Molecular Aspects of MAFLD-New Insights on Pathogenesis and Treatment.

Metabolic-associated liver disease (MAFLD) affects up to 70% of overweight and more than 90% of morbidly obese people, and its pathogenesis is rather complex and multifactorial. The criteria for MAFLD include the presence of hepatic steatosis in addition to one of the following three criteria: overweight or obesity, presence of type 2 diabetes mellitus (T2DM), or evidence of metabolic dysregulation. If the specific criteria are present, the diagnosis of MAFLD can be made regardless of alcohol consumption and previous liver disease. The pathophysiological mechanisms of MAFLD, including inflammation, lipotoxicity, mitochondrial disfunction, and oxidative stress, as well as the impact of intestinal gut microbiota, are constantly being elucidated. Treatment strategies that are continually emerging are based on different key points in MAFLD pathogenesis. Yet, the ideal therapeutic option has still not been found and future research is of great importance, as MAFLD represents a multisystemic disease with numerous complications.

Investigational new drugs for the treatment of Dravet syndrome: an update.

INTRODUCTION: While there are already approved anticonvulsants for treatment of children with Dravet syndrome, disease modifying therapy is at its beginning. AREAS COVERED: This narrative review is updating the latest information about efficacy and safety of both anticonvulsant and disease modifying investigational drugs for Dravet syndrome. Relevant publications were searched for in MEDLINE, GOOGLE SCHOLAR, SCINDEKS, and CLINICALTRIALS.GOV databases, from the dates of their foundation till January 2023. EXPERT OPINION: The main advancements were made in the treatment of Dravet syndrome with confirmed haploinsufficiency of SCN1A gene. The application of antisense oligonucleotides has so far proven to be the most successful within disease-modifying therapy, but it also requires further refinement of the methodology of application and delivery to target cells, as well as additional testing of the effectiveness of antisense oligonucleotides outside of TANGO technology. Also, the full potential of gene therapy has yet to be explored, given that high capacity adenoviral vectors that can incorporate the SCN1A gene have recently been prepared.

Gastrointestinal and Hepatological Manifestations in Severe Acute Respiratory Syndrome Coronavirus 2 Infection: Results from the Major COVID Hospital in Serbia.

The coronavirus disease of 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), includes a clinical spectrum of diseases from mild to severe progressive pneumonia, which has affected and still affects the human population worldwide. Most commonly, it is presented by respiratory symptoms, but studies have shown that about 50% of patients with SARS-CoV-2 infection have at least one gastrointestinal symptom (GI), predominantly nausea, diarrhea, vomiting, or loss of appetite. In addition, abnormal liver functional tests are commonly present in the SARS-CoV-2 virus. The aim of our study was to examine the GI and hepatic manifestations of COVID-19 in patients hospitalized due to COVID-19 pneumonia in "COVID hospital Batajnica", University Clinical Center of Serbia in Belgrade. The study included 498 consecutive patients, and the data was obtained from the patient's electronic medical history. GI symptoms included nausea, vomiting, diarrhea, and anorexia. Collected laboratory values included baseline and peak values of blood count, inflammatory parameters, liver function tests, renal function tests, and cardiac enzyme tests. The results have shown that GI symptoms occurred in 26% of cases at diagnosis, which indicates the great susceptibility of the GI system to SARS-CoV-2. There was a high risk of liver injury in patients with COVID-19 pneumonia (>60%). The level of AST is more often increased compared to ALT, which is different from other virus-induced liver lesions and may be a useful indicator of SARS-CoV-2 infection. Further research should focus on the causes of liver damage in SARS-CoV-2 virus and the impact on treatment and outcome of COVID-19 disease.

Post COVID-19 irritable bowel syndrome.

