A Comprehensive Review of Dietary Approaches in Maintaining Remission of Inflammatory Bowel Diseases in Adults.

Inflammatory bowel disease (IBD) poses significant challenges in its management, encompassing a spectrum of conditions from Crohn's disease to ulcerative colitis. Dietary interventions have emerged as integral components of the multidisciplinary approach to IBD management, with implications ranging from disease prevention to treatment of active manifestations and addressing complications such as malnutrition. While dietary interventions show promise in improving outcomes for some patients with IBD, there is no consensus in the existing literature regarding remission maintenance in those patients. Furthermore, many patients explore dietary modifications often guided by anecdotal evidence or personal experiences and this could lead to malnutrition and decreased quality of life. This comprehensive review synthesizes existing literature to elucidate the complex interplay between diet and IBD, offering insights into the efficacy and safety of various dietary modalities in maintaining disease remission. It also highlights the importance of patient education in navigating dietary choices and potential risks associated with food avoidance, including the heightened risk of micronutrient deficiencies. Furthermore, it emphasizes the pivotal role of a multidisciplinary care team comprising clinicians and dietitians in providing personalized dietary guidance tailored to individual patient needs and goals. By synthesizing the latest evidence and providing insights into both the potential benefits and risks of dietary interventions, this review could be used as a resource for healthcare professionals and patients alike in navigating the complex landscape of dietary management in IBD.

Role of an Exclusion Diet (Reduced Disaccharides, Saturated Fats, Emulsifiers, Red and Ultraprocessed Meats) in Maintaining the Remission of Chronic Inflammatory Bowel Diseases in Adults.

Background and Objectives: Inflammatory bowel diseases are a main focus in current research, with diet being an emerging therapeutic line due to its links in both onset and progression. A Western-style diet high in processed foods, food additives, red meat, and animal fat has been linked to a higher risk of developing IBD. The aim of this study was to establish an association between an anti-inflammatory exclusion diet and maintenance of remission in IBD. Also, we assessed the efficacy and safety of this diet compared to a non-dietary group and the possible therapeutic effect of this diet in the maintenance of IBD remission. Materials and Methods: A total of 160 patients with IBD were screened for inclusion, but 21 did not met the inclusion criteria. Thus, 139 patients were assigned to either an exclusion diet or a regular diet according to their choice. Results: Clinical remission after six months was maintained in the exclusion diet arm (100%). In the control arm, four patients had clinically active disease (one patient with UC and three with CD), and 90 patients maintained the clinical remission state (95.7%) (p-value = 0.157). Regarding biochemical markers, ESR at baseline was higher in the exclusion diet arm: 29 (5-62) versus in the control arm 16 (4-48) (p-value = 0.019), but six months after, the groups were similar (p-value = 0.440). Conclusions: Patients who followed an exclusion diet maintained clinical remission more frequently. However, the threshold for statistical significance was not achieved. There was also a trend of improvement in inflammation tests in the intervention group.

Diet as an environmental trigger in inflammatory bowel disease: a retrospective comparative study in two European cohorts.

BACKGROUND AND AIMS: inflammatory bowel disease development has been associated with several environmental factors, among which, diet can play a key role, probably due to a westernized lifestyle. However, its involvement in the pathogenesis of inflammatory bowel disease (IBD) is difficult to demonstrate. The aim of this study was to analyze dietary composition in a Romanian and Belgian population with IBD. METHODS: an observational retrospective comparative study was performed using two European cohorts (Romanian and Belgian). The IBD group included 76 Romanian and 53 Belgian patients with an IBD diagnosis, while the control group included a total of 56 healthy people (35 Romanians and 21 Belgians). All subjects were interviewed and asked to fill in a questionnaire regarding diet. RESULTS: in the entire IBD cohort (Romanian + Belgian), a significantly increased consumption of sweets (OR 3.36 [95 % CI 1.6,7]), processed and high fat meat (OR 2.5 [95 % CI 1.4, 4.7], fried food (OR 9.5 [3.8, 23.6]), salt (OR 2.8 [1.5, 5.3]), ice cream (OR 3.25 [1.1, 9.8]), mayonnaise (OR 3.49 [1.1, 10.3]), margarine (OR 5.63 [1.64, 19.33]) and chips/nachos/other snacks (OR 2.3 [0.97, 5.73]) were found compared to the healthy control group. The intake of seeds, nuts (OR 0.26 [0.14, 0.52]) and yoghurt consumption (OR 0.44 [0.23, 0.83]) was lower in the IBD group compared to the control group. CONCLUSION: a westernized diet with increased consumption of sweets, processed food, high fat meat, fried food, salt, margarine, snacks, ice cream and mayonnaise seems to be a risk factor for IBD in Romanian and Belgian IBD patients. Intake of seeds, nuts and yoghurt may be a protective factor.

