New Insights on Using Oral Semaglutide versus Dapagliflozin in Patients with Type 2 Diabetes and Metabolic Dysfunction-Associated Steatotic Liver Disease.

BACKGROUND AND AIMS: Increases in both the prevalence and severity of metabolic dysfunction-associated steatotic liver disease (MASLD) and obesity are closely related. Type 2 diabetes (T2DM) has been associated with metabolic dysfunction-associated steatohepatitis (MASH)-related cirrhosis and hepatocellular carcinoma. Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist approved for the treatment of T2DM and has an important role in weight loss. Also, it may represent a new therapeutic option for the treatment of MASH in obese diabetic patients. The main outcomes were changes from baseline in liver steatosis and fibrosis at week 24. MATERIAL AND METHODS: A total of one hundred eighty-seven patients with T2DM were eligible for this prospective study; ninety-five subjects were treated with oral semaglutide, and ninety-two patients were treated with dapagliflozin as an add-on to metformin. All the subjects were evaluated using Vibration Controlled Transient Elastography (VCTE) from June to December 2022. RESULTS: From our cohort, 54% of the patients were females, with a mean age of 59.92 ± 11.89 years and a mean body mass index (BMI) of 29.53 ± 5.33 kg/m2. Following a six-month medication period, we observed a substantial reduction in anthropometric measurements, including the BMI, waist circumference (WC), and waist-to-hip ratio (WtHr), in both groups. Regarding HbA1c, a notable decrease was observed in the semaglutide group (p < 0.001) when compared to the dapagliflozin group (p = 0.011). In addition, the liver stiffness measurement (LSM) according to VCTE improved significantly in the semaglutide group participants from 8.07 ± 2.90 kPa at baseline to 6.51 ± 3.09 kPa after medication (p < 0.001). CONCLUSION: The superior metabolic effects of semaglutide, correlated to dapagliflozin, may contribute to a more efficient decrease in hepatic stress and injury, leading to a substantial enhancement of liver function in T2DM patients. Further investigations conducted over an ideal timeframe are necessary to confirm the evidence presented in this study.

Insights into the Natural and Treatment Courses of Hepatitis B in Children: A Retrospective Study.

Chronic Hepatitis B virus (HBV) infection in children remains a significant public health challenge. The natural history and treatment outcomes of HBV can vary widely, influencing management strategies. This retrospective study was conducted in Northeast Romania and involved a cohort of 148 pediatric patients diagnosed with chronic viral Hepatitis B. Of these, 59 children underwent antiviral treatment while 89 were not treated. One of the main objectives was the rate of HBeAg (Hepatitis B-e antigen) seroconversion, a marker of disease progression and response to therapy. Among the treated group, 26 children (44%) achieved HBeAg seroconversion following therapy. In contrast, 44 of the untreated children (49%) experienced spontaneous HBeAg seroconversion, indicating a substantial rate of natural resolution within this population subset. The findings highlight a significant proportion of spontaneous seroconversion in untreated pediatric patients, suggesting a potential re-evaluation of treatment criteria and timing for children with chronic HBV infection. The comparable rates of seroconversion between treated and untreated cohorts underscore the need for individualized treatment approaches based on a combination of virological, biochemical, and clinical parameters. Further studies are required to refine management strategies to optimize long-term outcomes in pediatric HBV infections.

The value of presepsin and procalcitonin as prognostic factors for mortality in patients with alcoholic liver cirrhosis and acute on chronic liver failure.

