Iulia Cristina Marginean

Background: Increased intestinal permeability is a proposed pathophysiological mechanism in irritable bowel syndrome (IBS), and zonulin, a putative regulator of tight junctions, has been investigated as a non-invasive serum biomarker. However, the diagnostic utility of circulating zonulin in IBS remains controversial. Objectives: To systematically review studies comparing serum or plasma zonulin concentrations between adult IBS patients and healthy controls, and to evaluate the influence of assay methodology on reported outcomes. Methods: A systematic literature search of PubMed was performed up to April 2026; the most recent eligible study was published in June 2024. Studies that enrolled adults with IBS diagnosed by Rome criteria, included healthy control groups, and measured zonulin by enzyme-linked immunosorbent assay (ELISA) were eligible. Studies lacking a healthy control group, non-original reports, animal studies, and mixed functional gastrointestinal disorder cohorts without extractable IBS data were excluded. Findings were synthesised narratively due to substantial methodological heterogeneity and concerns regarding the validity of commercially available zonulin kits. Risk of bias was assessed using the Newcastle–Ottawa Scale for case–control studies; six studies were at low risk and two at intermediate risk. The review is reported in accordance with the PRISMA 2020 statement, and this abstract follows the PRISMA 2020 for Abstracts checklist. Results: Eight case–control studies were included, comprising 421 IBS patients and 428 controls. Of the seven studies contributing to the primary synthesis, two reported significantly elevated zonulin in IBS, one produced opposite results with two different assays applied to the same samples, and four found no significant difference compared with controls. An eighth study, which combined IBS with inflammatory bowel disease and did not report IBS-specific data, was retained as supportive, non-primary evidence. Crucially, the studies employed different ELISA kits (ALPCO, Cusabio, Immundiagnostik, Zellbio) and different units of measurement. Independent validation studies have demonstrated that the most frequently used commercial kits do not recognise the pre-haptoglobin-2 molecule claimed to be zonulin, but instead detect haptoglobin, complement C3, or properdin. The only study employing a monoclonal antibody specific for pre-haptoglobin-2 observed lower, rather than higher, concentrations in IBS. Conclusions: The existing literature based on commercial ELISAs cannot determine whether pre-HP2/zonulin is altered in IBS, and the single genotype-controlled monoclonal assay suggests lower, not higher, concentrations in IBS. The disparate results are largely attributable to the application of ELISA kits that lack analytical specificity for the proposed target. Future research must use analytically validated assays, such as monoclonal antibody-based methods with concomitant genotyping for haptoglobin polymorphisms, before zonulin can be considered a meaningful biomarker in IBS. Funding: The Article Processing Charges were funded by the University of Medicine and Pharmacy of Craiova, Romania. Registration: The review was not prospectively registered; a retrospective protocol registration is available on OSF [10.17605/OSF.IO/MFA6J].

Irritable bowel syndrome (IBS) and metabolic dysfunction-associated steatotic liver disease (MASLD) are two of the most common gastroenterological conditions worldwide. Traditionally viewed as unrelated, with one serving a canonical functional role and the other a purely metabolic function, these two processes have recently been linked by compelling evidence, challenging their traditional segregation and pointing to a significant, biologically relevant association. This review aims to evaluate the current evidence for a potential causal contribution of IBS to hepatic steatosis, critically examining the proposed pathophysiological mechanisms via the gut–liver axis while acknowledging that the available data are primarily observational. Notably, epidemiological studies demonstrate a 1.4–2.0-fold increased association between IBS and MASLD, independent of obesity and metabolic syndrome, though causality remains to be established. The primary mechanism is increased intestinal permeability (“leaky gut”) leading to endotoxemia, activation of hepatic toll-like receptor 4 (TLR4) receptors, and subsequent de novo lipogenesis. The relationship is bidirectional, with steatosis also worsening gut barrier function. Therefore, we highlight emerging evidence suggesting that irritable bowel syndrome, particularly the diarrhea-predominant subtype (IBS-D), may contribute to hepatic steatosis through plausible biological mechanisms, though direct causal evidence in humans remains limited. Accordingly, routine screening for metabolic dysfunction-associated steatotic liver disease (MASLD) may be warranted in patients with long-standing IBS-D.

