are confirmed. Translation of the lipidomic signature into a scalable diagnostic blood test for pediatric inflammatory bowel disease has the potential to support clinical decision making.
Assuntos
Biomarcadores , Doenças Inflamatórias Intestinais , Lipidômica , Humanos , Criança , Lipidômica/métodos , Masculino , Feminino , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/sangue , Doenças Inflamatórias Intestinais/metabolismo , Biomarcadores/sangue , Adolescente , Fezes/química , Fosfatidilcolinas/sangue , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo , Pré-Escolar , Complexo Antígeno L1 Leucocitário/sangue , Complexo Antígeno L1 Leucocitário/análise , Estudos de CoortesRESUMO
INTRODUCTION: Rapidity of effect of advanced therapies for patients with Crohn's disease (CD) can be an essential decision parameter; however, comparative evaluation is lacking. We aimed to compare early response for advanced CD therapies in a network meta-analysis (NMA). METHODS: We searched systematically MEDLINE, Embase, and CENTRAL up to 19 February 2024, for randomised controlled trials. The co-primary outcomes were induction of clinical remission (Crohn's Disease Activity Index (CDAI) ≤150) and clinical response (≥100-point reduction in CDAI) within the first 6 weeks of treatment. We incorporated any assessment within this time point in a Bayesian random-effects NMA following PRISMA-NMA guidance (PROSPERO ID: CRD42022368509). RESULTS: Twenty-five studies, comprising 7414 patients, were included. Infliximab combined with azathioprine or monotherapy ranked highest for induction of clinical remission within 6 weeks and was significantly superior to certolizumab, ustekinumab, guselkumab, vedolizumab, and upadacitinib. However, superiority over risankizumab 600 mg and adalimumab 160/80 mg was non-significant. Accordingly, infliximab in combination with azathioprine and guselkumab 600 mg ranked highest in the corresponding analysis of clinical response with no statistical significance demonstrated. Among bio-exposed patients, none of whom received infliximab, upadacitinib, and risankizumab induced the highest clinical responses. On the other hand, vedolizumab, certolizumab, and ustekinumab ranked lowest across the analyses. CONCLUSIONS: We found infliximab to be ranked highest and superior to all other agents but risankizumab and adalimumab, demonstrating the highest probability of early induction of remission. Upadacitinib and risankizumab induced the highest clinical responses in bio-exposed patients. However, infliximab was not investigated in this population.
Assuntos
Doença de Crohn , Metanálise em Rede , Humanos , Doença de Crohn/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto , Quimioterapia Combinada , Infliximab/uso terapêutico , Fármacos Gastrointestinais/uso terapêutico , Indução de Remissão , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Inflammatory bowel disease (IBD) and Parkinson's disease (PD) are chronic disorders that have been suggested to share common pathophysiological processes. LRRK2 has been implicated as playing a role in both diseases. Exploring the genetic basis of the IBD-PD comorbidity through studying high-impact rare genetic variants can facilitate the identification of the novel shared genetic factors underlying this comorbidity. METHODS: We analyzed whole exomes from the BioMe BioBank and UK Biobank, and whole genomes from a cohort of 67 European patients diagnosed with both IBD and PD to examine the effects of LRRK2 missense variants on IBD, PD and their co-occurrence (IBD-PD). We performed optimized sequence kernel association test (SKAT-O) and network-based heterogeneity clustering (NHC) analyses using high-impact rare variants in the IBD-PD cohort to identify novel candidate genes, which we further prioritized by biological relatedness approaches. We conducted phenome-wide association studies (PheWAS) employing BioMe BioBank and UK Biobank whole exomes to estimate the genetic relevance of the 14 prioritized genes to IBD-PD. RESULTS: The analysis of LRRK2 missense variants revealed significant associations of the G2019S and N2081D variants with IBD-PD in addition to several other variants as potential contributors to increased or decreased IBD-PD risk. SKAT-O identified two significant genes, LRRK2 and IL10RA, and NHC identified 6 significant gene clusters that are biologically relevant to IBD-PD. We observed prominent overlaps between the enriched pathways in the known IBD, PD, and candidate IBD-PD gene sets. Additionally, we detected significantly enriched pathways unique to the IBD-PD, including MAPK signaling, LPS/IL-1 mediated inhibition of RXR function, and NAD signaling. Fourteen final candidate IBD-PD genes were prioritized by biological relatedness methods. The biological importance scores estimated by protein-protein interaction networks and pathway and ontology enrichment analyses indicated the involvement of genes related to immunity, inflammation, and autophagy in IBD-PD. Additionally, PheWAS provided support for the associations of candidate genes with IBD and PD. CONCLUSIONS: Our study confirms and uncovers new LRRK2 associations in IBD-PD. The identification of novel inflammation and autophagy-related genes supports and expands previous findings related to IBD-PD pathogenesis, and underscores the significance of therapeutic interventions for reducing systemic inflammation.