Background: Acute on chronic liver failure (ACLF) is typically characterized by a rapid progression of liver failure in patients with liver cirrhosis and it is triggered by a precipitant factor, usually a bacterial infection (BI). Considering the low accuracy of the inflammation biomarkers in liver cirrhosis, presepsin and procalcitonin have demonstrated a good diagnostic performance for BI. Understanding the key prognostic factors that influence patient outcomes can significantly impact clinical decision-making and improve patient care in ACLF which can lead to lower mortality rates. Aim: To evaluate the prognostic factors associated with 30-day mortality in patients with alcohol-related liver cirrhosis and ACLF. Methods: This retrospective study on 227 patients diagnosed with ACLF and alcohol-related liver cirrhosis analyzed the prognostic role of presepsin and procalcitonin serum levels. Results: The survival analysis according to the grade of ACLF showed that more than 80% of patients with ACLF grade 1 survived after 30 days, with a mean estimated time of death of 29 ±0.44 days (95 % CI: 28.17-29.92) compared to ACLF grade 2 (24.9±1.064 days; 95 % CI: 22.82-26.99) and ACLF grade 3 (21.05±1.17 days; 95 % CI: 18.75-23.34), with a mean overall survival on entire cohort of 25.69±0.52 days (95 % CI: 24.65-26.73). Presepsin (OR: 4.008, CI 95:3.130-6.456, p=0.001) and procalcitonin (OR: 3.666, CI 95:2.312-5.813, p=0.001) were the most significant factors associated with 30-day mortality. In ACLF grade 2, presepsin provides a better prediction of mortality at the cutoff value of 1050 pg/mL (Sensitivity 72%, Specificity 69%) than procalcitonin (AUC=0.727 95% CI 0.594-0.860, p<0.002) whereas in ACLF grade 3, a cutoff of 1450 pg/mL (Sensitivity 89%, Specificity 91%) presepsin had a more significant accuracy of mortality prediction (AUC=0.93 95% CI 0.81-0.99, p<0.001) than procalcitonin (AUC=0.731 95% CI 0.655-0.807, p<0.001). Conclusion: ACLF is associated with a high mortality rate and the risk of death increases with the grade of ACLF. Presepsin and procalcitonin serum levels are good prognostic factors for 30-day mortality and should be used in clinical practice to stratify the risk and provide and early and efficient treatment in patients with ACLF.

Clinical Implications and Management of Spontaneous Portosystemic Shunts in Liver Cirrhosis.

Portal hypertension from chronic liver disease leads to the formation of collateral blood vessels called spontaneous portosystemic shunts (SPSS). These shunts may form from existing vessels or through neo-angiogenesis. Their location affects clinical outcomes due to varying risks and complications. This review summarizes current knowledge on SPSS, covering their clinical impact and management strategies. Recent data suggest that SPSS increases the risk of variceal bleeding, regardless of shunt size. The size of the shunt is crucial in the rising incidence of hepatic encephalopathy (HE) linked to SPSS. It also increases the risk of portopulmonary hypertension and portal vein thrombosis. Detecting and assessing SPSS rely on computed tomography (CT) and magnetic resonance imaging. CT enables precise measurements and the prediction of cirrhosis progression. Management focuses on liver disease progression and SPSS-related complications, like HE, variceal bleeding, and portopulmonary hypertension. Interventional radiology techniques such as balloon-occluded, plug-assisted, and coil-assisted retrograde transvenous obliteration play a pivotal role. Surgical options are rare but are considered when other methods fail. Liver transplantation (LT) often resolves SPSS. Intraoperative SPSS ligation is still recommended in patients at high risk for developing HE or graft hypoperfusion.

The Staging of Newly Diagnosed Hepatocellular Carcinoma in Romania. A National Multicentric Study.

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) is a significant public health issue, with an increasing incidence and prevalence and a high incidence-to-mortality ratio. The prognosis of HCC depends on two competing factors, tumor burden and underlying liver disease severity, encompassed in the Barcelona Clinic Liver Cancer (BCLC) classification. To assess HCC staging and the way staging affects eligibility for treatment at the time of the first diagnosis in Romania in the setting of opportunistic diagnosis, in the absence of a national HCC screening policy. METHODS: Data regarding HCC staging, underlying liver disease, and eligibility for treatment at the time of diagnosis was analyzed using a prospectively maintained multicentric database, which included patients from the five largest tertiary care hepatology units in the country between June 2016 and February 2020. RESULTS: A consecutive series of 477 patients was included. The distribution within BCLC classes was as follows: very early (0) 7.1%, early (A) 34.3%, intermediate (B) 19.4%, advanced (C) 14.2%, terminal (D) 24.7%. At the time of the diagnosis, 198 (41.5%) were eligible for a curative intent treatment, while 359 (75.2%) were eligible for a disease-modifying therapy. 228 patients (47.8%) had decompensated liver disease at the time of diagnosis, the most common decompensating event being ascites (78.1%). CONCLUSIONS: A large proportion of HCC cases are diagnosed at the time of a decompensating event, severely restricting the therapeutic potential. Proactive diagnostic strategies should be implemented to improve the rate of actionable diagnosis.

