Pediatric endocarditis - a stone left after the pandemic cascade.

Infective endocarditis is a rare disease in children. The etiology is mainly bacterial. However, viral infective endocarditis, possibly related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has also been reported. The pathophysiological principle of the connection between the two entities seems to be attributed to the transient immune deficiency of the body during the infection. Additionally, SARS-CoV-2 is reported in the literature as a direct cardiopathic virus. Therefore, the new coronavirus seems to have the ability to affect both the intact cardiac tissue and the previously damaged one both during the acute episode and at a distance from it. Consequently, we propose to review the main pathophysiological aspects of pediatric cardiac damage caused by SARS-CoV-2. The ultimate goal is to deepen existing knowledge, broaden the horizon of understanding and analysis regarding the systemic damage induced by viral infections, and strengthen an information base from which to start a meta-analysis. Next, we performed a non-systematized screening of the specialized literature with reference to cases of endocarditis in the pediatric population, reported in the period 2020-2023. From the total of articles found, we chose to include in the review a number of 6 case reports, including a number of 7 patients (5 children and 2 adolescents). Analysis of reports suggests that SARS-CoV-2 infection could play a role in the development of endocarditis, either directly through active infection or indirectly through a post-infectious immune response. Also, pre-existing conditions and complex medical history predispose to an increased risk of developing a severe, complicated form of endocarditis. Also, the lack of data on the vaccination history and the failure to categorize the infection depending on the type of antibodies (IgM or IgG) in some studies represent a major bias in the reports. The latter make it difficult to evaluate the influence of vaccination and the impact of acute versus chronic infection on the course of cases.

The Etiology of the Thrombotic Phenomena Involved in the Process of Coronary Artery Disease-What Is the Role of Thrombophilic Genes in the Development of This Pathology?

Cardiovascular diseases, among which includes coronary artery disease, represent one of the most important causes of mortality and morbidity worldwide. Research aimed at determining the risk factors involved recognizes a group of "traditional" risk factors, but also more recent studies identified over 100 "novel" ones which may have a role in the disease. Among the latter is the thrombophilia profile of a patient, a pathology well-established for its involvement in venous thromboembolism, but with less studied implications in arterial thrombosis. This paper reviews the literature, explaining the pathophysiology of the thrombophilia causes associated most with coronary thrombosis events. Results of several studies on the subject, including a meta-analysis with over 60,000 subjects, determined the significant involvement of factor V Leiden, prothrombin G20210A mutation, plasminogen activator inhibitor-1 and antiphospholipid syndrome in the development of coronary artery disease. The mechanisms involved are currently at different stages of research, with some already established and used as therapeutic targets.

Characteristics of Tuberculous Meningitis in HIV-Positive Patients from Northeast Romania.

BACKGROUND AND OBJECTIVES: One of the most severe forms of extrapulmonary tuberculosis (EPTB) is tuberculous meningitis (TBM), which is linked to significant morbidity and high mortality. It is well recognized that human immunodeficiency virus (HIV)-positive people are more likely to develop EPTB, including TBM, especially if they have severe immunodeficiencies. We aim to highlight the profile and the characteristics of TBM in HIV-infected patients. MATERIAL AND METHODS: We conducted a retrospective clinical study based on hospital medical records of patients diagnosed with HIV/AIDS (acquired immunodeficiency syndrome) and TBM in Northeast Romania, hospitalized at "St. Parascheva" Clinical Hospital of Infectious Diseases of Iasi from 1 January 2010 to 1 December 2022. RESULTS: From a total number of 1692 patients on record in our center, 195 had a HIV-tuberculosis (TB) coinfection, and 19 cases were HIV-TBM coinfected. Six cases were newly HIV-diagnosed late presenters, and thirteen patients' names were already found in the center's records with deficient immunological viral status (median CD4 lymphocyte level 47/mm3). The average age in the study group was 27 years old. The clinical manifestations and cerebrospinal fluid (CSF) variables were typical in most cases, despite the severe immunodepression of the patients. The Thwaites scoring system correctly identified 89.5% of the patients. The median admission period was 18 days; the lethality rate was 31.6%, despite access to ART and anti-TB drugs, and was associated with a more severe immunosuppression. No rifampicin resistance was detected. CONCLUSIONS: TBM appeared in a minority of our HIV cohort and affected severely immunodepressed patients; the clinical and CSF variables had a typical aspect in most cases, and the Thwaites scoring system performed well for this type of patient. The lethality rate was high and was correlated with a more severe immunodepression.

