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1.
  • Axelrad, Jordan, et al. (författare)
  • Inflammatory Bowel Disease and Risk of Colorectal Polyps : A nationwide population-based cohort study from Sweden
  • 2023
  • Ingår i: Journal of Crohn's & Colitis. - : Oxford University Press. - 1873-9946 .- 1876-4479. ; 17:9, s. 1395-1409
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Inflammatory bowel disease (IBD) has been linked to an increased risk of colorectal neoplasia. However, the types and risks of specific polyp types in IBD are less clear.METHODS: We identified 41,880 individuals with IBD [Crohn's disease (CD: n=12,850); Ulcerative colitis (UC): n=29,030)] from Sweden matched with 41,880 reference individuals. Using Cox regression, we calculated adjusted hazard ratios (aHRs) for neoplastic colorectal polyps (Tubular, Serrated/Sessile, Advanced and Villous) defined by histopathology codes.RESULTS: During follow-up, 1648 (3.9%) IBD patients and 1143 (2.7%) reference individuals had an incident neoplastic colorectal polyp, corresponding to an incidence rate of 46.1 and 34.2 per 10,000 person-years, respectively. This correlated to an aHR of 1.23 (95% CI 1.12-1.35) with the highest HRs seen for sessile serrated polyps (8.50, 95% CI 1.10-65.90) and traditional serrated adenomas (1.72, 95% CI 1.02-2.91). aHRs for colorectal polyps were particularly elevated in those diagnosed with IBD at a young age and after 10 years after diagnosis. Both absolute and relative risks of colorectal polyps were higher in UC than in CD (aHRs 1.31 vs. 1.06, respectively), with a 20-year cumulative risk differences of 4.4% in UC and 1.5% in CD, corresponding to one extra polyp in 23 patients with UC and one in 67 CD patients during the first 20 years after IBD diagnosis.CONCLUSIONS: In this nationwide population-based study, there was an increased risk of neoplastic colorectal polyps in IBD patients. Colonoscopic surveillance in IBD appears important, especially in UC and after 10 years of disease.
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2.
  • Bergman, David, et al. (författare)
  • Microscopic Colitis and Risk Of Cancer-AA Population-Based Cohort Study
  • 2021
  • Ingår i: Journal of Crohn's & Colitis. - : Oxford University Press. - 1873-9946 .- 1876-4479. ; 15:2, s. 212-221
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Aims: The association between microscopic colitis [MC] and cancer risk is unclear. Large, population-based studies are lacking.Methods: We conducted a nationwide cohort study of 11 758 patients with incident MC [diagnosed 1990-2016 in Sweden], 50 828 matched reference individuals, and 11 614 siblings to MC patients. Data were obtained through Sweden's pathology departments and from the Swedish Cancer Register. Adjusted hazard ratios [aHRs] were calculated using Cox proportional hazards models.Results: At the end of follow-up [mean: 6.7 years], 1239 [10.5%] of MC patients had received a cancer diagnosis, compared with 4815 [9.5%] of reference individuals (aHR 1.08 [95% confidence interval1.02-1.16]). The risk of cancer was highest during the first year of follow up. The absolute excess risks for cancer at 5, 10, and 20 years after MC diagnosis were + 1.0% (95% confidence interval [C1]0.4%-1.6%), +1.5% [0.4%-2.6%], and + 3.7% [-2.3-9.6%], respectively, equivalent to one extra cancer event in every 55 individuals with MC followed for 10 years. MC was associated with an increased risk of lymphoma (aHR 1.43 [1.06-1.92]) and lung cancer (aHR 1.32 [1.04-1.68]) but with decreased risks of colorectal (aHR 0.52 [0.40-0.66]) and gastrointestinal cancers (aHR 0.72 [0.60-0.85]). We found no association with breast or bladder cancer. Using siblings as reference group to minimise the impact of shared genetic and early environmental factors, patients with MC were still at an increased risk of cancer (HR 1.20 [1.06-1.36]).Conclusions: This nationwide cohort study demonstrated an 8% increased risk of cancer in MC patients. The risk was highest during the first year of follow-up.
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3.
  • Bergman, David, et al. (författare)
  • Two waves of coeliac disease incidence in Sweden : a nationwide population-based cohort study from 1990 to 2015
  • 2022
  • Ingår i: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 71:6, s. 1088-1094
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To assess the incidence of biopsy-verified coeliac disease (CD) in Sweden and examine the incidence of duodenal/jejunal biopsies with normal mucosa over time as a proxy for CD awareness and investigation.Design: Nationwide population-based cohort study 1990-2015 based on biopsy reports indicating villous atrophy (VA) or normal mucosa in the duodenum/jejunum.Results: We identified 44 771 individuals (63% females) with a biopsy report specifying VA and 412 279 (62% females) with a biopsy report indicating normal mucosa (without a prior biopsy indicating VA). The median age at diagnosis of CD was 28 years. The mean age-standardised incidence rate during the study period was 19.0 per 100 000 person-years (95% CI 17.3 to 20.8). The incidence reached a peak in 1994 for both sexes and a second higher peak in 2002-2003 for females and in 2006 for males. The lifetime risk of developing CD was 1.8% (2.3% in females and 1.4% in males). Prior to 2015, there was a parallel rise in rates for biopsies showing normal duodenal/jejunal mucosa.Conclusions: In Sweden, the incidence of CD increased until 2002-2003 in females and until 2006 in males. Since then, the incidence of CD has declined despite increasing duodenal/jejunal biopsies, suggesting that increased awareness and investigation are unlikely to elevate the incidence of the disease in Sweden. Across a lifetime, 1 in 44 females and 1 in 72 males are expected to be diagnosed with CD in Sweden, indicating a relatively high societal burden of disease.
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4.
  • Bledsoe, Adam C., et al. (författare)
  • Mortality and cancer in eosinophilic gastrointestinal disorders distal to the esophagus : nationwide cohort study 1990-2017
  • 2022
  • Ingår i: Journal of gastroenterology. - : Springer. - 0944-1174 .- 1435-5922. ; 57, s. 735-747
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Eosinophilic gastrointestinal disorders (EGIDs) include inflammatory conditions with enteric infiltration of eosinophils and resulting symptoms. This study aims to examine a population-based sample of patients for prevalence, mortality, and cancer risk in EGIDs distal to the esophagus.Methods: Nationwide, population-based cohort study. EGID was identified through relevant biopsy codes from Sweden's all 28 pathology departments through the ESPRESSO cohort. Individuals with EGID were then matched to general population reference individuals with similar age and sex. Study participants were linked to Swedish healthcare registers. Through Cox regression, we calculated adjusted hazard ratios (aHRs) adjusting for sex, age, county, calendar period, and education.Results: In total, 2429 patients (56% female) were found to have EGID distal to the esophagus, representing a prevalence of about 1/4800 in the Swedish population. Mean age was 44 years with 11% children at the time of diagnosis. Mortality was increased 17% in patients with EGIDs compared to reference individuals (aHR = 1.17; 95%CI = 1.04-1.33). Excess mortality was seen in gastric and small bowel eosinophilic disease, but not colonic disease (aHR = 1.81; 95%CI = 1.32-2.48, aHR = 1.50; 95%CI = 1.18-1.89, and aHR = 0.99; 95%CI = 0.85-1.16, respectively). Cause specific mortality was driven by cancer-related death (aHR = 1.33; 95%CI = 1.05-1.69). However, this study failed to show an increase in incident cancers (aHR = 1.14; 95%CI = 0.96-1.35). Comparison of EGID individuals with their siblings yielded similar aHRs.Conclusions: This study found an increased risk of death in patients with EGIDs distal to the esophagus, with cancer death driving the increase. Proximal gut disease seems to confer the greatest risk. There was no increase in incident cancers.
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5.
  • Boberg, Julia, et al. (författare)
  • Swedish multimodal cohort of patients with anxiety or depression treated with internet-delivered psychotherapy (MULTI-PSYCH)
  • 2023
  • Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 13:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose Depression and anxiety afflict millions worldwide causing considerable disability. MULTI-PSYCH is a longitudinal cohort of genotyped and phenotyped individuals with depression or anxiety disorders who have undergone highly structured internet-based cognitive-behaviour therapy (ICBT). The overarching purpose of MULTI-PSYCH is to improve risk stratification, outcome prediction and secondary preventive interventions. MULTI-PSYCH is a precision medicine initiative that combines clinical, genetic and nationwide register data.Participants MULTI-PSYCH includes 2668 clinically well-characterised adults with major depressive disorder (MDD) (n=1300), social anxiety disorder (n=640) or panic disorder (n=728) assessed before, during and after 12 weeks of ICBT at the internet psychiatry clinic in Stockholm, Sweden. All patients have been blood sampled and genotyped. Clinical and genetic data have been linked to several Swedish registers containing a wide range of variables from patient birth up to 10 years after the end of ICBT. These variable types include perinatal complications, school grades, psychiatric and somatic comorbidity, dispensed medications, medical interventions and diagnoses, healthcare and social benefits, demographics, income and more. Long-term follow-up data will be collected through 2029.Findings to date Initial uses of MULTI-PSYCH include the discovery of an association between PRS for autism spectrum disorder and response to ICBT, the development of a machine learning model for baseline prediction of remission status after ICBT in MDD and data contributions to genome wide association studies for ICBT outcome. Other projects have been launched or are in the planning phase.Future plans The MULTI-PSYCH cohort provides a unique infrastructure to study not only predictors or short-term treatment outcomes, but also longer term medical and socioeconomic outcomes in patients treated with ICBT for depression or anxiety. MULTI-PSYCH is well positioned for research collaboration.
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6.
  • Cameron, Raquel, et al. (författare)
  • Mortality risk increased in colonic diverticular disease : a nationwide cohort study
  • 2022
  • Ingår i: Annals of Epidemiology. - : Elsevier. - 1047-2797 .- 1873-2585. ; 76, s. 39-49
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: There are limited population cohort data on overall and cause-specific mortality in colonic diverticular disease.Objective: To measure overall and cause-specific mortality in colonic diverticular disease, compared to matched reference individuals and siblings.Methods: Population-based cohort study ("the ESPRESSO study") in Sweden. There were 97,850 cases with a medical diagnosis of diverticular disease (defined by international classification of disease codes) and colorectal histology identified in 1987-2017 from histopathology reports. The mortality risk between individuals with colonic diverticular disease and matched reference individuals ( n = 453/634) from the general population was determined. Cox regression models adjusted for comorbidity estimated hazard ratios (HRs) for all-cause mortality.
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7.
  • Doyle, John B., et al. (författare)
  • Risk of Juvenile Idiopathic Arthritis and Rheumatoid Arthritis in Patients With Celiac Disease : A Population-Based Cohort Study
  • 2022
  • Ingår i: American Journal of Gastroenterology. - : Wolters Kluwer. - 0002-9270 .- 1572-0241. ; 117:12, s. 1971-1981
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: Celiac disease (CD) is associated with many immune-mediated conditions, but a definitive epidemiological association between CD and juvenile idiopathic arthritis (JIA) or rheumatoid arthritis (RA) has not been established. We quantified the risk of JIA and RA among patients with CD using a population-based cohort.METHODS: We identified patients diagnosed with biopsy-proven CD between 2004 and 2017 using data from a national histopathology cohort in Sweden. Each patient was matched by age, sex, calendar year, and geographic region to reference individuals in the general population. We calculated the incidence and estimated the relative risk, through Cox proportional hazards models, of JIA in individuals with CD aged ≥18.RESULTS: We identified 24,014 individuals with CD who were matched to 117,397 reference individuals from the general population. Among individuals aged <18, the incidence rate of JIA was 5.9 per 10,000 person-years in patients with CD and 2.2 per 10,000 person-years in the general population (n events = 40 and 73, respectively; hazard ratio [HR] 2.68, 95% confidence interval 1.82-3.95) over a follow-up of 7.0 years. Among individuals aged >= 18, the incidence of RA was 8.4 per 10,000 person-years in CD and 5.1 per 10,000 person-years in matched comparators (n events = 110 and 322, respectively; HR 1.70, 95% confidence interval 1.36-2.12) over a follow-up of 8.8 years.DISCUSSION: Among children with CD, JIA develops nearly 3 times as often as it does in the general population, and among adults with CD, RA occurs nearly 2 times as often. Clinicians caring for patients with CD with joint symptoms should have a low threshold to evaluate for JIA or RA.
