Bogdan Cotruta

Inflammatory gene expression profiles in Crohn's disease and ulcerative colitis: A comparative analysis using a reverse transcriptase multiplex ligation-dependent probe amplification protocol

BACKGROUND AND AIMS Cytokines and their receptors play a critical role in the pathogenesis of the inflammatory bowel disease (IBD). The aim of this study was to investigate the expression profiles of inflammatory genes in inflamed and non-inflamed colonic tissue samples in patients with Crohns disease (CD) and ulcerative colitis (UC), and to identify molecular signatures for different IBD phenotypes. METHODS Seventy-one patients diagnosed with IBD (38 CD, 33 UC) and 15 non-IBD controls have been included in the study. For each patient, biopsy samples were obtained during colonoscopy from inflamed (L) and healthy (N) mucosa. We investigated by commercially available reverse-transcriptase multiplex ligation-dependent probe amplification (RT-MLPA) kit the mRNA expression of a set of 40 genes involved in inflammation: cytokines, chemokines, receptors, signal transduction molecules and transcription factors. RESULTS In L biopsies from patients with CD, higher expression levels were found for IL-4 (p=0.009) and IL-12p35 (p=0.0005), whereas in L biopsy samples from patients with UC higher expression levels were found for IL-8 (p=0.03), chemokines SCYA3 (p=0.05), SCYA4 (p=0.01) and glutathione S-transferase P1 (p=0.01). In N biopsies of patients with CD higher expression levels were found for IL-1R (p=0.01) and IL-12p35 (p=0.007), whereas in N biopsies of patients with UC higher expression levels were found for IL-15 (p=0.009) and SCYA8 (p=0.001). The logistic regression analysis has indicated that low expression levels of IL-2 and IL-10, together with higher ASCA IgG titers were independently associated with penetrating/stricturing CD. CONCLUSIONS RT-MLPA is a sensitive and effective method for the evaluation of the profiles of inflammatory genes in IBD, with potential future applications for diagnosis, phenotypic stratification and targeted therapy.

Drug-induced Sweet's syndrome secondary to hepatitis C antiviral therapy

Pegylated interferon‐alpha in combination with ribavirin currently represents the therapeutic standard for the hepatitis C virus infection. Interferon based therapy may be responsible for many cutaneous side effects. We report a case of drug‐induced Sweets syndrome secondary to hepatitis C antiviral therapy. To our knowledge, this is the first reported case of Sweets syndrome in association with pegylated interferon‐alpha therapy.

The Romanian National Program for Liver Transplantation - 852 Procedures in 815 Patients over 17 Years (2000-2017): A Continuous Evolution to Success

Background: Liver transplantation (LT) has become an established treatment for end-stage liver disease, with more than 20.000 procedures yearly worldwide. The aim of this study was to analyze the results of Romanian National Program of LT. Methods: Between April 2000 and April 2017, 817 pts received 852 LTs in Romania. Male/female ratio was 487/330, while adult/pediatric ratio was 753/64, with a mean age of 46 years (median 50 yrs; range 7 months - 68 yrs). Main LT indications were HBV cirrhosis (230 pts; 28.2%), HCC (173 pts; 21.2%), and HCV cirrhosis (137 pts; 16.8%). Waiting time and indications for LT, patient and donor demographics, graft features, surgical procedures, and short and long-term outcomes were analyzed. Results: DDLT was performed in 682 pts (83.9%): whole LT in 662 pts (81%), split LT in 16 pts (2.3%), reduced LT in 2 pts (0.2%), and domino LT in 1 pts (0.1%). LDLT was performed in 135 pts (16.5%): right hemiliver in 93 pts (11.4%), left lateral section in 28 pts (3.4%), left hemiliver in 8 pts (1%), left hemiliver with segment 1 in 4 pts (0.5%), and dual graft LDLT in 2 pts (0.2%). Overall major morbidity rate was 31.4% (268 pts), while perioperative mortality was 7.9% (65 pts). Retransplantation rate was 4.3% (35 pts): 27 whole LTs, 3 reduced LTs, 3 split LTs, and 2 LDLT. Long-term overall 1-, 3-, and 5-year estimated survival rates for patients were 87.9%, 81.5%, and 79.1%, respectively. One-, 3-, and 5-year overall mortality on waiting list also decreased significantly over time from 31.4%, 54.1% and 63.5%, to 4.4%, 13.9% and 23.6%, respectively. Conclusions: The Romanian National program for liver transplantation addresses all causes of acute and chronic liver failure or liver tumors in adults and children, using all surgical techniques, with good long-term outcome. The program constantly evolved over time, leading to decreased mortality rate on the waiting list.