OBJECTIVES: The long-term consequences of COVID-19 infection on the gastrointestinal tract remain unclear. Here, we aimed to evaluate the prevalence of gastrointestinal symptoms and post-COVID-19 disorders of gut-brain interaction after hospitalisation for SARS-CoV-2 infection. DESIGN: GI-COVID-19 is a prospective, multicentre, controlled study. Patients with and without COVID-19 diagnosis were evaluated on hospital admission and after 1, 6 and 12 months post hospitalisation. Gastrointestinal symptoms, anxiety and depression were assessed using validated questionnaires. RESULTS: The study included 2183 hospitalised patients. The primary analysis included a total of 883 patients (614 patients with COVID-19 and 269 controls) due to the exclusion of patients with pre-existing gastrointestinal symptoms and/or surgery. At enrolment, gastrointestinal symptoms were more frequent among patients with COVID-19 than in the control group (59.3% vs 39.7%, p<0.001). At the 12-month follow-up, constipation and hard stools were significantly more prevalent in controls than in patients with COVID-19 (16% vs 9.6%, p=0.019 and 17.7% vs 10.9%, p=0.011, respectively). Compared with controls, patients with COVID-19 reported higher rates of irritable bowel syndrome (IBS) according to Rome IV criteria: 0.5% versus 3.2%, p=0.045. Factors significantly associated with IBS diagnosis included history of allergies, chronic intake of proton pump inhibitors and presence of dyspnoea. At the 6-month follow-up, the rate of patients with COVID-19 fulfilling the criteria for depression was higher than among controls. CONCLUSION: Compared with controls, hospitalised patients with COVID-19 had fewer problems of constipation and hard stools at 12 months after acute infection. Patients with COVID-19 had significantly higher rates of IBS than controls. TRIAL REGISTRATION NUMBER: NCT04691895.

Abnormal Liver Blood Tests: Hepatologist Approach.

BACKGROUND: Available data suggest that the prevalence of chronic liver disease (CLD) and primary liver cancer is rising in Europe and represents a major public health problem. Predictions are showing that these trends will continue to rise in the upcoming years. SUMMARY: Alcohol-related liver disease, nonalcohol fatty liver disease, and viral hepatitis B and hepatitis C are the leading causes of liver cirrhosis and primary liver cancer in Europe. Drug-induced liver injury represents a major cause of acute hepatitis, while liver transplantation is the second most common solid organ transplantation in the world. Patients with CLD have increasing rates of hospitalization, longer hospital stays, and more adverse outcomes compared to the other chronic conditions. Direct targeting of risk factors can prevent complications of advanced liver disease and improve outcome. Patients with CLD should be referred to a hepatologist for assessment of the stage of liver disease, for specific treatment and screening for hepatocellular carcinoma. Moreover, patients with unknown etiology of abnormal liver blood tests should be referred to a hepatologist for assessment of liver disease, as well as for prevention and treatment of complications of cirrhosis and/or portal hypertension. Key Messages: CLD is amenable to prevention and treatment, while disease management strategies need to improve in order to reduce the burden of liver disease and deaths due to end-stage liver diseases.

Diarrhea as a Clinical Challenge: General Practitioner Approach.

BACKGROUND: Diarrhea is defined as the passage of loose stools and increase in stool frequency, weight, or volume. Diarrhea is an important health issue since it accounts for 2.5 million deaths in the world each year. SUMMARY: Diarrhea can be acute, persistent, or chronic. Acute diarrhea (AD) is usually infectious, caused by viruses, less frequently by bacteria and parasites. The majority of cases of AD are self-limiting and do not require diagnostic workup. The use of diagnostic tests in AD should be limited to patients with signs of severe dehydration, bloody stools, persistent fever and those suffering from immunodeficiencies using immunosuppressive therapy or to cases of suspected nosocomial infection. These patients should be referred to gastroenterologists or infectious disease specialists. Therapy in AD consists of early oral refeeding, antidiarrheal medications, antibiotics, and probiotics. Chronic diarrhea (CD) has diverse etiology. The majority of patients have self-limiting symptoms or functional gastrointestinal disorders. Patients with blood in stool, weight loss, clinical and laboratory signs of anemia, and palpable mass in the abdomen (red flag symptoms) need urgent gastroenterology referral. Therapy in CD is possible when the underlying cause of symptoms is identified. KEY MESSAGES: The general practitioner should identify high-risk patients with AD and/or red flag symptoms for urgent gastroenterology referral.

Chronic Abdominal Pain: Gastroenterologist Approach.

BACKGROUND: Abdominal pain is a common symptom of gastroenterology examination. Chronic abdominal pain is present for >3 months. SUMMARY: Gastroesophageal reflux disease (GERD) is one of the most common gastrointestinal diseases encountered by both gastroenterologists and general practitioners. GERD is usually a chronic disease presented with a set of symptoms including heartburn and/or regurgitation, and less commonly epigastric pain. Epigastric pain syndrome is characterized by the following symptoms: epigastric pain and/or burning. It does not necessarily occur after meal ingestion, may occur during fasting, and can be even improved by meal ingestion. Duodenal ulcers tend to cause abdominal pain that is localized in the epigastric region and commence several hours after eating, often at night. Hunger provokes pain in most of the cases and decreases after meal. Gastric ulcer pain occurs immediately after eating, and consuming food increases pain. Pain is localized in the epigastrium and can radiate to the back. Abdominal pain in irritable bowel syndrome is related to defecation. A typical symptom of chronic pancreatitis is pain that radiates to the back. In Crohn's disease, inflammation causes pain. Key Messages: Pain can occur at different locations with diverse intensity and propagation and is often associated with other symptoms. For any gastroenterologist, abdominal pain is a big challenge.