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8.
  • Forss, Anders, et al. (författare)
  • A nationwide cohort study of the incidence of inflammatory bowel disease in Sweden from 1990 to 2014
  • 2022
  • Ingår i: Alimentary Pharmacology and Therapeutics. - : Wiley-Blackwell Publishing Inc.. - 0269-2813 .- 1365-2036. ; 55:6, s. 691-699
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Epidemiological studies have shown inconsistent incidence rates (IRs) for inflammatory bowel disease (IBD).AIM: To assess the incidence and temporal trends of IBD in Sweden.METHODS: Nationwide cohort study based on diagnostic codes for IBD and biopsy reports registered through the ESPRESSO cohort in 1990-2014. Age-specific and age-standardised IRs and cumulative incidence were calculated.RESULTS: Overall, we identified 65 908 cases of incident IBD: ulcerative colitis (UC, n = 38 261, 58%), Crohn's disease (CD, n = 18 577, 28%) and IBD-U (n = 9070, 14%). During 1990-2014, the overall IRs per 100 000 person-years were 29.0 (95% CI: 27.3-30.7) for IBD, 16.9 (15.9-17.9) for UC, and 8.1 (7.7-8.6) for CD. For IBD-U, the IR was 5.2 (4.9-5.6) in 2002-2014. The annual incidence of IBD, UC and CD increased by approximately 7% per year between 1990 and 2001 (P < 0.001) and then decreased by 1%-2% per year from 2002 onwards (P < 0.001). IRs for IBD, UC and IBD-U were higher in males while the IR for CD was higher in females. The lifetime risk of IBD was about 2.5% for both sexes.CONCLUSIONS: In Sweden, the incidence of IBD in all subtypes increased in 1990-2001 but has since declined. One in 40 individuals is expected to be diagnosed with IBD during their lifetime.
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9.
  • Forss, Anders, et al. (författare)
  • Patients With Microscopic Colitis Are at Higher Risk of Major Adverse Cardiovascular Events : A Matched Cohort Study
  • 2023
  • Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 21:13
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND AIMS: Inflammatory diseases are associated with an increased risk of incident major adverse cardiovascular events (MACE). However, data on MACE are lacking in large population-based histopathology cohorts of microscopic colitis (MC).METHODS: This study included all Swedish adults with MC without previous cardiovascular disease (1990- 2017; N = 11,018). MC and subtypes (collagenous colitis and lymphocytic colitis) were defined from prospectively recorded intestinal histopathology reports from all pathology departments (n = 28) in Sweden. MC patients were matched for age, sex, calendar year, and county with up to 5 reference individuals (N = 48,371) without MC or cardiovascular disease. Sensitivity analyses included full sibling comparisons, and adjustment for cardiovascular medication and healthcare utilization. Multivariable-adjusted hazard ratios for MACE (any of ischemic heart disease, congestive heart failure, stroke, and cardiovascular mortality) were calculated using Cox proportional hazards modelling. RESULTS: Over a median of 6.6 years of follow-up, 2181 (19.8%) incident cases of MACE were confirmed in MC patients and 6661 (13.8%) in reference individuals. MC patients had a higher overall risk of MACE outcomes compared with reference individuals (adjusted hazard ratio [aHR], 1.27; 95% confidence interval [CI], 1.21-1.33) and higher risk of its components: ischemic heart disease (aHR, 1.38; 95% CI, 1.28-1.48), congestive heart failure (aHR, 1.32; 95% CI, 1.22-1.43), and stroke (aHR, 1.12; 95% CI, 1.02-1.23) but not cardiovascular mortality (aHR, 1.07; 95% CI, 0.98-1.18). The results remained robust in the sensitivity analyses.CONCLUSIONS: Compared with reference individuals, MC patients had a 27% higher risk of incident MACE, equal to 1 extra case of MACE for every 13 MC patients followed for 10 years.
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10.
  • Garber, John J., et al. (författare)
  • Increasing incidence of eosinophilic esophagitis in Sweden : a nationwide population study
  • 2022
  • Ingår i: Esophagus. - : Springer. - 1612-9059 .- 1612-9067. ; 19:4, s. 535-541
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Eosinophilic esophagitis (EoE) is a chronic inflammatory condition of the esophagus associated with dysphagia and esophageal fibrosis. The incidence of EoE is not precisely known, and significant heterogeneity in study design and disease definition have led to widely variable estimates. Through the ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden) study we performed a nationwide population-based study to estimate the incidence and temporal patterns of biopsy-verified EoE.Methods: Between October 2015 and April 2017, we contacted all pathology departments in Sweden (n = 28) to obtain biopsy report data on EoE. To assure a high degree of completeness, we restricted the study to 2004-2015. We then calculated age-specific and age-standardized incidence rates.Results: We identified 1412 incident EoE cases between 2004-2015. The overall age-standardized incidence rates of EoE in Sweden was 1.22 per 100,000 person-years. During the study period, there was a significant increase of 33% [95%CI = 31-36%] (P < 0.001) per year in EoE incidence, and in the last 3 years of follow-up (2013-2015) the incidence was 2.79 per 100,000 person-years. This corresponds to a lifetime risk of biopsy-verified EoE for men of 0.33% (1 in 295 men) and for women 0.12% (1 in 813 women). We observed an early peak of EoE disgnosed at age 15-19 years for both males and females, and a second peak in the late 30 s for males, and early 40 s for females. We noted a 3:1 male-to-female predominance, which did not significantly vary over time.Conclusions: EoE seems to be increasing in Sweden, with an overall age-standardized incidence of EoE of 1.22 per 100,000 person-years in the last decade.
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11.
  • Garber, John J., et al. (författare)
  • Risk of fractures in individuals with eosinophilic esophagitis : nationwide population-based cohort study
  • 2022
  • Ingår i: Esophagus. - : Springer. - 1612-9059 .- 1612-9067. ; 19:4, s. 542-553
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and aims: Eosinophilic esophagitis (EoE) is an emerging, chronic immune-mediated disease for which swallowed topical steroids and proton pump inhibitors (PPIs) represent first-line treatments. Immune-mediated diseases, steroids, and PPI use have been linked to osteoporosis. We assessed the risk of fractures in patients with EoE and determined whether the most commonly used treatments for EoE were associated with increased fracture risk.Methods: We followed a nationwide cohort of 1263 individuals in Sweden with biopsy-verified EoE diagnosed between 2005 and 2016 for first-time fracture of any type. Age- and sex-matched reference individuals were retrieved from the Total Population Register (n = 5164). We estimated hazard ratios (HRs) for fracture in relation to EoE diagnosis, steroid exposure, and PPI use. In a separate analysis, we compared fracture risk among individuals with EoE to their siblings (n = 1394).Results: During 4521 person-years of follow-up, 69 individuals with EoE experienced a first-time fracture (15.3/1000 person-years) compared with 234 reference individuals (12.6/1000 person-years). After adjusting for age, sex, birth year, and county of residence, EoE was not associated with a statistically significantly increased risk of fractures (HR = 1.2, 95% CI = 0.9-1.6). Among EoE individuals, exposure to PPIs and swallowed steroids did not modify the risk of fracture (p for heterogeneity 0.20 and 0.07 respectively). There was no increased risk of fractures in EoE compared to EoE-free siblings.Conclusion: The risk of fracture in EoE was not statistically significantly elevated compared to non-EoE reference individuals. Fracture risk in EoE was not modified by PPIs or steroid use.
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12.
  • Hagström, Hannes, et al. (författare)
  • Cardiovascular Outcomes in Patients With Biopsy-proven Alcohol-related Liver Disease
  • 2023
  • Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 21:7, s. 1841-1853.e12
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND & AIMS: Patients with alcohol-related liver disease (ALD) frequently have risk factors for cardiovascular disease (CVD), but their long-term risk of CVD is not well-known, especially considering the competing risk of death from liver-related causes. It is further unknown if any excess risk varies across histological subgroups.METHODS: We investigated the risk of CVD outcomes in 3488 persons with ALD and an available liver biopsy in Sweden between 1969 and 2016, compared with a matched reference population (n = 15,461). Administrative coding from national diagnostic and histopathology registers were used to define exposures and outcomes. Competing risk regression, taking non-CVD death into account and adjusting for potential confounders, was used to estimate subdistribution hazard ratios for incident CVD up until Dec 31, 2019.RESULTS: At baseline, patients with ALD had a median age of 58 years, 64% were men, and 2039 (58%) had cirrhosis on histology. The incidence rate of CVD was 35.6 per 1000 person-years in ALD compared with 19.0 per 1000 person-years in reference individuals. ALD was associated with a 2-fold increased short-term risk for CVD compared with matched reference individuals (subdistribution hazard ratio during the first year after diagnosis, 2.29; 95% confidence interval, 1.79-2.95), but this risk decreased with time. Incidence rates of CVD were comparable across histological subgroups (ranging from 27.4 CVD cases per 1000 person-years in those with normal histology to 39.2 cases per 1000 person-years in those with cirrhosis).CONCLUSIONS: Persons with biopsy-proven ALD have increased rates of CVD across histological subgroups compared with matched reference individuals, particularly just after ALD diagnosis. Active surveillance of modifiable CVD risk factors should be considered by clinicians treating patients with ALD.
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13.
  • Hagström, Hannes, et al. (författare)
  • Maternal obesity increases the risk and severity of NAFLD in offspring
  • 2021
  • Ingår i: Journal of Hepatology. - : Elsevier. - 0168-8278 .- 1600-0641. ; 75:5, s. 1042-1048
  • Tidskriftsartikel (refereegranskat)abstract
    • Background & Aims: Maternal obesity has been linked to the development of cardiovascular disease and diabetes in offspring, but its relationship to non-alcoholic fatty liver disease (NAFLD) is unclear.Methods: Through the nationwide ESPRESSO cohort study we identified all individuals <= 25 years of age in Sweden with biopsy verified NAFLD diagnosed between 1992 and 2016 (n = 165). These were matched by age, sex, and calendar year with up to 5 controls (n = 717). Through linkage with the nationwide Swedish Medical Birth Register (MBR) we retrieved data on maternal early-pregnancy BMI, and possible confounders, in order to calculate adjusted odds ratios (aORs) for NAFLD in offspring.Results: Maternal BMI was associated with NAFLD in offspring: underweight (aOR 0.84; 95% CI 0.14-5.15), normal weight (reference, aOR 1), overweight (aOR 1.51; 0.95-2.40), and obese (aOR 3.26; 1.72-6.19) women. Severe NAFLD (biopsy-proven fibrosis or cirrhosis) was also more common in offspring of overweight (aOR 1.94; 95% CI 0.96-3.90) and obese (aOR 3.67; 95% CI 1.61-8.38) mothers. Associations were similar after adjusting for maternal pre-eclampsia and gestational diabetes. Socio-economic parameters (smoking, mother born outside the Nordic countries and less than 10 years of basic education) were also associated with NAFLD in offspring but did not materially alter the effect size of maternal BMI in a multivariable model.Conclusions: This nationwide study found a strong association between maternal overweight/obesity and future NAFLD in offspring. Adjusting for socio-economic and metabolic parameters in the mother did not affect this finding, suggesting that maternal obesity is an independent risk factor for NAFLD in offspring.Lay summary: In a study of all young persons in Sweden with a liver biopsy consistent with fatty liver, the authors found that compared to matched controls, the risk of fatty liver was much higher in those with obese mothers. This was independent of available confounders and suggests that the high prevalence of obesity in younger persons might lead to a higher risk of fatty liver in their offspring.
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14.