A significant clinical challenge is represented by the use of anticoagulants in patients with chronic liver diseases—such as metabolic steatohepatitis (MASH), metabolic associated steatotic liver disease (MASLD), and liver cirrhosis (LC). There is a well-established association between alcohol-related LC and atrial fibrillation (AF). These individuals often require anticoagulation, but treatment must carefully balance the heightened risks of both thrombosis and bleeding. Direct oral anticoagulants (DOACs) are recognized as effective and safe alternatives to warfarin, offering superior stroke prevention and a more favorable safety profile regarding major bleeding. They are generally considered safe for use in patients with LC classified as Child–Pugh A and B—excluding rivaroxaban—but are contraindicated in those with Child–Pugh C cirrhosis. DOACs also offer practical advantages, including convenience of administration, fewer drug interactions, and a high level of safety and efficacy. Comprehensive randomized controlled trials with well-defined cirrhosis stages and standardized anticoagulation protocols are essential to guide clinical decision-making. Until then, a multidisciplinary, individualized approach remains critical in managing patients with both AF and LC. The present review aims to explore the complex interplay between alcohol-related LC and the therapeutic use of direct oral anticoagulants (DOACs), particularly in the presence of cardiovascular risk factors such as atrial fibrillation, and the associated thrombotic complications.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is an escalating global health burden and a leading cause of chronic liver disease. Without intervention, MASLD can progress to steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Although lifestyle modification is the cornerstone of management, specific dietary patterns are a primary driver of its development. The progression of MASLD is closely linked to micronutrient status, as these nutrients are critical for key biological functions such as antioxidant defense and immune regulation. Micronutrient deficiencies—particularly in essential vitamins and minerals—have been widely studied as independent contributors to MASLD pathogenesis. Similarly, the role of the gut microbiota in disease development has gained attention. However, the interplay between micronutrient deficiencies and gut dysbiosis is often underestimated. Emerging evidence suggests that micronutrient depletion not only directly exacerbates MASLD but also alters gut microbial composition, perpetuating a cycle of metabolic and hepatic dysfunction. This review aims to highlight the bidirectional relationship between micronutrient deficiency and gut microbiome imbalance in MASLD. It explores how dysbiosis impairs the bioavailability of micronutrients, thereby reinforcing a vicious cycle of disease progression. Therefore, effective MASLD management should address both nutritional deficiencies and microbial imbalances. Interventions such as prebiotic and probiotic supplementation may help restore microbial equilibrium and improve micronutrient absorption. Looking forward, personalized therapeutic strategies that combine targeted microbiota modulation with micronutrient repletion may offer promising approaches to curb the rising global burden of MASLD.

Non-alcoholic fatty liver disease (NAFLD) is the main cause of chronic liver disease globally. NAFLD is a complex pathology, considered to be the hepatic expression of metabolic syndrome (MetS). It is supposed to become the main indication for liver transplantation in the coming years and is estimated to affect 57.5–74.0% of obese people, 22.5% of children and 52.8% of obese children, with 50% of individuals with type 2 diabetes being diagnosed with NAFLD. Recent research has proved that an increase in adipose tissue insulin resistance index is an important marker of liver injury in patients with NAFLD. Despite being the main underlying cause of incidental liver damage and a growing worldwide health problem, NAFLD is mostly under-appreciated. Currently, NAFLD is considered a multifactorial disease, with various factors contributing to its pathogenesis, associated with insulin resistance and diabetes mellitus, but also with cardiovascular, kidney and endocrine disorders (polycystic ovary syndrome, hypothyroidism, growth hormone deficiency). Hepatitis B and hepatitis C, sleep apnea, inflammatory bowel diseases, cystic fibrosis, viral infections, autoimmune liver diseases and malnutrition are some other conditions in which NAFLD can be found. The aim of this review is to emphasize that, from the clinician’s perspective, NAFLD is an actual and valuable key diagnosis factor for multiple conditions; thus, efforts need to be made in order to increase recognition of the disease and its consequences. Although there is no global consensus, physicians should consider screening people who are at risk of NAFLD. A large dissemination of current concepts on NAFLD and an extensive collaboration between physicians, such as gastroenterologists, internists, cardiologists, diabetologists, nutritionists and endocrinologists, is equally needed to ensure we have the knowledge and resources to address this public health challenge.

Vascular cognitive impairments are the expression of complex interactions between vascular etiology, risk factors (brain diseases, white matter lesions, etc.) and cellular changes at the brain level. Consequently, vascular cognitive impairment is highly dependent on the location, extent (volume of brain tissue affected) and number of lesions. Memory impairment is not necessarily characteristic of vascular cognitive decline, usually having an evolution with episodic exacerbations and multiple cerebrovascular attacks (cumulative effect), thus producing a gradual deterioration. In recent years, the concept of mild cognitive impairment has emerged as a potential form of predementia, but which can progress to different types of dementia, including Alzheimer's disease or vascular dementia. This review presents recent data related to the etiological and risk factors of cognitive decline after stroke, the associated neuropsychological and behavioral changes, the clinical forms/diagnosis and general principles of vascular dementia therapy. As preliminary conclusions, the Hachinski score is a very useful tool in differentiating vascular dementia from Alzheimer's dementia. A score greater than 7 points (especially when associated with imaging and anamnestic criteria) suggests a vascular etiology of dementia, whereas a score of 4 points or less excludes such an etiology. Although it is not the only factor involved, vascular etiology is still intensively studied because it is the only one that can be prevented and treated.