Anemia as a Problem: GEH Approach.

BACKGROUND: Anemia is present in almost 5% of adults worldwide and accompanies clinical findings in many diseases. Diseases of the gastrointestinal (GI) tract and liver are a common cause of anemia, so patients with anemia are often referred to a gastroenterologist. SUMMARY: Anemia could be caused by various factors such as chronic bleeding, malabsorption, or chronic inflammation. In clinical practice, iron deficiency anemia and the combined forms of anemia due to different pathophysiological mechanisms are most common. Esophagogastroduodenoscopy, colonoscopy, and the small intestine examinations in specific situations play a crucial role in diagnosing anemia. In anemic, GI asymptomatic patients, there are recommendations for bidirectional endoscopy. Although GI malignancies are the most common cause of chronic bleeding, all conditions leading to blood loss, malabsorption, and chronic inflammation should be considered. From a gastroenterologist's perspective, the clinical spectrum of anemia is vast because many different digestive tract diseases lead to bleeding. Key Messages: The gastroenterological approach in solving anemia's problem requires an optimal strategy, consideration of the accompanying clinical signs, and the fastest possible diagnosis. Although patients with symptoms of anemia are often referred to gastroenterologists, the diagnostic approach requires further improvement in everyday clinical practice.

Prevalence of Gastrointestinal Symptoms in Severe Acute Respiratory Syndrome Coronavirus 2 Infection: Results of the Prospective Controlled Multinational GI-COVID-19 Study.

INTRODUCTION: Gastrointestinal (GI) symptoms in coronavirus-19 disease (COVID-19) have been reported with great variability and without standardization. In hospitalized patients, we aimed to evaluate the prevalence of GI symptoms, factors associated with their occurrence, and variation at 1 month. METHODS: The GI-COVID-19 is a prospective, multicenter, controlled study. Patients with and without COVID-19 diagnosis were recruited at hospital admission and asked for GI symptoms at admission and after 1 month, using the validated Gastrointestinal Symptom Rating Scale questionnaire. RESULTS: The study included 2036 hospitalized patients. A total of 871 patients (575 COVID+ and 296 COVID-) were included for the primary analysis. GI symptoms occurred more frequently in patients with COVID-19 (59.7%; 343/575 patients) than in the control group (43.2%; 128/296 patients) (P < 0.001). Patients with COVID-19 complained of higher presence or intensity of nausea, diarrhea, loose stools, and urgency as compared with controls. At a 1-month follow-up, a reduction in the presence or intensity of GI symptoms was found in COVID-19 patients with GI symptoms at hospital admission. Nausea remained increased over controls. Factors significantly associated with nausea persistence in COVID-19 were female sex, high body mass index, the presence of dyspnea, and increased C-reactive protein levels. DISCUSSION: The prevalence of GI symptoms in hospitalized patients with COVID-19 is higher than previously reported. Systemic and respiratory symptoms are often associated with GI complaints. Nausea may persist after the resolution of COVID-19 infection.

IL 33 Correlates With COVID-19 Severity, Radiographic and Clinical Finding.