  • Hagström, Hannes, et al. (författare)
  • Mortality in biopsy-proven alcohol-related liver disease : a population-based nationwide cohort study of 3453 patients
  • 2021
  • Ingår i: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 70:1, s. 170-179
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Patients with alcohol-related liver disease (ALD) are at increased risk of death, but studies have rarely investigated the significance of histological severity or estimated relative risks compared with a general population. We examined mortality in a nationwide cohort of biopsy-proven ALD.Design: Population-based cohort study in Sweden comparing 3453 individuals with an International Classification of Disease (ICD) code for ALD and a liver biopsy from 1969 to 2017 with 16 535 matched general population individuals. Swedish national registers were used to ascertain overall and disease-specific mortality, starting follow-up at the latest of first ICD diagnosis or liver biopsy plus 3 months. Cox regression adjusted for relevant confounders was used to estimate HRs in ALD and histopathological subgroups.Results: Median age at diagnosis was 58 years, 65% were men and 52% had cirrhosis at baseline. Five-year cumulative mortality was 40.9% in patients with ALD compared with 5.8% in reference individuals. The risk for overall mortality was significantly increased (adjusted HR (aHR)=4.70, 95% CI 4.35 to 5.08). The risk of liver-related death was particularly high (43% of all deaths, aHR=167.6, 95% CI 101.7 to 276.3). Mortality was significantly increased also in patients with ALD without cirrhosis and was highest in the first year after baseline but persisted after >= 10 years of follow-up (aHR=2.74, 95% CI 2.37 to 3.16).Conclusion: Individuals with biopsy-proven ALD have a near fivefold increased risk of death compared with the general population. Individuals with ALD without cirrhosis were also at increased risk of death, reaffirming the need to increase vigilance in the management of these individuals.
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15.
  • Hagström, Hannes, et al. (författare)
  • Risk of Cancer in Biopsy-Proven Alcohol-Related Liver Disease : A Population-Based Cohort Study of 3410 Persons
  • 2022
  • Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 20:4, s. 918-929
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND & AIMS: Persons with alcohol-related liver disease (ALD) are at an increased risk of death and liver-related endpoints, but the association with incident cancer is not well understood, and whether it differs across histopathological subgroups is undefined.METHODS: We investigated the risk of cancer in 3,410 persons with a diagnosis of ALD and an available liver biopsy in Sweden between 1969-2016, compared to a matched reference population. Administrative coding from national registers and liver biopsy data were used to define exposure and outcome status. Competing risk regression, adjusted for available confounders and using non-cancer mortality as the competing risk, was used to estimate subdistribution hazard ratios (sHRs) for incident cancer.RESULTS: At baseline, persons with ALD had a median age of 58.2 years, 67% were men, and 2,042 (60%) had cirrhosis. ALD was not associated with cancer in general (sHR = 1.01, 95%CI = 0.92-1.11), although the risk was increased in persons surviving >= 1 year (sHR = 1.19, 95% CI = 1.08-1.32). The risk of liver cancer was elevated sHR = 12.80, 95%CI = 9.38-17.45). HCC incidence among ALD persons with cirrhosis was 8.6 cases/1,000 person-years, corresponding to a cumulative incidence after 10 years of 5.0%.CONCLUSIONS: Persons with biopsy-proven ALD that survive the initial time after diagnosis are at an elevated risk for cancer, in particular HCC compared with the general population. Although the risk for HCC was elevated, data do not suggest that routine surveillance for HCC in ALD cirrhosis is cost-effective.
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16.
  • Hagström, Hannes, et al. (författare)
  • Risk of infections and their role on subsequent mortality in biopsy-proven alcohol-related liver disease
  • 2022
  • Ingår i: United European Gastroenterology journal. - : John Wiley & Sons. - 2050-6406 .- 2050-6414. ; 10:2, s. 198-211
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Aims: The risk for infection in alcohol-related liver disease (ALD) has rarely been investigated at a population level, nor if the underlying liver histopathology is associated with infection risk. We examined the rate of hospital-based infections in a nationwide cohort of biopsy-proven ALD, and the subsequent risk of death.Methods: Population-based cohort study in Sweden comparing 4028 individuals with an international classification of disease (ICD) code for ALD and a liver biopsy from 1969 to 2017 with 19,296 matched general population individuals. Swedish national registers were used to ascertain incident infections in secondary or tertiary care and subsequent mortality until 2019. We used Cox regression, adjusted for sex, age, education, country of birth, diabetes, and number of hospitalizations in the year preceding liver biopsy date, to estimate hazard ratios (HRs) in ALD and histopathological subgroups compared to reference individuals.Results: Median age at ALD diagnosis was 59 years, 65% were men and 59% had cirrhosis at baseline. Infections were more common in patients with ALD (84 cases/1000 person-years [PY]) compared to reference individuals (29/1000 PYs; adjusted hazard ratio [aHR] 3.06, 95% CI = 2.85-3.29). This excess risk corresponded to one additional infection per 18 ALD patients each year. The rate of infections was particularly high in individuals with cirrhosis (aHR = 3.46) and in those with decompensation (aHR = 5.20). Restricting our data to those with an infection, ALD (aHR = 3.63, 95%CI = 3.36-3.93), and especially ALD cirrhosis (aHR = 4.31, 95%CI = 3.89-4.78) were linked to subsequent death.Conclusions: Individuals with biopsy-proven ALD have a three-fold increased rate of infections compared with the general population. The risk of death after an infection is also considerably higher in individuals with ALD.
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17.
  • Kang, Xiaoying, et al. (författare)
  • Association between Microscopic Colitis and Parkinson's Disease in a Swedish Population
  • 2021
  • Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 96:15
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Gastrointestinal inflammation has been linked with Parkinson's disease (PD). Microscopic colitis (MC) is an intestinal inflammatory disease with unknown relationship with PD.Objective: This study aimed to examine the association of MC with PD risk.Methods: In this nationwide matched cohort study in Sweden, PD incidence was compared between 12,609 patients with histologically confirmed MC and a matched population cohort of 58,879 MC-free individuals and a sibling cohort comprising all unaffected siblings of the MC patients (N-MC/N-Sibling = 6281/12,351). Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression models.Results: During a mean follow-up of similar to 7 years, we identified 449 incident PD diagnoses among the MC patients and the population cohort. Overall, MC was associated with an adjusted HR of 1.76 for PD, but the association attenuated substantially during follow-up. In the time-varying effects model, PD hazard was 3.45-fold (95% CI: 2.42, 4.93) higher during the first 2 years after biopsy and 1.80-fold (95% CI: 1.23, 2.64) higher during the following 3 years among MC versus MC-free individuals but was not different beyond 5 years after biopsy (HR: 1.03; 95% CI: 0.68, 1.54). This temporal pattern of MC-PD associations persisted when comparing MC patients to their siblings. In a post hoc case-control analysis, we also detected a strong association between MC and preexisting PD (odds ratio: 3.46; 95% CI: 2.91, 4.12).Conclusions: Our findings suggest that MC may not be a risk factor for PD; instead, it may co-occur with PD as a comorbidity or develop after a diagnosis of PD.
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18.
  • Kang, Xiaoying, et al. (författare)
  • Association between Microscopic Colitis and Parkinson's Disease in a Swedish Population
  • 2021
  • Ingår i: Neurology. - : Wolters Kluwer. - 0028-3878 .- 1526-632X. ; 96:15 Suppl.
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Objective: To examine the association between microscopic colitis (MC) and Parkinson’s disease (PD) risk.Background: Gastrointestinal inflammation has been linked with PD. MC is a chronic intestinal inflammatory disease; however, its relationship with PD is unknown.Design/Methods: A population-based matched cohort study was conducted to estimate the association between MC and incident PD diagnosis using Cox regression models. An exposed cohort of 12,609 MC patients diagnosed 1990–2017 and aged ≥35 years at diagnosis was identified from the Epidemiology Strengthened by histoPathology Reports in Sweden cohort (ESPRESSO). Two unexposed cohorts were compared to: a population cohort comprising 58,879 MC-free individuals randomly selected from the population and 1:5 matched to each MC patient by age, sex, year of biopsy and county of residence at the time of biopsy; and a sibling cohort (NMC/NSibling=6,281/12,351) including all siblings of the MC patients. Follow-up was from the date of biopsy until December 31st 2016 at latest.Results: During a mean follow-up of ~7 years, we identified 449 incident PD diagnoses among the MC patients and their matched population cohort. The overall PD risk was 76% higher among MC versus MC-free individuals; but the association attenuated substantially during follow-up. In the time-varying effects model, PD risk was 3.45-fold (95% CI: 2.42, 4.93) higher during the first 2 years after biopsy and 1.80-fold (95% CI: 1.23, 2.64) higher during the following 3 years among MC versus MC-free individuals, but was not differential beyond 5 years after biopsy (hazard ratio=1.03; 95% CI: 0.68, 1.54). This temporal pattern of MC-PD associations persisted in sibling analyses. Using a matched case-control design, we also observed a higher prevalence of prior PD diagnosis among MC patients than the matched MC-free individuals (odds ratio=3.46; 95% CI: 2.91, 4.12).Conclusions: Our findings suggest that MC may not be a risk factor, but rather a comorbidity or complication of PD.
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19.
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20.
  • Khalili, Hamed, et al. (författare)
  • Gastrointestinal Infection and Risk of Microscopic Colitis : A Nationwide Case-Control Study in Sweden
  • 2021
  • Ingår i: Gastroenterology. - : American Gastroenterology Association Institute. - 0016-5085 .- 1528-0012. ; 160:5, s. 1599-1607
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND AIMS: Gastrointestinal infections have been linked to changes in the composition and function of gut microbiome and development of inflammatory bowel diseases. We therefore sought to examine the relationship between gastroenteritis and risk of microscopic colitis (MC).METHODS: We conducted a case-control study of all adult patients with MC diagnosed between 1990 and 2016 in Sweden matched to up to 5 general population controls according to age, sex, calendar year, and county. Cases of MC were identified using Systematized Nomenclature of Medicine codes from the ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden) study, a cohort of gastrointestinal pathology reports from all 28 pathology centers in Sweden. We used logistic regression modeling to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs).RESULTS: Through December of 2016, we matched 13,468 MC cases to 64,479 controls. The prevalence of previous diagnosed gastrointestinal infection was 7.5% among patients with MC, which was significantly higher than in controls (3.0%, P-comparison < .001). After adjustment, gastroenteritis was associated with an increased risk of MC (aOR 2.63; 95% CI 2.42-2.85). Among specific pathogens, Clostridioides difficile (aOR 4.39; 95% CI 3.42-5.63), Norovirus (aOR 2.87; 95% CI 1.66-4.87), and Escherichia species (aOR 3.82; 95% CI 1.22-11.58), but not Salmonella species, were associated with an increased risk of MC. The association between gastrointestinal infections and risk of MC was stronger for collagenous subtype (aOR 3.23; 95% CI 2.81-3.70) as compared with lymphocytic colitis (aOR 2.51; 95% CI 2.28-2.76; P-heterogeneity = .005). The associations remained significant after adjustment for immune-mediated conditions and polypharmacy and when compared with unaffected siblings.CONCLUSION: In a nationwide study, we found that gastrointestinal infection, particularly Clostridioides difficile, is associated with an increased risk of subsequent MC.
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21.
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22.
  • Khalili, Hamed, et al. (författare)
  • Mortality of Patients With Microscopic Colitis in Sweden
  • 2020
  • Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 18:11, s. 2491-2499
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND & AIMS: Microscopic colitis is one of the most common causes of chronic diarrhea in older populations. We investigated all-cause and cause-specific mortality in patients with microscopic colitis.METHODS: We conducted a nationwide cohort study of all cases of microscopic colitis (n = 14,333) diagnosed from 1990 through 2017 in Sweden. Cases of microscopic colitis were identified using SNOMED codes from gastrointestinal histopathology reports collected from Sweden's 28 pathology departments. Each case of microscopic colitis was matched to 5 population comparators (n = 68,700). Mortality data were ascertained from Sweden's cause of death register. We used Cox proportional hazards modeling to estimate adjusted hazard ratios (aHRs) and 95% CIs.RESULTS: Through December of 2017, we confirmed 3014 deaths in patients with microscopic colitis (27.4/1000 person-years) and 12,534 deaths in matched population comparators (23.3/1000 person-years). This corresponded to a 10-year absolute risk difference of 3.4% (95% CI, 2.1%-4.6%) and an aHR of 1.17 (95% CI, 1.12-1.22). However, further adjustment of models for comorbidity burden reduced the relative risk of death for patients with microscopic colitis (aHR, 0.98; 95% CI, 0.94-1.02). In analyses of cause-specific death, microscopic colitis was associated with an increased risk of gastrointestinal-related death (aHR, 1.68; 95% CI, 1.38-2.05) and infection-related death (aHR, 1.42; 95% CI, 1.11-1.83), but not cancer-related death (aHR, 0.83; 95% CI, 0.76-0.91) or cardiovascular-related death (aHR, 1.02; 95% CI, 0.96-1.10).CONCLUSIONS: In a nationwide cohort study in Sweden, we found that patients with microscopic colitis were at increased risk of death. However, the increase appears to be related to higher burden of comorbidities in this population.
