Razvan Iacob

Epidemiology of inflammatory bowel disease in adults who refer to gastroenterology care in Romania: a multicentre study.

Aim The Romanian Society of Gastrointestinal Endoscopy developed a multicentre, prospective study to evaluate the frequency and epidemiological features of inflammatory bowel disease (IBD) in an adult population that refers to gastroenterology centres in Romania. Material and methods Eighteen centres with adequate diagnostic and therapeutic facilities uniformly distributed across Romania reported through a proforma the new and old IBD cases between 1 June 2002 and 1 June 2003. The rates of incidence and prevalence of ulcerative colitis (UC) and Crohns disease (CD) have been reported per 100 000 inhabitants. Epidemiological features and disease characteristics were analysed. Results During the study, 407 cases of UC (163 incident cases) and 254 cases of CD (85 incident cases) were identified. The incidence in the referral population was 0.97/100 000 and 0.50/100 000 for UC and CD, respectively, whereas the prevalences was 2.42/100 000 and 1.51/100 000 for UC and CD, respectively. A slight male predominance, wider age distribution and predominant urban residence were the main demographic features of incident cases; smoking and appendectomy/appendicitis were infrequent in UC, while a higher proportion of CD patients were smokers. Lower rates of severe, extensive or complicated IBD were noted as compared with the literature. Conclusion Incidence and prevalence rates of IBD in Romania are low. Predominant male involvement and a wider distribution of incident cases were the main demographic features in our population. IBD in our patients had a more ‘benign’ course as compared with the literature, with lower rates of severe, extensive or complicated disease and a small proportion of patients who need surgery.

Frequency and predictive factors for overlap syndrome between autoimmune hepatitis and primary cholestatic liver disease.

Objectives To evaluate the frequency of cholestatic pattern in patients with autoimmune hepatitis (AIH) and to identify predictive factors associated with the development of the overlap syndrome. Methods Eighty-two consecutive patients diagnosed with AIH at the referral centre between January 1998 and June 2002 were included in the study. The new scoring system modified by the International Autoimmune Hepatitis Group was used to classify patients as definite/probable. Overlap syndrome was considered when the patient had clinical, serological and histological characteristics of two conditions: AIH and primary biliary cirrhosis (PBC) or AIH and primary sclerosing cholangitis (PSC). Results From the 82 AIH patients (76 female and six male), 84.1% presented definite AIH (> 15 points) and 15.9% probable AIH (10–15 points). The frequency of the overlap syndrome was 20%: 13% with PBC and 7% with PSC. In the univariate analysis the overlap syndrome was associated with male gender (P = 0.01), age < 35 years (P < 0.0001), histopathological aspect of cholestasis (P < 0.0001), suboptimal response to treatment (P < 0.0001) and probable AIH (P < 0.0001). Age < 35 years, probable AIH and the absence of anti-nuclear antibody (ANA) have been identified as independent indicators of the overlap diagnosis by the logistic regression analysis. Conclusion Patients with overlap syndrome between AIH and primary cholestatic liver disease are frequently diagnosed in clinical practice, representing 20% of AIH cases in our study. The independent predictive factors associated with the diagnosis of overlap syndrome are young age, ANA(−) profile, and probable diagnosis according with the scoring system for AIH.

Predictors of graft and patient survival in hepatitis C virus (HCV) recipients : Model to predict HCV cirrhosis after liver transplantation

