Association of extraintestinal manifestations and anaemia with disease outcomes in patients with inflammatory bowel disease.

OBJECTIVE: The association between extraintestinal manifestations (EIMs) and disease activity suggest a common pathogenetic link with inflammatory bowel disease (IBD). We report on the association of EIMs and anaemia with long-term disease outcomes, including treatment steps, hospitalization, and surgery in the prospective population-based IBD inception cohort from Veszprem province. METHODS: Data of 678 incident IBD patients (Crohn's disease/ulcerative colitis(CD/UC): 331/347) diagnosed from 1st January 2000 to 31st December 2012 were analyzed (CD: m/f: 176/155, median age at diagnosis: 28, IQR: 21-40 years, disease duration: 6, IQR: 2-9 years; UC: m/f: 200/147, median age at diagnosis: 36, IQR: 26-50 years, duration: 7, IQR: 4-10 years). RESULTS: EIMs were present in 30% of the CD and 17.3% of the UC patients. In CD, female gender (p = 0.02) need for steroid (p  < 0.001) and azathioprine (AZA) (p = 0.02), while in UC, young age at onset (p = 0.03), extensive disease (p = 0.003), female gender (p = 0.07), need for steroids (p < 0.001) and AZA (p = 0.004) and need for IBD-related hospitalization (p = 0.01) were associated with the presence of EIMs. Anaemia was present in 56.7% of the CD and 30.2% of the UC patients. In both CD and UC anaemia was associated with age at onset (pCD = 0.001, pUC = 0.04), disease location/extent (pCD = 0.02, pUC < 0.001), steroid and AZA use (for both pCD,UC < 0.001), need for surgery/colectomy (pCD < 0.001, pUC = 0.002) and hospitalization (pCD = 0.004, pUC < 0.001) and in CD, it was associated with anti TNF therapy(p = 0.002). CONCLUSIONS: The presence of EIMs was associated with disease phenotype in UC and with treatment strategy in both CD and UC. Additionally, anaemia was associated with hospitalization and surgery in both CD and UC, suggesting that EIMs and anaemia may be helpful in stratifying disease severity in IBD.

Low incidence of venous thromboembolism in inflammatory bowel diseases: prevalence and predictors from a population-based inception cohort.

OBJECTIVE: Patients with inflammatory bowel diseases (IBD) are considered to have an increased risk for venous thromboembolism (VTE). The aim of the present study was to analyze the incidence and risk factors of VTE in a population-based inception cohort in the Veszprem province database between 1977 and 2012. MATERIAL AND METHODS: A total of 1708 incepted IBD patients were included (male/female: 879/829; CD (Crohn's disease): 648, age at onset: 29, interquartile range (IQR): 22-39; UC (ulcerative colitis): 1060, age at onset: 36, IQR: 26-50 years). Both in- and outpatient records were collected and comprehensively reviewed and followed up for a total of 21,369 patient-years. RESULTS: Twenty-two VTE events were identified in 19 patients (6 events in 5 CD and 16 in 14 UC patients). The incidence rate of VTE in IBD was 1.03 per 1000 patient-years. The risk of VTE in UC was associated with extensive location (odds ratio (OR): 3.25, 95% confidence interval (CI): 1.13-9.35), presence of fulminant episode during the disease course (OR: 4.15, 95% CI: 1.28-13.5), smoking (OR: 3.46, 95% CI: 1.14-10.5), and need for steroids (OR: 2.97, 95% CI: 0.99-8.92). CONCLUSION: The incidence of VTE was lower than previously reported. The incidence was higher in males and in UC it was associated with extensive disease, fulminant episodes, corticosteroids-requiring disease and smoking, but not with age at onset.

Burden of perianal disease in Crohn's disease: Accelerating medical therapy and high rates of perianal surgery over the last four decades - Results from a population-based study over four decades.

BACKGROUND: Few population-based studies have investigated the prevalence and disease course of perianal manifestation in Crohn's disease. AIMS: To analyse the prevalence and outcomes of perianal Crohn's disease including medical therapies and need for perianal surgery, over different therapeutic eras based on the time of diagnosis; cohort A (1977-1995), cohort B (1996-2008), and cohort C (2009-2018) METHODS: Patient inclusion lasted between 1977 and 2018. We followed patients prospectively, and regularly reviewed both in-hospital and outpatient records. We defined a perianal surgical procedure as any perianal incision and excision, fistulotomy, or abscess drainage. RESULTS: We included 946 incident patients. Perianal disease at diagnosis was present in 17.4% (n = 165) of the total cohort, with a declining prevalence in cohorts A/B/C, respectively (24.7%/18.5%/13.2%; p = 0.001). By the end of follow-up, an additional 9.3% (n = 88) of the total cohort developed perianal disease. Cumulative immunosuppressive and biologic exposure increased over time; biologic use was higher in patients with perianal disease [pLog Rank < 0.001]. The overall rate of perianal surgery was 44.7% (113/253), with a probability of 28.3% (95% CI: 25.4-31.2) after 10 years, 41.0% (95% CI: 37.5-44.5) after 20 years, and 64.1% (95% CI: 59-69.2) after 30 years. There was no statistically significant difference in the probability of first perianal surgery among cohorts A/B/C [Log Rank = 0.594]. CONCLUSIONS: The burden of perianal disease and perianal surgery rates were high in this cohort. Therapeutic strategy was accelerated in patients with perianal Crohn's over time with higher exposure to immunosuppressives and biologics. Surgical management of perianal disease remained unchanged amongst the cohorts.