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23.
  • Lebwohl, Benjamin, et al. (författare)
  • Cancer Risk in 47,241 Individuals with Celiac Disease : A Nationwide Cohort Study
  • 2022
  • Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 20:2, s. e111-e131
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Celiac disease (CD) is associated with increased mortality, in part due to cancer. Most studies investigating this cancer risk involved patients diagnosed before widespread increases in CD diagnosis rates and access to gluten-free food. We performed a population-based study of the risk of cancer in CD.METHODS: We identified all patients in Sweden with CD as defined as duodenal villus atrophy, using the ESPRESSO cohort. Each patient was matched to ≤5 controls by age, sex, and county. We used stratified Cox proportional-hazards model, following patients from diagnosis until first cancer, or by December 31, 2016.RESULTS: Among 47,241 patients with CD, 30,080 (64%) were diagnosed since 2000. After a median follow-up of 11.5 years, the incidence of cancer was 6.5 and 5.7 per 1000 person-years in CD patients and controls, respectively. The overall risk of cancer was increased (hazard ratio[HR] 1.11; 95%CI 1.07-1.15), but was only significantly elevated in the first year after CD diagnosis (HR 2.47; 95%CI 2.22-2.74), and not subsequently (HR 1.01; 95%CI 0.97-1.05), though the risks of hematologic, lymphoproliferative, hepatobiliary, and pancreas cancers persisted. The overall risk was highest in those diagnosed with CD after age 60 years (HR 1.22; 95%CI 1.16-1.29) and was not increased in those diagnosed before age 40. The cancer risk was similar among those diagnosed with CD before or after the year 2000.CONCLUSIONS: There is an increased risk of cancer in CD, even in recent years, but this risk increase is confined to those diagnosed with CD after age 40, and is primarily present within the first year of diagnosis.
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24.
  • Lebwohl, Benjamin, et al. (författare)
  • Psychiatric disorders in patients with a diagnosis of celiac disease during childhood from 1973 to 2016
  • 2021
  • Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 19:10, s. 2093-2101.e13
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND & AIMS: Few studies have explored the link between childhood celiac disease and long-term psychiatric comorbidities. We performed a population-based cohort study of associations between childhood celiac disease and psychiatric disorders and investigated whether risk persists into adulthood.METHODS: We performed a nationwide study in Sweden using data from the ESPRESSO cohort. In this cohort, 19,186 children with a diagnosis of biopsy-verified celiac disease from 1973 through 2016 were identified from Sweden's 28 pathology departments. Each patient was matched with as many as 5 reference children (controls, n=94,249). Data on psychiatric disorders were obtained from the patient register. We used Cox proportional modeling to estimate hazard ratios (HRs).RESULTS: During a median follow-up time of 12.3 years, 3174 children (16.5%) with celiac disease received a new diagnosis of a psychiatric disorder, compared with 13,286 controls (14.1%). Corresponding incidence rates were 12.2 per 1000 person-years (95% Cl, 11.8-12.7) vs 10.3 per 1000 person-years (95% Cl, 10.2-10.5). Childhood celiac disease was associated with a 19% increase in risk of any psychiatric disorder (95% Cl, 1.14-1.23); the increase in risk was observed in all childhood age groups. The highest HRs were seen in the first year after celiac diagnosis (HR, 1.70; 95% Cl, 1.41-2.05). The risk increase persisted into adulthood (older than 18 years: HR, 1.11; 95% Cl, 1.04-1.17). We found increased risks of mood disorders (HR, 1.20; 95% CI, 1.12-1.28), anxiety disorders (HR, 1.12; 95% CI, 1.06-1.19), eating disorders (HR, 1.34; 95% CI, 1.18-1.51), attention deficit hyperactivity disorder (HR, 1.29; 95% CI, 1.20-1.39), and autism spectrum disorder (HR, 1.47; 95% CI, 1.32-1.64). We found no statistically significant risk increase for psychotic disorders, psychoactive substance misuse, behavioral disorders, personality disorders, suicide attempt, or suicide. Celiac disease was also linked to an increased use of psychiatric drugs (HR, 1.34; 95% CI, 1.24-1.43). A conditional logistic regression found that psychiatric disorders were also more common prior to diagnosis of celiac disease (odds ratio, 1.56; 95% Cl, 1.39-1.76).CONCLUSIONS: Childhood celiac disease is associated with increased risk of subsequent psychiatric disorders, which persists into adulthood. Mental health surveillance should be integral in the care of celiac disease.
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25.
  • Lebwohl, Benjamin, et al. (författare)
  • Risk of Severe Covid-19 in Patients with Celiac Disease : A Population-Based Cohort Study
  • 2021
  • Ingår i: Clinical Epidemiology. - : Dove Medical Press Ltd.. - 1179-1349. ; 13, s. 121-130
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Patients with celiac disease (CeD) are at increased risk of certain viral infections and of pneumococcal pneumonia, raising concerns that they may be susceptible to severe coronavirus disease 2019 (Covid-19). We aimed to quantify the association between CeD and severe outcomes related to Covid-19.Methods: We performed a population-based cohort study, identifying individuals with CeD in Sweden, as defined by small intestinal villus atrophy diagnosed at all (n=28) Swedish pathology departments during the years spanning 1969-2017, and alive on February 1, 2020. We compared these patients to controls matched by sex, age, county, and calendar period. We performed Cox proportional hazards with follow-up through July 31, 2020, assessing risk of 1) hospital admission with a primary diagnosis of laboratory-confirmed Covid-19 (co-primary outcome); and 2) severe disease as defined by admission to intensive care unit and/or death attributed to Covid-19 (co-primary outcome).Results: Among patients with CeD (n=40,963) and controls (n=183,892), the risk of hospital admission for Covid-19 was 2.9 and 2.2 per 1000 person-years respectively. After adjusting for comorbidities, the risk of hospitalization for Covid-19 was not significantly increased in patients with CeD (HR 1.10; 95% CI 0.80-1.50), nor was the risk of severe Covid-19 increased (HR 0.97; 95% CI 0.59-1.59). Results were similarly null when we compared CeD patients to their non-CeD siblings with regard to these outcomes. Among all patients with CeD and controls hospitalized with a diagnosis of Covid-19 (n=58 and n=202, respectively), there was no significant difference in mortality (HR for CeD compared to controls 0.96; 95% CI 0.46-2.02).Conclusion: In this population-based study, CeD was not associated with an increased risk of hospitalization for Covid-19 or intensive care unit and/or death attributed to Covid-19.
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26.
  • Lebwohl, Benjamin, et al. (författare)
  • Risk of Skin Disorders in Patients with Celiac Disease : A Population-Based Cohort Study
  • 2021
  • Ingår i: The Journal of American Academy of Dermatology. - : Elsevier. - 0190-9622 .- 1097-6787. ; 85:6, s. 1456-1464
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND AIMS: Although dermatitis herpetiformis is closely associated with celiac disease (CD), data on the relationship between CD and other dermatologic disorders have been mixed. We aimed to quantify the risk of skin disorders in patients after CD diagnosis in a population-based setting.METHODS: Using data from all 28 pathology departments in Sweden 1969-2016, we identified patients with CD. Each patient was matched by age, sex, calendar year, and geographic region to up to 5 population controls. We calculated the risk of any skin disease and specific skin diseases using Cox proportional hazards.RESULTS: We identified 43,300 patients with CD and 198,532 matched controls. After a median follow-up time of 11.4 years, the incidences of skin disease in CD patients and controls were 22.6 and 14.8 per 1000 person-years respectively (HR=1.55; 95%CI 1.51-1.58). Increased risks were present for eczema (HR=1.67; 95%CI 1.56-1.79), psoriasis (HR=1.55; 95%CI 1.43-1.68), urticaria (HR=1.52; 95% CI 1.42-1.64), vitiligo (HR=1.90; 95%CI 1.52-2.39), acne (HR=1.39; 95%CI 1.29-1.50), and alopecia areata (HR=1.78; 95%CI 1.43-2.20).CONCLUSIONS: Compared to the general population, patients with CD are at increased risk of multiple common skin disorders, a risk that persists in the long-term.
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27.
  • Ludvigsson, Jonas F., 1969-, et al. (författare)
  • Inflammatory bowel disease and risk of severe COVID-19 : A nationwide population-based cohort study in Sweden
  • 2021
  • Ingår i: United European Gastroenterology journal. - : Sage Publications. - 2050-6406 .- 2050-6414. ; 9:2, s. 177-192
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: There are concerns that individuals with chronic immune-mediated diseases are at increased risk of COVID-19 and related severe adverse outcome, including intensive care admission or death. We aimed to explore the absolute and relative risk of severe COVID-19 in inflammatory bowel disease (IBD).METHODS: This population-based cohort study used nationwide registers in Sweden, with 67,292 individuals with a diagnosis of IBD 1969-2017 (Crohn's disease, n = 21,599; ulcerative colitis: n = 43,622; IBD-unclassified: n = 2071) and alive on 1 February 2020. Patients with IBD were matched to up to five controls from the general population (n = 297,910). Cox regression estimated hazard ratios (HRs) for (i) hospital admission with laboratory-confirmed COVID-19 as the primary diagnosis, and (ii) severe COVID-19 (composite outcome consisting of (a) COVID-19 intensive care admission, or (b) death from COVID-19 or (c) death within 30 days of COVID-19 hospital admission), were calculated. Analyses were conditioned on age, sex, calendar period, and county and adjusted for other comorbidities.RESULTS: Between 1 February and 31 July 2020, 179 (0.27%) IBD patients and 500 (0.17%) general population controls were admitted to hospital with COVID-19 (adjusted HR [aHR] = 1.43; 95% CI = 1.19-1.72). The corresponding numbers for severe COVID-19 was 65 (0.10%) and 183 (0.06%; aHR = 1.11; 95% CI = 0.81-1.52). Adjusted HRs were similar in Crohn's disease and ulcerative colitis. In a propensity score-matched model taking comorbidity into account until 2016, the increased risk for COVID-19 hospital admission remained (aHR = 1.32; 1.12-1.56), but there was no increased risk of severe COVID-19 (aHR = 1.12; 0.85-1.47).CONCLUSIONS: While individuals with IBD were more likely to be admitted to hospital for COVID-19 than the general population, the risk of severe COVID-19 was not higher.
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28.