Mucosal gene expression changes induced by anti-TNF treatment in inflammatory bowel disease patients.

In the last two decades anti-tumor necrosis factor (anti-TNF) therapy for inflammatory bowel disease (IBD) has been widely used to induce and maintain clinical and endoscopical remission, completely changing management of the disease. In this study, we aimed to identify gene expression changes in inflamed mucosa from Crohn's disease and ulcerative colitis patients treated with 5-aminosalicylic acid (5-ASA) (N = 25) or anti-TNF agents (N = 12) compared to drug-free IBD patients (N = 12) and non-IBD control subjects (N = 18). The mucosal expression of 84 genes previously associated with IBD was evaluated by qPCR. We found that both therapeutic regimens induce a decrease in LCN2, NOS2, and TFF1, the levels of which are overexpressed in drug-free patients compared to non-IBD control subjects. Interestingly, a stronger effect of anti-TNF drugs was observed on LCN2 and TFF1 levels. However, 5-ASA seems to induce a more robust reduction of NOS2 expression. Moreover, we found that anti-TNF treatment significantly increased ABCB1, leading to levels similar to those found in non-IBD control subjects.

Sylimarin Versus Essential Phospholipids in Metabolic Associated Steatotic Liver Disease (MASLD) - A Prospective Comparative Randomized Trial.

Introduction:Metabolic dysfunction-associated steatotic liver disease (MASLD) is an entity with a growing incidence but only a few pharmacological options. In Romania, the prevalence of MASLD has been increasing, while that of viral hepatitis has been decreasing. The purpose of this study is to compare two supplements for the treatment of MASLD. Methods:Between January 2020 and May 2022, 90 patients with MASLD were randomized to receive either silymarin 150 mg b.i.d (45 subjects) or essential phospholipids (EPLs) 825 mg b.i.d. (45 subjects) for six months. All study participants received recommendations for lifestyle and diet modifications. Assessment of the severity of steatosis and liver fibrosis was performed using FibroScan® with controlled attenuated parameter (CAP) at the beginning and end of treatment. Results:A total of 68 patients completed the trial. The two groups were statistically comparable in terms of clinical, biological and FibroScanR parameters. Aspartate transferase (AST) decreased from a median of 40 to 28 IU/L in the EPL arm (compared to 25→¨25.5 IU/L in the silymarin arm) (p-value=0.11) and alanine transaminase (ALT) decreased from 46 to 37.5 IU/L (compared to 31→30 IU/L) (p-value = 0.38). Plasma cholesterol levels also decreased significantly in the EPL group (218→189.5 mg/dL) compared to the silymarin arm (217→209 mg/dL) (p = 0.01). At the end of treatment, liver stiffness decreased by 0.7 KPa (6.9→6.2 KPa) in the EPL group but increased by 2.3 KPa (7.2→9.5 KPa) in the silymarin group (p = 0.1). The reduction in hepatic steatosis was comparable between the two groups: it decreased by 5% of the initial value. Conclusion:In our study, a six-month treatment with EPLs was superior to silymarin in MASLD patients because it succeeded in improving both laboratory parameters and liver fibrosis, as estimated by FibroScan®.

Diet Optimization in Inflammatory Bowel Disease: Impact on Disease Relapse and Inflammatory Markers. A 1-year Prospective Trial.