[Role of pulse oximetric monitoring during gastrointestinal endoscopy. Prospective multicenter study of the Gastroenterology Working Group of the Veszprém Regional Committee of the Hungarian Academy of Sciences (VEAB)]. / Az endoszkópos vizsgálatok pulzoximetriás monitorozásának jelentosége. Az MTA VEAB Gasztroenterológiai Munkabizottságának prospektív multicentrikus vizsgálata.

INTRODUCTION: Recent guidelines recommend routine pulse oximetric monitoring during endoscopy, however, this has not been the common practice yet in the majority of the local endoscopic units. AIMS: To draw attention to the importance of the routine use of pulse oximetric recording during endoscopy. METHOD: A prospective multicenter study was performed with the participation of 11 gastrointestinal endoscopic units. Data of pulse oximetric monitoring of 1249 endoscopic investigations were evaluated, of which 1183 were carried out with and 66 without sedation. RESULTS: Oxygen saturation less than 90% was observed in 239 cases corresponding to 19.1% of all cases. It occurred most often during endoscopic retrograde cholangiopancreatography (31.2%) and proximal enteroscopy (20%). Procedure-related risk factors proved to be the long duration of the investigation, premedication with pethidine (31.3%), and combined sedoanalgesia with pethidine and midazolam (34.38%). The age over 60 years, obesity, consumption of hypnotics or sedatives, severe cardiopulmonary state, and risk factor scores III and IV of the American Society of Anestwere found as patient-related risk factors. CONCLUSION: To increase the safety of patients undergoing endoscopic investigation, pulse oximeter and oxygen supplementation should be the standard requirement in all of the endoscopic investigation rooms. Pulse oximetric monitoring is advised routinely during endoscopy with special regard to the risk factors of hypoxemia.

Declining Trends of Reoperations and Disease Behaviour Progression in Crohn's Disease over Different Therapeutic Eras-A Prospective, Population-Based Study from Western Hungary between 1977-2020, Data from the Veszprem Cohort.

BACKGROUND AND AIMS: Few population-based studies have investigated long-term surgery rates for Crohn's disease [CD]. Our aim was to analyse disease progression and surgery rates in a population-based cohort over different therapeutic eras, based on the time of diagnosis: cohort-A [1977-1995], cohort-B [1996-2008], and cohort-C [2009-2018]. METHODS: A total of 946 incident CD patients were analysed (male/female: 496/450; median age at diagnosis: 28 years [y]; interquartile range [IQR]: 22-40]). Patient inclusion lasted between 1977 and 2018. Immunomodulators have become widespread in Hungary since the mid-1990s and biologic therapies since 2008. Patients were followed prospectively, with both in-hospital and outpatient records reviewed regularly. RESULTS: The probability of disease behaviour progression from inflammatory [B1] to stenosing or penetrating phenotype [B2/B3] significantly decreased (27.1 ±â€…5.3%/21.5 ±â€…2.5%/11.3 ±â€…2.2% in cohorts A/B/C, respectively, after 5 years; 44.3 ±â€…5.9%/30.6 ±â€…2.8%/16.1 ±â€…2.9% after 10 years, respectively; [pLogRank <0.001]). The probability of first resective surgery between cohorts A/B/C were 33.3 ±â€…3.8%/26.5 ±â€…2.1%/28.1 ±â€…2.4%, respectively, after 5 years; 46.1 ±â€…4.1%/32.6 ±â€…2.2%/33.0 ±â€…2.7% after 10 years, respectively; and 59.1 ±â€…4.0%/41.4 ±â€…2.6% [cohorts A/B] after 20 years. There was a significant decrease in first resective surgery risk between cohorts A and B [plog rank = 0.002]; however, no further decrease between cohorts B and C [plog rank = 0.665]. The cumulative probability of re-resection in cohorts A/B/C was decreasing over time (17.3 ±â€…4.1%/12.6 ±â€…2.6%/4.7 ±â€…2.0%, respectively, after 5 years [plog rank = 0.001]). CONCLUSION: We report a continuous decline in reoperation rates and disease behaviour progression in CD over time, with the lowest values in the biologic era. In contrast, there was no further decrease in the probability of first major resective surgery after the immunosuppressive era.

Long-term Colectomy Rates of Ulcerative Colitis over 40 Years of Different Therapeutic Eras-Results from a Western Hungarian Population-based Inception Cohort Between 1977 and 2020.