  • Ludvigsson, Jonas F., 1969-, et al. (författare)
  • Normal Gastrointestinal Mucosa at Biopsy and Overall Mortality : Nationwide Population-Based Cohort Study
  • 2022
  • Ingår i: Clinical Epidemiology. - : Dove Medical Press Ltd.. - 1179-1349. ; 14, s. 889-900
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Normal gastrointestinal (GI) mucosa on endoscopy has been linked to a lower risk of colorectal cancer (CRC) but its association to overall death is unknown.Methods: We identified 466,987 individuals with a first GI biopsy 1965-2016 with normal mucosa (60.6% upper GI and 39.4% lower GI) through all Swedish pathology departments (n = 28). They were individually matched to 2,321,217 reference individuals without a GI biopsy and also compared to 505,076 full siblings. Flexible parametric models were applied to estimate hazard ratio (HRs) and 95% confidence interval (95% CI) for death.Results: During a median follow-up of ~11 years, 85,859 (18.39%) of individuals with normal mucosa and 377,653 (16.27%) of reference individuals died. This corresponded to incidence rates of 147.56/10,000 vs 127.90/10,000 person-years respectively (rate difference: 19.66/10,000 person-years), with the multivariable-adjusted HR of 1.21 (95% CI: 1.20-1.22). Excess mortality was seen for both upper and lower biopsy with normal mucosa. Particularly higher HRs for death were seen in males, individuals biopsied when aged <40 years, those without a prior record of GI disease, and those with high education. Mortality risk was most increased in the first five years after biopsy (HR = 1.34; 95% CI: 1.32-1.36) but decreased thereafter. Having a GI biopsy with normal mucosa was associated with excess mortality from cardiovascular (CVD)disease (HR = 1.02; 95% CI: 1.01-1.03), cancer (HR = 1.58; 95% CI: 1.56-1.61), GI disease (HR = 1.65; 95% CI: 1.58-1.71), and other causes (HR = 1.10; 95% CI: 1.08-1.11). Sibling comparisons yielded similar results.Conclusion: Compared with individuals without a GI biopsy, those with a normal GI biopsy due to clinical symptoms had a higher mortality particularly in the first five years after biopsy, and especially from GI disease and cancer.
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29.
  • Ma, Wenjie, et al. (författare)
  • Cancer risk in patients with diverticular disease : A nationwide cohort study
  • 2022
  • Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105.
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: There are little data on diverticular disease and cancer development other than colorectal cancer.Methods: We conducted a population-based, matched cohort study with linkage of nationwide registers to the Epidemiology Strengthened by histoPathology Reports in Sweden histopathology cohort. We included 75 704 patients with a diagnosis of diverticular disease and colorectal histopathology and 313 480 reference individuals from the general population matched on age, sex, calendar year, and county. Cox proportional hazards models estimated multivariable-adjusted hazard ratios (HRs) for associations between diverticular disease and overall cancer and specific cancers.Results: Over a median follow-up of 6 years, we documented 12 846 incident cancers among patients with diverticular disease and 43 354 incident cancers among reference individuals from the general population. Compared with reference individuals, patients with diverticular disease had statistically significantly increased overall cancer incidence (24.5 vs 18.1 per 1000 person-years), equivalent to 1 extra cancer case in 16 individuals with diverticular disease followed-up for 10 years. After adjusting for covariates, having a diagnosis of diverticular disease was associated with a 33% increased risk of overall cancer (95% confidence interval [CI] = 1.31 to 1.36). The risk increases also persisted compared with siblings as secondary comparators (HR = 1.26, 95% CI = 1.21 to 1.32). Patients with diverticular disease also had an increased risk of specific cancers, including colon cancer (HR = 1.71, 95% CI = 1.60 to 1.82), liver cancer (HR = 1.72, 95% CI = 1.41 to 2.10), pancreatic cancer (HR = 1.62, 95% CI = 1.42 to 1.84), and lung cancer (HR = 1.50, 95% CI = 1.39 to 1.61). The increase in colorectal cancer risk was primarily restricted to the first year of follow-up, and especially early cancer stages.Conclusions: Patients with diverticular disease who have colorectal histopathology have an increased risk of overall incident cancer.
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30.
  • Maret-Ouda, John, et al. (författare)
  • Appendectomy and future risk of microscopic colitis : a population-based case-control study in Sweden
  • 2023
  • Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 21:2, s. 467-475.e2
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND AIMS: Microscopic colitis (MC) is an inflammatory bowel disease and a common cause of chronic diarrhea. Appendectomy has been suggested to have immunomodulating effects in the colon, influencing the risk of gastrointestinal disease. The relationship between appendectomy and MC has only been sparsely studied.METHODS: This was a case-control study based on the nationwide ESPRESSO cohort, consisting of histopathological examinations in Sweden, linked to national registers. Patients with MC were matched to population controls by age, sex, calendar year of biopsy and county of residence. Data on antecedent appendectomy and comorbidities were retrieved from the Patient Register. Unconditional logistic regression models were conducted presenting odds ratios (ORs) and 95% confidence intervals (Cl) adjusted for country of birth and matching factors. Further sub-analyses were made based on MC subtypes (lymphocytic colitis [LC] and collagenous colitis [CC]), follow-up time post appendectomy and severity of appendicitis.RESULTS: The study included 14,520 cases of MC and 69,491 controls, among these 7.6% (n=1,103) and 5.1% (n=3,510), respectively, had a previous appendectomy ≥1 year prior to MC/matching date. Patients with a previous appendectomy had an increased risk of MC in total (OR 1.50, 95% CI 1.40-1.61); and per subtype CC (OR 1.67, 95% CI 1.48-1.88), LC (OR 1.42, 95% CI 1.30-1.55). The risk remained elevated throughout follow-up, and the highest risk was observed in non-complicated appendicitis.CONCLUSIONS: This nationwide case-control study found a modestly increased risk of developing MC following appendectomy.
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31.
  • Mitselou, Niki, 1982-, et al. (författare)
  • Association of celiac disease with eosinophilic esophagitis : Nationwide register-based cohort study with sibling analyses
  • 2024
  • Ingår i: The journal of allergy and clinical immunology. Global. - : Elsevier. - 2772-8293. ; 3:3
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Celiac disease (CeD) is associated with several immune-mediated disorders, but it is unclear whether it is associated with eosinophilic esophagitis (EoE).OBJECTIVE: We sought to examine the risk of EoE in patients with biopsy-verified CeD compared with matched controls and siblings.METHODS: Using nationwide population-based histopathology data, we identified 27,338 patients with CeD diagnosed in the period 2002 to 2017 in Sweden. Patients with CeD were age- and sex-matched with up to 5 reference individuals (n = 134,987) from the general population. Cox Regression was used to estimate hazard ratios (HRs) for developing biopsy-verified EoE. In a secondary analysis, we used unaffected siblings of patients with CeD as comparators to adjust for intrafamilial confounding.RESULTS: The median age at CeD diagnosis was 27 years, and 63.3% were female patients. During a median follow-up of 8.1 years, 17 patients with CeD and 13 matched reference individuals were diagnosed with EoE. This corresponded to incidence rates of 0.08 versus 0.01 per 1000 person-years, respectively, and an adjusted HR for EoE of 6.65 (95% CI, 3.26-13.81). Compared with their siblings without CeD, patients with CeD were however at a no increased risk of EoE (HR, 1.39; 95% CI, 0.55-3.51).CONCLUSIONS: In this study, individuals with CeD were at a 6.6-fold increased risk of later EoE compared with the general population. This association might be explained by an altered health-seeking behavior or through shared genetic or early environmental factors because the excess risk disappeared in sibling analyses.
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32.
  • Nguyen, Long H., et al. (författare)
  • Antibiotic Therapy and Risk of Early-Onset Colorectal Cancer : A National Case-Control Study
  • 2022
  • Ingår i: Clinical and Translational Gastroenterology. - : Nature Publishing Group. - 2155-384X. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: Antibiotic use has emerged as a risk factor for colorectal neoplasia and is hypothesized as a contributor to the rising incidence of colorectal cancer under age 50 years or early-onset colorectal cancer (EOCRC). However, the impact of antibiotic use and risk of EOCRC is unknown.METHODS: We conducted a population-based case-control study of CRC among individuals aged >= 18 years in the Epidemiology Strengthened by histoPathology Reports in Sweden (ESPRESSO) cohort (2006-2016). The primary outcome was EOCRC. A secondary outcome was CRC at any age. Incident CRC was pathologically confirmed, and for each, up to 5 population-based controls were matched on age, sex, county of residence, and calendar year. We assessed prescriptions until 6 months before CRC diagnosis. Conditional logistic regression was used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs).RESULTS: We identified 54,804 cases of CRC (2,557 EOCRCs) and 261,089 controls. Compared with none, previous antibiotic use was not associated with EOCRC risk after adjustment for potential confounders (aOR 1.06, 95% CI: 0.96, 1.17) with similarly null findings when stratified by anatomic tumor site. In contrast, previous antibiotic use was weakly associated with elevated risk for CRC at any age (aOR 1.05, 95% CI: 1.02, 1.07). A potential but modest link between broad-spectrum antibiotic use and EOCRC was observed (aOR 1.13, 95% CI: 1.02, 1.26).DISCUSSION: We found no conclusive evidence that antibiotics are associated with EOCRC risk. Although antibiotic use was weakly associated with risk of CRC at any age, the magnitude of association was modest, and the study period was relatively short.
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33.
  • Nguyen, Long H., et al. (författare)
  • Antibiotic use and the development of inflammatory bowel disease : a national case-control study in Sweden
  • 2020
  • Ingår i: The Lancet Gastroenterology & Hepatology. - : Elsevier. - 2468-1253. ; 5:11, s. 986-995
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Use of antibiotics in early life has been linked with childhood inflammatory bowel disease (IBD), but data for adults are mixed, and based on smaller investigations that did not compare risk among siblings with shared genetic or environmental risk factors. We aimed to investigate the association between antibiotic therapy and IBD in a large, population-based study.Methods: In this prospective case-control study, we identified people living in Sweden aged 16 years or older, with a diagnosis of IBD based on histology and at least one diagnosis code for IBD or its subtypes (ulcerative colitis and Crohn's disease). We identified consecutive patients with incident IBD from the ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden) study, cross-referenced with the Swedish Patient Register and the Prescribed Drug Register. We accrued data for cumulative antibiotic dispensations until 1 year before time of matching for patients and up to five general population controls per patient (matched on the basis of age, sex, county, and calendar year). We also included unaffected full siblings as a secondary control group. Conditional logistic regression was used to estimate multivariable-adjusted odds ratios (aORs) and 95% CIs for diagnosis of incident IBD.Findings: We identified 23 982 new patients with IBD (15 951 ulcerative colitis, 7898 Crohn's disease, 133 unclassified IBD) diagnosed between Jan 1, 2007, and Dec 31, 2016. 117 827 matched controls and 28 732 siblings were also identified. After adjusting for several risk factors, aOR in patients who had used antibiotics versus those who had never used antibiotics was 1.88 (95% CI 1.79-1.98) for diagnosis of incident IBD, 1.74 (1.64-1.85) for ulcerative colitis, and 2.27 (2.06-2.49) for Crohn's disease. aOR was higher in patients who had received one antibiotic dispensation (1.11, 1.07-1.15), two antibiotic dispensations (1.38, 1.32-1.44), and three or more antibiotic dispensations (1.55, 1.49-1.61) than patients who had none. Increased risk was noted for ulcerative colitis (aOR with three or more antibiotic dispensations 1.47, 95% CI 1.40-1.54) and Crohn's disease (1.64, 1.53-1.76) with higher estimates corresponding to broad-spectrum antibiotics. Similar but attenuated results were observed when siblings were used as the reference group, with an aOR of 1.35 (95% CI 1.28-1.43) for patients who had received three or more dispensations, compared with general population controls.Interpretation: Higher cumulative exposure to systemic antibiotic therapy, particularly treatments with greater spectrum of microbial coverage, may be associated with a greater risk of new-onset IBD and its subtypes. The association between antimicrobial treatment and IBD did not appear to differ when predisposed siblings were used as the reference controls. Our findings, if substantiated by longer-term prospective studies in humans or mechanistic preclinical investigations, suggest the need to further emphasise antibiotic stewardship to prevent the rise in dysbiosis-related chronic diseases, including IBD.
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34.