BACKGROUND AND AIMS: Recent research has shown that Western-style diets have been associated with an increased risk of inflammatory bowel diseases (IBD). Our aim was to examine the link between an anti-inflammatory diet and the maintenance of IBD remission, as well as to assess the potential therapeutic advantages of this dietary approach in preserving IBD remission. METHODS: The inclusion and exclusion criteria were applied to a total of 189 individuals with IBD, with 21 individuals not meeting the criteria. Therefore, 168 eligible patients were enrolled in the study and allocated to either an anti-inflammatory diet or a regular diet, based on their personal preference. RESULTS: A cohort of 168 IBD adult patients was recruited for the study: 88 patients with ulcerative colitis and 80 with Crohn's disease. The intervention group received an anti-inflammatory diet consisting of the removal of red and processed meat, fried foods, high-lactose foods, fast food, white bread, sugar, and vegetable oils rich in omega-6 for a period of 1 year. The clinical response was maintained in 80 patients (95.2%) in the intervention group and in 72 patients (85.7%) in the control group (p-value=0.036). Although not statistically significant, fecal calprotectin was higher in the control group than in the intervention group at follow-up. CONCLUSIONS: Patients who adhered to an anti-inflammatory diet exhibited a higher rate of maintenance of clinical remission. Furthermore, improvement in inflammation tests was observed in the intervention group, reinforcing the proposition that IBD is a lifestyle-related disease.

Introducing Colorectal Cancer Screening in Romania - Preliminary Results from the Regional Pilot Programs (ROCCAS).

BACKGROUND AND AIMS: Colorectal cancer (CRC) is the third cause of cancer-related death worldwide. Screening programs can reduce CRC mortality rates by up to 60%. In line with the European Union recommendations, Romania started the first four regional pilot screening programs in 2020 (the ROCCAS II projects). This study reports the interim screening performance indicators. METHODS: People aged 50 to 74 years were invited to the screening program. General practitioners (GPs) evaluated CRC risk based on a survey. High-risk or symptomatic individuals were referred directly to colonoscopy. The average risk participants received a fecal immunochemical test (FIT). Positive cases were invited to colonoscopy. Three regions were screened using the OC-SENSOR® (South-Muntenia, Bucharest-Ilfov, South-East) and one region (South-West) used the FOB GOLD®. The data was collected in the ROCCAS screening electronic registry. The following FIT parameters were evaluated: rates of return, invalidity, positivity, and colonoscopy acceptance rate according to age group, gender, region of provenience, and vulnerability status. RESULTS: We included all cases screened between January 1, 2022 and September 30, 2023. In total, 168,958 people received the FIT test within the projects. The global FIT return rate was 90%. Factors associated with a higher return rate were female gender (90.77% vs 88.83%, p<0.0001), vulnerable status (91.23% vs 88.83%; p<0.00001), and rural residence (91.84% vs 88.42%, p<0.00001). The overall positivity rate was 5.75%. It was higher in males (7.64% vs 4.57% in females, p<0.00001) and progressively increased with the age group. The total invalid FIT rate was 5.87%, significantly lower for OC-SENSOR® (2.24%) than for the FOB GOLD® (13.6%). The overall acceptability rate for colonoscopy was 51.3%. CONCLUSIONS: According to our preliminary data, GP's participation in the pilot programs ensured adequate adherence to screening through FIT. The rate for FIT return and positivity were acceptable for both tests, while the invalid rate was much higher in FOB GOLD® compared to the OC-SENSOR®. Moreover, colonoscopy acceptance needs to be improved. Our preliminary analysis revealed the screening performance indicators meet the EU recommendations and fulfill the premises for national-level expansion of the program starting in 2024.

Impact of Dietary Patterns in Inflammatory Bowel Disease Subtypes Versus Healthy Subjects: a Retrospective Cohort Study.