360-Degree Perspectives on Obesity.

Alarming statistics show that the number of people affected by excessive weight has surpassed 2 billion, representing approximately 30% of the world's population. The aim of this review is to provide a comprehensive overview of one of the most serious public health problems, considering that obesity requires an integrative approach that takes into account its complex etiology, including genetic, environmental, and lifestyle factors. Only an understanding of the connections between the many contributors to obesity and the synergy between treatment interventions can ensure satisfactory outcomes in reducing obesity. Mechanisms such as oxidative stress, chronic inflammation, and dysbiosis play a crucial role in the pathogenesis of obesity and its associated complications. Compounding factors such as the deleterious effects of stress, the novel challenge posed by the obesogenic digital (food) environment, and the stigma associated with obesity should not be overlooked. Preclinical research in animal models has been instrumental in elucidating these mechanisms, and translation into clinical practice has provided promising therapeutic options, including epigenetic approaches, pharmacotherapy, and bariatric surgery. However, more studies are necessary to discover new compounds that target key metabolic pathways, innovative ways to deliver the drugs, the optimal combinations of lifestyle interventions with allopathic treatments, and, last but not least, emerging biological markers for effective monitoring. With each passing day, the obesity crisis tightens its grip, threatening not only individual lives but also burdening healthcare systems and societies at large. It is high time we took action as we confront the urgent imperative to address this escalating global health challenge head-on.

The Implication of the Gut Microbiome in Heart Failure.

Heart failure is a worldwide health problem with important consequences for the overall wellbeing of affected individuals as well as for the healthcare system. Over recent decades, numerous pieces of evidence have demonstrated that the associated gut microbiota represent an important component of human physiology and metabolic homeostasis, and can affect one's state of health or disease directly, or through their derived metabolites. The recent advances in human microbiome studies shed light on the relationship between the gut microbiota and the cardiovascular system, revealing its contribution to the development of heart failure-associated dysbiosis. HF has been linked to gut dysbiosis, low bacterial diversity, intestinal overgrowth of potentially pathogenic bacteria and a decrease in short chain fatty acids-producing bacteria. An increased intestinal permeability allowing microbial translocation and the passage of bacterial-derived metabolites into the bloodstream is associated with HF progression. A more insightful understanding of the interactions between the human gut microbiome, HF and the associated risk factors is mandatory for optimizing therapeutic strategies based on microbiota modulation and offering individualized treatment. The purpose of this review is to summarize the available data regarding the influence of gut bacterial communities and their derived metabolites on HF, in order to obtain a better understanding of this multi-layered complex relationship.

Can Bioactive Food Substances Contribute to Cystic Fibrosis-Related Cardiovascular Disease Prevention?

Advances in cystic fibrosis (CF) care have significantly improved the quality of life and life expectancy of patients. Nutritional therapy based on a high-calorie, high-fat diet, antibiotics, as well as new therapies focused on CFTR modulators change the natural course of the disease. They do so by improving pulmonary function and growing BMI. However, the increased weight of such patients can lead to unwanted long-term cardiovascular effects. People with CF (pwCF) experience several cardiovascular risk factors. Such factors include a high-fat diet and increased dietary intake, altered lipid metabolism, a decrease in the level of fat-soluble antioxidants, heightened systemic inflammation, therapeutic interventions, and diabetes mellitus. PwCF must pay special attention to food and eating habits in order to maintain a nutritional status that is as close as possible to the proper physiological one. They also have to benefit from appropriate nutritional counseling, which is essential in the evolution and prognosis of the disease. Growing evidence collected in the last years shows that many bioactive food components, such as phytochemicals, polyunsaturated fatty acids, and antioxidants have favorable effects in the management of CF. An important positive effect is cardiovascular prevention. The possibility of preventing/reducing cardiovascular risk in CF patients enhances both quality of life and life expectancy in the long run.

Tackling Dyslipidemia in Obesity from a Nanotechnology Perspective.