  • Rockert Tjernberg, Anna, et al. (författare)
  • Celiac Disease and Serious Infections: A Nationwide Cohort Study From 2002 to 2017
  • 2022
  • Ingår i: American Journal of Gastroenterology. - : LIPPINCOTT WILLIAMS & WILKINS. - 0002-9270 .- 1572-0241. ; 117:10, s. 1675-1683
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: Patients with celiac disease (CD) have an increased risk of encapsulated bacterial infections. Less is known about other serious infections in CD, especially in patients diagnosed in the 21st century. METHODS: We contacted all 28 pathology departments in Sweden through the Epidemiology Strengthened by histoPathology Reports in Sweden (ESPRESSO) cohort study and identified 20,088 individuals with CD (defined as villous atrophy) diagnosed in 2002-2017. Patients were matched for sex, age, and calendar year to 80,152 general population comparators and followed up until December 31, 2019. Serious infections were defined as having a hospital-based (inpatient and outpatient) diagnosis in the National Patient Register. Cox regression yielded adjusted hazard ratios (aHR) controlling for education, country of birth, and comorbidities. RESULTS: During 173,695 person-years of follow-up, 6,167 individuals with CD (35.5/1,000 person-years) had a serious infection. This was compared with 19,131 infections during 743,260 person-years (25.7/1,000 person-years) in matched comparators, corresponding to an aHR of 1.29 (95% confidence interval [CI] = 1.25-1.33). aHR were similar when restricted to infection requiring hospital admission (1.23; 95% CI = 1.17-1.29). The excess risk of serious infections also persisted beyond the first year after CD diagnosis (aHR = 1.24; 95% CI = 1.20-1.29). Patients with CD were at risk of sepsis (aHR = 1.26; 95% CI = 1.09-1.45) and gastrointestinal infections (1.60; 95% CI = 1.47-1.74). Mucosal healing during CD follow-up did not influence the risk of subsequent serious infections. DISCUSSION: This nationwide study of patients with celiac disease diagnosed in the 21st century revealed a significantly increased risk of serious infections. While absolute risks were modest, vaccinations should be considered during CD follow-up care.
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35.
  • Röjler, Lovisa, 1983-, et al. (författare)
  • Individuals With Eosinophilic Esophagitis Are at Greater Risk of Later Psychiatric Disorder
  • 2022
  • Ingår i: American Journal of Gastroenterology. - : Lippincott Williams & Wilkins. - 0002-9270 .- 1572-0241. ; 117:7, s. 1046-1055
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: Several gastrointestinal and allergic diseases have been linked to psychiatric disease, but there are limited data on psychiatric disease in eosinophilic esophagitis (EoE). Our aim was to study the association between EoE and later psychiatric disorders.METHODS: This was a population-based nationwide cohort study. Individuals with EoE diagnosed during 1989-2017 in Sweden (n = 1,458) were identified through the ESPRESSO histopathology cohort that represents all gastrointestinal biopsy reports in Sweden's 28 pathology departments. Individuals with EoE were matched with up to 5 reference individuals on sex, age, county, and calendar year (n = 6,436). Cox proportional hazard modeling estimated adjusted hazard ratios (HRs). In a secondary analysis, we compared individuals with EoE with their siblings to adjust for intrafamilial confounding. RESULTS: The median age at EoE diagnosis was 39 years, and 76% of the enrolled individuals with EoE were male. During a median follow-up of 4 years, 106 individuals with EoE (15.96/1,000 person-years) developed a psychiatric disorder compared with 331 reference individuals (10.93/1,000 person-years), corresponding to an HR of 1.50 (95% confidence interval = 1.20-1.87). The increased risk was seen in the first 5 years of follow-up, but not thereafter. The highest relative risks were seen in individuals diagnosed with EoE in childhood. Compared with siblings, individuals with EoE were at an increased risk of psychiatric disease (HR = 1.62; 95% confidence interval = 1.14-2.31). EoE was linked to mood disorders, anxiety disorder, and attention-deficit hyperactivity disorder.DISCUSSION: Individuals with EoE may be at greater risk of psychiatric disease than their siblings and the general population. This risk needs to be considered in clinical care to detect, prevent, and treat comorbidity.
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36.
  • Röjler, Lovisa, 1983-, et al. (författare)
  • Mortality in Eosinophilic Esophagitis - a nationwide, population-based matched cohort study from 2005 to 2017
  • 2021
  • Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 126:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: There is a lack of knowledge about mortality in eosinophilic esophagitis (EoE). Therefore, this study aimed to examine the mortality in EoE.Methods: A nationwide, population- based matched cohort study was conducted of all EoE patients in Sweden diagnosed between July 2005 and December 2017. Individuals with EoE (n = 1,625) were identified through prospectively recorded histopathology codes from all gastrointestinal pathology-reports in Sweden, representing 28 pathology departments (the ESPRESSO study). Each individual with EoE was then matched with up to five reference individuals from the general population (n = 8,003) for age, sex, year of birth, and place of residence. We used the Cox proportional hazard modeling to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (95% CI) while adjusting for other potential confounders. In sensitivity analyses, mortality in EoE patients was compared with mortality in their siblings.Results: Through December 2017, 34 deaths were confirmed in EoE patients (4.60 per 1,000 person-years) compared with 165 in reference individuals (4.57 per 1,000 person-years). This rate corresponds to an aHR of 0.97 (95% CI = 0.67-1.40). HRs were similar in males (aHR = 1.00 [0.66-1.51]) and females (aHR = 0.92 [0.38-2.18]). We observed no increased risk in mortality due to esophageal or other gastrointestinal cancers in patients with EoE (aHR = 1.02 [0.51- 2.02]). Mortality was similar in EoE patients and their siblings (aHR = 0.91 [0.44-1.85]).Conclusion: In this nationwide, population-based matched cohort study in Sweden, there was no -increased risk of death in patients with EoE compared with their siblings and the general population.
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37.
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38.
  • Sharma, Rajani, et al. (författare)
  • Increased Mortality Risk in Autoimmune Hepatitis : A Nationwide Population-based Cohort Study With Histopathology
  • 2021
  • Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 19:12, s. 2636-2647.e13
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND AIMS: Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease that may lead to cirrhosis and liver failure, but data on overall mortality in AIH are conflicting.METHODS: This was a nationwide population-based cohort study in Sweden from 1969-2017 of 6,016 adults with AIH and 28,146 matched general population reference individuals. AIH was defined by a combination of a medical diagnosis of AIH plus a liver biopsy from any of Sweden's 28 pathology departments. Through Cox regression, we estimated hazard ratios (HRs) for overall and cause-specific death. Liver transplant was included in our main outcome of death.RESULTS: During follow-up, 3,185 individuals with AIH died (41.4/1000 person-years) compared with 10,477 reference individuals (21.9/1000 person-years). The 10-year cumulative incidence of death was 32.3% (95%CI=31.1-33.6) for AIH individuals and 14.1% (95%CI=13.7-14.5) for reference individuals. This corresponded to an adjusted HR of 2.29 (95%CI=2.17-2.41), which remained elevated ≥20 years follow-up. AIH individuals with cirrhosis on biopsy had a high risk of death (HR=4.55; 95%CI=3.95-5.25), while mortality in patients with fibrosis, inflammation without fibrosis, or necrosis did not differ. Portal hypertension and overlap with cholestatic liver diseases were also associated with death. AIH was associated with an increased risk of death from cardiovascular disease (HR=1.27; 95%CI=1.15-1.40), liver disease (HR=66.24; 95%CI=48.19-91.03) and extrahepatic malignancy (HR=1.69; 95%CI=1.51-1.89). In a sibling comparison, AIH individuals remained at increased risk of death.CONCLUSION: AIH is associated with a 2-fold increased risk of death. Risks were particularly high in individuals with cirrhosis, portal hypertension, and overlap with cholestatic liver disease.
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39.
  • Simon, Tracey G., et al. (författare)
  • Cancer Risk in Patients With Biopsy-Confirmed Nonalcoholic Fatty Liver Disease : A Population-Based Cohort Study
  • 2021
  • Ingår i: Hepatology. - : Wiley-Interscience Publishers. - 0270-9139 .- 1527-3350. ; 74:5, s. 2410-2423
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Aims: Recent studies link NAFLD to an increased incidence of HCC and extrahepatic cancers. However, earlier studies were small or lacked liver histology, which remains the gold standard for staging NAFLD severity.Approach and Results: We conducted a population-based cohort study of all adults with histologically defined NAFLD in Sweden from 1966 to 2016 (N = 8,892). NAFLD was defined from prospectively recorded liver histopathology submitted to all 28 Swedish pathology departments and categorized as simple steatosis, nonfibrotic NASH, noncirrhotic fibrosis, and cirrhosis. NAFLD patients were individually matched to <= 5 general population controls without NAFLD by age, sex, calendar year, and county (N = 39,907). Using Cox proportional hazards modeling, we calculated multivariable adjusted HRs (aHRs) and 95% CIs. Over a median of 13.8 years, we documented 1,691 incident cancers among NAFLD patients and 6,733 among controls. Compared with controls, NAFLD patients had significantly increased overall cancer incidence (10.9 vs. 13.8 per 1,000 person-years [PYs]; difference = 2.9 per 1,000 PYs; aHR, 1.27 [95% CI, 1.18-1.36]), driven primarily by HCC (difference = 1.1 per 1,000 PYs; aHR, 17.08 [95% CI, 11.56-25.25]). HCC incidence rates increased monotonically across categories of simple steatosis, nonfibrotic NASH, noncirrhotic fibrosis, and cirrhosis (0.8 per 1,000 PYs, 1.2 per 1,000 PYs, 2.3 per 1,000 PYs, and 6.2 per 1,000 PYs, respectively; P-trend < 0.01) and were further amplified by diabetes (1.2 per 1,000 PYs, 2.9 per 1,000 PYs, 7.2 per 1,000 PYs, and 15.7 per 1,000 PYs, respectively). In contrast, NAFLD was associated with modestly increased rates of pancreatic cancer, kidney/bladder cancer, and melanoma (differences = 0.2 per 1,000 PYs, 0.1 per 1,000 PYs, and 0.2 per 1,000 PYs, respectively), but no other cancers.Conclusions: Compared with controls, patients with biopsy-proven NAFLD had significantly increased cancer incidence, attributable primarily to HCC, whereas the contribution of extrahepatic cancers was modest. Although HCC risk was highest with cirrhosis, substantial excess risk was also found with noncirrhotic fibrosis and comorbid diabetes.
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40.
  • Simon, Tracey G., et al. (författare)
  • Cardiovascular disease risk in paediatric and young adult non-alcoholic fatty liver disease
  • 2023
  • Ingår i: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 72:3, s. 573-580
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Longitudinal evidence is lacking regarding the long-term risk of major adverse cardiovascular events (MACE) in children and young adults with non-alcoholic fatty liver disease (NAFLD).DESIGN: This nationwide cohort study included all Swedish children and young adults ≤25 years old with histologically confirmed NAFLD and without underlying cardiovascular disease (CVD) at baseline (1966-2016; n=699). NAFLD was defined from prospectively recorded histopathology, and further categorised as simple steatosis or non-alcoholic steatohepatitis (NASH). NAFLD patients were matched to ≤5 population controls without NAFLD or CVD (n=3353). Using Cox proportional hazards modelling, we calculated multivariable-adjusted HRs (aHRs) and 95% CIs for incident MACE (ie, ischaemic heart disease, stroke, congestive heart failure or cardiovascular mortality). In secondary analyses, we also explored rates of incident cardiac arrhythmias.RESULTS: Over a median follow-up of 16.6 years, incident MACE was confirmed in 33 NAFLD patients and 52 controls. NAFLD patients had significantly higher rates of MACE than controls (3.1 vs 0.9/1000 person-years (PY); difference=2.1/1000 PY; aHR=2.33, 95% CI=1.43 to 3.78), including higher rates of ischaemic heart disease (difference=1.4/1000 PY; aHR=3.07, 95% CI 1.62 to 5.83) and congestive heart failure (difference=0.5/1000 PY; aHR=3.89, 95% CI=1.20 to 12.64). Rates of incident MACE outcomes appeared to be further augmented with NASH (aHR=5.27, 95% CI=1.96 to 14.19). In secondary analyses, NAFLD patients also had significantly higher rates of cardiac arrythmias (aHR=3.16, 95% CI=1.49 to 6.68).CONCLUSION: Compared with matched population controls, children and young adults with biopsy-proven NAFLD had significantly higher rates of incident MACE, including ischaemic heart disease and congestive heart failure. Research to better characterise cardiovascular risk in children and young adults with NAFLD should be prioritised.
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41.