Objectives:Inflammatory bowel diseases (IBD) have been associated with multiple environmental factors, including diet. A dietary pattern characterized by low fiber content, high fat content and high carbohydrate content has been linked to the development of IBD. The objective of the current investigation is to examine the potential link between dietary patterns and the occurrence of IBD and to investigate whether there are any differences in relation to the type of IBD and specific food groups. Material and methods:We conducted an observational retrospective comparative study using three cohorts: 89 Crohn's disease (CD) patients, 40 ulcerative colitis (UC) patients and 64 healthy subjects. All participants underwent structured interviews and were required to complete a questionnaire regarding their dietary habits either prior to the onset of IBD or within the last year for control subjects. Results:A higher proportion of CD patients reported a higher rate of salt intake (71.9% vs. 53.1%, p-value = 0.043), sweetened beverages (38.2% vs. 17.2%, p-value=0.022), processed meat (66.3% vs. 40.6%, p-value=0.007), fatty meat (50.6% vs. 28.1%, p-value=0.021), fried foods (47.2% vs. 9.4%, p-value<0.001) and mayonnaise (21.3% vs. 6.2%, p-value=0.032) and a lower intake of nuts and seeds (20.2% vs. 43.8%, p-value=0.004) and yogurt (23.6% vs. 43.8%, p-value=0.030) compared to healthy subjects. Compared to controls, in the UC group there was a higher consumption of salt (85% vs. 53.1%, p-value=0.003), sweetened beverages (47.5% vs. 17.2%, p-value=0.005), fatty meat (55% vs. 28.1%, p-value=0.025) and fried foods (55% vs. 9.4%, p-value<0.001) and a lower intake of nuts and seeds (10% vs. 43.8%, p-value=0.001). Conclusion:Diet patterns before the onset of the disease are similar in patients with Crohn's disease and patients with ulcerative colitis: increased consumption of sweetened beverages, processed and fatty meat, fried food, salt, store-bought ice cream, and mayonnaise, and decreased intake of seeds, nuts, and yogurt.

The seen and the unseen: Molecular classification and image based-analysis of gastrointestinal cancers.

Gastrointestinal cancers account for 22.5% of cancer related deaths worldwide and represent circa 20% of all cancers. In the last decades, we have witnessed a shift from histology-based to molecular-based classifications using genomic, epigenomic, and transcriptomic data. The molecular based classification revealed new prognostic markers and may aid the therapy selection. Because of the high-costs to perform a molecular classification, in recent years immunohistochemistry-based surrogate classification were developed which permit the stratification of patients, and in parallel multiple groups developed hematoxylin and eosin whole slide image analysis for sub-classifying these entities. Hence, we are witnessing a return to an image-based classification with the purpose to infer hidden information from routine histology images that would permit to detect the patients that respond to specific therapies and would be able to predict their outcome. In this review paper, we will discuss the current histological, molecular, and immunohistochemical classifications of the most common gastrointestinal cancers, gastric adenocarcinoma, and colorectal adenocarcinoma, and will present key aspects for developing a new artificial intelligence aided image-based classification of these malignancies.

Let-7 microRNAs Are Possibly Associated with Perineural Invasion in Colorectal Cancer by Targeting IGF Axis.

Increased insulin-like growth factor (IGF) axis activity is associated with the development and progression of different types of malignancies, including colorectal cancer (CRC). MicroRNAs (miRNAs) belonging to the let-7 family have been reported to target genes involved in this axis and are known as tumor suppressors. In this study, in silico bioinformatic analysis was performed to assess miRNA-mRNA interactions between eight miRNAs belonging to the let-7 family and genes involved in the IGF signaling pathway, coding for receptors and substrates. miRNAs' expression analysis revealed that hsa-let-7a-5p, hsa-let-7b-5p, hsa-let-7c-5p, hsa-let- 97 7d-5p, hsa-let-7e-5p, hsa-let-7f-5p, and hsa-let-7g-5p were significantly down-regulated in 25 CRC tumoral tissues (T) compared to the corresponding adjacent peritumoral tissues (PT). Moreover, our results showed an upregulation of miR-let-7e-5p in CRC tissues with mutations in KRAS codon 12 or 13, and, for the first time, found a specific dysregulation of let-7a-5p, let-7b-5p, let-7c-5p, let-7d-5p, and let-7i-5p in CRC with perineural invasion. Our results sustain the relationship between the IGF axis, let-7 miRNAs, and CRC and suggest an association between the expression of these miRNAs and perineural invasion.

HLA Genotyping in Romanian Adult Patients with Celiac Disease, their First-degree Relatives and Healthy Persons.

