29 research outputs found
Is thioguanine-associated sinusoidal obstruction syndrome avoidable? Lessons learned from 6-thioguanine treatment of inflammatory bowel disease and a mouse model
Hepatotoxicity associated with 6-methyl mercaptopurine formation during azathioprine and 6-mercaptopurine therapy does not occur on the short-term during 6-thioguanine therapy in IBD treatment
Diagnosing nodular regenerative hyperplasia of the liver is thwarted by low interobserver agreement
Background and Aims: Nodular regenerative hyperplasia (NRH) of the liver is associated with several diseases and drugs. Clinical symptoms of NRH may vary from absence of symptoms to full-blown (noncirrhotic) portal hypertension. However, diagnosing NRH is challenging. The objective of this study was to determine inter- and intraobserver agreement on the histopathologic diagnosis of NRH. Methods: Liver specimens (n=48) previously diagnosed as NRH, were reviewed for the presence of NRH by seven pathologists without prior knowledge of the original diagnosis or clinical background. The majority of the liver specimens were from thiopurine using inflammatory bowel disease patients. Histopathologic features contributing to NRH were also assessed. Criteria for NRH were modified by consensus and subsequently validated. Interobserver agreement was evaluated by using the standard kappa index. Results: After review, definite NRH, inconclusive NRH and no NRH were found in 35% (23-40%), 21% (13-27%) and 44% (38-56%), respectively (median, IQR). The median interobserver agreement for NRH was poor (κ = 0.20, IQR 0.14-0.28). The intraobserver variability on NRH ranged between 14% and 71%. After modification of the criteria and exclusion of biopsies with technical shortcomings, the interobserver agreement on the diagnosis NRH was fair (κ = 0.45). Conclusions: The interobserver agreement on the histopathologic diagnosis of NRH was poor, even when assessed by well-experienced liver pathologists. Modification of the criteria of NRH based on consensus effort and exclusion of biopsies of poor quality led to a fairly increased interobserver agreement. The main conclusion of this study is that NRH is a clinicopathologic diagnosis that cannot reliably be based on histopathology alone
W1209 Azathioprine or 6-Mercaptopurine Associated Hepatotoxicity Diminishes Upon Administration of 6-Thioguanine in IBD Patients
Oxidation-Mediated DNA Crosslinking Contributes to Toxicity of 6-Thioguanine in Human Cells — Letter
W1099 Adequately Dosed 6-Thioguanine Is a Well Tolerated and Safe Rescue Drug in Azathioprine or 6-Mercaptopurine Intolerant IBD Patients
Nodular Regenerative Hyperplasia of the Liver in Patients with IBD Treated with Allopurinol-Thiopurine Combination Therapy
Background: Thiopurine therapy, particularly thioguanine, has been associated with nodular regenerative hyperplasia (NRH) of the liver. Combination therapy of allopurinol and an adapted low-dose thiopurine leads to a pharmacokinetic profile that has similarities to that of thioguanine. Therefore, allopurinol-Thiopurine combination therapy may also be associated with NRH of the liver. We assessed the prevalence of NRH in patients with inflammatory bowel disease (IBD) treated with allopurinol-Thiopurine combination therapy by liver biopsy specimen examination. Methods: An observational, cross-sectional study was conducted in a Dutch IBD-referral center. Adult patients with IBD, treated for at least 1 year with allopurinol-Thiopurine combination therapy were eligible. All patients underwent a liver biopsy, after standard laboratory and thiopurine metabolite concentration assessments. Histopathology was assessed by an experienced liver pathologist. Results: Twenty-Two patients with IBD were included. The mean duration of combination therapy at the time of the liver biopsy was 24.7 months (SD 5.7). NRH was observed in one of the biopsies (4.8%), any grade of nodularity was observed in 3 biopsy specimens (14%). Other findings included phlebosclerosis (24%), perisinusoidal fibrosis (81%), sinusoidal dilatation (43%), perivenular fibrosis (14%), and periportal fibrosis (29%). Around the time of biopsy, the median 6-Thioguanine nucleotide and 6-methylmercaptopurine ribonucleotide concentrations were 705 pmol × 10 8 red blood cells (RBC) (interquartile range 498-915) and 355 pmol × 10 8 RBC (interquartile range 225-670). Conclusions: The prevalence of histologically assessed NRH in patients with IBD, who were treated with allopurinol-Thiopurine combination therapy, was 5%. This percentage is in line with thiopurine-naive and thioguanine-using patients with IBD. None of the included patients had clinical symptoms or signs suggestive of (noncirrhotic) portal hypertension
Systematic Review of Development and Content Validity of Patient-reported Outcome Measures in Inflammatory Bowel Disease: Do We Measure What We Measure?
BACKGROUND AND AIMS: Patient-reported outcome measures are increasingly important in daily care and research in inflammatory bowel disease [IBD]. This study provides an overview of the content and content validity of IBD-specific patient-reported outcome measures on three selected constructs. METHODS: Databases were searched up to May 2019 for development and/or content validity studies on IBD-specific self-report measures on health-related quality of life, disability, and self-report disease activity in adults. Evidence was synthesised on content validity in three aspects: relevance, comprehensiveness, and comprehensibility following the COnsensus-based Standards for the selection of health Measurement INstruments methodology. Questionnaire items were organised in themes to provide an overview of important aspects of these constructs. RESULTS: For 14/44 instruments, 25 content validity studies were identified and 25/44 measures had sufficient content validity, the strongest evidence being of moderate quality, though most evidence is of low or very low quality. The Crohn's Life Impact Questionnaire and IBD questionnaire-32 on quality of life, the IBD-Control on disease activity, and the IBD Disability Index Self-Report and its 8-item version on disability, have the strongest evidence of sufficient relevance, comprehensiveness, and comprehensibility, ranging from moderate to very low quality. A fair number of recurring items themes, possibly important for the selected constructs, was identified. CONCLUSIONS: The body of evidence for content validity of IBD-specific health-related quality of life, self-report disease activity, and disability self-report measures is limited. More content validity studies should be performed after reaching consensus on the constructs of interest for IBD, and studies should involve patients