Gwo-Tzer Ho

Guidelines for the management of inflammatory bowel disease in adults

The management of inflammatory bowel disease represents a key component of clinical practice for members of the British Society of Gastroenterology (BSG). There has been considerable progress in management strategies affecting all aspects of clinical care since the publication of previous BSG guidelines in 2004, necessitating the present revision. Key components of the present document worthy of attention as having been subject to re-assessment, and revision, and having direct impact on practice include: The data generated by the nationwide audits of inflammatory bowel disease (IBD) management in the UK in 2006, and 2008. The publication of ‘Quality Care: service standards for the healthcare of people with IBD’ in 2009. The introduction of the Montreal classification for Crohns disease and ulcerative colitis. The revision of recommendations for the use of immunosuppressive therapy. The detailed analysis, guidelines and recommendations for the safe and appropriate use of biological therapies in Crohns disease and ulcerative colitis. The reassessment of the role of surgery in disease management, with emphasis on the importance of multi-disciplinary decision-making in complex cases. The availablity of new data on the role of reconstructive surgery in ulcerative colitis. The cross-referencing to revised guidelines for colonoscopic surveillance, for the management of metabolic bone disease, and for the care of children with inflammatory bowel disease. Use of the BSG discussion forum available on the BSG website to enable ongoing feedback on the published document http://www.bsg.org.uk/forum (accessed Oct 2010). The present document is intended primarily for the use of clinicians in the United Kingdom, and serves to replace the previous BSG guidelines in IBD, while complementing recent consensus statements published by the European Crohns and Colitis Organisation (ECCO) https://www.ecco-ibd.eu/index.php (accessed Oct 2010).

Fecal Calprotectin Predicts the Clinical Course of Acute Severe Ulcerative Colitis

OBJECTIVES:Calprotectin is a granulocyte neutrophil-predominant cytosolic protein. Fecal concentrations are elevated in intestinal inflammation and may predict relapse in quiescent inflammatory bowel disease. We aim to investigate fecal calprotectin (FC) as a biomarker in predicting the clinical course of acute severe ulcerative colitis (ASUC).METHODS:In 90 patients with ASUC requiring intensive in-patient medical therapy (January 2005–September 2007), we investigated the discriminant ability of FC to predict colectomy and corticosteroid and infliximab nonresponse. All patients received parenteral corticosteroids as first-line treatment; 21 (23.3%) were also treated with infliximab (5 mg/kg), after failure of corticosteroid therapy.RESULTS:Of 90 patients, 31 (34.4%) required colectomy, including 11 (52.4%) of those treated with infliximab. Overall FC was high (1,020.0 μg/g interquartile range: 601.5–1,617.5). FC was significantly higher in patients requiring colectomy (1,200.0 vs. 887.0; P=0.04), with a trend toward significance when comparing corticosteroid nonresponders and responders (1,100.0 vs. 863.5; P=0.08), as well as between infliximab nonresponders and responders (1,795.0 vs. 920.5; P=0.06). Receiver–operator characteristic curve analysis yielded an area under the curve of 0.65 to predict colectomy (P=0.04), with a maximum likelihood ratio of 9.23, specificity 97.4%, and sensitivity 24.0% at a cutoff point of 1,922.5 μg/g. Kaplan–Meier analyses showed that using 1,922.5 μg/g over a median follow-up of 1.10 years, 87% of patients will need subsequent colectomy.CONCLUSIONS:This is the first data set to demonstrate that FC levels are dramatically elevated in severe UC. These data raise the possibility that this biomarker can predict response to first or second-line medical therapy in this setting.

The safety profile of anti-tumour necrosis factor therapy in inflammatory bowel disease in clinical practice: analysis of 620 patient-years follow-up.

Background  Anti‐TNF agents are now widely used in Crohn’s disease (CD), and in ulcerative colitis (UC).

A British Society of Paediatric Gastroenterology, Hepatology and Nutrition survey of the effectiveness and safety of adalimumab in children with inflammatory bowel disease

Aliment Pharmacol Ther 2011; 33: 946–953

The use of adalimumab in the management of refractory Crohn’s disease

Background Adalimumab is a humanized monoclonal antibody targeting tumour necrosis factor‐α. Recent clinical trials have demonstrated its efficacy in Crohn’s disease; however, experience in clinical practice remains limited.

The clinical course of ulcerative colitis after orthotopic liver transplantation for primary sclerosing cholangitis: further appraisal of immunosuppression post transplantation.