Assuntos
Comorbidade , Predisposição Genética para Doença , Doenças Inflamatórias Intestinais , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina , Doença de Parkinson , Humanos , Doença de Parkinson/genética , Doenças Inflamatórias Intestinais/genética , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/genética , Feminino , Masculino , Mutação de Sentido Incorreto , Estudo de Associação Genômica Ampla , Variação Genética , Pessoa de Meia-Idade , IdosoRESUMO
BACKGROUND AND AIMS: Despite advances in the medical treatment of Crohn's disease (CD), many patients will still need bowel resections and face the subsequent risk of recurrence and re-resection. We describe contemporary re-resection rates and identify disease-modifying factors and risk factors for re-resection. METHODS: We conducted a retrospective, population-based, individual patient data cohort study covering 47.4% of the Danish population, including all CD patients who underwent a primary resection between 2010 and 2020. RESULTS: Among 631 primary resected patients, 24.5% underwent a second resection, and 5.3% a third. Re-resection rates after one, five, and 10 years were 12.6%, 22.4%, and 32.2%, respectively. Reasons for additional resections were mainly disease activity (57%) and stoma reversal (40%). Disease activity-driven re-resection rates after one, five, and 10 years were 3.6%, 10.1%, and 14.1%, respectively. Most stoma reversals occurred within one year (80%). The median time to recurrence was 11.0 months. Biologics started within one year of the first resection revealed protective effect against re-resection for stenotic and penetrating phenotypes. Prophylactic biologic therapy at primary ileocecal resection reduced disease recurrence and re-resection risk (HR 0.58, 95% CI (0.34-0.99), p=0.047). Risk factors for re-resection were location of resected bowel segments at the primary resection, disease location, disease behavior, smoking, and perianal disease. CONCLUSION: Re-resection rates, categorized by disease activity, are lower than those reported in other studies and are closely associated with disease phenotype and localization. Biological therapy may be disease-modifying for certain subgroups when initiated within one year of resection.
RESUMO
Ulcerative colitis and Crohn's disease are chronic inflammatory bowel diseases. Recent pivotal phase 3 trials involving treatments like interleukin-23-, sphingosin-1-phosphate- and Janus kinase inhibitors have demonstrated notable effectiveness. However, they have also unveiled significant side effects such as herpes zoster, lymphopenia and bradycardia. The introduction of novel treatments raises valid concerns necessitating increased collaboration with diverse medical specialities to address potentially severe side effects, and this is vital for enhancing the future care of individuals with inflammatory bowel diseases, as argued in this review.
Assuntos
Produtos Biológicos , Colite Ulcerativa , Doença de Crohn , Humanos , Doença de Crohn/tratamento farmacológico , Colite Ulcerativa/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Produtos Biológicos/efeitos adversos , Inibidores de Janus Quinases/uso terapêutico , Moduladores do Receptor de Esfingosina 1 Fosfato/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversosRESUMO
BACKGROUND AND OBJECTIVE: The influence of concomitant prednisolone on clinical outcomes and safety in infliximab-treated ulcerative colitis (UC) patients is unknown. DESIGN, SETTING, PARTICIPANTS AND OUTCOME MEASURES: A retrospective cohort study was performed, including 147 UC patients treated with infliximab at a tertiary inflammatory bowel disease (IBD) centre. Primary outcome was corticosteroid-free clinical remission (CFCR) at week 14 and week 52. Patients were grouped according to prednisolone tapering regimens: standard (≤5 mg/week), fast (>5 mg/week), direct discontinuation or no prednisolone. Patients intolerant to corticosteroids and patients stopping corticosteroids in preparation for surgery including colectomy during their initial admission were excluded. RESULTS: There was no overall association between prednisolone exposure or no exposure and CFCR at weeks 14 or 52 of infliximab. The proportion of patients with C reactive protein ≤5 mg/L was higher in the standard tapering at week 14 as compared with faster regimens or no prednisolone. In subgroup analyses, the standard tapering was associated with a higher rate of CFCR at week 14 compared with the fast-tapering regimen in patients receiving ≥40 mg prednisolone at initiation of infliximab (64.3% vs 26.3%, p=0.04) and among patients admitted with acute severe UC (66.6% vs 23.5%, p<0.05). Similar data were seen at week 52. Prednisolone did not affect infliximab trough levels but increased infection rates (10/77 vs 2/70, p=0.03), in particular C. difficile infection. CONCLUSION: In UC patients with limited disease burden, prednisolone did not affect effectiveness of infliximab. However, patients with increased disease burden seem to benefit from corticosteroid combination therapy.