Objective: The increased level of interleukin (IL)-33 is considered as a predictor of severe coronavirus disease 2019 (COVID-19) infection, but its role at different stages of the disease is still unclear. Our goal was to analyze the correlation of IL-33 and other innate immunity cytokines with disease severity. Methods: In this study, 220 patients with COVID-19 were included and divided into two groups, mild/moderate and severe/critical. The value of the cytokines, clinical, biochemical, radiographic data was collected and their correlation with disease severity was analyzed. Results: Most patients in the severe/critical group were male (81.8%) and older (over 64.5 years). We found a statistically significant difference (p < 0.05) in these two groups between clinical features (dyspnea, dry cough, fatigue, and auscultatory findings); laboratory [(neutrophil count, lymphocyte count, monocyte count, hemoglobin, plasma glucose, urea, creatinine, total bilirubin (TBIL), direct bilirubin (DBIL), aspartate aminotransferase (AST), albumin (ALB), lactate dehydrogenase (LDH), creatinine kinase (CK), D-dimer, C-reactive protein (CRP), procalcitonin (PCT), Fe, and Ferritin)], arterial blood gases (oxygen saturation-Sa02, partial pressure of oxygen -p02), and chest X-rays (CXR) lung findings (p = 0.000). We found a significantly higher serum concentration (p < 0.05) of TNF-α, IL-1ß, IL-6, IL-12, IL-23, and IL-33 in patients with COVID-19 with severe disease. In the milder stage of COVID-19, a positive correlation was detected between IL-33 and IL-1ß, IL-12 and IL-23, while a stronger positive correlation between the serum values of IL-33 and TNF-α, IL-1ß, IL-6, and IL-12 and IL-23 was detected in patients with COVID-19 with severe disease. A weak negative correlation (p < 0.05) between pO2 and serum IL-1ß, IL-12, and IL-33 and between SaO2 and serum IL-33 was noted. The positive relation (p < 0.05) between the serum values of IL-33 and IL-12, IL-33 and IL-6, and IL-6 and IL-12 is proven. Conclusion: In a more progressive stage of COVID-19, increased IL-33 facilitates lung inflammation by inducing the production of various innate proinflammatory cytokines (IL-1ß, IL-6, TNF-α, IL-12, and IL-23) in several target cells leading to the most severe forms of the disease. IL-33 correlates with clinical parameters of COVID-19 and might represent a promising marker as well as a therapeutic target in COVID-19.

The New Therapeutic Approaches in the Treatment of Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease which is characterized by extremely complex pathogenetic mechanisms and multifactorial etiology. Some of the many pathophysiological mechanisms involved in the development of NAFLD include oxidative stress, impaired mitochondrial metabolism, inflammation, gut microbiota, and interaction between the brain-liver-axis and the regulation of hepatic lipid metabolism. The new therapeutic approaches in the treatment of NAFLD are targeting some of these milestones along the pathophysiological pathway and include drugs like agonists of peroxisome proliferator-activated receptors (PPARs), glucagon-like peptide-1 (GLP-1) agonists, sodium/glucose transport protein 2 (SGLT2) inhibitors, farnesoid X receptor (FXR) agonists, probiotics, and symbiotics. Further efforts in biomedical sciences should focus on the investigation of the relationship between the microbiome, liver metabolism, and response to inflammation, systemic consequences of metabolic syndrome.

Novel and emerging therapeutics for genetic epilepsies.

INTRODUCTION: Disease-specific treatments are available only for a minority of patients with genetic epilepsies, while the rest are treated with anticonvulsants, which are ineffective in almost one-third of patients. AREAS COVERED: Recently approved and the most effective emerging therapeutics under development for the treatment of genetic epilepsies are overviewed after systematic search and analysis of relevant literature. EXPERT OPINION: New and emerging drugs for genetic epilepsies exploit one of the two approaches: inhibiting hyperactive brain foci through blocking excitatory or augmenting inhibitory neurotransmission, or correcting the underlying genetic defect. The first is limited by insufficient selectivity of available compounds, and the second by imperfection of currently used vectors of genetic material, unselective and transient transgene expression. Besides, the treatment may come too late, after structural abnormalities and epilepsy deterioration takes place. However, with recent improvements, we can expect to see soon gradual decline in the number of patients with therapy-resistant genetic epilepsies.

Risk factors for cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage.

INTRODUCTION: Aneurysmal subarachnoid hemorrhage is a type of spontaneous hemorrhagic stroke, which is caused by a ruptured cerebral aneurysm. Cerebral vasospasm (CVS) is the most grievous complication of subarachnoid hemorrhage (SAH). The aim of this study was to examine the risk factors that influence the onset of CVS that develops after endovascular coil embolization of a ruptured aneurysm. MATERIALS AND METHODS: The study was designed as a cross-sectional study. The patients included in the study were 18 or more years of age, admitted within a period of 24 h of symptom onset, diagnosed and treated at a university medical center in Serbia during a 5-year period. RESULTS: Our study showed that the maximum recorded international normalized ratio (INR) values in patients who were not receiving anticoagulant therapy and the maximum recorded white blood cells (WBCs) were strongly associated with cerebrovascular spasm, increasing its chances 4.4 and 8.4 times with an increase of each integer of the INR value and 1,000 WBCs, respectively. CONCLUSIONS: SAH after the rupture of cerebral aneurysms creates an endocranial inflammatory state whose intensity is probably directly related to the occurrence of vasospasm and its adverse consequences.