BACKGROUND AND AIMS: Few populaion-based studies have investigated the long-term colectomy rates of ulcerative colitis [UC]. We aimed to assess the colectomy rates over 40 years of different therapeutic eras in a prospective population-based inception cohort from Veszprem Province, Western Hungary. METHODS: Patient inclusion lasted between January1, 1977, and December31, 2018. Patient follow-up ended December 31, 2020. Colectomy rates and disease course were examined in three different eras based on the time of UC diagnosis; cohort A [1977-1995], cohort B [1996-2008], and cohort C [2009-2018]. RESULTS: A total of 1370 incident UC patients were included [male 51.2%, median age at diagnosis 37 years]. Median follow-up was 17 years (interquartile range [IQR] 9-24); 87 patients [6.4%] underwent colectomy. The cumulative probability of colectomy in the total population was 2.6% (95% confidence interval [CI] 2.2-3.0), 4.2% [95% CI 3.6-4.8], 7.0% [95% CI 6.2-7.8], and 10.4% [95% CI 9.1-11.7] after 5, 10, 20, and 30 years, respectively. The proportion of extensive colitis at diagnosis increased over time [24.2%/24.3%/34.9% in cohorts A/B/C, respectively, p = 0.001]. Overall exposure to immunomodulators [11.3%/20.9%/34.4% in cohorts A/B/C, respectively, p <0.001], as well as the probability for biologic therapy initiation increased over time (0%/3.3% [95% CI 2.6-4.0]/13.9% [95% CI 12.1-15.7], p <0.001). There were no statistically significant differences in the cumulative probability of colectomies between cohorts A/B/C: 1.7% [95% CI 1.0-2.4], 2.5% [95% CI 1.9-3.1], and 3.7% [95% CI 2.7-4.7] after 5 years; 3.5% [95% CI 2.5-4.5], 4.2% [95% CI 3.4-5.0], and 4.5% [95% CI 3.3-5.7] after 10 years; and 7.5% [95% CI 6.1-8.9] and 6.3% [95% CI 5.2-7.4] in cohorts A/B after 20 years [log-rank = 0.588]. Extensive colitis (hazard ratio [HR] 2.24, 95% CI 1.55-3.23) and continuous active disease activity [HR 6.36, 95% CI 3.46-11.67] were independent predictors for colectomy. CONCLUSION: No differences in colectomy rates have been observed in the incident UC patients over 40 years despite increasing use of immunomodulators and biologic therapies.

Incidence, Prevalence, Disease Course, and Treatment Strategy of Crohn's Disease Patients from the Veszprem Cohort, Western Hungary: A Population-based Inception Cohort Study Between 2007 and 2018.

BACKGROUND AND AIMS: The number of prospective population-based studies on Crohn's disease[CD] is still limited from Eastern Europe. The present study is a continuation of the Veszprem IBD cohort. Our aim was to analyse incidence, prevalence, disease phenotype, treatment strategy, disease course, and surgical outcomes in a prospective population-based inception cohort including CD patients diagnosed between 2007 and 2018. METHODS: A total of 421 consecutive inception patients were included [male/female:237/184; mean age at diagnosis: 33.3 ±â€…16.2years]. Both in-hospital and outpatient records were collected and comprehensively reviewed. Demographic data were derived from the Hungarian Central Statistical Office. RESULTS: Mean incidence rate was 9.9 [95% CI: 9.0-10.9]/105 person-years in this 12-year period. Prevalence rate was 236.8 [95% CI: 220.8-252.8] in 2015; 17.6% and 20.0% of the patients had stenosing[B2] and penetrating[B3] disease behavior at diagnosis,respectively. The probability of disease behaviour progression from luminal to B2/B3 phenotype was 14.7% (standard error [SE]: 2.2) at 5 years after diagnosis. Distribution of maximal therapeutic steps during the total follow-up (8.5 years [8.5y], standard deviation [SD]: 3.3) was 5-aminosalicylic acid [5-ASA] in 15.7%, corticosteroids in 14.3%, immunosuppressives in 42.5%, and biologic therapy in 26.2%. The probability of receiving biologictherapy after diagnosis was 20.9% [SE: 2.0] at 5 years. The probability of first resective surgery was 20.7% [SE: 2.0] at 1 year, 26.1% [SE: 2.2] at 5 years, and 30.7% [SE: 2.4] at 10 years. The perianal surgery rate was 31.3% among patients with perianal involvement. CONCLUSIONS: The incidence of CD in Hungary was high, similar to high-incidence areas in Western Europe. Treatment strategies are reflecting the biologic era. Disease behaviour progression was lower, as well as long-term [10y] surgery rates decreasing compared with data from previous decades.

Epidemiology, Treatment Strategy, Natural Disease Course and Surgical Outcomes of Patients with Ulcerative Colitis in Western Hungary - A Population-based Study Between 2007 and 2018: Data from the Veszprem County Cohort.

