Limited relevance and progression of histological alterations in the liver during thioguanine therapy in inflammatory bowel disease patients.

Background: Thioguanine is associated with liver toxicity, especially nodular regenerative hyperplasia (NRH). We assessed if liver histology alters during long-term maintenance treatment with thioguanine in patients with inflammatory bowel disease (IBD). Methods: Liver specimens of thioguanine treated IBD patients with at least two liver biopsies were revised by two independent liver pathologists, blinded to clinical characteristics. Alterations in histopathological findings between first and sequential liver specimen were evaluated and associated clinical data, including laboratory parameters and abdominal imaging reports, were collected. Results: Twenty-five IBD patients underwent sequential liver biopsies prior to, at time of, or after cessation of thioguanine treatment. The median time between the first and second biopsy was 25 months (range: 14-54). Except for one normal liver specimen, any degree of irregularities including inflammation, steatosis, fibrosis and some vascular disturbances were observed in the biopsies. The rates of perisinusoidal fibrosis (91%), sinusoidal dilatation (68%) and nodularity (18%) were the same in the first and second liver biopsies. A trend towards statistical significance was observed for phlebosclerosis (36% of the first vs. 68% of the second biopsies, p = .092). Presence of histopathological liver abnormalities was not associated with clinical outcomes. Furthermore, two patients in this cohort had portal hypertension in presence of phlebosclerosis. In another two patients, nodularity of the liver resolved upon thioguanine withdrawal. Conclusion: Vascular abnormalities of the liver were commonly observed in thioguanine treated IBD patients, although these were not progressive and remained of limited clinical relevance over time.

Telemedicine for management of inflammatory bowel disease (myIBDcoach): a pragmatic, multicentre, randomised controlled trial.

BACKGROUND: Tight and personalised control of inflammatory bowel disease in a traditional setting is challenging because of the disease complexity, high pressure on outpatient clinics, and rising incidence. We compared the effects of self-management with a telemedicine system, which was developed for all subtypes of inflammatory bowel disease, on health-care utilisation and patient-reported quality of care versus standard care. METHODS: We did this pragmatic, randomised trial in two academic and two non-academic hospitals in the Netherlands. Outpatients aged 18-75 years with inflammatory bowel disease and without an ileoanal or ileorectal pouch anastomosis, who had internet access and Dutch proficiency, were randomly assigned (1:1) to care via a telemedicine system (myIBDcoach) that monitors and registers disease activity or standard care and followed up for 12 months. Randomisation was done with a computer-generated sequence and used the minimisation method. Participants, health-care providers, and staff who assessed outcome measures were not masked to treatment allocation. Primary outcomes were the number of outpatient visits and patient-reported quality of care (assessed by visual analogue scale score 0-10). Safety endpoints were the numbers of flares, corticosteroid courses, hospital admissions, emergency visits, and surgeries. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT02173002. FINDINGS: Between Sept 9, 2014, and May 18, 2015, 909 patients were randomly assigned to telemedicine (n=465) or standard care (n=444). At 12 months, the mean number of outpatient visits to the gastroenterologist or nurse was significantly lower in the telemedicine group (1·55 [SD 1·50]) than in the standard care group (2·34 [1·64]; difference -0·79 [95% CI -0·98 to -0·59]; p<0·0001), as was the mean number of hospital admissions (0·05 [0·28] vs 0·10 [0·43]; difference -0·05 [-0·10 to 0·00]; p=0·046). At 12 months, both groups reported high mean patient-reported quality of care scores (8·16 [1·37] in the telemedicine group vs 8·27 [1·28] in the standard care group; difference 0·10 [-0·13 to 0·32]; p=0·411). The mean numbers of flares, corticosteroid courses, emergency visits, and surgeries did not differ between groups. INTERPRETATION: Telemedicine was safe and reduced outpatient visits and hospital admissions compared with standard care. This self-management tool might be useful for reorganising care of inflammatory bowel disease towards personalised and value-based health care. FUNDING: Maastricht University Medical Centre and Ferring.

Novel Perceived Stress and Life Events Precede Flares of Inflammatory Bowel Disease: A Prospective 12-Month Follow-Up Study.