P492 Endoscopic follow up of patients with IBD and biological treatment: achievement and persistence of mucosal healing in patients with clinical remission

Background and aim: Biological therapy is now the mainstay treatment for the patients with moderate/severe IBD. The efficacy of treatment is no longer measured only in the induction of clinical remission, endoscopic healing being considered more important since its achievement can influence the long term outcome of the disease. The majority of clinical trials report endoscopic results after one year of maintenance treatment. The aim of our study was to observe the frequency of mucosal healing and its persistence in a group of IBD patients with clinical response to biological therapy during long term follow up (over 2 years). Methods: All patients with IBD that received biological treatment admitted in our department were prospectively followed. In all ileocolonoscopies were performed at 6 months intervals with description of all lesions encountered (periodic endoscopic or radiologic evaluations are part of the protocol issued by National Health Insurance House and are required for the approval of reimbursed biological treatment). Mucosal healing (MH) was defined as lack of ulcers, ulcerations or aftous erosions. The presence of erythema, edema, and inflammatory pseudopolyps did not preclude the diagnosis of MH. Demographic and clinical data were noted as well as the type, dose, and frequency of biological and associated (e.g. immunosuppressive) treatments. Only patients treated over 2 years were included in the analysis. Results: 52 patients (27 males, 25 females, mean age 36.9+/-12.2 years) received biological therapy (38 infliximab and 14 adalimumab) for a period longer than 24 months (24-72, mean 38.67 months), 43 with Crohns disease (CD) and 9 with ulcerative colitis (UC). Mucosal healing was obtained in 80.77% patients. The mean time to MH was of 10.85 (6-36) months. 26.19% of patients needed more than one year to achieve MH. From patients with MH, 40.48% experienced recurrent endoscopic lesions and clinical flare during follow up. The only factor associated with long term MH (maintained during the observation period) was the presence of MH 6 months after initiation of maintenance treatment with biologics (p=0.022). The combined treatment with immunosupressors or the use of biological therapy at first flare of disease did not influence the occurrence or persistence of MH in our group of patients. Conclusions: In patients with clinical remission obtained with biological treatment long term endoscopic follow up shows that mucosal healing can be achieved in the majority of cases. A rapid endoscopic response (mucosal healing after the first 6 months of maintenance therapy) predicts sustained, long term, endoscopic remission.

Sa1263 Endoscopic Follow Up of Patients With IBD and Biological Treatment: Achievement and Persistence of Mucosal Healing in Patients With Clinical Remission

Background and aim: Biological therapy is now the mainstay treatment for the patients with moderate/severe IBD. The efficacy of treatment is no longer measured only in the induction of clinical remission, endoscopic healing being considered more important since its achievement can influence the long term outcome of the disease. The majority of clinical trials report endoscopic results after one year of maintenance treatment. The aim of our study was to observe the frequency of mucosal healing and its persistence in a group of IBD patients with clinical response to biological therapy during long term follow up (over 2 years). Methods: All patients with IBD that received biological treatment admitted in our department were prospectively followed. In all ileocolonoscopies were performed at 6 months intervals with description of all lesions encountered (periodic endoscopic or radiologic evaluations are part of the protocol issued by National Health Insurance House and are required for the approval of reimbursed biological treatment). Mucosal healing (MH) was defined as lack of ulcers, ulcerations or aftous erosions. The presence of erythema, edema, and inflammatory pseudopolyps did not preclude the diagnosis of MH. Demographic and clinical data were noted as well as the type, dose, and frequency of biological and associated (e.g. immunosuppressive) treatments. Only patients treated over 2 years were included in the analysis. Results: 52 patients (27 males, 25 females, mean age 36.9+/-12.2 years) received biological therapy (38 infliximab and 14 adalimumab) for a period longer than 24 months (24-72, mean 38.67 months), 43 with Crohns disease (CD) and 9 with ulcerative colitis (UC). Mucosal healing was obtained in 80.77% patients. The mean time to MH was of 10.85 (6-36) months. 26.19% of patients needed more than one year to achieve MH. From patients with MH, 40.48% experienced recurrent endoscopic lesions and clinical flare during follow up. The only factor associated with long term MH (maintained during the observation period) was the presence of MH 6 months after initiation of maintenance treatment with biologics (p=0.022). The combined treatment with immunosupressors or the use of biological therapy at first flare of disease did not influence the occurrence or persistence of MH in our group of patients. Conclusions: In patients with clinical remission obtained with biological treatment long term endoscopic follow up shows that mucosal healing can be achieved in the majority of cases. A rapid endoscopic response (mucosal healing after the first 6 months of maintenance therapy) predicts sustained, long term, endoscopic remission.