Assuntos
Colite Ulcerativa , Fármacos Gastrointestinais , Infliximab , Prednisolona , Indução de Remissão , Humanos , Colite Ulcerativa/tratamento farmacológico , Infliximab/administração & dosagem , Infliximab/uso terapêutico , Estudos Retrospectivos , Prednisolona/administração & dosagem , Prednisolona/uso terapêutico , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Resultado do Tratamento , Indução de Remissão/métodos , Fármacos Gastrointestinais/administração & dosagem , Fármacos Gastrointestinais/uso terapêutico , Redução da Medicação/métodos , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/efeitos adversos , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Glucocorticoides/efeitos adversos , Quimioterapia CombinadaRESUMO
Autoimmune liver diseases are associated with an increased risk of diabetes, yet the underlying mechanisms remain unknown. In this cross-sectional study, we investigated the glucose-regulatory disturbances in patients with autoimmune hepatitis (AIH, n = 19), primary biliary cholangitis (PBC, n = 15), and primary sclerosing cholangitis (PSC, n = 6). Healthy individuals (n = 24) and patients with metabolic dysfunction-associated steatotic liver disease (MASLD, n = 18) were included as controls. Blood samples were collected during a 120-min oral glucose tolerance test. We measured the concentrations of glucose, C-peptide, insulin, glucagon, and the two incretin hormones, glucose insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1). We calculated the homeostasis model assessment of insulin resistance (HOMA-IR), whole body insulin resistance (Matsuda index), insulin clearance, and insulinogenic index. All patient groups had increased fasting plasma glucose and impaired glucose responses compared with healthy controls. Beta-cell secretion was increased in AIH, PBC, and MASLD but not in PSC. Patients with AIH and MASLD had hyperglucagonemia and hepatic, as well as peripheral, insulin resistance and decreased insulin clearance, resulting in hyperinsulinemia. Patients with autoimmune liver disease had an increased GIP response, and those with AIH or PBC had an increased GLP-1 response. Our data demonstrate that the mechanism underlying glucose disturbances in patients with autoimmune liver disease differs from that underlying MASLD, including compensatory incretin responses in patients with autoimmune liver disease. Our results suggest that glucose disturbances are present at an early stage of the disease.NEW & NOTEWORTHY Patients with autoimmune liver disease but without overt diabetes display glucose disturbances early on in their disease course. We identified pathophysiological traits specific to these patients including altered incretin responses.
Assuntos
Glicemia , Hepatite Autoimune , Resistência à Insulina , Insulina , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Glicemia/metabolismo , Estudos Transversais , Adulto , Insulina/sangue , Hepatite Autoimune/sangue , Hepatite Autoimune/metabolismo , Hepatite Autoimune/complicações , Peptídeo 1 Semelhante ao Glucagon/sangue , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Fígado Gorduroso/metabolismo , Fígado Gorduroso/sangue , Polipeptídeo Inibidor Gástrico/sangue , Polipeptídeo Inibidor Gástrico/metabolismo , Idoso , Teste de Tolerância a Glucose , Colangite Esclerosante/sangue , Colangite Esclerosante/metabolismo , Colangite Esclerosante/complicações , Glucagon/sangue , Glucagon/metabolismo , Cirrose Hepática Biliar/sangue , Cirrose Hepática Biliar/metabolismo , Cirrose Hepática Biliar/complicações , Peptídeo C/sangueRESUMO
In the Danish Polyposis Register, patients with over 100 cumulative colorectal adenomas of unknown genetic etiology, named in this study colorectal polyposis (CP), is registered and treated as familial adenomatous polyposis (FAP). In this study, we performed genetic analyses, including whole genome sequencing (WGS), of all Danish patients registered with CP and estimated the detection rate of pathogenic variants (PV). We identified 231 families in the Polyposis Register, 31 of which had CP. A polyposis-associated gene panel was performed and, if negative, patients were offered WGS and screening for mosaicism in blood and/or adenomas. Next-generation sequencing (NGS) was carried out for 27 of the families (four declined). PVs were detected in 11 families, and WGS revealed three additional structural variants in APC. Mosaicism of a PV in APC was detected in two families. As the variant detection rate of eligible families was 60%, 93% of families in the register now have a known genetic etiology.