BACKGROUND AND AIMS: The number of population-based studies in ulcerative colitis [UC] from Eastern Europe is limited. Our aim here was to analyse the incidence, prevalence, disease phenotype, treatment strategy, disease course and colectomy rates in a prospective population-based inception cohort including UC patients diagnosed between 2007 and 2018. The present study is a continuation of the Veszprem IBD cohort since 1977. METHODS: In total, 467 UC patients were included [male/female: 236/231; median age at diagnosis: 36 years, IQR: 25-54 years]. Both in-hospital and outpatient records were collected and comprehensively reviewed. The mean length of follow-up was 8.34 ±â€…3.6 years. Demographic data were derived from the Hungarian Central Statistical Office. RESULTS: The mean incidence rate was 11.02/105 person-years in this 12-year period. Prevalence was 317.79/105 persons in 2015. Disease extent at diagnosis was proctitis [E1] in 22.3%, left-sided colitis [E2] in 43.9% and extensive colitis [E3] in 33.8%. The probability of disease extent progression was 11.6% [SE: 1.8] after 5 years. The distribution of maximal therapeutic steps was 5-ASA in 46.9%, corticosteroids in 16.3%, immunosuppressives in 19.3% and biologicals in 16.5%. The probability of receiving biological therapy after diagnosis was 9.9% [SE: 1.4] at 3 years. The overall colectomy rate was 4.1% in the population. The probability of colectomy was 1.5% [SE: 0.6] at 1 year, 3.6% [SE: 0.9] at 5 years and 4.4% [SE: 1.0] at 10 years. CONCLUSIONS: The incidence of UC was high in Hungary, similar to high-incidence areas in Western Europe. Treatment strategies are in line with the biological era. The probability of progressing to proximal disease, and the medium- and long-term colectomy rates were both lower compared with data from Western European centres.

Time Trends of Environmental and Socioeconomic Risk Factors in Patients with Inflammatory Bowel Disease over 40 Years: A Population-Based Inception Cohort 1977-2020.

BACKGROUND: Data from population-based studies investigating trends in environmental factors associated with inflammatory bowel disease (IBD) is lacking. We aimed to assess long-term time trends of environmental and socioeconomic factors in IBD patients from a well-defined population-based cohort from Veszprem, Hungary. METHODS: Patients were included between 1 January 1977, and 31 December 2020. Trends of environmental and socioeconomic factors were evaluated in three periods based on the decade of diagnosis, representing different therapeutic eras: cohort-A,1977-1995; cohort-B,1996-2008 (immunomodulator era); and cohort-C, 2009-2020 (biological era). RESULTS: A total of 2240 incident patients with IBD were included (ulcerative colitis (UC) 61.2%, male 51.2%, median age at diagnosis: 35 years (IQR 29-49)). Rates of active smoking significantly decreased over time in Crohn's disease (CD): 60.2%, 49.9%, and 38.6% in cohorts A/B/C (p < 0.001). In UC, the rates were low and stable: 15.4%, 15.4%, and 14.5% in cohorts A/B/C (p = 0.981). Oral contraceptive use was more common in CD compared to UC (25.0% vs. 11.6%, p < 0.001). In UC, prevalence of appendectomy before diagnosis decreased over time: 6.4%, 5.5%, and 2.3% in cohorts A/B/C (p = 0.013). No significant changes were found in the socio-geographic characteristics of the IBD population (urban living: UC, 59.8%/64.8%/ 62.5% (p = 0.309) and CD, 62.5%/ 62.0%/ 59.0% (p = 0.636), in cohorts A/B/C). A greater percentage of patients had completed secondary school as the highest education level in later cohorts in both UC (42.9%/50.2%/51.6%, p < 0.001) and CD (49.2%/51.7%/59.5%, p = 0.002). A higher percentage of skilled workers (34.4%/36.2%/38.9%, p = 0.027) was found in UC, but not in CD (p = 0.454). CONCLUSION: The association between trends of known environmental factors and IBD is complex. Smoking has become less prevalent in CD, but no other major changes occurred in socioeconomic factors over the last four decades that could explain the sharp increase in IBD incidence.

Has there been a change in the natural history of Crohn's disease? Surgical rates and medical management in a population-based inception cohort from Western Hungary between 1977-2009.