Obesity and dyslipidemia are the main features of metabolic syndrome, expressed mainly by adipose tissue dysfunction and connected by similar pathways and pharmacotherapy. Conventional drugs used in these two associated disorders are limited due to poor drug efficiency, non-specificity, and toxic side effects. Therefore, novel solutions for tackling obesity-associated diseases and providing insights into the development of innovative or improved therapies are necessary. Targeted nanotherapy is a revolutionary technology, offering a promising solution for combatting the disadvantages of currently available therapies for treating obesity and dyslipidemia due to its superior features, which include specific cell targeting, the protection of drugs against physiological degradation, and sustained drug release. This review presents a brief assessment of obesity and dyslipidemia, their impacts on human health, current treatment, and limitations, and the role and potential use of nanotechnology coupled with targeted drug delivery and nutraceuticals as emerging therapies. To the best of our knowledge, this paper presents, for the first time in the literature, a comparison between obesity and dyslipidemia nano-formulations based on drugs and/or natural extracts applied in experimental studies.

The Role of Phytosterols in Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease is now recognized as the most common cause of chronic liver disease with an increasing prevalence in both adults and children. Although the symptoms are absent or poorly expressed in most cases, some patients may progress to end-stage liver disease. The pathogenesis of NAFLD is known to be multifactorial. Current therapeutic recommendations focus on lifestyle changes in order to reduce the incidence of risk factors and drugs targeting major molecular pathways potentially involved in the development of this disease. Given that a pharmacological treatment, completely safe and effective, is not currently known in recent years more research has been done on the effects that some bio-active natural compounds, derived from plants, have in preventing the onset and progression of NAFLD. Numerous studies, in animals and humans, have shown that phytosterols (PSs) play an important role in this pathology. Phytosterols are natural products that are found naturally in plant. More than 250 phytosterols have been identified, but the most common in the diet are stigmasterol, ß-sitosterol, and campesterol. Consumption of dietary PSs can reduce serum cholesterol levels. Due to these properties, most studies have focused on their action on lipid metabolism and the evolution of NAFLD. PSs may reduce steatosis, cytotoxicity oxidative stress, inflammation, and apoptosis. The purpose of this review is to provide an overview of the importance of dietary phytosterols, which are a window of opportunity in the therapeutic management of NAFLD.

Mechanistic Insights in Hemophagocytic Lymphohistiocytosis: Subsequent Acute Hepatic Failure in a Multiple Myeloma Patient Following Therapy with Ixazomib-Lenalidomide-Dexamethasone.

Hemophagocytic lymphohistiocytosis (HLH) is a rare, elusive, and life-threatening condition that is characterized by the pathologic and uncontrolled secondary activation of the cytotoxic T-cells, natural killer cells (NK-cells), and macrophages of the innate immune system. This condition can develop in sporadic or familial contexts associated with hematological malignancies, as a paraneoplastic syndrome, or linked to an infection related to immune system deficiency. This leads to the systemic inflammation responsible for the overall clinical manifestations. Diagnosis should be thorough, and treatment should be initiated as soon as possible. In the current manuscript, we focus on classifying the HLH spectrum, describing the pathophysiology and the tools needed to search for and correctly identify HLH, and the current therapeutic opportunities. We also present the first case of a multiple myeloma patient that developed HLH following therapy with the ixazomib-lenalidomide-dexamethasone protocol.

Variations in Biochemical Values under Stress in Children with SARS-CoV-2 Infection.

In the case of SARS-CoV-2 infection, children seem to be less affected than adults, but data regarding epidemiologic characteristics and biochemical values are poor and essentially based on limited case series. The aim of our study is to highlight the predictive value of some biochemical markers at hospitalization, for the correct classification of the patient in the form of disease. Methods: We performed an analytical retrospective study on 82 pediatric patients diagnosed with COVID-19 in the emergency department, with moderate or severe form of disease, and treated in our tertiary hospital. We analyzed the epidemiologic characteristics, symptomatology and biochemical values and compare the data according to the form of disease. Results: The mean age at admission was 4.5 years (median 1 year) and the masculine/feminine ratio was 1.5. Comparing the data between the two groups of patients (42 severe/40 moderate), we observed that the severe form presented with a lower pH at admission (p = 0.02), hyperglycemia (p = 0.01), increased values of transaminases (p = 0.01 and 0.02) and hypoproteinemia (p = 0.01). Also, the severe form was statistically significantly associated with comorbidities, acute respiratory distress, rising of the inflammatory markers during hospitalization. Hyperlactatemia (Lactate > 1.5 mmol/L) was significantly associated with the age under one year (p < 0.001). Mortality rate was 9.75% and the median age at death was 3 months. Univariate logistic regression model shows that the presence of anemia increased the probability of death 88 times, comorbidities 23.3 times and ketoacidosis 16.4 times. Conclusions: Metabolic acidosis, hyperlactatemia, hyperglycemia, modified hepatic values and hypoproteinemia are biochemical markers associated with the severe form of disease in SARS-CoV-2 infection in children. Presence of anemia, comorbidities and ketoacidosis are important risk factors for death of pediatric patients with SARS-CoV-2 infection.

