Geographic Distribution, Phenotype and Epidemiological Tendency in Inflammatory Bowel Disease Patients in Romania.

Background and objective: The incidence of inflammatory bowel disease (IBD) over the past years in Romania has been on the rise, but epidemiologic data are lacking. The aim of this study was to define the characteristics of IBD, the trends and phenotype among IBD patients in Romania. Material and methods: We conducted a prospective study over a period of 12 years, from 2006 to 2017. All patients diagnosed with IBD on clinical, radiological, endoscopic and histological features were included. We divided the country into eight regions: west (W), north-east (NE), north-west (NW), south-east (SE), south-west (SW), south (S), central (C) and Bucharest-Ilfov (B), and data were analyzed accordingly. Results: A total of 2724 patients were included in this database, but only 2248 were included in the final analysis, with all data available. Of the 2248 patients, 935 were Crohn's disease (CD), 1263 were ulcerative colitis (UC) and 50 were IBD-undetermined. In UC phenotypes we observed more frequent left-sided colitis (50.5%, p < 0.0001), and in CD phenotype we observed more frequent colonic and ileo-colonic localization (37.8% and 37.6%, p < 0.0001). The region with the most IBD cases was NE (25.1%) and with the least IBD cases was SW (4.9%). UC was found more frequently in NE (32%), while CD was found more frequently in Bucharest (28.6%). Conclusions: In Romania, ulcerative colitis is more frequent than CD. UC is predominant in the northern part of Romania, while CD has become predominant in the southern part of the country. IBD occurs more in the male population, and in urban and industrialized areas. There are differences between the regions in Romania regarding IBD phenotypes, gender distributions, age distribution, treatment, smoking status and complications.

Effectiveness of 8- and 12-Week Treatment with Ombitasvir/ Paritaprevir/Ritonavir and Dasabuvir in Treatment-Naïve HCV Patients in a Real-Life Setting in Romania: the AMETHYST Study.

BACKGROUND AND AIMS: The 12-week regimen of ombitasvir/paritaprevir/ritonavir and dasabuvir (OPrD) has shown high efficacy and tolerability in clinical trials for the treatment of chronic hepatitis C virus (HCV). The shorter 8-week regimen has been recently incorporated into clinical guidelines and on-label indications, but real-world evidence on its use is limited. Given this knowledge gap, the AMETHYST study aimed to evaluate the effectiveness of the 8- and 12-week regimens of OPrD in treatment-naive patients with HCV with mild to moderate liver fibrosis in Romanian clinical practice. METHODS: This was a secondary data collection study analyzing data from a 1-year Patient Support Program in HCV in Romania. Patients received OPrD treatment for 8 or 12 weeks. The effectiveness endpoint was sustained virologic response 12 weeks post-treatment (SVR12). RESULTS: A total of 1,835 treatment-naive patients with HCV with mild or moderate fibrosis were included in the study. Of these, 426 and 1,375 completed the 8-week and 12-week regimens, respectively. SVR12 was 98.1% in the 8-week treatment group and 98.7% in the 12-week treatment group. CONCLUSION: The study provides real-world evidence that 8-week and 12-week treatment regimens of OPrD are highly effective in treatment-naive patients with HCV with mild to moderate liver fibrosis.

Contrast-enhanced ultrasound for the assessment of focal nodular hyperplasia - results of a multicentre study.

AIM: Contrast-enhanced ultrasound (CEUS) has become a relevant imaging method for the evaluation of focal liver le-sions (FLL). The aim of this study was to evaluate the performance of CEUS for the assessment of focal nodular hyperplasia (FNH) in a large study group. MATERIAL AND METHODS: We performed a multicentre prospective observational study, which included successive CEUS examinations from fourteen Romanian centres. CEUS examinations were performed in de novo FLL, using low mechanical index ultrasound, following an intravenous bolus of 2.4 ml SonoVue. CEUS was considered conclusive for FNH if a typical pattern was present following contrast (rapid "spoke-wheel" enhancement during the arterial phase, hyperenhanced lesion during venous phase, hyper- or isoenhanced in the late phase). In all cases a reference method was available (contrast enhanced CT or MRI or biopsy). The trial was registered in clinicaltrials.gov (Identifier NCT01329458). RESULTS: During the 6 years study, 2062 "de novo" FLL were evaluated by CEUS. From this cohort, 94/2062 (4.5%) had a typical enhancing pattern for FNH as described in the EFSUMB guidelines. Contrast enhanced CT/MRI and biopsy diagnosed additional 15 FNH. From the 94 cases diagnosed as FNH by CEUS, in nine the final diagnosis was different (five of them adenomas). CEUS had 85% sensitivity, 99.5% specificity, 90.4% positive predictive value, 99.2% negative predictive value and 98.8% diagnostic accuracy for the diagnosis of FNH. CONCLUSIONS: CEUS is a sensitive and very specific method for the diagnosis of FNH.