  • Simon, Tracey G., et al. (författare)
  • Incident cardiac arrhythmias associated with metabolic dysfunction-associated steatotic liver disease : a nationwide histology cohort study
  • 2023
  • Ingår i: Cardiovascular Diabetology. - : BioMed Central (BMC). - 1475-2840. ; 22
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Prior studies suggest a link between metabolic dysfunction-associated steatotic liver disease (MASLD) and incident arrhythmias, including atrial fibrillation (AF). However, robust data are lacking from cohorts with liver histology, which remains the gold standard for staging MASLD severity.Methods: This population-based cohort included all Swedish adults with histologically-confirmed MASLD and without prior cardiac arrhythmias (1966-2016; n = 11,206). MASLD was defined from prospectively-recorded histopathology, and characterized as simple steatosis, non-fibrotic steatohepatitis (MASH), non-cirrhotic fibrosis, or cirrhosis. MASLD patients were matched to <= 5 controls without MASLD or arrhythmias, by age, sex, calendar year and county (n = 51,856). Using Cox proportional hazards modeling, we calculated multivariable-adjusted hazard ratios (aHRs) for incident arrhythmias (including AF, bradyarrhythmias, other supraventricular arrhythmias, ventricular arrhythmias/cardiac arrest).Results: Over a median follow-up of 10.8 years, incident arrhythmias were confirmed in 1351 MASLD patients (10.3/1000 person-years [PY]) and 6493 controls (8.7/1000PY; difference = 1.7/1000PY; aHR = 1.30, 95%CI 1.22-1.38), and MASLD patients had significantly higher rates of incident AF (difference = 0.9/1000PY; aHR = 1.26, 95%CI 1.18-1.35). Rates of both overall arrhythmias and AF were significantly elevated across all MASLD histological groups, particularly cirrhosis (differences, 8.5/1000PY and 5.3/1000PY, respectively). In secondary analyses, MASLD patients also had significantly higher rates of incident ventricular arrhythmias/cardiac arrest (aHR = 1.53, 95%CI 1.30-1.80), bradyarrhythmias (aHR = 1.26, 95%CI 1.06-1.48), and other supraventricular arrhythmias (aHR = 1.27, 95%CI 1.00-1.62), compared to controls.Conclusions: Compared to matched controls, patients with biopsy-confirmed MASLD had modest but significantly higher incidence of cardiac arrhythmias, including AF, bradyarrhythmias, other supraventricular arrhythmias and ventricular arrhythmias/cardiac arrest. Excess risk was observed across all stages of MASLD and was highest with cirrhosis.
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42.
  • Simon, Tracey G., et al. (författare)
  • Mortality in biopsy-confirmed nonalcoholic fatty liver disease : results from a nationwide cohort
  • 2021
  • Ingår i: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 70:7, s. 1375-1382
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Population-based data are lacking regarding the risk of overall and cause-specific mortality across the complete histological spectrum of non-alcoholic fatty liver disease (NAFLD).Design: This nationwide, matched cohort study included all individuals in Sweden with biopsy-confirmed NAFLD (1966 to 2017; n=10 568). NAFLD was confirmed histologically from all liver biopsies submitted to Sweden's 28 pathology departments, after excluding other etiologies of liver disease, and further categorised as, simple steatosis, non-fibrotic steatohepatitis (NASH), non-cirrhotic fibrosis and cirrhosis. NAFLD cases were matched to <= 5 general population comparators by age, sex, calendar year and county (n=49 925). Using Cox regression, we estimated multivariable-adjusted HRs (aHRs) and 95% CIs.Results: Over a median of 14.2 years, 4,338 NAFLD patients died. Compared with controls, NAFLD patients had significantly increased overall mortality (16.9 vs 28.6/1000 PY; difference=11.7/1000 PY; aHR=1.93, 95% CI=1.86 to 2.00). Compared with controls, significant excess mortality risk was observed with simple steatosis (8.3/1000 PY, aHR=1.71, 95% CI=1.64 to 1.79), non-fibrotic NASH (13.4/1000 PY, aHR=2.14, 95% CI=1.93 to 2.38), non-cirrhotic fibrosis (18.4/1000 PY, aHR=2.44, 95% CI=2.22 to 2.69) and cirrhosis (53.6/1000 PY, aHR=3.79, 95% CI=3.34 to 4.30)(p trend <0.01). This dose-dependent gradient was similar when simple steatosis was the reference (p trend <0.01). The excess mortality associated with NAFLD was primarily from extrahepatic cancer (4.5/1000 PY, aHR=2.16, 95% CI=2.03 to 2.30), followed by cirrhosis (2.7/1000 PY, aHR=18.15, 95% CI=14.78 to 22.30), cardiovascular disease (1.4/1000 PY, aHR=1.35, 95% CI=1.26 to 1.44) and hepatocellular carcinoma (HCC) (1.2/1000 PY, aHR=11.12, 95% CI=8.65 to 14.30).Conclusion: All NAFLD histological stages were associated with significantly increased overall mortality, and this risk increased progressively with worsening NAFLD histology. Most of this excess mortality was from extrahepatic cancer and cirrhosis, while in contrast, the contributions of cardiovascular disease and HCC were modest.
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43.
  • Simon, Tracey G., et al. (författare)
  • Non-alcoholic fatty liver disease and incident major adverse cardiovascular events : results from a nationwide histology cohort
  • 2022
  • Ingår i: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 71:9, s. 1867-1875
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Some data suggest a positive association between non-alcoholic fatty liver disease (NAFLD) and incident major adverse cardiovascular events (MACEs). However, data are lacking from large cohorts with liver histology, which remains the gold standard for staging NAFLD severity.Design: This population-based cohort included all Swedish adults with histologically confirmed NAFLD and without cardiovascular disease (CVD) at baseline (1966-2016, n=10 422). NAFLD was defined from prospectively recorded histopathology and categorised as simple steatosis, non-fibrotic steatohepatitis, non-cirrhotic fibrosis and cirrhosis. Patients with NAFLD were matched to <= 5 population controls without NAFLD or CVD, by age, sex, calendar year and county (n=46 517). Using Cox proportional hazards modelling, we calculated multivariable adjusted HRs (aHRs) and 95% CIs for MACE outcomes (ie, ischaemic heart disease (IHD), stroke, congestive heart failure (CHF) or cardiovascular (CV) mortality).Results: Over a median of 13.6 years, incident MACE was confirmed in 2850 patients with NAFLD and 10 648 controls. Patients with NAFLD had higher incidence of MACE than controls (24.3 vs 16.0/1000 person-years (PY); difference=8.3/1000 PY; aHR 1.63, 95% CI 1.56 to 1.70), including higher rates of IHD (difference=4.2/1000 PY; aHR 1.64, 95% CI 1.54 to 1.75), CHF (difference=3.3/1000 PY; aHR 1.75, 95% CI 1.63 to 1.87), stroke (difference=2.4/1000 PY; aHR 1.58, 95% CI 1.46 to 1.71) and CV mortality (difference=1.2/1000 PY; aHR 1.37, 95% CI 1.27 to 1.48). Rates of incident MACE increased progressively with worsening NAFLD severity (p(trend)=0.02), with the highest incidence observed with cirrhosis (difference vs controls=27.2/1000 PY; aHR 2.15, 95% CI 1.77 to 2.61).Conclusion: Compared with matched population controls, patients with biopsy-proven NAFLD had significantly higher incidence of MACE, including IHD, stroke, CHF and CV mortality. Excess risk was evident across all stages of NAFLD and increased with worsening disease severity.
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44.
  • Simon, Tracey G., et al. (författare)
  • Non-alcoholic fatty liver disease in children and young adults is associated with increased long-term mortality
  • 2021
  • Ingår i: Journal of Hepatology. - : Elsevier. - 0168-8278 .- 1600-0641. ; 75:5, s. 1034-1041
  • Tidskriftsartikel (refereegranskat)abstract
    • Background & Aims: Longitudinal data are scarce regarding the natural history and long-term risk of mortality in children and young adults with biopsy-confirmed non-alcoholic fatty liver disease (NAFLD).Methods: This nationwide, matched cohort study included all Swedish children and young adults (<= 25 years) with biopsy confirmed NAFLD (1966-2017; n = 718). NAFLD was confirmed histologically from all liver biopsies submitted to Sweden's 28 pathology departments, and further categorized as simple steatosis or steatohepatitis (NASH). Patients with NAFLD were matched to <= 5 general population controls by age, sex, calendar year and county (n = 3,457). To account for shared genetic and early-life factors, we also matched patients with NAFLD to full sibling comparators. Using Cox regression, we estimated multivariable-adjusted hazard ratios (aHRs) and 95% CIs.Results: Over a median of 15.8 years, 59 patients with NAFLD died (5.5/1,000 person-years [PY]) compared to 36 population controls (0.7/1,000 PY; difference = 4.8/1,000 PY; multivariable aHR 5.88; 95% CI 3.77-9.17), corresponding to 1 additional death per 15 patients with NAFLD, followed for 20 years. The 20-year absolute risk of overall mortality was 7.7% among patients with NAFLD, and 1.1% among controls (difference = 6.6%; 95% CI 4.0-9.2). Findings persisted after excluding those who died within the first 6 months (aHR 4.65; 95% CI 2.92-7.42), and after using full-sibling comparators (aHR 11.72; 95% CI 3.18-43.23). Simple steatosis was associated with a 5.26-fold higher adjusted rate of mortality compared to controls (95% CI 3.05-9.07), and this was amplified with NASH (aHR 11.51, 95% CI 4.77-27.79). Most of the excess mortality was from cancer (1.67 vs. 0.07/ 1,000PY; aHR 15.60; 95% CI 4.97-48.93), liver disease (0.93 vs. 0.04/1,000PY; aHR 16.46; 95% CI 2.75-98.43) and cardiometabolic disease (1.12 vs. 0.14/1,000PY; aHR 4.32, 95% CI 1.73-10.79).Conclusions: Swedish children and young adults with biopsy confirmed NAFLD have significantly higher rates of overall, cancer-, liver-and cardiometabolic-specific mortality compared to matched general population controls.Lay summary: Currently, the natural history and long-term risk of mortality in children and young adults with biopsy-confirmed non-alcoholic fatty liver disease (NAFLD) is unknown. This nationwide cohort study compared the risk of all-cause and cause-specific mortality in pediatric and young adult patients in Sweden with biopsy-confirmed NAFLD to matched general population controls. We found that compared to controls, children and young adults with biopsy-confirmed NAFLD and NASH have significantly higher rates of overall, cancer-, liver-and cardiometabolic-specific mortality.
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45.
  • Song, Mingyang, et al. (författare)
  • Long-Term Incidence and Mortality of Colorectal Cancer After Endoscopic Biopsy With Normal Mucosa : A Swedish-Matched Cohort Study
  • 2021
  • Ingår i: American Journal of Gastroenterology. - : Blackwell Publishing. - 0002-9270 .- 1572-0241. ; 116:2, s. 382-390
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: Endoscopic screening reduces colorectal cancer (CRC) incidence and mortality. Individuals with a negative result are recommended to undergo rescreening within a 10-year interval, but evidence supporting this advice is limited.METHODS: We performed a matched cohort study using prospectively collected data from 88,798 individuals in Sweden with normal mucosa at the first colorectal biopsy (aged ≥50 years) in the nationwide gastrointestinal epidemiology strengthened by histopathology reports (ESPRESSO) (1965-2016) and 424,150 matched reference individuals from the general population. Cox proportional hazards regression estimated multivariable hazard ratios and 95% confidence intervals (CIs) of CRC incidence and mortality of incident CRCs up to 44 years of follow-up.RESULTS: In the normal biopsy and reference groups, respectively, the 20-year incidences of CRC were 3.03% and 4.53% and the 20-year mortalities of incident CRC were 0.89% and 1.54%. The multivariable hazard ratio comparing the normal biopsy and reference groups was 0.62 for CRC incidence (95% CI = 0.58-0.66, P < 0.001) and 0.56 for mortality of incident CRC (95% CI = 0.49-0.64, P < 0.001). When assessed by time interval after biopsy, lower CRC incidence and mortality were observed throughout the follow-up. The association seemed weaker for proximal colon cancer than for rectal and distal colon cancer.DISCUSSION: A normal colorectal biopsy was associated with lower CRC incidence and mortality for at least 20 years after the examination. Our findings confirm previous data and suggest that the screening intervals after a normal colonoscopy could be longer than the commonly recommended 10 years. It may be time to open the discussion for a revision of the international guidelines.