BACKGROUND AND AIMS: Celiac disease is characterized by an inappropriate T-cell-mediated response to gluten in small bowel in genetically predisposed individuals, carriers of the DQ2 and/or DQ8 haplotypes of the human leukocyte antigen. The aim of our study was to asses HLA typing in adult patients with celiac disease, in their first degree relatives and in a healthy control group. METHODS: We conducted a prospective observational study on three cohorts: 117 patients diagnosed with celiac disease, 41 first-degree relatives of celiac patients and 57 asymptomatic healthy volunteers. Low resolution HLA typing for DQ alleles was performed in all study subjects with DNA extracted from peripheral blood, using SSP HLA-DQB1 kit (Innotrain Diagnostik GmbH, Germany).  Next Generation Sequencing (NGS) was used only in 18 patients for typing confirmation of DQB1 and DQA1 loci and whole gene sequencing. RESULTS: Prevalence of HLA-DQ2 was significantly higher in the CD group compared to the healthy subjects group (95.6% vs 29.8%, p <0.001), with no statistically significant differences in HLA-DQ8 and combined HLA-DQ2/DQ8 prevalences.Several HLA DQA1 and DQB1 alleles (HLA-DQA1* 05:01, HLA-DQB1*02:01, HLA-DQB1*02:02) and haplotypes (DQA1*02:01-DQB1*02:02,DQA1*05:01-DQB1*02:01) were strongly associated with celiac disease in our group: OR 4.28, 4.28, 4.67 and 5.43 and 4.28 respectively. Predominantly, patients presented with typical symptoms and iron deficiency anemia. 95.5% of them had histological Marsh type modifications ≥3a. A relatively poor response to gluten-free diet was observed and 9.4% developed complications (refractory celiac disease, enteropathy-associated T cell lymphoma, intestinal adenocarcinoma), with a death rate of 6.8%. 23% associated other autoimmune diseases.Screening adherence for 1st degree relatives was very low: only 16%. Familial screening diagnosed 4 cases of asymptomatic celiac disease. 32 relatives (78%) had HLA-DQ2 haplotype, 5 carried HLA-DQ8, 4 didn't carry any risk haplotype. CONCLUSIONS: This study demonstrated a higher prevalence of the HLA-DQ2 genotype in patients with celiac disease compared to the healthy population but not of HLA-DQ8 or combined HLA-DQ2/DQ8. Alleles HLA-DQA1* 05:01, HLA-DQB1*02:01, HLA-DQB1*02:02 and haplotypes (DQA1*02:01-DQB1*02:02,DQA1*05:01-DQB1*02:01) were strongly associated with celiac disease in our cohort.

Mucosal gene expression profile of stricturing Crohn's disease: A preliminary study.

Intestinal strictures are an important complication of Crohn's disease (CD), with ~40% of patients developing symptomatic obstruction within 10 years of diagnosis. However, there is a paucity of research examining the mechanisms driving the development of fibrotic strictures in CD. The present study aimed to identify the mucosal markers associated with stricturing complications by examining the differences in the gene expression profiles of two patient cohorts: Patients diagnosed with inflammatory CD (n=12) and patients with stricturing CD (n=9). For each patient, a paired sample of inflamed and uninflamed mucosa was isolated and assessed by quantitative PCR using a large panel of genes associated with inflammatory bowel disease. The presents study revealed a significantly increased level of four genes in the mucosa of patients with strictures compared with the inflammatory pattern of the disease: Formyl-peptide receptor 1 [P=0.019; fold change (FC)=11.6], C-C chemokine receptor type 1 (P=0.035; FC=5.44), IFN-γ-inducible protein 10 (P=0.037; FC=3.8) and C-C chemokine ligand 25 (P=0.048; FC=3.56). The augmented expression of these four genes in the CD stricturing phenotype, if confirmed in larger cohorts of patients, could help elucidate the mechanisms leading to disease-associated complications.

Real World Efficacy and Safety of Sofosbuvir + Velpatasvir + Voxilaprevir in Romanian Patients with Genotype 1b HCV Infection Non-reponders to DAAs Therapy.