Prospective study of hepatitis B and D epidemiology and risk factors in Romania: A 10-year update.

BACKGROUND: The global burden of hepatitis D virus (HDV) infection represents a major medical challenge and a public health crisis worldwide. However, there is a lack of accurate data on the epidemiology and risk factors for HDV. Hepatitis B virus (HBV) and HDV coinfection causes the most severe form of viral hepatitis, leading to a higher cumulative incidence of liver-related events compared with HBV monoinfection, including the need for liver transplantation and death. AIM: To investigate the epidemiology, natural history, risk factors and clinical management of HBV and HDV coinfection in Romanian patients. METHODS: This prospective study was conducted between January and July 2022 in six tertiary gastroenterology and hepatology referral centres in Romania. All consecutive adults admitted for any gastroenterology diagnosis who were HBV-positive were enrolled. Patients with acute hepatitis or incomplete data were excluded. Of the 25390 individuals who presented with any type of gastroenterology diagnosis during the study period, 963 met the inclusion criteria. Testing for anti-HDV antibodies and HDV RNA was performed for all participants. Demographic and risk factor data were collected by investigators using medical charts and patient questionnaires. All data were stored in an anonymized online database during the study. RESULTS: The prevalence of HBV was 3.8%; among these patients, the prevalence of HBV/HDV coinfection was 33.1%. The median age of the study population was 54.0 years, and it consisted of 55.1% men. A higher prevalence of HBV/HDV coinfection was observed in patients 50-69 years old. Patients with HBV/HDV coinfection were significantly older than those with HBV monoinfection (P = 0.03). Multivariate multiple regression analysis identified female gender (P = 0.0006), imprisonment (P < 0.0001), older age at diagnosis (P = 0.01) and sexual contact with persons with known viral hepatitis (P = 0.0003) as significant risk factors for HDV. CONCLUSION: This study shows that HDV infection among those with HBV remains endemic in Romania and updates our understanding of HDV epidemiology and associated risk factors. It emphasizes the need for systematic screening for HDV infection and collaborative initiatives for controlling and preventing HBV and HDV infection.

Bridging the gap: Unveiling the crisis of physical inactivity in inflammatory bowel diseases.

In this editorial we comment on the article titled "Inflammatory bowel diseases patients suffer from significant low levels and barriers to physical activity: The BE-FIT-IBD study" published in a recent issue of the World Journal of Gastroenterology 2023; 29 (41): 5668-5682. Inflammatory bowel diseases (IBD) are emerging as a significant global health concern as their incidence continues to rise on a global scale, with detrimental impacts on quality of life. While many advances have been made regarding the management of the disease, physical inactivity in these patients represents an underexplored issue that may hold the key for further and better understanding the ramifications of IBD. Chronic pain, fatigue, and fear of exacerbating symptoms promotes physical inactivity among IBD patients, while the lack of clear guidelines on safe exercise regimens contributes to a norm of physical inactivity. Physical activity (PA) is accepted to have a positive effect on disease outcomes and quality of life, while inactivity exacerbates comorbidities like cardiovascular disease and mental health disorders. The "BE-FIT-IBD" study, focusing on PA levels and barriers in IBD patients of Southern Italy, revealed that a significant proportion (42.9%) were physically inactive. This lack of PA is attributed to barriers such as fear of flare-ups and misconceptions about exercise exacerbating the disease. The study also highlighted the need for better communication between healthcare providers and patients regarding the benefits of PA and safe incorporation into lifestyles. Moreover, physical inactivity may also contribute to disability in IBD patients, having a great impact on employment status. Of note is the fact that IBD also comes with an important psychological burden with relevant evidence suggesting that regular PA can improve mood, reduce anxiety, and enhance mental health. The "BE-FIT-IBD" study advocated for the integration of PA into IBD management, emphasizing the bidirectional link between PA and IBD. Regular exercise can influence the course of IBD, potentially reducing symptom severity and prolonging remission periods. As such, it is mandatory that healthcare providers actively educate patients, dispel misconceptions, and tailor exercise recommendations to improve the quality of life and reduce IBD-related complications.

The Rate of Burnout Syndrome in A Tertiary Gastroenterology University Center in Romania.