OBJECTIVES: Medical therapy for Crohn's disease (CD) has changed significantly over the past 20 years with increasing use of immunosuppressives. In contrast, surgery rates are still high and there is little evidence that disease outcomes for CD have changed over the past decades. The objective of this study was to analyze the evolution of the surgical rates and medical therapy in the population-based Veszprem province database. METHODS: Data of 506 incident CD patients were analyzed (age at diagnosis: 31.5 years, s.d. 13.8 years). Both hospital and outpatient records were collected and comprehensively reviewed. The study population was divided into three groups by the year of diagnosis (cohort A: 1977-1989, cohort B: 1990-1998 and cohort C: 1999-2008). RESULTS: Overall, azathioprine (AZA), systemic steroid, and biological (only available after 1998) exposure was 45.8, 68.6, and 9.5%, respectively. The 1- and 5-year probability of AZA use were 3.2 and 6.2% in cohort A, 11.4 and 29.9% in cohort B, and 34.8 and 46.2% in cohort C. In a multivariate Cox-regression analysis, decade of diagnosis (P < 0.001, hazard ratio (HR)(cohorts B-C): 2.88-6.53), age at onset (P = 0.008, HR: 1.76), disease behavior at diagnosis (P < 0.001, HR(complicated): 1.76-2.07), and need for systemic steroids (P < 0.001, HR: 2.71) were significantly associated with the time to initiation of AZA therapy. Early AZA use was significantly associated with the time to intestinal surgery in CD patients; in a multivariate Cox analysis (HR: 0.43, 95% confidence interval (CI): 0.28-0.65) and after matching on propensity scores for AZA use (HR: 0.42, 95% CI: 0.26-0.67). CONCLUSIONS: This population-based inception cohort has shown that the recent reduction in surgical rates was independently associated with increased and earlier AZA use.

[The effect of early immunosuppressive therapy on the rate of resections performed in patients with Chron's disease, in Veszprém county, Hungary, a population-based cohort study]. / A korai immunszuppresszív kezelés hatása a reszekciós mutétek arányára Crohn-betegekben, Veszprém megyében, populációs alapú kohorszvizsgálat alapján.

UNLABELLED: Medical therapy for Crohn's disease has changed significantly over the past 20 years with the increasing use of immunosuppressants. In contrast, surgery rates are still high and evidence about the the changes in the outcome of Crohn's disease over the past decades is scarce. AIMS: The objective of this study was to analyze the evolution of the surgical rates and medical therapy in the population-based Veszprém county database. METHODS: Data of 506 Crohn's disease patients were analyzed (age at diagnosis: 31.5 years, SD: 13.8 years). Both hospital and outpatient records were collected and comprehensively reviewed. The study population was divided into three groups based on the year of diagnosis (cohort A: 1977-1989, cohort B: 1990-1998 and cohort C: 1999-2008). RESULTS: Overall azathioprine, systemic steroid, and biological (only available after 1998) exposure was 45.8, 68.6, and 9.5%, respectively. The 1 and 5-year probabilities of azathioprine use were 3.2 and 6.2% in cohort A, 11.4 and 29.9% in cohort B, and 34.8 and 46.2% in cohort C. In multivariate analysis, decade of diagnosis (P<0.001), age at onset (P = 0.008), disease behavior at diagnosis (P<0.001), and need for systemic steroids (P<0.001) were significantly associated with the time to initiation of azathioprine therapy. Early azathioprine use was significantly associated with the time to intestinal surgery in Crohn's disease patients; in a multivariate Cox analysis (HR: 0.43, 95% confidence interval (CI): 0.28-0.65) and after matching on propensity scores for azathioprine use (HR: 0.42,95% CI:0.26-0.67). CONCLUSIONS: This population-based inception cohort showed that reduction in surgical rates was independently associated with increased and earlier azathioprine use.

Risk factors for ulcerative colitis-associated colorectal cancer in a Hungarian cohort of patients with ulcerative colitis: results of a population-based study.

BACKGROUND: There is an increased risk of colorectal cancer (CRC) in ulcerative colitis (UC). The prevalence of UC-associated CRC is different in various geographic regions. The risk depends primarily on the duration and extent of disease. The aim of this study was to identify the risk factors for and the epidemiology of CRC in Hungarian patients with UC. METHODS: We retrospectively evaluated the relevant epidemiological and clinical data of all patients with UC in Veszprem province in our 30-year IBD database (723 patients with UC; male/female, 380/343; non-CRC related colectomies, 3.7%). RESULTS: CRC was diagnosed in 13 patients (13/8564 person-year duration) during follow-up. Age at diagnosis of CRC was at a median of 51 (range 27-70) years. Eight patients are still alive, 4 died of CRC, and 1 died of an unrelated cause. Longer disease duration, extensive colitis, primary sclerosing cholangitis, and dysplasia found in the biopsy specimen were identified as risk factors for developing CRC. The cumulative risk of developing CRC after a disease duration of 10 years was 0.6% (95% confidence interval [CI] 0.2%-1.0%); 20 years, 5.4% (95% CI 3.7%-7.1%); and 30 years, 7.5% (95% CI 4.8%-10.2%). CRC diagnosed at surveillance colonoscopy was associated with a tendency for longer survival (P = 0.08). CONCLUSIONS: The cumulative risk of CRC was high in our patients with UC; however, it was lower compared with that reported in Western European and North American studies. CRC developed approximately 15 years earlier compared with sporadic CRC patients in Hungary. Longer disease duration, extensive colitis, dysplasia, and primary sclerosing cholangitis were identified as important risk factors for developing CRC.

[Risk factors for ulcerative colitis associated colorectal cancers in a Hungarian cohort of ulcerative colitis patients]. / A colorectális rák rizikófaktorai colitis ulcerosás betegekben populációs alapú vizsgálat eredményei alapján.