Background. Hepatitis C virus (HCV) recurrence after liver transplantation (LT) is almost universal, but the natural history of recurrent HCV in the allograft is highly variable. Our study had two aims: 1) to assess the impact of different pre- and postLT factors on graft and patient survival in HCV transplant recipients and 2) to create a model which may predict the patients at risk for HCV-related graft cirrhosis at 5 years postLT. Methods. A total of 168 LTs were considered for this study. Univariate and multivariate Cox proportional hazards regression model was used, as well as logistic regression analysis to create a model of prediction of HCV cirrhosis within 5 years after LT. Results. Predictive factors for both decreased graft and patient survival included patients recently transplanted (2000–2004), induction without azathioprine, short-term therapy with mycophenolate mofetil and prednisone (≤6 months), presence of early cholestasis, histologically proven early recurrence of hepatitis C. Recipient human leukocyte antigen DR3 positivity, presence of early cholestasis, and donor age >50 years were identified as independent predictors of graft cirrhosis within 5 years. A predictive model was established in order to calculate at 6 months a risk score for graft HCV cirrhosis within 5 years postLT using a formula that included the identified independent predictors. The area under receiver operating characteristic curve was 0.83, indicating a good ability to predict medium-term HCV allograft cirrhosis. Conclusion. This model may be a useful tool for better identifying high-risk HCV patients who should be selected for early initiation of antiviral therapy.

Diagnostic Delay in Romanian Patients with Inflammatory Bowel Disease: Risk Factors and Impact on the Disease Course and Need for Surgery

BACKGROUND The epidemiology of inflammatory bowel disease [IBD] in Eastern Europe is poorly understood, particularly with regard to diagnostic delay. Here we investigated the factors leading to delayed diagnosis and the effect of the delay on several disease progression and outcome measures. METHODS A total of 1196 IBD cases [682 ulcerative colitis [UC], 478 Crohns disease [CD], 36 indeterminate colitis] from the Romanian national registry IBDPROSPECT were reviewed. Standard clinical and demographic factors were evaluated as predictors of a long diagnostic delay in both CD and UC. Diagnostic delay was subsequently evaluated as a potential risk factor for bowel stenoses, bowel fistulas, perianal fistulas, perianal surgery, and intestinal surgery in CD patients. RESULTS The median diagnostic delay was significantly longer in CD [5 months] than in UC [1 month] patients [p < 0.001]. Compared with 5 months for UC patients, 75% of CD patients were diagnosed within 18 months of symptom onset. In CD patients, extra-ileal location was a protective factor (odds ratio [OR], 0.5; p = 0.03), whereas being an active smoker [OR, 2.09; p = 0.01] and symptom onset during summer [OR, 3.35; p < 0.001] were independent risk factors for a long diagnostic delay [> 18 months]. In UC patients, an age > 40 years was a protective factor [OR, 0.68; p = 0.04] for a long delay. Regarding outcomes, a long diagnostic delay in CD patients positively correlated with bowel stenoses [OR, 3.38; p < 0.01] and any IBD-related surgery [OR, 1.95; p = 0.03] and had a positive trend for intestinal fistulas [OR, 2.64; p = 0.08] and perianal fistulas [OR, 2.9; p = 0.07]. Disease duration since diagnosis positively correlated with bowel stenoses [OR, 1.04; p = 0.04], any IBD-related surgery [OR, 1.04; p = 0.02], and intestinal surgery [OR, 1.07; p < 0.01]. CONCLUSIONS A long diagnostic delay in IBD correlates with an increased frequency of bowel stenoses and need for IBD-related surgery.

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.

Predictors of short term treatment outcome in patients with achalasia following endoscopic or surgical therapy

BACKGROUND/AIMS Pneumatic balloon dilation and surgical myotomy are the most effective treatments for achalasia. While there is controversy which method is best, the aim of the current study was to identify predictors of symptom recurrence after endoscopic or surgical therapy. METHODOLOGY Patients undergoing pneumatic balloon dilatation (30mm) or laparoscopic Heller myotomy with Dor fundoplication were included in the study. Analyzed parameters include total symptom score (sum of 0-5 point intensity for dysphagia, regurgitation and chest pain), width and height of esophageal column at 2 and 5 minutes after oral barium ingestion, lower esophageal sphincter (LES) length, resting (LESP) and residual pressure (LESRP) before and 3 months after intervention. Patients with symptoms score <3 at the 3-month follow-up visit were considered asymptomatic. RESULTS Twenty-one patients underwent pneumatic dilation (14) or laparoscopic myotomy (7). Total symptom score improved (p<0.01) from pre- (7.2±2.7) to post-intervention (1.7±2.6). Eleven (85.8%) patients in the endoscopic group vs. 7 (100%) patients in the surgical group were symptom-free 3 months after intervention. Therapies improved LESP (24.4±8.2mmHg pre- vs. 15.4±10.3mmHg post-therapy; p=0.003) and mean LESRP (7.9±4.3mmHg pre- vs. 5.3±6.7mmHg post-therapy; p=0.03). Univariate linear regression analysis identified barium contrast column width >5cm at 2 minutes (p=0.04), LES length <2cm (p=0.003) and LESRP >10mmHg (p=0.02) as predictors for persistent symptoms. CONCLUSIONS While >85% of achalasia patients responded well to 30mm pneumatic balloon dilation, patients with elevated LES pressure, short LES and wide esophagus should be considered as primary surgical candidates.