The Impact of Chronic Suppurative Otitis Media with and without Cholesteatoma in Patients from Northeastern Romania.

Quality of life is a widely used concept that tends to become an important part of clinical management. The present study performs an analysis of the impact of suppurative chronic otitis media with and without cholesteatoma on quality of life, using the COMQ-12 questionnaire. It was applied to a group of 40 healthy people and to 40 patients before surgery, and the answers to the questions were analyzed and correlated with socioeconomic factors. After the confirmation of the diagnosis based on clinical and imaging information, the patients completed the COMQ-12 questionnaire. It was observed that the chronic ear problems had negative impacts of varying degrees on daily and long-term activities. The evaluation and analysis of information can be used in setting therapeutic targets.

Predictive Markers of Early Cardiovascular Impairment and Insulin Resistance in Obese Pediatric Patients.

BACKGROUND: The increased prevalence of obesity among children determined the rising number of its comorbidities in children and adults, too. This study aimed to evaluate certain markers of inflammation and insulin resistance in obese pediatric patients, identifying those who are more likely to develop further complications. METHODS: We included 115 obese pediatric patients: 85 overweight and obese patients in the study group and 30 normal-weight patients in the control group. We calculated the body mass index (BMI) and we evaluated markers (biological, inflammatory) and the hormones profile. RESULTS: Low-threshold inflammation was assessed by measuring interleukin 6 IL-6 and Intercellular Adhesion Molecules (ICAM). The analysis showed that IL-6 is significantly correlated with glucose (p = 0.001) and BMI value (p = 0.031). ICAM correlates significantly with triglycerides (p = 0.001), glucose (p = 0.044) and BMI percentile (p = 0.037). For pediatric obese patients, endotoxemia has been significantly correlated only with BMI percentile (p = 0.001). Plasma cortisol did not show significant correlations with total cholesterol, triglycerides, glucose or BMI percentile. The results indicated a significant predictive power of BMI percentile on inflammatory markers: IL-6 (AUC = 0.803, p < 0.001), ICAM (AUC = 0.806, p < 0.001) and endotoxemia (AUC = 0.762, p = 0.019). Additionally, BMI percentile has a significant predictive power for metabolic markers of insulin resistance (insulin value: AUC = 0.72, p < 0.001 and HOMA index: AUC = 0.68, p = 0.003). CONCLUSIONS: The study highlighted the importance of early markers of cardiovascular risk in obese pediatric patients represented by IL-6, ICAM, endotoxemia and their correlation with metabolic markers of insulin resistance represented by insulinemia, HOMA index and plasma cortisol. It can clearly be considered that the BMI percentile has significant predictive power for metabolic markers of insulin resistance.

Waist circumference a clinical criterion for prediction of cardio-vascular complications in children and adolescences with overweight and obesity.

Overweight and obesity in childhood are associated with early cardiovascular dysfunction and promote heightened risk of cardiovascular morbidity and mortality in adulthood. Waist circumference (WC) correlates with visceral obesity, which is why obese children with elevated WC need to be carefully monitored to prevent long-term cardio-metabolic complications. The purpose of our study was to establish if WC could be a predictor of cardiovascular complications in children.The authors conducted a retrospective study that included 160 overweight and obese children and adolescents, aged 6 to 18 years. Patients were evaluated completely anthropometrically, biologically, and imagistic. The anthropometric data tracked were height, weight, WC, and body mass index. Echocardiography evaluated the following parameters: the interventricular septum, left ventricular mass, the relative thickness of the ventricular wall, the pathological epicardial fat.Our results confirm that the presence of visceral obesity was significantly associated (χ = 11.72, P = .0006) with pathological epicardial fat. In children, visceral obesity is not a risk factor for vascular or cardiac impairment, but in adolescents, the results showed that visceral obesity is an important predictive factor for the occurrence of vascular (AUC = 0.669, P = .021) and cardiac (AUC = 0.697, P = .037) impairment. Concentric left ventricular (LV) hypertrophy is significantly influenced by the presence of visceral obesity (AUC = 0.664, P = .013 children; AUC = 0.716, P = .026 adolescents).WC above the 90th percentile is a predictive factor for increased LVM index and concentric hypertrophy in both children and adolescents.