BACKGROUND AND AIMS: The burnout syndrome (BOS) is commonly seen in healthcare professionals, particularly in physicians who are exposed to a high level of stress at work and has a negative impact on the medical activity. Physicians with BOS manifest a negative attitude, a reduction in compassion at work, and suboptimal patient care experiences. These all can lead to absenteeism, poor performance and more frequent medical errors. We aimed to assess the level of BOS in a tertiary gastroenterology university center in Romania. METHODS: This observational study involved 40 physicians from a tertiary gastroenterology university center. An online questionnaire assessed the presence of BOS using the Maslach Burnout Inventory. RESULTS: A total of 40 physicians responded to the questionnaire. The prevalence of overall BOS of 87.5%. In terms of high burnout, 15 doctors (37.5%) had emotional exhaustion, 10 doctors (25%) had depersonalization, and 30 doctors (80%) scored low for personal achievement. Men presented more frequently emotional exhaustion and women lower personal achievement scores, but there was no significant statistical difference. No significant relationship was found between marital status or the number of children and BOS. We identified multiple risk factors associated to BOS, the most important one being strict internal regulations. CONCLUSIONS: Physicians presented an increased risk for BOS. The high rate of BOS among physicians found in our study requires careful attention. Further studies aiming to identify other factors that contribute to BOS and to identify measures to combat this syndrome are necessary.

Real-World Utilization of Corticosteroids in Severe Alcoholic Hepatitis: Eligibility, Response, and Outcomes.

Background and Objectives: Alcoholic hepatitis (AH) poses a medical challenge, causing moderately severe to life-threatening episodes with high short- and long-term mortality. This study aimed to explore real-world corticosteroid utilization in severe AH, response predictors, and patient outcomes. Materials and Methods: We conducted a retrospective study on patients admitted for severe AH, defined as a Maddrey Discriminant Function score equal to or above 32, at a tertiary care center. We reviewed patients' medical observation charts to identify corticosteroid prescriptions, reasons for ineligibility, and response rates. Responders were defined based on the Lille score, and predictors of non-response were identified. Short-term (one-month) and long-term (one-year) mortality rates were calculated according to treatment and response. Results: Out of 310 patients enrolled with severe AH, 59% received corticosteroids, achieving a response rate of 75.4%. The reasons for not administering corticosteroids were as follows: uncontrolled infections (27.6%), renal dysfunction (20.4%), gastrointestinal bleeding (18.9%), acute pancreatitis (7.1%), uncontrolled diabetes (3.1%), and other or unknown causes (22.8%). The overall 1-month mortality rate was 12.2%, higher in non-responders (35.3%) and patients who did not receive corticosteroids (13.4%) compared to responders (3.6%). The overall 1-year mortality rate was 62.5%, similar between patients who did not receive corticosteroids (78.7%) and non-responders (77.7%) and higher compared to responders (42.8%). Predictive factors for non-response included older age (OR = 1.05, 95%CI: 1.01-1.08), concomitant cirrhosis (OR= 2.11, 95% CI: 1.064-4.20), MELD scores exceeding 30 (OR = 2.42, 95% CI: 1.21-4.80), severe hypoalbuminemia (OR = 2.46, 95%CI: 1.12-5.37), and increased serum creatinine (OR = 1.5, 95% CI: 1.1-2.03). Among the prognostic scores, MELD 3.0 score exhibited superior efficacy for short-term (AUC = 0.734, 95% CI 0.656-0.811) and long-term mortality (AUC = 0.777, 95% CI: 0.724-0.830) compared to alternative scoring systems. Conclusions: Low eligibility rate and poor prognosis underscore the need for effective therapies. Our findings contribute to refining risk stratification and early prediction of non-response, aiding clinicians in identifying more beneficial therapies.

Small Bowel Capsule Endoscopy and Enteroscopy: A Shoulder-to-Shoulder Race.

Traditional methods have their limitations when it comes to unraveling the mysteries of the small bowel, an area historically seen as the "black box" of the gastrointestinal tract. This is where capsule endoscopy and enteroscopy have stepped in, offering a remarkable synergy that transcends the sum of their individual capabilities. From their introduction, small bowel capsule endoscopy and device-assisted enteroscopy have consistently evolved and improved, both on their own and interdependently. Each technique's history may be told as a success story, and their interaction has revolutionized the approach to the small bowel. Both have advantages that could be ideally combined into a perfect technique: safe, non-invasive, and capable of examining the entire small bowel, taking biopsies, and applying therapeutical interventions. Until the realization of this perfect tool becomes a reality, the key for an optimal approach lies in the right selection of exploration method. In this article, we embark on a journey through the intertwined development of capsule endoscopy and enteroscopy, exploring the origins, technological advancements, clinical applications, and evolving inquiries that have continually reshaped the landscape of small bowel imaging.