BACKGROUND AND AIMS: Inflammatory bowel disease [IBD] is characterized by recurrent disease flares. The impact of psychosocial wellbeing on the occurrence of flares is unclear. In this prospective study, we aimed to evaluate the association between patient-reported psychosocial wellbeing and disease flares using continuous monitoring. METHODS: Consecutive IBD patients were recruited from the myIBDcoach telemedicine study cohort. Over 12 months, participants reported on disease activity together with anxiety, depression, fatigue, perceived stress and life events every 1-3 months. Flares were defined using a combination of clinical disease activity and additional measurements. Generalized estimating equation models were used to assess associations between psychosocial wellbeing and flares over time. The influences of both the presence of psychosocial symptoms in general as well as novel psychosocial symptoms were analysed. RESULTS: In total, 417 patients were included. Forty-nine patients [11.8%] experienced a flare during the study period. The occurrence of life events in the preceding 3 months was positively associated with flares (odds ratio [OR] = 1.81; 95% confidence interval [CI] = 1.04-3.17), while the presence of anxiety, depression, fatigue and perceived stress in general was not. However, novel perceived stress [OR = 2.92; 95% CI = 1.44-5.90] was associated with flares. CONCLUSIONS: The occurrence of life events and novel perceived stress are associated with disease flares in the next 3 months, while the presence of perceived stress in general is not. These findings underline the importance of continuous personalized monitoring of IBD patients and may contribute to the prevention of disease flares.

Risk of impaired nutritional status and flare occurrence in IBD outpatients.

BACKGROUND: Inflammatory bowel disease (IBD) patients are at risk of an impaired nutritional status. The impact thereof on the IBD relapse risk is clinically relevant, though sparsely investigated. AIM: The aim was to explore the association between an impaired nutritional status risk and the occurrence of disease flares in IBD outpatients participating in a longitudinal telemedicine study. METHODS: IBD outpatients were recruited from the myIBDcoach study cohort, with one year clinical follow-up. Through myIBDcoach, a telemedicine tool, patients reported on disease activity and risk of impaired nutritional status (i.e. Short Nutritional Assessment Questionnaire >1 and/or BMI < 18.5 kg/m2) every one to three months. Data was analysed by generalized estimating equation modelling. RESULTS: In total, 417 patients were included. During follow-up, 49 patients (11.8%) flared after initial clinical remission and 53 patients (12.7%) showed an increased risk of impaired nutritional status. The risk of impaired nutritional status was associated with flare occurrence (OR 2.61 (95% CI 1.02-6.69)). CONCLUSIONS: The risk of an impaired nutritional status was associated with subsequent flares in IBD outpatients. This emphasizes the importance of monitoring disease activity in IBD patients at risk of impaired nutritional status.

The Prevalence of Nodular Regenerative Hyperplasia in Inflammatory Bowel Disease Patients Treated with Thioguanine Is Not Associated with Clinically Significant Liver Disease.

BACKGROUND: Nodular regenerative hyperplasia (NRH) of the liver is associated with inflammatory-mediated diseases and certain drugs. There is conflicting data on the prevalence of NRH and its clinical implications in inflammatory bowel disease (IBD) patients treated with thioguanine. METHODS: A retrospective cohort study involving 7 Dutch centers comprised all IBD patients who were being treated with thioguanine and underwent a liver biopsy as part of the standard toxicity screening. Liver biopsy specimens were reviewed by 2 experienced liver pathologists. Clinical data as well as liver chemistry, blood counts, and abdominal imaging were collected. RESULTS: One hundred eleven IBD patients who submitted to liver biopsy were treated with thioguanine in a daily dose of 0.3 mg/kg for a median duration of 20 (4-64) months. NRH was detected in 6% of patients (7; 95% confidence interval, 3-14 patients). Older age (P = 0.02), elevated gamma-glutamyl transferase (P = 0.01) and alkaline phosphatase (P = 0.01) levels, a higher mean corpuscular volume (P = 0.02), and a lower platelet or leukocyte count (P < 0.01 and P = 0.02, respectively) were associated with NRH. Three of the 7 patients with NRH did not have any associated clinical symptoms or signs. The other 4 had minor biochemical abnormalities only. Ultrasonography revealed splenomegaly in 3 of the 78 patients (4%; 95% confidence interval, 0%-9%), only one of whom had NRH. There was no clinically overt portal hypertension. CONCLUSIONS: The prevalence of NRH was 6% in liver biopsies obtained from IBD patients treated with thioguanine. Histopathological irregularities including NRH were not associated with clinically significant findings over the period of observation.

Randomized Comparison of Surveillance Intervals in Familial Colorectal Cancer.