Recent Data on Irritable Bowel Syndrome from some Central and East European Countries.

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Exploring inflammatory and apoptotic signatures in distinct Crohn's disease phenotypes: Way towards molecular stratification of patients and targeted therapy.

BACKGROUND: Crohn's disease (CD) is chronic inflammatory bowel disease with different phenotypic characteristics influencing disease prognosis and therapeutic strategies. The aim of this pilot study was to analyze selected inflammatory and apoptotic markers in non-inflamed and inflamed samples of ileal mucosa of non-stricturing/non-penetrating (NS/NP) and stricturing (S) CD mucosal phenotypes in order to characterize their distinct profiles. METHODS: From twenty CD patients (9 NS/NP, 11 S) paired non-inflamed and inflamed ileal biopsies were collected and used for analysis of cytokine (TNF and IL6) and apoptotic (Bcl2, Bax, Fas and FasL) genes' expression levels by real-time PCR, while NFκB transcriptional potency was assessed by electromobility gel shift assay. RESULTS: Our results demonstrated significant upregulation of TNF and IL6 in inflamed area of both NS/NP (p = 0.03, p = 0.01) and S phenotypes (p = 0.04, p = 0.04), respectively. However, TNF increase was more prominent in NS/NP compared to S inflamed mucosa (p = 0.02). Also, level of proapoptotic Bax was significantly higher in NS/NP compared to S inflamed mucosa (p = 0.01). Opposing transcription potency of NFκB has been detected between two phenotypes: being decreased in NS/NP (p = 0.07) and increased in S (p = 0.1) inflamed compared to non-inflamed mucosa, demonstrating trend towards statistical significance. CONCLUSIONS: We found that two distinct CD phenotypes have specific molecular signatures. Obtained results could direct improvement of current and development of new therapeutic strategies based on more specific molecular stratification of CD patients.

Metabolic Syndrome in Inflammatory Bowel Disease: Association with Genetic Markers of Obesity and Inflammation.

Background: This study analyzed poorly understood relationship of two overlapping conditions: metabolic syndrome (MeS) and inflammatory bowel disease (IBD), both associated with inflammation in the visceral adipose tissue. Methods: Newly diagnosed 104 IBD patients, of which 50 Crohn's disease (CD) and 54 ulcerative colitis (UC), and 45 non-IBD controls were examined for MeS-related obesity and lipid markers. Th-17 immune genes IL17A, IL17F, IL23A, and TLR9 mRNAs were measured in intestinal mucosa by qRT-PCR. Subjects were genotyped for obesity-associated FTO variant rs9939609 by polymerase chain reaction-amplification refractory mutation system. Results: CD was associated with MeS (P = 0.01), while both CD and UC were associated with central obesity (P = 10-5, P = 0.002, respectively) and low levels of high-density lipoprotein (HDL) cholesterol (P = 5 × 10-6, P = 6 × 10-6, respectively). IBD lipid profile was characterized by decreased total and HDL cholesterol, while low-density lipoprotein cholesterol was reduced only in CD. Negative correlations were found between total cholesterol and CD activity index (P = 0.005), waist circumference and IL17A as well as IL17F mRNA levels in inflamed CD colon (P = 0.003, P = 0.001, respectively). Carriers of FTO rs9939609 AA genotype showed increased risk of CD (OR 2.6, P = 0.01). Conclusions: MeS, central obesity, and dyslipidemia could be important for IBD pathogenesis. This could influence therapeutic approaches and prevention strategies in high-risk groups.

Importance of TLR9-IL23-IL17 axis in inflammatory bowel disease development: Gene expression profiling study.

BACKGROUND AND AIMS: Mucosal gene expression have not been fully enlightened in inflammatory bowel disease (IBD). Aim of this study was to define IL23A, IL17A, IL17F and TLR9 expression in different IBD phenotypes. METHODS: Evaluation of mRNA levels was performed in paired non-inflamed and inflamed mucosal biopsies of newly diagnosed 50 Crohn's disease (CD) and 54 ulcerative colitis (UC) patients by quantitative real-time PCR analysis. RESULTS: IL17A and IL17F expression levels were significantly increased in inflamed IBD mucosa. Inflamed CD ileal and UC mucosa showed increased IL23A, while only inflamed CD ileal samples showed increased TLR9 mRNA level. Correlation between analysed mRNAs levels and endoscopic and clinical disease activity were found in UC, but only with clinical activity in CD. CONCLUSION: Both CD and UC presented expression of Th17-associated genes. Nevertheless, expression profiles between different disease forms varies which should be taken into account for future research and therapeutics strategies.