Malnutrition Prevalence in Newly Diagnosed Patients with Inflammatory Bowel Disease - Data from the National Romanian Database.

BACKGROUND AND AIMS: Prevalence of malnutrition in inflammatory bowel diseases (IBD) varies between 16% and 75%. Data on the nutritional status at initial diagnosis of ulcerative colitis (UC) or Crohn's Disease (CD) are scarce. It is believed that more than 50% of IBD patients suffer significant weight loss prior to diagnosis. The aims of our study were to assess malnutrition in patients recently diagnosed with IBD and to determine its predictive factors. METHODS: We retrospectively included 625 IBD patients registered in the Romanian "IBD Prospect" database between January 2006 and July 2017. All patients were diagnosed within 6 months prior to registration. We defined malnutrition as weight loss of more than 5% of the initial weight during the 3 months prior to registration. RESULTS: There were 361 new cases of UC, 241 CD and 23 cases of unclassified IBD. There was a slight male predominance (M/F=1.2). Prevalence of overall malnutrition was 36.3%. It was significantly more frequent in CD than in UC patients (41.1% vs. 32.4%, p=0.031). In multivariate analysis, malnutrition in UC patients was associated with male gender (p=0.001), more severe disease (p<0.0001) and more extensive disease (p=0.027), while in CD it was associated with younger age (p=0.013) and more severe disease (p<0.0001). CONCLUSIONS: About 1 in 3 newly diagnosed IBD patients presents with malnutrition at the time of diagnosis.

Gastrointestinal endoscopy in patients on direct oral anticoagulants. A consensus paper of the Romanian Society of Gastroenterology and Hepatology.

Management of patients undergoing endoscopy and under treatment with the newer direct oral anticoagulants (DOACs) is a common and a complex clinical issue that gastroenterologists have to face more and more often these days. The increasing use of DOACs in patients requiring both short- and long-term anticoagulation is mostly due to the advantages these agents offer, among which the lack of monitoring requirements and the reduced need of dose adjustments are perhaps the most important ones. Managing these patients in the peri-endoscopic period implies balancing the risk for thrombosis that a certain patient carries and the bleeding risk associated with the endoscopic procedure itself. The Romanian Society of Gastroenterology and Hepatology decided to create a consensus paper to serve to practitioners and teachers. After reviewing the available published data and existing recommendations, a Delphi consensus process was carried out involving the leaders of opinion in this field. After reaching expert consensus, we provide herein guidance for a practical approach of DOACs therapy management in patients with endoscopic interventions.

Real-Life Use of 3 Direct-Acting Antiviral Regimen in a Large Cohort of Patients with Genotype-1b HCV Compensated Cirrhosis.

BACKGROUND AND AIMS: Ombitasvir/Paritaprevir/ritonavir/Dasabuvir (OBV/PTV/r+DSV) is one of the elective direct-acting antivirals (DAAs) recommended by international guidelines and the only one covered by the National Insurance System in Romania until November 2016. Our aim was to present the first prospective Romanian cohort evaluating the effectiveness and safety in clinical practice of this 3DAA combination in patients with HCV genotype-1b Child A liver cirrhosis. METHODS: 681 patients received OBV/PTV/r+DSV+RBV for 12 weeks and were assessed clinically and biologically at baseline, week 4, 8, 12 (end of treatment, EOT), and 12 weeks after therapy (sustained viral response, SVR). RESULTS: Per protocol, EOT virological response was 99.8% and SVR12 rate was 99.4%. Adverse events were present in 36.4% of patients. Permanent discontinuation of 3DAA regimen due to side effects was reported in 11 patients (1.6%). In 47.6% (185/389) of patients, Transient Elastography values were >20kPa (defined as clinically significant portal hypertension, CSPH) at baseline. Independent variables associated with CSPH were: baseline cholesterol level (p=0.003), platelet count <120,000/mm³ (p=0.02), MELD score (p=0.01). Liver stiffness measurement has significantly improved between baseline (26.6+/-12.7kPa) and SVR12 (21.6+/-11.8kPa) (p<0.0001). The same was true for APRI score (2.66+/-0.15 at baseline vs 0.85+/-0.02 at SVR12, p<0.0001) and FIB4 score (5.53+/-0.28 vs 3.24+/-0.08, p<0.0001), but not for Lok score (0.57+/-0.01 vs 0.63+/-0.01, p<0.0001). CONCLUSIONS: We report a high efficacy of the 3DAA regimen in a homogeneous compensated HCV genotype-1b liver cirrhosis population, in a real-life setting. Noninvasive fibrosis scores significantly improved at SVR12.