Pediatric nonalcoholic fatty liver disease - a changing diagnostic paradigm.

Worldwide, nonalcoholic fatty liver disease (NAFLD) has emerged as the leading cause of chronic liver disease in children and adolescents, but also as a real public health issue. Over the last decades, the increase in the rates of obesity and overweight in children has led to the increase in the worldwide prevalence of pediatric NAFLD. Detection of a hyperechoic appearance of the liver at ultrasounds or elevated levels of transaminases, identified during a routine control in children, suggests NAFLD. The disorder can be diagnosed with either non-invasive strategies or through liver biopsy, which further allows the identification of specific histological aspects, distinct from those found in adults. Since NAFLD is a clinically heterogeneous disease, there is an imperative need to identify noninvasive biomarkers and screening techniques for early diagnosis in children, in order to prevent metabolic and cardiovascular complications later in adulthood. This review emphasizes the main diagnosis tools in pediatric NAFLD, a systemic disorder with multifactorial pathogenesis and varying clinical manifestations.

Current Practices and Potential Nanotechnology Perspectives for Pain Related to Cystic Fibrosis.

Pain is a complex, multidimensional process that negatively affects physical and mental functioning, clinical outcomes, quality of life, and productivity for cystic fibrosis (CF) patients. CF is an inherited multi-system disease that requires a complete approach in order to evaluate, monitor and treat patients. The landscape in CF care has changed significantly, with currently more adult patients than children worldwide. Despite the great advances in supportive care and in our understanding regarding its pathophysiology, there are still numerous aspects of CF pain that are not fully explained. This review aims to provide a critical overview of CF pain research that focuses on pain assessment, prevalence, characteristics, clinical association and the impact of pain in children and adults, along with innovative nanotechnology perspectives for CF management. Specifically, the paper evaluates the pain symptoms associated with CF and examines the relationship between pain symptoms and disease severity. The particularities of gastrointestinal, abdominal, musculoskeletal, pulmonary and chest pain, as well as pain associated with medical procedures are investigated in patients with CF. Disease-related pain is common for patients with CF, suggesting that pain assessment should be a routine part of their clinical care. A summary of the use of nanotechnology in CF and CF-related pain is also given. Further research is clearly needed to better understand the sources of pain and how to improve patients' quality of life.

Epidemiological study on accidental poisonings in children from northeast romania.

Accidental poisonongs are an important cause of morbidity and even mortality, especially in young children.We performed a retrospective observational study on a group of children admitted at the Regional Center of Toxicology at the Children's Emergency Hospital "St. Mary" Iasi with accidental intoxication within a period of 3 years. Data were collected from patients' files and processed with a SPPS 18.0 database and a 95% confidence interval.During this period, 480 children were admitted with accidental intoxication. Most of them were in the age group of 1 to 2 years (120 cases-24.3%). The etiology of these intoxications was dominated by nonmedication (67%), the most frequent being household chemicals, carbon monoxide, and insecticides. Accidental drug intoxication accounted for 33% of the cases, the main drugs involved being anticonvulsants, nonsteroidal anti-inflammatory drugs, and paracetamol. The mortality caused by accidental poisoning was 0.62%, all deaths owing to nonmedication intoxication.Identifying the epidemiological and evolutionary aspects of accidental intoxications must be a major objective for the health system, given that this pathology can be at least partially avoided and its incidence and severity may be reduced using appropriate measures.

Epidemiologic profile and triggering factors of voluntary poisoning in teenagers.