Assuntos
Proteína da Polipose Adenomatosa do Colo , Polipose Adenomatosa do Colo , Humanos , Polipose Adenomatosa do Colo/genética , Feminino , Proteína da Polipose Adenomatosa do Colo/genética , Masculino , Dinamarca , Adulto , Genótipo , Pessoa de Meia-Idade , Testes Genéticos/métodos , Mosaicismo , Sistema de RegistrosRESUMO
BACKGROUND: The association between inflammatory bowel disease (IBD) and malignancy remains disputed despite many observational studies. The Faroese population exhibits the highest occurrence of IBD in the world. This study aimed to investigate the cancer risk in Faroese IBD patients in a nationwide IBD cohort. METHODS: This study included all IBD patients diagnosed in the Faroe Islands between 1960 and 2020. Clinical demographics and cancer diagnoses were retrieved from patient files and the Faroese cancer registry. Cancer risk in IBD patients was calculated as standardized incidence ratios (SIRs) based on the Faroese background population's age- and sex-specific cancer incidence rates, retrievable from NORDCAN. RESULTS: The cohort consisted of 699 patients with a total follow-up time of 9,629 person-years. Overall, the risk of cancer was not statistically significantly increased compared to the background population. Patients diagnosed with cancer at age 50-59 years had higher overall cancer risk (SIR 1.8; 95% CI, 1.02-2.99) as did UC patients diagnosed with IBD at 50-59 (SIR 2.1; 95% CI, 1.10-3.54). Absolute numbers were small and no estimates for site-specific cancers reached statistical significance, though lung, breast, and cancer of the female reproductive organs were elevated among IBD and UC patients, and colorectal cancer in CD patients. CONCLUSIONS: This nationwide study found no statistically significantly increased risk of cancer among Faroese patients with CD or UC, except from age 50 to 59 years. While the incidence of IBD is significantly higher in the Faroe Islands than in other countries, risk estimates of cancers are comparable.
Assuntos
Doenças Inflamatórias Intestinais , Neoplasias , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/epidemiologia , Humanos , Masculino , Feminino , Neoplasias/epidemiologia , Pessoa de Meia-Idade , Dinamarca/epidemiologia , Incidência , Estudos de Coortes , Fatores de Risco , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Adulto , Idoso , Idoso de 80 Anos ou mais , Colite Ulcerativa , Doença de CrohnRESUMO
OBJECTIVES: Musculoskeletal [MSK] manifestations in patients with inflammatory bowel disease [IBD] are common and associated with poorer outcomes. Hence, early detection is important to optimally tailor treatment. We aimed to determine the prevalence and distribution of inflammatory lesions in peripheral joints and entheses in newly diagnosed IBD patients. DESIGN: Patients with newly diagnosed IBD from a prospective population-based inception cohort were consecutively included. Data on MSK symptoms were collected by questionnaires and by structured rheumatological interview. Peripheral joints and entheses were assessed clinically and by ultrasound [US], using standardized definitions. RESULTS: Of 110 included patients (mean age: 42 years, 40% male, 70 with ulcerative colitis [UC], 40 with Crohn's disease [CD]), a history of ≥1 peripheral musculoskeletal symptom was reported by 49%. Clinical examination revealed peripheral MSK manifestations in 56 [52.3%] patients; 29 [27.1%] had ≥1 tender and/or swollen joints and 49 [45.8%] ≥1 tender entheses. Small peripheral joints were predominantly affected. US found inflammation in ≥1 joint or enthesis in 52 [49.5 %] patients; 29 [27.4 %] had US synovitis in ≥1 joint, while 36 [34%] had US enthesitis. Fibromyalgia classification criteria were fulfilled in seven [7.9%] patients. There was no difference in clinical or US findings between patients with UC and CD, nor between patients with active and inactive IBD. CONCLUSION: Half of the patients with newly diagnosed IBD had inflammation in their peripheral joints and/or entheses, documented by rheumatological clinical and US evaluations. This indicates a need for multidisciplinary collaboration to ensure an optimal therapeutic strategy for suppressing inflammation in all disease domains.