The Impact of Alcohol Consumption Pattern on Liver Fibrosis in Asymptomatic Patients.

INTRODUCTION: Alcohol consumption (AC) represents a widespread cause of liver diseases affecting 10-20% of the population. The study aimed to evaluate the relationship between advanced liver fibrosis (ALF) measured by transient elastography (TE), laboratory parameters, and the amount of AC depending on non-modifiable risk factors such as age and gender. METHODS: We examined 689 patients with an average age of 49.32 ± 14.31 years, 72.9% males, without liver pathology, who admitted a moderate/high consumption (female ≤ 7 versus > 7 drinks/week; male ≤ 14 versus > 14 drinks/week) for at least five years. The fibrosis level was adjusted according to transaminase levels. Predictive factors were established using univariate regression analysis. RESULTS: ALF (≥F3) was detected in 19.30% of subjects, predominantly males (14.1%) and patients over 55 years (12.5%). Excessive consumption of distilled spirits is associated with ALF in females (OR = 4.5), males (OR = 6.43) and patients over 55 years (OR = 3.73). A particularity highlighted in both genders, regardless of the age group, was the negative correlation between the decrease in the number of platelets, the albumin concentration, and the appearance of AFL. CONCLUSIONS: Screening using TE represents an approach for early detection of ALF in asymptomatic populations and the development of a risk stratification scheme.

Reclassification of Inflammatory Bowel Disease Type Unclassified by Small Bowel Capsule Endoscopy.

Background and Objectives: Ulcerative colitis (UC) and Crohn's disease (CD) are idiopathic inflammatory bowel diseases (IBDs) without a unique, gold standard diagnostic test. UC and Crohn's colitis are impossible to distinguish in approximately 10% of cases. The term IBD type unclassified (IBD-U) is recommended for cases of chronic colitis showing overlapping endoscopic, radiological, and biopsy histological features between UC and CD, while indetermined colitis is reserved for colectomy specimens. Our aim was to assess the role of small-bowel capsule endoscopy (SBCE) in the diagnostic work-up of IBD-U. Materials and Methods: We retrospectively studied the cases of IBD-U explored by SBCE in a tertiary referral gastroenterology center. Patients were investigated using SBCE after contraindications were excluded. Diagnostic criteria for small bowel CD consisted in more than three ulcerations, irregular ulcers, or stenosis, and the Lewis score was used for the quantification of inflammation. The immediate impact of reclassification and outcome data was recorded over a follow-up period of more than one year. Results: Twenty-eight patients with IBD-U were examined using SBCE. Nine patients had small bowel lesions that met the diagnostic criteria for CD, resulting in a reclassification rate of 32.1%. In five of these cases, the treatment was subsequently changed. In the remaining nineteen examinations, no significant findings were observed. There were no complications associated with SBCE. Median follow-up time was 32.5 months (range 12-60). During follow-up, twelve patients were classified as having UC, and seven remained as having an unclassified type; one case of colectomy, for medically refractory UC, was recorded. Conclusions: SBCE is a useful safe tool in the work-up of IBD-U, allowing reclassification in about one third of cases, with subsequent treatment modifications. SBCE may provide a definite diagnosis, enhance the comprehension of the disease's progression, and optimize the short- and long-term management strategy.

A Comprehensive Overview of the Past, Current, and Future Randomized Controlled Trials in Hepatic Encephalopathy.