Irritable bowel syndrome (IBS) is a common digestive disorder with a significant impact on both individuals and society in terms of quality of life and healthcare costs. A growing body of research has identified various communication pathways between the microbiota and the brain in relation to motility disorders, with the gut–brain axis being key to the pathogenesis of IBS. Multiple factors contribute to the pathogenetic pathways in IBS, including immune mechanisms, psychosocial factors, increased oxidative stress and pro-inflammatory cytokine release, as well as genetic and hormonal factors. Increased permeability of the normal intestinal barrier allows bacterial products to access the lamina propria, providing a mechanism for perpetuating chronic inflammation and characteristic symptoms. The microbiota influences inflammatory processes in IBS by altering the balance between pro-inflammatory factors and host defence. Probiotics modulate the pathophysiological mechanisms involved in IBS by influencing the composition of the microbiota and improving intestinal motility disorders, visceral hypersensitivity, immune function of the intestinal epithelium, metabolic processes in the intestinal lumen, dysfunction of the microbiota-GBA, and are recognised as effective and safe in IBS therapy. Our study aimed to provide a comprehensive overview of the relationship between the gut–brain axis, microbiota, and IBS, based on current information.

Hematological abnormalities are frequently linked to chronic liver disease of any etiology. About 75% of patients with advanced chronic liver disease experience anemia. The causes of anemia are complex and multifactorial, particularly in cirrhotic patients. Acute and long-term blood loss from the upper gastrointestinal tract, malnutrition, an enlarged spleen brought on by portal hypertension, hemolysis, and coagulation issues are the main causes of anemia. Alcohol, a common cause of chronic liver disease, determines anemia through direct toxicity on the bone marrow, with the suppression of hematopoiesis, through vitamin B6, B12, and folate deficiency due to low intake and malabsorption. In patients with chronic hepatitis C virus infection, antiviral drugs such as pegylated interferon and ribavirin can also cause significant anemia. The use of interferon has been linked to bone marrow toxicity, and hemolytic anemia brought on by ribavirin is a well-known dose-dependent side effect. Within six months of the infection with hepatitis B, hepatitis C, and Epstein–Barr viruses, aplastic anemia associated with hepatitis is seen. This anemia is characterized by pancytopenia brought on by hypocellular bone marrow. Esophageal varices, portal hypertensive gastropathy, and gastric antral vascular ectasia can all cause acute and chronic blood loss. These conditions can progress to iron deficiency anemia, microcytic anemia, and hypochromic anemia. Another common hematologic abnormality in liver cirrhosis is macrocytosis, with multifactorial causes. Vitamin B12 and folate deficiency are frequent in liver cirrhosis, especially of alcoholic etiology, due to increased intestinal permeability, dysbiosis, and malnutrition. Many chronic liver diseases, like viral and autoimmune hepatitis, have a chronic inflammatory substrate. Proinflammatory cytokines, including tumor necrosis factor and interleukin 1, 6, and 10, are the main factors that diminish iron availability in progenitor erythrocytes and subsequent erythropoiesis, leading to the development of chronic inflammatory, normochromic, normocytic anemia.

Acute-on-chronic liver failure (ACLF) is a syndrome characterized by acute and severe decompensation of chronic liver disease (CLD) correlated with multiple organ failure, poor prognosis, and increased mortality. In 40–50% of ACLF cases, the trigger is not recognized; for many of these patients, bacterial translocation associated with systemic inflammation is thought to be the determining factor; in the other 50% of patients, sepsis, alcohol consumption, and reactivation of chronic viral hepatitis are the most frequently described trigger factors. Other conditions considered precipitating factors are less common, including acute alcoholic hepatitis, major surgery, TIPS insertion, or inadequate paracentesis without albumin substitution. Host response is likely the primary factor predicting ACLF severity and prognosis, the host immune response having a particular significance in this syndrome, together with the inflammatory cascade. The management of ACLF includes both the prevention of the precipitating factors that lead to acute liver decompensation and the support of vital functions, the prevention and management of complications, the estimation of prognosis, and the opportunity for liver transplantation.

Background: The association of chronic heart failure (CHF) and iron deficiency (ID) with or without anemia is frequently encountered in current medical practice and has a negative prognostic impact, worsening patients’ exercise capacity and increasing hospitalization costs. Moreover, anemia is common in patients with chronic kidney disease (CKD) and CHF, an association known as cardio-renal anemia syndrome (CRAS) possessing a significantly increased risk of death. Aim: This review aims to provide an illustrative survey on the impact of ID in CHF patients—based on physiopathological traits, clinical features, and the correlation between functional and absolute ID with CHF—and the benefit of iron supplementation in CHF. Method: We selected the most recent publications with important scientific content covering the association of CHF and ID with or without anemia. Discussions: An intricate physiopathological interplay is described in these patients—decrease in erythropoietin levels, activation of the renin-angiotensin-aldosterone system, systemic inflammation, and increases in hepcidin levels. These mechanisms amplify anemia, CHF, and CKD severity and worsen patients’ outcomes. Conclusions: Anemia is frequently encountered in CHF and represents a negative prognostic factor. Data from randomized controlled trials have underlined the administration of intravenous iron therapy (ferric carboxymaltose) as the only viable treatment option, with beneficial effects on quality of life and exercise capacity in patients with ID and systolic heart failure.