HLA and autoimmune digestive disease: a clinically oriented review for gastroenterologists.

OBJECTIVES: The human leukocyte antigen (HLA) system includes genes involved in graft-vs-host rejection and in immune response. The discovery that HLAs are associated with several diseases led to appealing developments both in basic biomedical research and in clinical medicine, and offered the opportunity to improve the understanding of pathogenesis and classification of diseases, as well as to provide diagnostic and prognostic indicators. The aim of this article is to review the association between HLA alleles and autoimmune digestive disease and its current relationship with modern HLA nomenclature and clinical practice. METHODS: Articles dealing with the association between HLAs and autoimmune digestive disease (including celiac disease, inflammatory bowel disease, autoimmune hepatitis, sclerosing cholangitis and primary biliary cirrhosis) were searched for using Pubmed and SCOPUS databases from earliest records to January 2008. RESULTS: The review has provided two sections. In the first, we explain the basic principles of HLA structure, function, and nomenclature, as an introduction to the second section, which describes current associations between HLA alleles and digestive diseases. The clinical implications of each HLA association are critically discussed. Actually, a clinical role for HLA typing is suggested for only a few conditions, e.g., celiac disease. CONCLUSIONS: The knowledge of current HLA nomenclature and of its association with some digestive diseases such as celiac disease can be useful in clinical practice for diagnostic and prognostic purposes. This can avoid improper HLA typing as well as stressing the need for further studies on other possible clinical applications.

Management of NSAID-induced gastrointestinal toxicity: focus on proton pump inhibitors.

The association between NSAIDs and the presence of upper gastrointestinal (GI) complications is well established. Evidence that acid aggravates NSAID-induced injury provides a rationale for minimizing such damage by acid suppression. Proton pump inhibitors (PPIs) appear to be very effective in treating NSAID-related dyspepsia, and also in healing gastric and duodenal ulcers in patients continuing to receive the NSAID. An analysis of data from comparative studies of PPIs versus ranitidine, misoprostol and sucralfate shows a therapeutic advantage in favour of the PPI. Several studies now confirm the efficacy of co-therapy with PPIs in the short- and long-term prevention of NSAID-induced upper GI injury. PPIs are more effective than histamine H(2)-receptor antagonists at standard dosages in reducing the risk of gastric and duodenal ulcer, and are superior to misoprostol in preventing duodenal but not gastric lesions. However, when balancing effectiveness and tolerance, PPIs may be considered the treatment of choice in the short- and long-term prevention of NSAID-related mucosal lesions. To date, there are only a few published articles dealing with the role of PPIs in the prevention of upper GI complications. Recent epidemiological and interventional studies provide some evidence that PPIs are of benefit. However, more controlled studies using clinical outcomes are needed to establish the best management strategy (PPIs combined with traditional NSAIDs or with cyclo-oxygenase-2 selective inhibitors) especially in patients with multiple risk factors, in patients using concomitant low-dose aspirin, corticosteroids or anticoagulants (high risk group), or in patients with a history of ulcer complications (very high risk group). Furthermore, it should be underlined that Helicobacter pylori infection positively interacts with the gastroprotective effect of PPIs; therefore, the true efficacy of these drugs in preventing NSAID-related ulcer complications should be reassessed without the confounding influence of this microorganism.

Small bowel capsule endoscopy in clinical practice: a multicenter 7-year survey.

BACKGROUND AND AIM: Data about small bowel capsule endoscopy (SBCE) come from studies involving small and highly selected populations. The study aim was to describe extent of use, indications, results, complications, and practical issues of SBCE in clinical practice in a Northern Italian Region (Lombardia). MATERIALS AND METHODS: Twenty-three out of 29 invited centers fulfilled a specific questionnaire. RESULTS: Between 2001 and 2008, 2921 procedures were performed and both the number of centers performing SBCE (from 5 to 29) and the number of SBCE (from 7.2 to 69.2 per month) increased steadily. The main indications for SBCE were: obscure gastrointestinal bleeding (OGIB) (43.4%), unexplained anemia (23.9%), suspected Crohn's disease (7.8%) and abdominal pain (5.3%). Overall, SBCE was positive in 50% of cases, negative in 36% and undefined in 14%. The highest diagnostic yields were observed in patients with OGIB (62.5%), polypoid syndromes (74.1%), known (54.8%) or suspected (47.3%) inflammatory bowel disease, while the yields were low in patients examined for chronic diarrhea (27.4%) and abdominal pain (14.9%), 61 patients (2.1%) experienced capsule retention. Thirty-two of them eventually excreted the capsule naturally while endoscopic or surgical retrieval was necessary in 29 (1%) (in two because of obstruction). CONCLUSION: Over a period of 7 years the use of SBCE in Lombardia increased steadily confirming, in clinical practice, a high diagnostic yield and an acceptable safety profile.

IBD care in Europe: A comparative audit of the inpatient management of Crohn's disease and ulcerative colitis using the national UK IBD audit tool.

BACKGROUND AND AIMS: The National UK IBD audit tool is an electronic database created to improve the quality and safety of care for IBD patients by auditing individual patient care, service resources and organisation against national standards. We used the National UK IBD audit tool to compare the organisation and process of IBD care between services in Oxford (UK) and Milan (Italy), as a pilot study to evaluate its application outside national boundaries. METHODS: Clinical and demographic data of patients with CD and UC, consecutively admitted during a 2month period, were collected and compared between the centres, to each other and to the UK IBD standards obtained by previous audit analyses performed in Oxford in 2006. RESULTS: 20 and 26 patients with UC were admitted in Oxford and Milan, as well as 21 and 20 patients with CD, respectively. Most admissions in Milan were planned admissions for moderately active treatment-refractory disease. No patient died. Oxford had a higher surgery rate. Endoscopy for UC consisted mainly of colonoscopy in Milan (92%) and flexible sigmoidoscopy in Oxford (64%). In CD, Oxford data revealed a higher use of immununomodulators and CT scan, compared with higher use of bowel ultrasound in Milan. CRP was the preferred biomarker of disease activity. The following areas did not reach the standards set for the 2006 UK IBD Audit: the lack in Milan of IBD specialist nurses and few dietitian visits, as well as little attention to heparin prophylaxis and abdominal radiography in UC. Both sites paid little attention to stool cultures and revealed a high rate of active smokers in CD and little attention to bone protection in steroids users. Since the 2006 audit in Oxford, improvements include IBD specialist nurse visits, dietitian visits, number of active smokers, stool samples, prophylactic heparin, bone protection and nutritional assessment. CONCLUSIONS: Consistent procedural differences between Oxford and Milan identified by audits of both UC and CD could be resolved by organisational change, with an improvement in the service. The UK IBD audit tool is an easy instrument to assess the processes and outcomes of care delivery in IBD and can be applied also outside UK.