Vasileios E. Tsianos

Role of genetics in the diagnosis and prognosis of Crohn's disease

Considering epidemiological, genetic and immunological data, we can conclude that the inflammatory bowel diseases are heterogeneous disorders of multifactorial etiology in which hereditability and environment interact to produce the disease. It is probable that patients have a genetic predisposition for the development of the disease coupled with disturbances in immunoregulation. Several genes have been so far related to the diagnosis of Crohns disease. Those genes are related to innate pattern recognition receptors, to epithelial barrier homeostasis and maintenance of epithelial barrier integrity, to autophagy and to lymphocyte differentiation. So far, the most strong and replicated associations with Crohns disease have been done with NOD2, IL23R and ATG16L1 genes. Many genes have so far been implicated in prognosis of Crohns disease and many attempts have been made to classify genetic profiles in Crohns disease. CARD15 seems not only a susceptibility gene, but also a disease-modifier gene for Crohns disease. Enriching our understanding on Crohns disease genetics is important but when combining genetic data with functional data the outcome could be of major importance to clinicians.

Inflammatory bowel disease and hepatitis B and C in Western Balkans: A referral centre study and review of the literature

BACKGROUND AND AIMS There is limited data on IBD patients diagnosed with viral hepatitis B and C. The aim of the study was to assess the prevalence of chronic HBV or HCV infection in IBD patients followed by our centre and to describe and review the course of bowel and liver disease during therapy. METHODS Single centre retrospective study on 482 consecutive IBD patients. Laboratory investigation for HBV and HCV was performed with routine methods. Treatment protocols for HBV included IFNa and nucleot(s)ide administration and for HCV combined IFNa and ribavirin. RESULTS We diagnosed 15 patients (15/482, 3.1%) with HBV or HCV. Of these, 11 were HBV (11/482, 2.3%) and 4 were HCV (4/482, 0.8%). Nine of eleven HBV patients received antiviral therapy (8 lamivudine, 1 IFNa). Five lamivudine patients were switched to tenofovir and in another one adefovir dipivoxil were added. Bowel disease was in remission in ten of the eleven HBV patients. One patient was diagnosed with carcinoid tumor. Two HCV patients received IFNa that was well tolerated. One HCV patient denied therapy and one died from hepatocellular cancer. Of the seven patients on azathioprine only one achieved sustained response. Four patients on Infliximab achieved bowel disease remission but experienced biochemical or virological flare. CONCLUSIONS This study demonstrates that prevalence of HBV and HCV infection in a large IBD cohort from Western Balkans is compared to that of the background population. IBD patients under immunosuppressants may apparently be treated with safety if preventive antiviral treatment is administered.

Neutrophil anti-neutrophil cytoplasmic autoantibody proteins: bactericidal increasing protein, lactoferrin, cathepsin, and elastase as serological markers of inflammatory bowel and other diseases.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract comprising Crohn’s disease and ulcerative colitis. Although the pathogenesis of the disease is not clearly defined yet, environmental, genetic and other factors contribute to the onset of the disease. Apart from the clinical and histopathological findings, several serological biomarkers are also employed to detect IBD. One of the most thoroughly studied biomarker is anti-neutrophil cytoplasmic autoantibody (ANCA). We herein provide an overview of the current knowledge on the use of ANCA and certain ANCA proteins, such as bactericidal increasing protein, lactoferrin, cathepsin G and elastase, as serological markers for IBD and other diseases.

Prevalence of inflammatory bowel disease related dysplasia and cancer in 1500 colonoscopies from a referral center in northwestern Greece

BACKGROUND AND AIM To report on the prevalence of inflammatory bowel disease (IBD) related intestinal dysplasia and cancer in northwestern Greece. PATIENTS AND METHODS Single referral center retrospective study. The policy among all gastroenterologists of the area regarding medical treatment, patient follow up and bowel surveillance strategies including risk factors is the same. RESULTS We analyzed 1494 colonoscopies from 696 consecutive IBD patients (494 UC). The follow up time [median, IQR] was 16 [8-23] years and the age at diagnosis was 28 [21-49] years. The number of patient years at risk was 16.219. Disease location for UC was: pancolitis 761 (59%), left sided colitis 455 (35%), and proctitis 69 (6%). Disease location for CD was: colitis 142 (66%), ileitis 45 (22%) and ileocolitis 21 (10%). Disease activity was in remission in 1240 (83%) of them. In total, 498 (72%) patients were on mesalazine, 169(24%) on immunosuppression and 29 (4%) on biologicals. Biopsies were taken randomly in 1429 (96%) endoscopies and were targeted in 65 (4%) of them. We recorded 69 (9.4%) cases with dysplasia and 10 (1.4%) cases with intestinal cancer (9 in UC). No difference was found for dysplasia and cancer in patients who followed up for 10-20 years or for more than 20 years. CONCLUSIONS The prevalence of dysplasia and cancer is increased in UC compared to CD but the prevalence of high-grade dysplasia is comparatively low. Intestinal cancer prevalence is increasing after the first decade and then practically remains stable.

Adult-onset Still's disease preceding Crohn's disease.