Background and aims The course of ulcerative colitis (UC) following orthotopic liver transplantation (OLT) for primary sclerosing cholangitis (PSC) is unclear. We documented the nationwide experience of the course of UC, before and after OLT for PSC. Methods and results A total of 470 liver transplants were performed for 413 patients between 1992 and 2003, in the Scottish Liver Transplantation Unit, UK. Twenty-six patients had co-existing UC/PSC. Of these, data from 20 patients were studied over a median period of 11.9 years before OLT and 4.4 years after OLT; of the others, four patients required colectomy prior to OLT, one died within 7 days of transplant, and one developed UC after transplant. A significantly higher relapse rate (number of relapses/year of follow-up) was seen after OLT (median 1.0 versus 0.3; interquartile range, 0.10–1.42 and 0.01–0.40, respectively; P=0.007). The corticosteroids requirement (number of courses/year of follow-up) after OLT was also significantly higher (0.40 versus 0.10; interquartile range, 0.51–1.13 and 0.05–0.12, respectively; P=0.003). Twenty per cent of patients (4/20) became corticosteroid dependent after OLT. Thirty-five per cent of patients (7/20) underwent colectomy after OLT: three for severe disease and four for neoplasia/dysplasia. Five patients (19%) developed neoplasia following OLT. Conclusion Despite immunosuppression, UC follows a more aggressive clinical course after OLT and is associated with a high rate of neoplasia.

Efficacy and complications of adalimumab treatment for medically-refractory Crohn's disease : analysis of nationwide experience in Scotland (2004-2008)

Background  Adalimumab is a second generation humanized anti‐tumour necrosis factor (TNF) monoclonal antibody with established efficacy in Crohn’s disease (CD).

Advances in the understanding of mitochondrial DNA as a pathogenic factor in inflammatory diseases

Mitochondrial DNA (mtDNA) has many similarities with bacterial DNA because of their shared common ancestry. Increasing evidence demonstrates mtDNA to be a potent danger signal that is recognised by the innate immune system and can directly modulate the inflammatory response. In humans, elevated circulating mtDNA is found in conditions with significant tissue injury such as trauma and sepsis and increasingly in chronic organ-specific and systemic illnesses such as steatohepatitis and systemic lupus erythematosus. In this review, we examine our current understanding of mtDNA-mediated inflammation and how the mechanisms regulating mitochondrial homeostasis and mtDNA release represent exciting and previously under-recognised important factors in many human inflammatory diseases, offering many new translational opportunities.

Gut mucosal DAMPs in IBD: from mechanisms to therapeutic implications.

Endogenous damage-associated molecular patterns (DAMPs) are released during tissue damage and have increasingly recognized roles in the etiology of many human diseases. The inflammatory bowel diseases (IBD), ulcerative colitis (UC) and Crohn’s disease (CD), are immune-mediated conditions where high levels of DAMPs are observed. DAMPs such as calprotectin (S100A8/9) have an established clinical role as a biomarker in IBD. In this review, we use IBD as an archetypal common chronic inflammatory disease to focus on the conceptual and evidential importance of DAMPs in pathogenesis and why DAMPs represent an entirely new class of targets for clinical translation.

Cyclooxygenase-2 (COX-2) Polymorphisms and Risk of Inflammatory Bowel Disease in a Scottish and Danish Case-Control Study

Background: Inflammatory bowel diseases (IBDs) are a result of interactions between luminal pathogens and the intestinal immune response. Cyclooxygenase‐2 (COX‐2) plays a key role in the regulation of the inflammatory response upon stimulation by luminal pathogens via Toll‐like receptors. Methods: Genotypes of the COX‐2/PTGS2/PGHS2 A‐1195G (rs689466), G‐765C (rs20417), and T8473C (rs5275) polymorphisms were assessed in a Scottish and Danish case–control study including 732 Crohns disease (CD) cases, 973 ulcerative colitis (UC) cases, and 1157 healthy controls using logistic regression. Results: Carriers of the COX‐2 A‐1195G variant allele had increased risk of UC (odds ratio [OR], 95% confidence interval [CI] = 1.25 [1.02–1.54], P = 0.03) and of both UC and IBD among never smokers (OR [95% CI] = 1.47 [1.11–1.96], P = 0.01 and OR [95% CI] = 1.37 [1.06–1.77], P = 0.02, respectively). Furthermore, this variant genotype was associated with increased risk of diagnosis of UC before age 40 years and with extensive UC (OR [95% CI] = 1.34 [1.11–1.62], P = 0.002 and OR [95% CI] = 1.32 [1.03–1.69], P = 0.03, respectively). Conclusions: COX‐2 A‐1195G polymorphism was associated with the risk of UC, especially among never‐smokers, suggesting that low activity of COX‐2 may predispose to UC. Our results suggest that inclusion of smoking status may be essential for the evaluation of the role of genetic predisposition to IBD. (Inflamm Bowel Dis 2011)