BACKGROUND: There is an increased risk of colorectal cancer (CRC) in ulcerative colitis (UC). The prevalence of UC associated CRC is different in various geographical regions. The risk depends primarily on the duration and extent of disease. AIM: The aim of the study was to identify risk factors for and epidemiology of CRC in UC patients in Veszprem province. PATIENTS AND METHODS: From our thirty-year IBD database we retrospectively studied the relevant epidemiological and clinical data of all UC patients in Veszprem province. The data of 723 UC patients (m/f: 380/343) were evaluated. The rate of familial disease was 5.2%, the rate of non-CRC related colectomies was 3.7% in our UC patients. RESULTS: CRC was diagnosed in 13 patients (m/f: 6/7, 13/8564 person year duration) during follow-up. The onset of UC in the 13 patients with UC-CRC was 34.5 (13-61) years, 4.1 years younger compared to UC patients without CRC. Mean age of UC-CRC patients at diagnosis of CRC was 50.9 (27-70) years (duration of UC: 16.5 +/- 8.2 years), almost 15 years younger than the average in sporadic CRC population in Hungary. Eight patients are still alive (survival: 67.9 (10-163) months), four patients died because of CRC (survival: 8.0 months), one died due to unrelated cause after 10 years of the diagnosis of CRC. Longer disease duration, chronic continuous disease, more extensive colitis, the presence of iron deficiency or chronic anaemia, primary sclerosing cholangitis (PSC) and dysplasia in the biopsy were identified as risk factors for developing CRC. In a logistic regression model longer disease duration, extensive colitis, PSC and dysplasia were still associated with increased risk. The cumulative risk for developing CRC after a disease duration of 10 years was 0.6% (95% CI: 0.2-1.0%), at 20 years 5.4 % (95% CI: 3.7-7.1%) and at 32 years 12.6% (95% CI: 7.0-18.2%). CRC diagnosed at surveillance colonoscopy was associated with longer survival (p = 0.04). CONCLUSION: The cumulative risk of CRC was high in our UC patients, however it was lower compared to that reported in Western European and North American studies. CRC developed approximately fifteen years earlier compared to the sporadic CRC cases. Long disease duration, extensive colitis, the presence of iron deficiency or chronic anaemia, dysplasia and primary sclerosing cholangitis (PSC) seem to be important risk factor for developing CRC in UC patients.

Prevalence and predictors of hospitalization in Crohn's disease in a prospective population-based inception cohort from 2000-2012.

AIM: To analyze the prevalence, length and predictors of hospitalization in the biological era in the population-based inception cohort from Veszprem province. METHODS: Data of 331 incident Crohn's disease (CD) patients diagnosed between January 1, 2000 and December 31, 2010 were analyzed (median age at diagnosis: 28; IQR: 21-40 years). Both in- and outpatient records were collected and comprehensively reviewed. RESULTS: Probabilities of first CD-related hospitalization and re-hospitalization were 32.3%, 45.5%, 53.7% and 13.6%, 23.9%, 29.8%, respectively after one, three and five years of follow-up in Kaplan-Meier analysis. First-year hospitalizations were related to diagnostic procedures (37%), surgery or disease activity (27% and 21%). Non-inflammatory disease behavior at diagnosis (HR = 1.32, P = 0.001) and perianal disease (HR = 1.47, P = 0.04) were associated with time to first CD-related hospitalization, while disease behavior change (HR = 2.38, P = 0.002) and need for steroids (HR = 3.14, P = 0.003) were associated with time to first re-hospitalization in multivariate analyses. Early CD-related hospitalization (within the year of diagnosis) was independently associated with need for immunosuppressives (OR = 2.08, P = 0.001) and need for surgeries (OR = 7.25, P < 0.001) during the disease course. CONCLUSION: Hospitalization and re-hospitalization rates are still high in this cohort, especially during the first-year after the diagnosis. Non-inflammatory disease behavior at diagnosis was identified as the pivotal predictive factor of both hospitalization and re-hospitalization.

Does Hospitalization Predict the Disease Course in Ulcerative Colitis? Prevalence and Predictors of Hospitalization and Re-Hospitalization in Ulcerative Colitis in a Population-based Inception Cohort (2000-2012).