BACKGROUND AND AIMS: The sofosbuvir (SOF) / velpatasvir (VEL) / voxilaprevir (VOX) combination has been evaluated in more than 800 patients enrolled in phase II and phase III studies, where it demonstrated excellent safety and efficacy, achieving overall sustained viral response (SVR) rates of more than 95%. We aimed to assess the efficacy and safety of SOF/VEL/VOX in a real-world study, including patients previously treated for genotype 1b hepatitis C virus (HCV) infection that did not obtain a sustained viral response with previous direct-acting antivirals (DAAs) therapy. METHODS: In Romania, through a nationwide government-funded program in 2019-2020, 213 patients with chronic hepatitis C non-responders to previous DAAs therapy, received treatment with SOF/VEL/ VOX 400/100/100 mg/day for 12 weeks. We performed a retrospective longitudinal study that included 143 individuals who were treated in Bucharest, Iași, Craiova and Constanța clinics, all with genotype 1b HCV infection. Efficacy was assessed by the percentage of patients achieving SVR 12 weeks post-treatment (SVR12). Serious adverse events (SAE) were registered. RESULTS: Our cohort comprised 53% males with a median age of 60 years (27÷77); 47% were pre-treated with ombitasvir/paritaprevir/ritonavir+dasabuvir ± ribavirin, 40% with ledipasvir/SOF, 13% with elbasvir/ grazoprevir. 42% of patients associated co-morbidities, 45% had compensated liver cirrhosis, 2% had treated hepatocellular carcinoma (HCC) and 1% had hepatitis B virus co-infection. SVR by intention to treat was reported in 139/143 (97.2%) and per protocol in 141/143 (98.6%). No predictive factors for SVR were identified. Rate of liver decompensation in patients with cirrhosis was 6% and was statistically associated in multivariate analysis with Child-Pugh score (p<0.01) and with severe steatosis (p=0.004). Occurrence of new HCC was reported in 3.6% of all patients with cirrhosis and was associated with poor liver function [higher Child-Pugh score (p=0.001) and low albumin levels (p=0.02)]. Serious adverse events related to therapy were reported in 1/143(0.7%). CONCLUSIONS: SOF/VEL/VOX was highly efficient in our population of patients with a 97.2% SVR. Liver decompensation occurred in 6% of cirrhotic patients at SVR, related to hepatic dysfunction.

miRNAs-Based Molecular Signature for KRAS Mutated and Wild Type Colorectal Cancer: An Explorative Study.

microRNAs (miRNAs) have been proposed as promising molecular biomarkers for diagnosis, prognosis, and responsive therapeutic targets in different types of cancer, including colorectal cancer (CRC). In this study, we evaluated the expression levels of 84 cancer-associated miRNAs in a cohort of 39 human samples comprising 13 peritumoral and 26 tumoral tissues from surgical specimens of CRC patients. KRAS mutations were detected in 11 tumoral samples. In a first analysis, we found 5 miRNAs (miR-215-5p, miR-9-5p, miR-138-5p, miR378a-3p, and miR-150-5p) that were significantly downregulated and one upregulated (miR-135b-5p) in tumoral tissues compared with the peritumoral tissues. Furthermore, by comparing miRNA profile between KRAS mutated CRC tissues respect to wild type CRC tissues, we found 7 miRNA (miR-27b-3p, miR-191-5p, miR-let7d-5p, miR-15b-5p, miR-98-5p, miR-10a-5p, and miR-149-5p) downregulated in KRAS mutated condition. In conclusion, we have identified a panel of miRNAs that specifically distinguish CRC tissues from peritumoral tissue and a different set of miRNAs specific for CRC with KRAS mutations. These findings may contribute to the discovering of new molecular biomarkers with clinic relevance and might shed light on novel molecular aspects of CRC.

Somatostatinoma and Neurofibromatosis Type 1-A Case Report and Review of the Literature.

Somatostatinomas are rare neuroendocrine tumors (NET) that arise in the gastrointestinal (GI) tract. Because of their insidious growth, they are usually asymptomatic until late stages, presenting as malignant disease. We report the case of a 50-year-old woman who presented with epigastric abdominal pain, diarrhea and significant weight loss in the last two years. On clinical examination the patient met the criteria for neurofibromatosis type 1 (NF1). Abdominal CT and MRI revealed an infiltrative duodenal mass, with pancreatic invasion, locoregional enlarged lymph nodes and disseminated hepatic nodules. Microscopy and immunohistochemistry uncovered a neuroendocrine tumor, staining positive for chromogranin A (CgA), synaptophysin and somatostatin, with a Ki67 = 1%. Somatostatin receptors (SSTRs) type 2 were negative and SSTRs type 5 were positive in less than 50% of tumoral cells. Our patient was classified as a T3N1M1 stage IV metastatic duodenal grade 1 somatostatinoma and treatment with somatostatin analogues and chemotherapy with capecitabine and temozolomide was started, with so far abdominal imaging follow-up showing stable disease. When a patient is diagnosed with a rare NET, such as a somatostatinoma, it is of utmost importance to determine if it is a sporadic tumor or just a feature of a genetic disorder.