P548 Deep remission: a recurrent feature in patients with Crohn's disease and long term biologic therapy

Background: The new therapeutic goal in patients with Crohn’s disease (CD) is long term mucosal healing, due to its proven association with better outcome (better quality of life, fewer complications, less hospitalization). Not all CD patients treated with biologics achieve deep remission and in those patients that achieve it, it can be shortly lived. The aim of our study was to assess the frequency and durability of deep remission in CD patients on biological treatment in a clinical setting. Methods: All CD patients treated with biologics in our department were followed prospectively. Demographical data (age, sex), disease characteristics (Montreal classification, time between diagnosis and start of biological therapy, previous surgeries), type of biologic therapy, other treatments, endoscopic findings were noted. All patients had ileocolonoscopy performed at 6 12 months interval. Deep remission was defined when both clinical (CDAI <150) and endoscopic (no ulcers) remissions were achieved. Results: 49 CD patients, mean age 37±13.06 (20 65) years were followed for a median of 38 (12 72) months. Localization of the disease was ileal in 12.24%, ileocolonic in 32.65% and colonic in 55.1% patients, with 26.53% having associated perianal fistulas. Mean time from diagnosis till biologic therapy was started was of 4.83±4.66 (0 18) years. The majority of patients (41) received Infliximab, the rest Adalimumab. Mean treatment time with biologics was 30.57±15.73 (12 72) months. During this time a mean number of 5.36 (2 11) ileocolonoscopies were performed per patient. Deep remission was achieved in 79.6% of cases after a mean of 8.23±7.52 (2 36) months and was sustained in 51.28% of cases. 48.71% of patients lost deep remission after a mean time of 12±6.48 (3 30) months. In 42.10% of cases (8 patients) after 8.25±3.1 months deep remission was induced again: in 5 cases with biologic dose escalation +/ immunosupressor, one with local budesonide treatment and in 2 cases (with clinical remission) spontaneous healing of ulcerations was observed at follow up ileocolonoscopies, without any therapeutic intervention. Conclusions: In clinical setting deep remission can be achieved in a great proportion of patients after a variable time interval, sometimes over one year of biologic therapy. In patients with flares while on biologic treatment deep remission can be re induced with various therapeutic strategies. Our study showed that transitory, clinically silent, endoscopic relapse is possible during biologic maintenance therapy. P549 Dose optimization is effective in patients with ulcerative colitis losing response to infliximab: a collaborative multicentre retrospective study M. Cesarini1 *, K. Katsanos2, P. Ellul3, P. Lakatos4, K. Papamichael5, F. Caprioli6, E. Tsianos2, G. Mantzaris5, S. Danese7, G. Fiorino7. 1Sapienza University of Rome, Medicina Interna e Specialita Mediche, Rome, Italy, 2University of Ioannina, Greece, 3Mater Dei Hospital, Malta, 4Semmelweis University, Budapest, Hungary, 5Evangelismos Hospital, Athens, Greece, 6University of Milan, Italy, 7 IRCCS Humanitas, IBD Center, Rozzano, Italy

P227 - Inflammatory genes expression profiles in patients with IBD investigated using multiplex ligation-dependent probe amplification (MLPA)

P226 High incidence of Crohn’s disease in Western Hungary between 2002 2006 L. Lakatos1, G. David1, T. Pandur1, Z. Erdelyi1, G. Mester2, M. Balogh2, I. Szipocs3, C. Molnar4, E. Komaromi5, O. Gemela6, P.L. Lakatos6 *. 1Department of Medicine, Csolnoky F. Province Hospital, Veszprem, Hungary, 2Department of Medicine, Grof Eszterhazy Hospital, Papa, Hungary, 3Department of Medicine, Municipal Hospital, Tapolca, Hungary, 4Department of Infectious Diseases, Magyar Imre Hospital, Ajka, Hungary, 5Department of Gastroenterology Municipal Hospital, Varpalota, Hungary, 6Semmelweis University, Budapest, Hungary