Modeling the Vortical Structures in Hemodynamics of Small Vessels and Capillaries

The paper is dedicated to the flow modeling in micro‐bifurcations, with application in hemodynamics of vessels and capillaries located in the endothelial wall. In particular, the present study is focused to the experimental and numerical simulations of the vortical patterns in micro‐junctions for Newtonian and Carreau—Yasuda models at Re≪1.

P626 Extraintestinal manifestations in Romanian IBD patients – evaluation of a cohort of over 1000 patients

Results: Two hundred seventy-five patients (143 males and 132 females) were colliged. Mean age was 31.8 years old [8 65]. They were followed during a mean period of 23.3 months. Familial form (FF) of CD was diagnosed in 32 patients (11.6%). Age at onset of CD, site and phenotype of CD were similar in FF and sporadic forms (SF) (respectively p = 0.2, p = 0.6 and p = 0.9). Upper gastrointestinal tract involvement, anoperineal lesions and complications such as abcess and severe acute colitis were as common in FF as in SF of CD. Extraintestinal manifestations were significantly more frequent in FF than SF (45.1% versus 21.5%, p = 0.005). Corticosteroids were more commonly prescribed in FF than in SF (75% versus 55%, p = 0.026). Overall, patients with FF receive more immunosuppressive therapy than patients with SF (65.6% versus 48.5%, p = 0.05) mainly methotrexate (12.5% versus 1.6%; p = 0.008). There was no difference between FF and SF of CD with regard of Biotherapy with anti-TNF agents (15% versus 8%; p = 0.1) and surgery (8% versus 35%, p = 0.2). Conclusions: Despite comparable clinical characteristics of both groups, extraintestinal manifestations may result in more common use of corticosteroids and immunosuppressive therapy in FF than in SF of CD.

P630 Epidemiological and phenotypic characteristics of IBD patients in Romania – results of a nationwide hospital-based registry

C. Gheorghe1, A. Dimitriu1 *, R. Iacob1, M. Cojocaru1, C. Lupei1, R. Vadan1, D. Dobru2, A. Trifan3, M. Tantau4, A. Goldis5, G. Constantinescu6, S. Gologan7, B. Mateescu8, D. Gheonea9, L. Gheorghe1, M. Diculescu1, on behalf of the IBDPROSPECT Study Group. 1Fundeni Clinical Institute, Digestive Diseases and Liver Transplantation Center, Bucharest, Romania, 2Municipal Hospital Targu Mures, Gastroenterology, Targu Mures, Romania, 3Gastroenterology and Hepatology Institute Iasi, Gastroenterology, Iasi, Romania, 43rd Medical Clinic Cluj-Napoca, Gastroenterology, Cluj-Napoca, Romania, 5District Hospital Timisoara, Gastroenterology, Timisoara, Romania, 6Floreasca Emergency Hospital, Gastroenterology, Bucharest, Romania, 7Elias Universitary Hospital, Gastroenterology, Bucharest, Romania, 8Colentina Clinical Hospital, Gastroenterology, Bucharest, Romania, 9University of Medicine and Pharmacy Craiova, Romania, Immunology, Craiova, Romania

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.