Molecular Signature of Persistent Histological Inflammation in Ulcerative Colitis with Mucosal Healing.

BACKGROUND AND AIMS: Therapeutic targets in ulcerative colitis (UC) have evolved over time from clinical remission to biological and endoscopic remission. Histologic remission remains a debatable outcome due to lack of data regarding its impact on long-term evolution. The development of histologic activity scores has brought standardization. We aimed to identify mucosal markers differentiating histological inflammation from histological remission in UC patients. METHODS: The gene expression levels of 84 genes associated with inflammatory bowel diseases have been analyzed in 43 colonic mucosa samples from 30 patients with UC. The gene expression levels have been correlated with histological inflammation score of Geboes. Patients with endoscopic remission were divided by histological activity into two groups and molecular results were compared in order to identify differences in the mucosal gene expression. RESULTS: We found a significant Pearson correlation (p<0.001 and r>0.5) between the Geboes score and the expression of 29 genes, whereas negative correlation (p<0.001 and r<-0.50) was observed with two genes in the entire UC cohort. In the subgroup of patients with endoscopic remission three transcripts: formyl-peptide receptor 1 (FPR1), matrix metalloproteinases 1 (MMP1) and mucine 1 (MUC1) were significantly up-regulated in patients with histological inflammation compared to patients with histologic remission. CONCLUSION: Our study further emphasizes the importance of histological assessment when endoscopic mucosal healing is present, as FPR1, MMP-1 and MUC1 were all significantly upregulated in patients with histological alterations.

Signification of Serum Alpha-Fetoprotein Levels in Cases of Compensated Cirrhosis and Hepatitis C Virus without Hepatocellular Carcinoma.

AFP (alpha-fetoprotein) levels are increased during the development of HCC (hepatocellular carcinoma); nonetheless, it can also be produced by non-tumoral hepatocytes in conditions of high cell turnover. Our study aims to provide additional data regarding the causes of elevated AFP in patients with liver cirrhosis due to hepatitis C virus (HCV) infection. We conducted an observational prospective cohort study that included 2068 patients with compensated cirrhosis and chronic hepatitis C genotype 1b infection. The two main inclusion criteria were the presence of advanced liver fibrosis - Metavir stage F4 - diagnosed by FibroMax testing, Fibroscan or liver biopsy, and the presence of detectable HCV RNA in the serum. Plasmatic AFP levels were determined through the electrochemiluminescence method, with a standard value ranging from 0 to 7 ng/ml. All data were obtained from the Romanian National Health Agency. The average AFP serum levels in patients with compensated cirrhosis without HCC were 9.4 ng/ml (range 0.5 ÷ 406 ng/ml); 30.1% of patients had significantly increased levels of AFP (>15 ng/ml). High values of serum AFP in patients with compensated liver cirrhosis without HCC was correlated with more advanced age (p<0.001), severe necroinflammatory activity detected by FibroMax (p<0.001), severe NASH (p<0.001), severe steatosis (p<0.001), low platelets (p<0.001), increased values of AST and ALT (p<0.001).

Recurrence rate of hepatocellular carcinoma in patients with treated hepatocellular carcinoma and hepatitis C virus-associated cirrhosis after ombitasvir/paritaprevir/ritonavir+dasabuvir+ribavirin therapy.