Position Paper on Treatment of Hepatitis C in Romania 2017. Part Two.

BACKGROUND AND AIMS: Hepatitis C virus (HCV) infection is a common condition with endemic prevalence in some areas of the world. In Romania, the mean prevalence is about 3%. New treatments have become available on the market in recent years and new drugs are in the pipeline. A re-evaluation of HCV therapy was considered mandatory. The Romanian Society of Gastroenterology and Hepatology undertook this task for the practitioners of this country. METHODOLOGY: A group of recognized experts was created who screened the available literature and the major available guidelines. A list of items requiring attention was created and these were discussed and rated. Decisions were taken by consensus. RECOMMENDATIONS: We present here the second part of the Society's recommendations for chronic HCV infection treatment. An agreement between experts was reached regarding the therapy of the special categories of patients infected with HCV, complications and monitoring of the therapy, follow-up of the patients who reached sustained virologic response and re-treatment of the patients with therapy failure. CONCLUSIONS: This Position Paper represents a guide for the assessment and the therapy of HCV infection. The recommendations are in concordance with other guidelines but are applied to real-life conditions in Romania.

Position paper on treatment of hepatitis C in Romania, 2017. Part one.

BACKGROUND AND AIMS: Hepatitis C Virus (HCV) infection is a common condition with endemic prevalence in some areas of the world. In Romania the mean prevalence is about 3%. New treatments became available on the market in recent years and new drugs are in the pipeline. A re-evaluation of HCV therapy was considered mandatory. The Romanian Society of Gastroenterology and Hepatology undertook this task for the practitioners of this country. METHODOLOGY: A group of recognized experts was created who screened the available literature and the major available guidelines. A list of items requiring attention has been created. These items were discussed and rated. Decisions were taken by consensus. RECOMMENDATIONS: We present here the first of the two parts of our Society's recommendations for chronic HCV infection treatment. An agreement was reached regarding the diagnostic tools, the assessment of severity and the up-dated therapy schedules. CONCLUSIONS: This Position Paper represents a guide for the assessment and the therapy of HCV infection. The recommendations are in concordance with other guidelines but are applied to the real-life conditions in this country.

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 Crohn's 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.

Osteoporosis in liver cirrhosis.

BACKGROUND: Osteoporosis is still an underestimated complication of liver cirrhosis (LC). AIM. To study the prevalence of osteoporosis and osteopenia in patients with LC and to identify the principal risk factors associated. MATERIAL AND METHODS: The prevalence of osteoporosis and osteopenia was studied in 150 patients with alcoholic or viral LC who were admitted to the Institute of Gastroenterology and Hepatology, Iasi in 2003. Osteoporosis was diagnosed by measuring their bone density using dual energy X-ray absorptiometry (DXA). Patients with liver disease due to multiple aetiologies or with other liver conditions (primary biliary cirrhosis, autoimmune or metabolic causes, etc.) as well post menopausal women were excluded from the study. The variables taken into consideration were: gender, nutritional status (body mass index - BMI), etiology of liver disease, presence of cholestasis, severity and duration of disease. RESULTS: Fifty-seven patients with LC (38%) were found to have osteoporosis or osteopenia. There was a statistically significant correlation between the presence of bone changes and a BMI of <20 kg/m2, cholestasis, Child class C and long duration of disease (>10 years). During the study period, despite the relatively high rate of bone metabolism abnormalities, there were no pathological fractures in the patients group. CONCLUSIONS: Osteoporosis has a raised prevalence in patients with LC. It is important to be diagnosed and treated early, especially when risk factors such as malnutrition, cholestasis and a severe liver disease are present for a long period of time.

Romanian guidelines on the diagnosis and treatment of exocrine pancreatic insufficiency.