BACKGROUND AND AIMS: Limited data are available on the hospitalization rates in population-based studies. Since this is a very important outcome measure, the aim of this study was to analyze prospectively if early hospitalization is associated with the later disease course as well as to determine the prevalence and predictors of hospitalization and re-hospitalization in the population-based ulcerative colitis (UC) inception cohort in the Veszprem province database between 2000 and 2012. METHODS: Data of 347 incident UC patients diagnosed between January 1, 2000 and December 31, 2010 were analyzed (M/F: 200/147, median age at diagnosis: 36, IQR: 26-50 years, follow-up duration: 7, IQR 4-10 years). Both in- and outpatient records were collected and comprehensively reviewed. RESULTS: Probabilities of first UC-related hospitalization were 28.6%, 53.7% and 66.2% and of first re-hospitalization were 23.7%, 55.8% and 74.6% after 1-, 5- and 10- years of follow-up, respectively. Main UC-related causes for first hospitalization were diagnostic procedures (26.7%), disease activity (22.4%) or UC-related surgery (4.8%), but a significant percentage was unrelated to IBD (44.8%). In Kaplan-Meier and Cox-regression analysis disease extent at diagnosis (HR extensive: 1.79, p=0.02) or at last follow-up (HR: 1.56, p=0.001), need for steroids (HR: 1.98, p<0.001), azathioprine (HR: 1.55, p=0.038) and anti-TNF (HR: 2.28, p<0.001) were associated with the risk of UC-related hospitalization. Early hospitalization was not associated with a specific disease phenotype or outcome; however, 46.2% of all colectomies were performed in the year of diagnosis. CONCLUSION: Hospitalization and re-hospitalization rates were relatively high in this population-based UC cohort. Early hospitalization was not predictive for the later disease course.

Association of extraintestinal manifestations of inflammatory bowel disease in a province of western Hungary with disease phenotype: results of a 25-year follow-up study.

AIM: IBD is a systemic disease associated with a large number of extraintestinal manifestations (EIMs). Our aim was to determine the prevalence of EIMs in a large IBD cohort in Veszprem Province in a 25-year follow-up study. METHODS: Eight hundred and seventy-three IBD patients were enrolled (ulcerative colitis/UC/: 619, m/f: 317/302, mean age at presentation: 38.3 years, average disease duration: 11.2 years; Crohn's disease/CD/: 254, m/f: 125/129, mean age at presentation: 32.5 years, average disease duration: 9.2 years). Intestinal, extraintestinal signs and laboratory tests were monitored regularly. Any alteration suggesting an EIMs was investigated by a specialist. RESULTS: A total of 21.3% of patients with IBD had EIM (UC: 15.0%, CD: 36.6%). Age at presentation did not affect the likelihood of EIM. Prevalence of EIMs was higher in women and in CD, ocular complications and primary sclerosing cholangitis (PSC) were more frequent in UC. In UC there was an increased tendency of EIM in patients with a more extensive disease. Joint complications were more frequent in CD (22.4% vs UC 10.2%, P<0.01). In UC positive family history increased the risk of joint complications (OR:3.63). In CD the frequency of type-1 peripheral arthritis was increased in patients with penetrating disease (P=0.028). PSC was present in 1.6% in UC and 0.8% in CD. Dermatological complications were present in 3.8% in UC and 10.2% in CD, the rate of ocular complications was around 3% in both diseases. Rare complications were glomerulonephritis, autoimmune hemolytic anaemia and celiac disease. CONCLUSION: Prevalence of EIM in Hungarian IBD patients is in concordance with data from Western countries. The high number of EIM supports a role for complex follow-up in these patients.

[Extra-intestinal manifestation of IBD in Veszprém county (of Hungary): results of a 25-years follow-up study]. / A gyulladásos bélbetegségek extraintestinalis tünetei Veszprém megyében 25 éves betegkövetés adatai alapján.

INTRODUCTION: IBD is a systemic disease associated with a number of extraintestinal manifestations (EIM). The author's aim was to determine the prevalence and features of EIM in a large IBD population in Veszprém county in a 25-year follow-up study. PATIENTS AND METHODS: 873 IBD patients were enrolled in the study (UC: 619, m/f: 317/302, age at presentation: 38.3 yrs, disease duration: 11.2 yrs; CD: 254, m/f: 125/129, age at presentation: 32.5 yrs, disease duration: 9.2 yrs). Intestinal, extraintestinal symptoms and laboratory tests were monitored regularly. Any alteration suggesting an EIM was investigated by specialist. RESULTS: A total of 21.3% of patients with IBD patients had EIM (UC: 15.0%, CD: 36.6%). Age at presentation did not affect the likelihood of EIM. Prevalence of EIM was higher in women and in CD, ocular complications and PSC were more frequent in UC. In UC there was an increased tendency of EIM in patients having a more extensive disease. In CD patients colonic location increased the frequency of axial and type-1 peripheral arthritis. In UC positive family history increased the risk of joint (OR: 3.63) complications. Joint complications were more frequent in CD (22.4%) than in UC (10.2%, p < 0.01). PSC was present in 1.6% in UC and 0.8% in CD. Dermatological complications were present in 3.8% in UC and 10.2% in CD, the rate of ocular complications was around 3% in both diseases. Erythema nodosum, pyoderma gangrenosum and uveitis were the most frequent manifestations among them. Rare complications were glomerulonephritis, autoimmune haemolytic anaemia and celiac disease. CONCLUSION: The prevalence of EIM in Hungarian IBD patients was in concordance with data from Western countries. The high number of EIM supports a role for complex follow-up in these patients.