Genetic and environmental factors significant for the presentation and development of inflammatory bowel disease.

OBJECTIVES: The aim of the study was to evaluate associations between inflammatory bowel disease (IBD) presentation and variants in NOD2, TLR4, TNF-α, IL-6, IL-1ß, and IL-RN genes in order to identify possible environmental factors that may affect IBD occurrence, investigate potential predictors for surgical treatment of IBD, and correlate the presence of granulomas in biopsy specimens with clinical characteristics of Crohn's disease (CD) patients. PATIENTS AND METHODS: We genotyped 167 IBD patients using PCR-based methodology and tested for disease genotype-phenotype associations. RESULTS: In CD patients ileal localization of disease was more frequent in NOD2 variant carriers. Ileal CD was associated with IL-6 GC+CC genotypes, identifying C allele as a possible marker of increased risk for ileal CD. In CD patients a positive family history for IBD was related to earlier onset of disease, higher risk for CD-related surgery, and appendectomy. CD patients who are TLR4 299Gly carriers are at higher risk for surgery at onset of the disease compared with TLR4 299Asp variant carriers. The presence of granuloma in biopsy specimens was more frequent in patients in whom a diagnosis of CD was made during emergency surgery. Multivariate analysis showed that CD carriers of the 299Gly allele had a 4.6-fold higher risk for emergency surgery before CD diagnosis is established compared with noncarriers, suggesting an aggressive disease course. Granuloma in endoscopic biopsies is detected 5.4-fold more frequently in patients treated surgically at the time of diagnosis. CONCLUSION: Genetic variants together with epidemiological and clinical data of IBD patients could potentially be used as predictors of the disease course.

Diagnostic Accuracy of Platelet Count and Platelet Indices in Noninvasive Assessment of Fibrosis in Nonalcoholic Fatty Liver Disease Patients.

Objective: Keeping in mind the rising prevalence of nonalcoholic fatty liver disease (NAFLD) and the need to establish noninvasive tests for its detection, the aim of our study was to investigate whether platelet count (PC), mean platelet volume (MPV), and platelet distribution width (PDW) can predict the presence of liver fibrosis in this group of patients. Methods: In 98 patients with NAFLD and 60 healthy volunteers, complete blood counts with automated differential counts were performed and values of PC, PDW, MPV, and PCT were analyzed. Results: Patients with NAFLD had lower PC and higher MPV, PCT, and PDW compared to the controls (P < 0.05). When NAFLD group was stratified according to severity of liver fibrosis, there was a statistically significant difference in the average values of PDW and PC between the groups (P < 0.05). Conclusion: Patients with NAFLD have significantly higher values of PCT, PDW, and MPV when compared to the healthy controls. Further studies are needed to establish their potential use for prediction of the degree of liver steatosis and fibrosis in NAFLD patients.

Variations in inflammatory genes as molecular markers for prediction of inflammatory bowel disease occurrence.

OBJECTIVE: Research on inflammatory bowel disease (IBD) has highlighted genes involved in the regulation of inflammatory responses as contributors to disease pathogenesis. This study aimed to evaluate the associations between IBD and variations in NOD2, TLR4, TNF-α, IL-6, IL-1ß and IL-1RN genes, and to use the genetic data obtained in predictive modeling. METHODS: A total of 167 IBD patients and 101 healthy controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism. Using the genotype data attained as the input to various classification algorithms, IBD prediction models were designed. The area under the receiver operating characteristic curve (AUROC) was used to measure their performance. RESULTS: Significant associations were found between Crohn's disease (CD) and minor NOD2 variants, as well as TLR4 299Gly, TNF-α G-308A, IL-6 G-174C and IL-1RN VNTR A2 variants, while ulcerative colitis (UC) was associated only with IL-1RN VNTR A2 variants. CD and UC showed highly significant difference in the allelic distribution of TNF-α G-308A, where the A allele was found to be related to CD, and the G allele to UC. A combined effect of patients' gender and TLR4 variants was observed among CD patients. When all analyzed genotype and gender data were used, prediction performance achieved a maximum AUROC of 0.690 for CD and 0.601 for UC dataset. CONCLUSION: Variations in the genes involved in immune regulation are genetic factors of importance in IBD susceptibility that could potentially be used as predictors of disease development.