Introduction: Recent studies have suggested a higher recurrence rate of hepatocellular carcinoma (HCC) in patients with a history of HCC and hepatitis C virus (HCV)-associated cirrhosis treated with direct-acting antiviral (DAA) agents. Material and methods: We conducted a prospective analysis of 24 patients with HCV-associated cirrhosis and treated HCC who received ombitasvir/paritaprevir/ritonavir+dasabuvir+ribavirin for 12 weeks. Prior therapies for HCC included resection (9/24 patients), radiofrequency ablation (RFA) (7/24) and trans-arterial chemoembolization (TACE) (8/24). All patients were eligible for treatment if they had no HCC recurrence 6 months after their last procedure. A control group was defined. All patients were followed every 6 months, with dynamic computed tomography and/or magnetic resonance imaging. Results: The sustained virological response rate per protocol was 21/24 (87.5%). The study group included 14 (59%) males, median age 64 years (51-77), 50% with associated non-alcoholic steatohepatitis and 24% with Child-Pugh A6 points. HCC recurrence rate/100 patient-years was lower in the DAA-HCC group versus control: 5.5 versus 24.6% patient-years for the resection+RFA group (p = 0.044), respectively, and 18.6 versus 72.7% patient-years for TACE group (p = 0.002). Survival without recurrence was higher in the resection+RFA group (45 compared to 18 months (p < 0.001)) and also in the TACE group (44 compared to 11.5 months (p = 0.002)). Conclusions: DAA therapy significantly reduced the recurrence rate of HCC and improved survival without recurrence in patients with treated HCV-associated HCC.

Environmental Factors in Romanian and Belgian Patients with Inflammatory Bowel Disease - a Retrospective Comparative Study.

Background:Several environmental factors have been associated with onset of inflammatory bowel diseases (IBD): smoking, hygiene, microorganisms, oral contraceptive pills (OCPs), non-steroid anti-inflammatory drugs, antibiotics, appendectomy, diet, breastfeeding, vitamin D, stress and ambient air pollution. The aim of this study was to investigate the prevalence of these factors in a Romanian and Belgian population with IBD. Material and methods:A total of 129 patients with an IBD diagnosis (76 from Romania and 53 from Belgium) participated in an interview and were asked to fill in a questionnaire regarding environmental factors before and after the onset of IBD; 35 Romanian and 21 Belgian healthy individuals constituted the control group. Results:A total of 40 patients with ulcerative colitis (UC) and 89 with Crohn's disease (CD) were included. Gender distribution was 43% males and 57% females. They had a median age of 42 years (range between 19-74 years), a median disease duration of eight years and 79% were in clinical remission. Both Romanian and Belgian IBD patients reported an increased antibiotic consumption before IBD onset compared to controls: 58% vs 10% (p<0.001) and 51% vs 5% (p<0.001), respectively. Belgian IBD patients declared significantly more frequent OCP use (53% vs 9%, p <0.001), they were breastfed in a lower proportion (49% vs 76%, p <0.001) and had experienced a higher level of psychosocial stress (p<0.001). Conclusion:Antibiotic consumption before IBD onset may play a pivotal role in IBD development in both Romanian and Belgian populations. In Belgian patients, OCP consumption, a higher level of psychosocial stress and lack of breastfeeding may also be involved.

Differential Intestinal Mucosa Transcriptomic Biomarkers for Crohn's Disease and Ulcerative Colitis.

Genetic research has shaped the inflammatory bowel disease (IBD) landscape identifying nearly two hundred risk loci. Nonetheless, the identified variants rendered only a partial success in providing criteria for the differential diagnosis between ulcerative colitis (UC) and Crohn's disease (CD). Transcript levels from affected intestinal mucosa may serve as tentative biomarkers for improving classification and diagnosis of IBD. The aim of our study was to identify gene expression profiles specific for UC and CD, in endoscopically affected and normal intestinal colonic mucosa from IBD patients. We evaluated a panel of 84 genes related to the IBD-inflammatory pathway on 21 UC and 22 CD paired inflamed and not inflamed mucosa and on age-matched normal mucosa from 21 non-IBD controls. Two genes in UC (CCL11 and MMP10) and two in CD (C4BPB and IL1RN) showed an upregulation trend in both noninflamed and inflamed mucosa compared to controls. Our results suggest that the transcript levels of CCL11, MMP10, C4BPB, and IL1RN are candidate biomarkers that could help in clinical practice for the differential diagnosis between UC and CD and could guide new research on future therapeutic targets.