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46.
  • Song, Mingyang, et al. (författare)
  • Risk of colorectal cancer in first degree relatives of patients with colorectal polyps : nationwide case-control study in Sweden
  • 2021
  • Ingår i: The BMJ. - : BMJ Publishing Group Ltd. - 1756-1833. ; 373
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To assess the risk of colorectal cancer (CRC) in first degree relatives (parents and full siblings) of patients with precursor lesions (polyps) for CRC.DESIGN: Case-control study.SETTING: Linkage to the multi-generation register and gastrointestinal ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden) histopathology cohort in Sweden.PARTICIPANTS: 68 060 patients with CRC and 333 753 matched controls.MAIN OUTCOME MEASURES: Multivariable adjusted odds ratios of CRC according to the number of first degree relatives with a colorectal polyp and the histology of polyps and age at diagnosis in first degree relatives. Subgroup analysis was also performed according to age at CRC diagnosis and evaluated the joint association of family history of colorectal polyps and family history of CRC.RESULTS: After adjusting for family history of CRC and other covariates, having a first degree relative with a colorectal polyp (8.4% (5742/68 060) in cases and 5.7% (18 860/333 753) in controls) was associated with a higher risk of CRC (odds ratio 1.40, 95% confidence interval 1.35 to 1.45). The odds ratios ranged from 1.23 for those with hyperplastic polyps to 1.44 for those with tubulovillous adenomas. To better put this risk in perspective, the age specific absolute risk of colon and rectal cancers was estimated according to family history of polyps based on the 2018 national CRC incidence in Sweden. For example, the absolute risk of colon cancer in individuals aged 60-64 years with and without a family history of colorectal polyp was, respectively, 94.3 and 67.9 per 100 000 for men and 89.1 and 64.1 per 100 000 for women. The association between family history of polyps and CRC risk was strengthened by the increasing number of first degree relatives with polyps (≥2 first degree relatives: 1.70, 1.52 to 1.90, P<0.001 for trend) and decreasing age at polyp diagnosis (<50 years: 1.77, 1.57 to 1.99, P<0.001 for trend). A particularly strong association was found for early onset CRC diagnosed before age 50 years (≥2 first degree relatives: 3.34, 2.05 to 5.43, P=0.002 for heterogeneity by age of CRC diagnosis). In the joint analysis, the odds ratio of CRC for individuals with two or more first degree relatives with polyps but no CRC was 1.79 (1.52 to 2.10), with one first degree relative with CRC but no polyps was 1.70 (1.65 to 1.76), and with two or more first degree relatives with both polyps and CRC was 5.00 (3.77 to 6.63) (P<0.001 for interaction).CONCLUSIONS: After adjusting for family history of CRC, the siblings and children of patients with colorectal polyps are still at higher risk of CRC, particularly early onset CRC. Early screening for CRC might be considered for first degree relatives of patients with polyps.
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47.
  • Staller, Kyle, et al. (författare)
  • Antibiotic use as a risk factor for irritable bowel syndrome: Results from a nationwide, case–control study
  • 2023
  • Ingår i: Alimentary Pharmacology and Therapeutics. - 0269-2813 .- 1365-2036. ; 58:11-12, s. 1175-1184
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The microbiome plays an important role in the pathophysiology of irritable bowel syndrome (IBS). Antibiotic use can fundamentally alter gut microbial ecology. We examined the association of antibiotic use with IBS in a large population-based investigation. Methods: A case–control study with prospectively collected data on 29,111 adult patients diagnosed with IBS in Sweden between 2007 and 2016 matched with 135,172 controls. Using a comprehensive histopathology cohort, the Swedish Patient Register, and the Prescribed Drug Register, we identified all consecutive cases of IBS in addition to cumulative antibiotic dispensations accrued until 1 year prior to IBS (exclusionary period) for cases and time of matching for up to five general population controls matched on the basis of age, sex, country and calendar year. Conditional logistic regression estimated multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of IBS. Results: Patients with IBS (n = 29,111) were more likely than controls (n = 135,172) to have used antibiotics up to 1 year prior to diagnosis (74.9% vs. 57.8%). After multivariable adjustment, this translated to a more than twofold increased odds of IBS (OR 2.21, 95% CI 2.14–2.28) that did not differ according to age, sex, year of IBS diagnosis or IBS subtype. Compared to none, 1–2 (OR 1.67, 95% CI 1.61–1.73) and ≥3 antibiotics dispensations (OR 3.36, 95% CI 3.24–3.49) were associated with increased odds of IBS (p for trend <0.001) regardless of the antibiotic class. Conclusions: Prior antibiotics use was associated with an increased odds of IBS with the highest risk among people with multiple antibiotics dispensations.
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48.
  • Sun, Jiangwei, et al. (författare)
  • Gastrointestinal biopsies and amyotrophic lateral sclerosis : results from a cohort study of 1.1 million individuals
  • 2021
  • Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. - : Informa Healthcare. - 2167-8421 .- 2167-9223. ; 22:5-6, s. 410-418
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Evidence has accumulated to support the involvement of gastrointestinal (GI) dysfunction, possibly via gut microbial dysbiosis and alterations in the enteric nervous system, in the pathophysiology of different neurodegenerative diseases. However, whether patients with GI dysfunction have altered risk of amyotrophic lateral sclerosis (ALS) remains unknown.Methods: Based on a historical nationwide cohort study-ESPRESSO-in Sweden, we compared the risk of ALS among individuals with a previous GI biopsy finding of normal mucosa or non-specific inflammation, as two conditions of GI dysfunction, to that of individuals without any GI biopsy. We identified all individuals with a GI biopsy result of either normal mucosa (n = 483,442) or non-specific inflammation (n = 566,663) during 1965-2016 in Sweden as the exposed groups. For each exposed individual, we randomly selected up to five controls from the general Swedish population after individual matching by age and sex. Both the exposed and unexposed individuals were followed from date of biopsy (exposed individuals) or date of selection (unexposed individuals) until ALS diagnosis, emigration out of Sweden, death, or 31 December 2016, whichever came first. Stratified Cox regression models were used to estimate hazard ratios (HRs) and their 95% confidence intervals (CIs).Results: Compared to individuals without GI biopsy, individuals with a GI biopsy result of normal mucosa had an increased risk of ALS (HR = 1.22; 95%CI: 1.04-1.42) after excluding the first 2 years of follow-up to alleviate concern of surveillance bias. This increased risk was noted among male (HR = 1.20; 95%CI: 0.94-1.51) and female (HR = 1.23; 95%CI: 1.01-1.50), as well as among younger (<60 years; HR = 1.17; 95%CI: 0.94-1.44) and older (>= 60 years; HR = 1.24; 95%CI: 0.99-1.56) individuals. In contrast, no association was observed for a GI biopsy result of non-specific inflammation (HR = 1.00; 95%CI: 0.88-1.15). Neither of the GI biopsy results was related to the mortality risk after ALS diagnosis.Conclusions: Individuals with a GI biopsy result of normal mucosa-representing potentially a distinct type of GI dysfunction-had a higher future risk of ALS. No association was however noted for a GI biopsy result of non-specific inflammation. Further studies are needed to validate this finding and to understand the underlying reasons for the contrasting result pattern.
  •  
49.
  • Sun, Jiangwei, et al. (författare)
  • Gastrointestinal biopsy of normal mucosa or nonspecific inflammation and risk of neurodegenerative disease : Nationwide matched cohort study
  • 2023
  • Ingår i: European Journal of Neurology. - : Blackwell Publishing. - 1351-5101 .- 1468-1331. ; 30:11, s. 3430-3439
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and purpose: Evidence has accumulated to support the early involvement of altered gastrointestinal (GI) function in neurodegenerative disease. However, risk of Alzheimer disease (AD) and Parkinson disease (PD) among individuals with a GI biopsy of normal mucosa or nonspecific inflammation is unknown.Methods: This matched cohort study included all individuals in Sweden with a GI biopsy of normal mucosa (n = 480,346) or nonspecific inflammation (n = 655,937) during 1965-2016 (exposed group) as well as their individually matched population references and unexposed full siblings. A flexible parametric model and stratified Cox model were used to estimate hazard ratio (HR) and its 95% confidence interval (CI).Results: Individuals with normal mucosa or nonspecific inflammation had a higher risk of AD and PD during the 20 years after biopsy. Compared with the population references, individuals with normal mucosa had an increased risk of AD (incidence rate [IR] difference = 13.53 per 100,000 person-years, HR [95% CI] = 1.15 [1.11-1.20]) and PD (IR difference = 6.72, HR [95% CI] = 1.16 [1.10-1.23]). Elevated risk was also observed for nonspecific inflammation regarding AD (IR difference = 13.28, HR [95% CI] = 1.11 [1.08-1.14]) and PD (IR difference = 6.83, HR [95% CI] = 1.10 [1.06-1.14]). Similar results were observed in subgroup and sensitivity analyses and when comparing with their unexposed siblings.Conclusions: Individuals with a GI biopsy of normal mucosa or nonspecific inflammation had an increased risk of AD and PD. This adds new evidence of the early involvement of GI dysfunction in neurodegenerative disease.
  •  
50.
  • Sun, Jiangwei, et al. (författare)
  • Long-term risk of arrhythmias in patients with inflammatory bowel disease : A population-based, sibling-controlled cohort study
  • 2023
  • Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 20:10
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundAlthough previous evidence has suggested an increased risk of cardiovascular disease (CVD) in patients with inflammatory bowel disease (IBD), its association with arrhythmias is inconclusive. In this study, we aimed to explore the long-term risk of arrhythmias in patients with IBD.Methods and findingsThrough a nationwide histopathology cohort, we identified patients with biopsy-confirmed IBD in Sweden during 1969 to 2017, including Crohn's disease (CD: n = 24,954; median age at diagnosis: 38.4 years; female: 52.2%), ulcerative colitis (UC: n = 46,856; 42.1 years; 46.3%), and IBD-unclassified (IBD-U: n = 12,067; 43.8 years; 49.6%), as well as their matched reference individuals and IBD-free full siblings. Outcomes included overall and specific arrhythmias (e.g., atrial fibrillation/flutter, bradyarrhythmias, other supraventricular arrhythmias, and ventricular arrhythmias/cardiac arrest). Flexible parametric survival models estimated hazard ratios (aHR) with 95% confidence intervals (95% CIs), after adjustment for birth year, sex, county of residence, calendar year, country of birth, educational attainment, number of healthcare visits, and cardiovascular-related comorbidities. Over a median of approximately 10 years of follow-up, 1,904 (7.6%) patients with CD, 4,154 (8.9%) patients with UC, and 990 (8.2%) patients with IBD-U developed arrhythmias, compared with 6.7%, 7.5%, and 6.0% in reference individuals, respectively. Compared with reference individuals, overall arrhythmias were increased in patients with CD [54.6 versus 46.1 per 10,000 person-years; aHR = 1.15 (95% CI [1.09, 1.21], P < 0.001)], patients with UC [64.7 versus 53.3 per 10,000 person-years; aHR = 1.14 (95% CI [1.10, 1.18], P < 0.001)], and patients with IBD-U [78.1 versus 53.5 per 10,000 person-years; aHR = 1.30 (95% CI [1.20, 1.41], P < 0.001)]. The increased risk persisted 25 years after diagnosis, corresponding to 1 extra arrhythmia case per 80 CD, 58 UC, and 29 IBD-U cases over the same period. Patients with IBD also had a significantly increased risk of specific arrhythmias, except for bradyarrhythmias. Sibling comparison analyses confirmed the main findings. Study limitations include lack of clinical data to define IBD activity, not considering the potential role of IBD medications and disease activity, and the potential residual confounding from unmeasured factors for arrhythmias.ConclusionsIn this study, we observed that patients with IBD were at an increased risk of developing arrhythmias. The excess risk persisted even 25 years after IBD diagnosis. Our findings indicate a need for awareness of this excess risk among healthcare professionals.
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