Incidence rates and disease course of paediatric inflammatory bowel diseases in Western Hungary between 1977 and 2011.

BACKGROUND: Limited data are available on paediatric inflammatory bowel diseases in Eastern Europe. Our aim was to analyse disease characteristics in the population-based Veszprem province database between 1977 and 2011. METHODS: 187 (10.5%, ulcerative colitis/Crohn's disease/undetermined colitis: 88/95/4) out of 1565 incident patients were diagnosed with a paediatric onset in this population-based prospective inception cohort. RESULTS: The incidence of Crohn's disease and ulcerative colitis increased from 0 and 0.7 in 1977-1981 to 7.2 and 5.2 in 2007-2011 per 100,000 person years. Ileocolonic location (45%) and inflammatory disease behaviour (61%) were most frequent in Crohn's disease, while azathioprine use was frequent (66%) and surgical resection rates were high (33% at 5 years) in cases with paediatric onset. In ulcerative colitis, 34% of patients were diagnosed with extensive disease, with high rates of disease extension (26% and 41% at 5 and 10 years), fulminant episodes (19.3%) and systemic steroid use (52.3%). The cumulative rate of colectomy was low (6.9%). CONCLUSIONS: The incidence of paediatric inflammatory bowel diseases has rapidly increased in the last three decades in Western Hungary. Ileocolonic disease and a need for azathioprine were characteristic in paediatric Crohn's disease, while paediatric onset ulcerative colitis was characterised by extensive disease and disease extension, while the need for colectomy was low.

Is current smoking still an important environmental factor in inflammatory bowel diseases? Results from a population-based incident cohort.

BACKGROUND: Previous studies suggest that smoking is an important environmental factor in inflammatory bowel diseases (IBDs), with dichotomous effects in ulcerative colitis (UC) and Crohn's disease (CD). The aim of this study was to analyze the relationship between smoking and IBD risk in a population-based database from Veszprem Province, which included incident cases diagnosed between January 1, 1977, and December 31, 2008. METHODS: Data from 1420 incident patients were analyzed (UC: 914, age at diagnosis: 38.9 years; CD: 506, age at diagnosis: 31.5 years). Both inpatient and outpatient records were collected and comprehensively reviewed. Overall, smoking frequency in the adult general population was 36.1%. RESULTS: Of patients with CD, 47.2% were current smokers at diagnosis. Smoking was more frequent in male patients (P = 0.002) and was associated with an increased risk of CD (odds ratio, 1.96; 95% confidence interval, 1.63-2.37; P < 0.001). In contrast, current smoking was protective against UC (odds ratio, 0.33; 95% confidence interval, 0.27-0.41). The effect of smoking was linked to gender (in CD, more deleterious in male patients) and age at diagnosis and was most prominent in young adults, with a difference already being seen in 18- to 19-year-olds. In CD, a change in disease behavior (P = 0.02), location from ileal or colonic to ileocolonic (P = 0.003), arthritis/arthropathy (P = 0.002), need for steroids (P = 0.06), or AZA (P = 0.038) was more common in current smokers. Smoking in UC was associated with more extensive disease (P = 0.01) and a tendency for decreased need for colectomy (P = 0.06). CONCLUSIONS: Current smoking was associated with the risk of IBD. This effect was linked to gender and age at diagnosis and was most prominent in young adults. No association was observed in pediatric or elderly patients. The deleterious and protective effects of smoking on the course in CD and UC were partially confirmed.

The risk of lymphoma and immunomodulators in patients with inflammatory bowel diseases: results from a population-based cohort in Eastern Europe.

BACKGROUND AND AIMS: Prior studies suggest a small but significantly increased risk of lymphoma in adults with inflammatory bowel disease (IBD), especially in patients treated with thiopurines. No data was available from Eastern Europe. The aim of this study was to analyze the incidence of lymphomas as related to drug exposure, in a population-based Veszprem province database, which included incident cases diagnosed between January 1, 1977 and December 31, 2008. METHODS: Data from 1420 incident patients were analyzed (UC: 914, age at diagnosis: 36.5 years; CD: 506, age at diagnosis: 28.5.5 years). Both in- and outpatient records were collected and comprehensively reviewed. The rate of lymphoma was calculated as patient-years of exposure per medication class, of medications utilized in IBD. RESULTS: Of the 1420 patients, we identified three patients who developed lymphoma (one CLL, two low-grade B-cell NHL including one rectal case), during 19,293 patient-years of follow-up (median follow-up: 13 years). All three patients were male. None had received azathioprine or biologicals. The absolute incidence rate of lymphoma was 1.55 per 10,000 patient-years, with 3 cases observed vs. 2.18 expected, with a standardized incidence ratio (SIR) of 1.37 (95% confidence interval [CI]: 0.44-4.26). No cases have been exposed to either azathioprine or biologicals. CONCLUSIONS: The overall risk of lymphoma in IBD was not increased; only three cases were seen in this population-based incident cohort over a 30-year period. An association with thiopurine exposure was not found.