Background: Hepatic encephalopathy (HE) caused by cirrhosis has severe consequences on an individual's lifespan, leading to long-term liver complications and potentially life-threatening outcomes. Despite recent interest in this condition, the effectiveness of secondary prophylaxis involving rixafimin, lactulose, or L-ornithine L-aspartate (LOLA) may be hindered by the unique microbial profiles each patient possesses. Methods: Thus, in this manuscript, we aimed to search, identify, and gather all randomized controlled trials (RCTs) published between 2000-2023 (November) in four major academic databases such as PubMed, ISI Web of Science, Scopus, and ScienceDirect by using a controlled terminology and web strings that reunite six main keywords. We complementarily retrieved data on the ongoing RCTs. Results: Regardless of the relatively high number of results displayed (n = 75), 46.66% (n = 35) were initially deemed eligible after the first evaluation phase after removing duplicates, n = 40 (53.34%). At the second assessment stage, we eliminated 11.42% (n = 4) studies, of which n = 22 finally met the eligibility criteria to be included in the main body of the manuscript. In terms of RCTs, otherwise found in distinct stages of development, n = 3 target FMT and n = 1 probiotics. Conclusions: Although we benefit from the necessary information and technology to design novel strategies for microbiota, only probiotics and synbiotics have been extensively studied in the last decade compared to FMT.

Eosinophilic enteritis: the great mimic.

Eosinophilic enteritis (EoN), a subtype of eosinophilic gastrointestinal disease, is a rare and complicated inflammatory condition affecting the small intestine. This case report discusses a 42-year-old patient who presented with acute gastrointestinal symptoms including diarrhea, nausea, and vomiting. Initial laboratory investigations revealed leukocytosis, peripheral eosinophilia, and distinctive imaging findings, prompting further evaluation. Endoscopic evaluation revealed extensive mucosal lesions in the small intestine, with subsequent biopsies confirming eosinophilic infiltration, ultimately leading to the diagnosis of chronic enteritis, probably of an eosinophilic nature. The case highlights the complex differential diagnostic process involved in identifying EoN, which requires a comprehensive understanding of all the clinical and histopathological features of the disease. The efficacy of budesonide therapy is also discussed in the management of EoN and it was evidenced by our patient's positive response to treatment. This case report contributes significant insights into the understanding and management of EoN, providing essential information for the medical community to facilitate accurate diagnosis and tailored therapeutic interventions for individuals experiencing this complex disorder.

Safety, Efficacy and Persistence of Advanced Therapies in Inflammatory Bowel Disease: Results from ORIGINS. A Retrospective Observational Study.

BACKGROUND AND AIMS: Real-world assessments of efficacy and safety of advanced therapies used for inflammatory bowel disease (IBD) patients are limited. We aimed to report safety, efficacy and treatment persistence of new molecules (infliximab, adalimumab, vedolizumab, tofacitinib, ustekinumab) in a retrospective multicentric national Romanian analysis. METHODS: We conducted a nationwide, retrospective observational multicentric study. Data were collected retrospectively from electronic and paper files. Patients who started on one of the five investigated molecules during December 2019-December 2021 were included. The main outcome measures were clinical remission, endoscopic healing, persistence on treatment and safety data. RESULTS: A total of 678 adult patients from 24 Romanian IBD centers with a diagnosis of ulcerative colitis or Crohn's disease were included. Participants had previously failure to one (268, 39.5%), two (108, 15%) or more treatment lines and only 38% (259) were biologic naïve. In the 24 months study period, most patients were started on vedolizumab (192, 28%), followed by adalimumab, infliximab, ustekinumab and tofacitinib. In biologic-naïve patients, most physicians (72%) preferred anti-TNF treatment as first line biologic (93 patients started on infliximab, 92 on adalimumab), followed by vedolizumab, ustekinumab and tofacitinib. During follow-up, 71% (470, p=0.05) of patients achieved clinical remission and 36% (134, p=0.03) achieved mucosal healing. The 6 months milestone for persistence was reached in 78% (530) of cases. Almost half of patients (47%, 316 patients) persisted on their current treatment for over 12 months. Overall, an adverse reaction was reported for 67 (10.4%) patients, with no lethal events. CONCLUSIONS: Population of biologic-experienced IBD patients in Romania is increasing and is becoming more difficult to achieve long-term disease control. Discontinuation rates for advanced therapies are high.