Self-poisoning is an important medical and social problem in adolescents.We performed an observational cross-sectional retrospective study on a group of 219 adolescents admitted for voluntary intoxications at "St. Mary" Children's Emergency Hospital, Iasi during 1 year period. Epidemiological aspects and triggering factors have been analyzed. Data collected from the patients' files were centralized in an SPSS 18.0 database and processed with confidence interval of 95%.We found that pharmaceutical drugs have been usually involved (34.7%), mostly in girls (56.3% vs. 15.5%; P = 0.0001). The most frequently cited reason for poisoning was family conflict, with a relative risk (RR) 1.43 times higher in girls, as well as scholar conflict (RR = 1.39). A great percentage of the monitored girls presented severe depression (23.3% vs. 6.9%; P = 0.001), with an RR more than 3 times higher than in the case of boys. All cases evolved favorably, no death having been recorded, even if 18 teenagers initially presented an extremely serious condition, being admitted in various stages of coma (Glasgow coma scale score < 8).We found that self-inflicted poisonings with pharmaceutical drugs was more common in girls and the use of drug and alcohol intoxication was found especially in boys. The most common pharmaceutical drug involved in self-poisoning was acetaminophen. Psychological disorders and family or school conflicts are the most important triggering factors of voluntary poisoning. Risk factors should be identified after stabilizing the patient, and actions should be taken in order to prevent a fatal recurrence.

Acrodermatitis Enteropathica: A Case Report.

Acrodermatitis enteropathica is a rare genetic autosomal recessive disorder, characterized by periorificial dermatitis, alopecia, and diarrhea. It is caused by mutations in the gene that encodes a membrane protein that binds zinc. We report a 14-month-old boy, admitted for erythematous, scaly and pustular lesions, initially located in the inguinal and perianal regions and on thighs, and very few erythematous lesions on the face. Due to the numerous bacterial skin superinfections with Staphylococcus aureus, including abscesses that required surgical incision, the clinical picture was modified, leading to a delayed establishment of the diagnosis. Later, the symptoms became suggestive for this disease, the diagnostic having been confirmed by low plasma zinc values. Under zinc therapy, skin lesions improved significantly in a few days, with favorable outcome. Two months later, the skin lesions almost disappeared.Abscesses due to bacterial skin superinfections may lead to initially misdiagnosed acrodermatitis enteropathica.

Topicalities in the Sudden Unexpected Death Syndrome in Infants.

Sudden Infant Death Syndrome (SIDS) represents the third cause in postnatal mortality. The pathogenesis is multifactorial. SIDS victims can present sign of preexisting chronic asphyxia, persistent increase in dendritic spine and delayed maturation of synapses in medullary respiratory centers, if a decreased reactivity of 5 hydroxytryptamine 1A (5-HT1A) and 5-HT2A in the dorsal nucleus of the vagus, solitary nucleus and ventrolateral medulla. SIDS is an exclusion diagnosis, so that inexplicable SIDS is the accepted term. The objective of this report is to present current data about the pathogenesis oh this syndrome and the medico-legal measures applied in preventive and curative aim. The "face-up" sleeping position has cut in half the SIDS frequency. In conclusion, the infant sleep studies represent an important line for the future research to provide sufficient explanation of the sudden death in these infants.

Gut-liver axis and fibrosis in nonalcoholic fatty liver disease: an input for novel therapies.

Non-alcoholic fatty liver disease is a multifactorial condition, ranging from simple steatosis to non-alcoholic steatohepatitis with or without fibrosis. In non-alcoholic fatty liver disease, alteration of gut microbiota and increased intestinal permeability increase exposure of the liver to gut-derived bacterial products: lipopolysaccharides and unmethylated CpG DNA. These products stimulate innate immune receptors, namely Toll-like receptors, which activate signalling pathways involved in liver inflammation and fibrogenesis. Currently, there are several studies on the involvement of lipopolysaccharide-activated Toll-like receptor 4 signalling in non-alcoholic fatty liver disease pathogenesis. There has been widespread interest in the study of the involvement of resident hepatic stellate cells and Kupffer cells activation in liver fibrogenesis upon TLR4 stimulation. Although the best evidence to support a role for gut microbiota in non-alcoholic fatty liver disease-induced fibrosis comes largely from animal models, data from human studies are accumulating and could lead to new therapeutic approaches. Therapeutic modulation of gut microflora may be an alternative strategy to develop an anti-fibrotic therapy. In this review, we discuss the relevant role of gut-liver axis in non-alcoholic liver disease-associated liver fibrosis and discuss the evidence on novel anti-fibrotic therapeutic approaches.