PURPOSE: Colonoscopic surveillance is recommended for individuals with familial colorectal cancer (CRC). However, the appropriate screening interval has not yet been determined. The aim of this randomized trial was to compare a 3-year with a 6-year screening interval. PATIENTS AND METHODS: Individuals between ages 45 and 65 years with one first-degree relative with CRC age < 50 years or two first-degree relatives with CRC were selected. Patients with zero to two adenomas at baseline were randomly assigned to one of two groups: group A (colonoscopy at 6 years) or group B (colonoscopy at 3 and 6 years). The primary outcome measure was advanced adenomatous polyps (AAPs). Risk factors studied included sex, age, type of family history, and baseline endoscopic findings. RESULTS: A total of 528 patients were randomly assigned (group A, n = 262; group B, n = 266). Intention-to-treat analysis showed no significant difference in the proportion of patients with AAPs at the first follow-up examination at 6 years in group A (6.9%) versus 3 years in group B (3.5%). Also, the proportion of patients with AAPs at the final follow-up examination at 6 years in group A (6.9%) versus 6 years in group B (3.4%) was not significantly different. Only AAPs at baseline was a significant predictor for the presence of AAPs at first follow-up. After correction for the difference in AAPs at baseline, differences between the groups in the rate of AAPs at first follow-up and at the final examination were statistically significant. CONCLUSION: In view of the relatively low rate of AAPs at 6 years and the absence of CRC in group A, we consider a 6-year surveillance interval appropriate. A surveillance interval of 3 years might be considered in patients with AAPs and patients with ≥ three adenomas.

Double-balloon endoscopy: an effective rescue procedure after incomplete conventional colonoscopy.

OBJECTIVE: A significant percentage of colonoscopies remain incomplete because of a failure to intubate the caecum. By double-balloon endoscopy (DBE), originally developed for deep enteroscopy, an otherwise incomplete examination of the colon might be completed. We evaluated the success rate of caecal intubation, the reasons for its failure and the therapeutic consequences of using DBE after incomplete conventional colonoscopy. METHODS: We report our single-centre experience of using DBE to complete an otherwise incomplete colonoscopy. A total of 114 consecutive patients, 45 male and 69 female, with a mean age of 64.8 years, who had undergone 116 procedures, were evaluated retrospectively by a review of their medical records. RESULTS: The main causes for failed caecal intubation using a conventional colonoscope were loop formation in 70 patients (61.4%) and an adhesive angulated sigmoid in 33 (28.9%). Caecal intubation by DBE was successful in 101 patients (88.6%). The rate of failure was not associated with the cause of failure of the previous colonoscopy. In 55 patients (48.2%) a relevant new diagnosis was made in the previously inaccessible part of the colon: carcinoma (n=4; 3.5%), one or more adenomas (n=48; 42.1%) and caecal flat hyperplastic polyps (n=4; 3.5%). Endoscopic polypectomy was performed in 51 patients (44.7%); two complications occurred, both being mild postpolypectomy bleedings. In seven patients (6.1%) a subsequent surgical resection was performed. CONCLUSION: Colonoscopy by DBE was useful in most patients in whom conventional colonoscopy was incomplete, irrespective of the cause of the failure. In nearly half the patients, a relevant new diagnosis was made with therapeutic consequences.

[Screening: management after incomplete colonoscopy could be improved]. / Screening: beleid na incomplete coloscopie kan beter.

In 2014 in the Netherlands a national screening programme for bowel cancer was started in which a colonoscopy is performed after a positive immunochemical faecal occult blood test. If colonoscopy is incomplete a CT colonography (CTC) is offered in order to visualize the remaining colon. Balloon endoscopy (BE), double- or single-balloon, is an effective and safe endoscopic alternative which has advantages over CTC, including the option of endoscopic polypectomy and histological examination. However, its cost and the need for an additional procedure on a different day are disadvantageous. BE deserves a place in the national screening programme for bowel cancer after an incomplete colonoscopy, as a possible alternative for CTC and certainly after finding polyps on CTC. Because expertise in BE and its availability are limited, in each screening region some centres should be appointed as designated referral centres to perform BE.

Severe hepatic side effects of ezetimibe.

BACKGROUND AND AIMS: Ezetimibe was introduced recently as a new class of cholesterol-lowering drugs. Until now only limited increases of transaminase levels were reported. METHODS: We studied 2 patients with severe hepatic side effects of ezetimibe in a general community hospital. RESULTS: Ezetimibe may lead to 2 distinct types of severe hepatic side effects. CONCLUSIONS: Ezetimibe may rarely cause hepatotoxicity, severe cholestatic hepatitis, or acute autoimmune hepatitis.