Coagulation Dysfunctions in Non-Alcoholic Fatty Liver Disease-Oxidative Stress and Inflammation Relevance.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases. Its incidence is progressively rising and it is possibly becoming a worldwide epidemic. NAFLD encompasses a spectrum of diseases accounting for the chronic accumulation of fat within the hepatocytes due to various causes, excluding excessive alcohol consumption. In this study, we aimed to focus on finding evidence regarding the implications of oxidative stress and inflammatory processes that form the multifaceted pathophysiological tableau in relation to thrombotic events that co-occur in NAFLD and associated chronic liver diseases. Recent evidence on the pathophysiology of NAFLD suggests that a complex pattern of multidirectional components, such as prooxidative, proinflammatory, and prothrombotic components, better explains the multiple factors that promote the mechanisms underlying the fatty acid excess and subsequent processes. As there is extensive evidence on the multi-component nature of NAFLD pathophysiology, further studies could address the complex interactions that underlie the development and progression of the disease. Therefore, this study aimed to describe possible pathophysiological mechanisms connecting the molecular impairments with the various clinical manifestations, focusing especially on the interactions among oxidative stress, inflammation, and coagulation dysfunctions. Thus, we described the possible bidirectional modulation among coagulation homeostasis, oxidative stress, and inflammation that occurs in the various stages of NAFLD.

Is There a Time and a Place for the Gluten-Free Diet in Potential Celiac Disease?

Potential celiac disease (PCD) is characterized by the absence of villous atrophy on duodenal biopsies (Marsh 0 or 1) despite positive celiac serology and HLA DQ2 or DQ8 heterodimers. Recent epidemiological studies report that PCD represents one fifth of the total CD diagnoses. Compared to patients with CD, the majority of adult patients with PCD show lower rates of nutrient deficiencies and extraintestinal symptoms at diagnosis. Recommending a gluten-free diet (GFD) to PCD patients depends on whether they have symptoms or not. A significant clinical improvement is reported by symptomatic patients, but for asymptomatic PCD, diet implementation is still a matter of debate. Some questions remain to be answered: does PCD serve as an intermediary phase leading to the progression of true CD? Is it reasonable to hypothesize that PCD and active CD represent different manifestations of the same condition? Is there a potential for both underdiagnosis and overdiagnosis of CD in those who may have the condition? Additional research is required to address these inquiries and ascertain the specific subset of people with potential progression to overt CD, as well as to determine the potential advantages of early implementation of a GFD for these individuals. The investigation of risk factors in CD warrants examination of variables such as the timing of diagnosis, the genetic profile, the extent of gluten exposure, and the composition of the microbiome.

Predictors of slow responsiveness and partial mucosal recovery in adult patients with celiac disease.

Aim: The present study aims to determine the rate of mucosal recovery and predictors of persistent mucosal damage after gluten free diet (GFD). Background: Celiac disease (CD) is a complex multi-systemic autoimmune disease triggered by exposure to dietary gluten in genetically predisposed individuals. There is still little evidence on the best method for assessing GFD adherence and mucosal recovery during treatment. Methods: The retrospective study included only adult patients (age≥18 years old), with biopsy-proven CD evaluated at a tertiary referral centre between 2016 and 2021. We performed a logistic regression analysis to identify factors associated with partial mucosal recovery (MR) after GFD. We included in the multivariate analysis parameters available at the time of CD diagnosis. Results: A total of 102 patients were enrolled, two thirds were females, median age of 39 years (yrs). The initial biopsy analysis showed different stages of villous atrophy (VA) in 79 (77.4%) cases, while in 23(22.5%) cases showed mild enteropathy (Marsh 1, 2). After at least 12 months of GFD, 26 (25.5%) patients had persistent VA despite good or excellent adherence to GFD. Younger patients (< 35yrs), who showed severe mucosal damage (Marsh 3c lesions) and who had increased anti-gliadin antibody (AGA) levels were at risk for failure to obtain mucosal recovery (MR). Logistic regression analysis demonstrated that complete mucosal atrophy (P=0.007) and high AGA antibody levels (cutoff 129 U/ml, P=0.001) were independent risk factors for lack of mucosal improvement after at least 12 months of GFD. Interestingly, genotype, tTG-IgA antibody levels, or duration of GFD levels did not influence the occurrence of MR. Conclusion: Although AGA seropositivity has lost much of their diagnostic significance in recent years due to the introduction of the more sensitive and specific antibody tests, our study reported that patients aged < 35 yrs, who showed severe mucosal damage (Marsh 3c lesions) and who had increased AGA antibody levels at diagnosis were at risk for failure to obtain MR. The elevated AGA levels at diagnosis could be used as a prognostic tool for assessing MR.