In assessing exocrine pancreatic insufficiency (EPI), its diverse etiologies and the heterogeneous population affected should be considered. Diagnosing this condition remains a challenge in clinical practice especially for mild-to-moderate EPI, with the support of the time-consuming breath test or the coefficient of fat absorption. The fecal elastase-1 test, less precise for the diagnosis, cannot be useful for assessing treatment efficacy. Pancreatic enzyme replacement therapy (PERT) is the mainstay of treatment, whereby enteric-coated mini-microspheres are taken with every meal, in progressive doses based on an individual's weight and clinical symptoms. The main indication for PERT is chronic pancreatitis, in patients who have clinically relevant steatorrhea, abnormal pancreatic function test or abnormal function tests associated with symptoms of malabsorption such as weight loss or meteorism. While enzyme replacement therapy is not recommended in the initial stages of acute pancreatitis, pancreatic exocrine function should be monitored for at least 6-18 months. In the case of unresectable pancreatic cancer, replacement enzyme therapy helps to maintain weight and improve overall quality of life. It is also indicated in patients with celiac disease, who have chronic diarrhea (in spite of gluten-free diet), and in patients with cystic fibrosis with proven EPI.

Osteoporosis in liver cirrhosis--overview.

Osteoporosis can occur as a result of liver cirrhosis. The pathogenesis of reduced bone mineral density in liver cirrhosis is multifactorial. It can be caused by alterations in calcium and vitamin D homeostasis, as well as nutritional and dietary factors. Dual-energy X-ray absorptiometry (DXA) has become the gold standard in assessing bone mineral density in patients with liver cirrhosis. In such cases, patients can be treated with calcium and vitamin D supplements, bisphosphonates and hormonal replacement therapy (HRT).

[Prophylaxis of colorectal cancer with non steroidal anti-inflammatory drugs- a new reality?]. / Profilaxia cancerelor colo-rectale cu antiinflamatorii nonsteroidiene: o noua realitate?

The use COX-2 inhibitors induces regression of adenoma polyps and disrupts the sequence adenoma colorectal carcinoma. So that, this can be used in chemoprevention of colorectal cancer and also in cancer localised in other segments of the digestive tract. So far there is no agreement regarding the beginning of the treatment, the minimal efficient dose, the span of time required for chemoprevention. As the current studies in this field are quite encouraging we believe that in the next future COX-2 inhibitors could be used not only in chemoprevention but also in tumoral regression, and as a codrug in chemiotherapy of colorectal cancer.

[Probiotics in gastrointestinal pathology]. / Probioticele si patologia gastrointestinala.

There are a variety of conditions in which the use of pro-biotics has proven effective:diarrhoea with its various causes, inflammatory bowel diseases, irritable bowel disease, colon cancer chemoprevention and hepato-portal encefalopathy. The pro-biotics have shown to be a promising therapeutical alternative for the future due to their lack of side effects and convenient mode of administration. Further, the potential of other pro-biotics is awaiting validation by clinical trials.

[Liver metastases with unknown primary site]. / Metastazele hepatice cu punct de plecare necunoscut.

Patients with unknown primary site cancer represents 5% to 10% of all neoplasia patients. Liver is a favourite site for gastrointestinal tumors, but not only. The adenocarcinomas represents 60% of patients from this group. A detailed physical examination, extensive laboratory and imaging procedures are necessary to locate the primary tumor. However, liver biopsy could be essential for histological diagnosis and important to identify the tumors who may benefit from specific and effective therapy (breast cancer, prostate cancer, ovarian cancer and small-cell carcinoma of the lung). Systemic chemotherapy represents the most frequently treatment, but only patients with good performance status and without co-morbidities may benefit. "Best supporting care" may be the optimal treatment for most patients, majority with poor performance status at the time of diagnosis.

[Abdominal pain in liver cirrhosis patient--an unusual case]. / Durerea abdominala la pacientul cirotic--un caz neobisnuit.

We present the case of a 62 years male subjects, known with liver cirrhosis diagnosed in 2000 during a laparoscopy. The subject presented with important atypical abdominal pain, leucocytosis, thrombocytosis, small ascites; pneumatosis and hydro-aeric images of small intestine at abdominal X Ray, thickened bowel wall at CT-scan. Laparoscopy revealed mesenteric venous thrombosis, intestinal infarction and the standard surgical treatment was enterectomy. Mesenteric thrombosis may rarely occur in liver cirrhosis due to portal hypertension. This rare but severe complication is usually difficult to diagnose..