Concomitant diagnosis of Crohns disease and juvenile or adult-onset idiopathic arthritis is rare. It is possible that both conditions share some genetic or immunological defects although sufficient data are lacking. We describe herein the first case of a patient with adult-onset Stills disease who was diagnosed on follow up with concomitant Crohns disease. A 38-year-old man diagnosed with adult onset Stills disease from the age of 24 was admitted in our hospital because of bloody diarrhea. On admission physical examination was unremarkable and all routine laboratory tests were normal except of Hg at 11.3 gr/dl, erythrocyte sedimentation rate at 27 mm/h and C-reactive protein at 14 mg/dl. Ileocolonoscopy revealed small aphthoid ulcers in the terminal ileum and capsule endoscopy revealed the source of bleeding and small aphthoid ulcers starting from the distal jejunum up to the terminal ileum. Terminal ileum biopsies were diagnostic of Crohns disease and patient had started on therapy with mesalamine 2 gr/day and azathioprine 2mg/kg and is currently on multidisciplinary follow up. We review all literature on co-existence of Crohns disease with chronic idiopathic arthritis and we discuss the possible difficulties in diagnosis and therapy of those patients also in the view of the new biological agents.

P249 Endoscopic extension of inflammation progresses more frequently in ulcerative colitis compared to Crohn's disease patients

P248 Endoscopic evaluation of colonic mucosa in ulcerative colitis patients in clinical remission O. Shchukina1 *, E. Kondrashina2, O. Orlov3, A. Vladimirova4, A. Botina5, E. Markova6, A. Kharitidis7. 1North-West State Medical University, Chair of Gastroenterology and Dietology, Saint-Petersburg, Russian Federation, 2North-West State University, Chair of Gastroenterology and Dietology, SaintPetersburg, Russian Federation, 3City clinical hospital #3, Saint-Petersburg, Russian Federation, 4Irkutsk Diagnostic Center, Irkutsk, Russian Federation, 5Saint-Petersburg state medical university named after I.P. Pavlov, Saint-Petersburg, Russian Federation, 6City clinical hospital #31, SaintPetersburg, Russian Federation, 7City Clinical Hospital #31, City Centre of IBD, Saint-Petersburg, Russian Federation

Intolerance of folic acid in a patient receiving methotrexate for Crohn's disease.

Dear Sir, Folic and folinic acid supplementation have been shown to reduce methotrexate oral and gastrointestinal side effects in rheumatoid arthritis patients1 and this seems to be also the case in patients with inflammatory bowel disease. Still, it is not clear whether folic is different from folinic acid in reducing methotrexate gastrointestinal side effects.2 We present herein a patient with a “difficult-to-treat” long-standing Crohns disease who was diagnosed with gastrointestinal intolerance due to accidental intake of high-dose folic acid. A 21-year …

P210 IBD and HIV: Does CD4 count remission hypothesis count?

Background: Patients with inflammatory bowel disease (IBD) and Human Immunodeficiency Virus (HIV) infection have shown controversial data concerning the remission hypothesis of IBD due to CD4 count depletion caused by HIV. The aim was to review the literature to investigate the hypothesis whether low CD4 count due to HIV is related to IBD remission. Methods: We systematically searched Pubmed for studies reporting on HIV infection in IBD patients. We extracted characteristics of IBD and HIV disease course and CD4 counts. Results: Thirteen papers (2 case controls studies, 2 case series and 9 case reports) were eligibleincluding 47 patients with IBD and HIV infection (43 males 4 females; 27 Crohn’s, 19 ulcerative colitis, 1 Indeterminate Colitis). The IBD diagnosis criteria were heterogeneous among studies. Remission was reported for patients with IBD and HIV infection in 5 studies, including 4 case control case series and 1 case report. Four out of 5 studies with IBD patient cases reported remission related to the CD4 count remission hypothesis but only 2 of them explicitly reported the CD4 count cut-off point (500 cells/microlitre and 200 cells/mm3 respectively). On the contrary, 7 case reports described an active IBD course or relapse even in patients under immunosuppression. Conclusions: Current literature cannot support or reject the DC4 count remission hypothesis in IBD patients with HIV infection. Prospective studies using criteria on IBD and HIV disease course are needed.

P565 Clinically significant safety issues during long-term azathioprine use in patients with ulcerative colitis

V0 to 83.0% in V12. The CDAI decreased from 194 (21 269) to 48 (10 122) (p < 0.001). The PDAI decreased from 4.0 (0.0 4.0) to 0.0 (0.0 4.0) (p < 0.001). The quality of life measured by the EQ-5D improved from 0.735 (0.633 0.790) to 0.797 (0.726 1.000) (p < 0.001). The IBDQ-9 score increased (p < 0.001) from 56.7 (51.6 61.5) to 66.5 (60.1 73.6) (p < 0.001). The work hours lost by the EC in the previous week decreased from 2.0 (0.0 27.0) at V0 to 0.0 (0.0 1.0) at V12 (p = 0.004) and the work productivity (0 10 scale) decreased from 3.0 (0.3 5.8) to 1.0 (0.0 to 2.0) (p = 0.006). Conclusions: In clinical practice, ADAhas proven to be effective with a statistically significant improvement in clinical variables, quality of life, and work productivity.

P222 Methotrexate use in inflammatory bowel disease: A referral centre's 30 years of experience

P222 Methotrexate use in inflammatory bowel disease: A referral centre’s 30 years of experience K.H. Katsanos1 *, D.E. Sigounas1, K. Strogyli1, A. Tatsioni2, E. Panagiotou1, I. Vagias1, V.E. Tsianos1, D.K. Christodoulou1, E.V. Tsianos1. 1Medical School of Ioannina, University of Ioannina, 1st Division of Internal Medicine and HepatoGastroenterology Unit, Ioannina, Greece, 2Tufts University School of Medicine and Institute for Clinical Research and Health Policy Studies, Department of Medicine, Boston, United States