Clinical characteristics, diagnosis, treatment, and outcome of patients with liver abscess due to Aspergillus spp: a systematic review of published cases.

BACKGROUND: Aspergillus spp liver abscess is a relatively rare entity and thus far no systematic review has been performed examining patients' demographics, clinical manifestations, diagnosis, management, and outcome. METHODS: We performed a systematic review of the literature using MEDLINE and LILACS databases. We searched for articles published in the period from January 1990 to December 24, 2022, to identify patients who developed liver abscesses due to Aspergillus spp. RESULTS: Our search yielded 21 patients all of whom had invasive aspergillosis confirmed on liver biopsy. Of these patients 81% were adults, and 60% were males. The majority (86%) of patients were immunocompromised and 95% had symptomatic disease at the time of diagnosis. The most common symptoms were fever (79%), abdominal pain (47%), and constitutional symptoms (weight loss, chills, night sweats, fatigue) (38%). Liver enzymes were elevated in 50%, serum galactomannan was positive in 57%, and fungal blood cultures were positive in only 11%. Co-infection with other pathogens preceded development of apsergillosis in one-third of patients, and the majority of the abscesses (43%) were cryptogenic. In the remaining patients with known source, 28% of patients developed liver abscess through dissemination from the lungs, 19% through the portal vein system, and in 10% liver abscess developed through contiguous spread. The most common imaging modality was abdominal computerized tomography done in 86% of patients. Solitary abscess was present in 52% of patients while 48% had multiple abscesses. Inadequate initial empiric therapy was prescribed in 60% of patients and in 44% of patients definite treatment included combination therapy with two or more antifungal agents. Percutaneous drainage of the abscesses was done in 40% of patients, while 20% required liver resection for the treatment of the abscess. Overall mortality was very high at 38%. CONCLUSION: Further studies are urgently needed for a better understanding of pathophysiology of liver aspergillosis and for developement of newer blood markers in order to expedite diagnosis and decrease mortality.

Atherosclerotic Cardiovascular Disease in Inflammatory Bowel Disease: The Role of Chronic Inflammation and Platelet Aggregation.

Background and Objectives: Atherosclerosis is one of inflammatory bowel disease's most significant cardiovascular manifestations. This research aimed to examine the relationship between biochemical, haemostatic, and immune parameters of atherosclerosis and ulcerative colitis patients and its relationship to platelet aggregation. Materials and Methods: A clinical, observational cross-sectional study was performed, during which the tested parameters were compared in the experimental and control groups. The patients were divided into four groups. The first group had 25 patients who had ulcerative colitis and atherosclerosis. The second group included 39 patients with ulcerative colitis without atherosclerosis. The third group comprised 31 patients suffering from atherosclerosis without ulcerative colitis, and the fourth group comprised 25 healthy subjects. Results: In our study, we registered statistically higher levels of inflammatory markers like SE, CRP, Le, fecal calprotectin, TNF-α, and IL-6, as well as the higher value of thrombocytes and thrombocyte aggregation in the group of patients with ulcerative colitis compared to the control group. Lower levels of total cholesterol and LDL were also recorded in patients with ulcerative colitis and atherosclerosis and ulcerative colitis without atherosclerosis compared to healthy control. Triglyceride and remnant cholesterol were higher in patients with ulcerative colitis and atherosclerosis when compared to patients with ulcerative colitis and healthy control but lower than in patients with atherosclerosis only. Conclusions: Several inflammatory markers and platelet aggregation could be good discrimination markers for subjects with ulcerative colitis with the highest risk of atherosclerosis.

Chronic Constipation: Gastroenterohepatologist's Approach.

BACKGROUND: Constipation is a common problem in gastroenterological practice. The prevalence of constipation is about 16%. Constipation can be primary or secondary. SUMMARY: The diagnostic and therapeutic approach to patients with constipation begins with a detailed history and physical examination. In selected cases, the use of additional diagnostic procedures is very important. This includes the use of laboratory, endoscopic, and radiological examinations, as well as advanced physiological testing (anorectal manometry, balloon expulsion test, colonic transit studies, and defecography). Constipation therapy can be both nonoperative and operative. Nonoperative therapy includes the application of a lifestyle measures, pharmacotherapy and biofeedback therapy. Key Messages: Two key things when taking a medical history and physical examination are to rule out the existence of alarm symptoms/signs and to rule out secondary constipation (primarily drug-induced). Therapy begins with lifestyle modification, and in case of failure, bulk or osmotic laxatives are used. In case of failure, the use of lubiprostone is indicated, as well as linaclotide. Surgical treatment of constipation is reserved for cases of refractory constipation, with delayed intestinal transit.

Anemia as a Problem: GP Approach.

BACKGROUND: Anemia is a presentation of an underlying disease or deficiency. As stated by the WHO, anemia is defined as hemoglobin (Hb) levels <12.0 g/dL in women and <13.0 g/dL in men. This review of clinical practice aimed to determine the diagnostic approach to anemia in primary care patients. SUMMARY: Nutritional deficiencies, medications, chronic inflammatory conditions, malignancy, renal dysfunction, and bone marrow and inherent disorders contribute to anemia development. Anemia is classified and diagnosed by the values of hematological parameters, underlying pathological mechanism, and patient history. The diagnostic approach of anemia in primary care settings is focused on history, physical examination, laboratory findings including complete blood cell count, reticulocyte count, and peripheral smear examination, fecal occult blood test, and ultrasound findings. KEY MESSAGES: Anemia is the most common hematological disorder that represents a major health burden worldwide. Hb levels alter with gender, ethnicity, and physiological status. Anemia is often multifactorial. The evaluation of a patient with anemia in primary care includes clinical history, physical examination, and laboratory findings with fecal occult blood test and abdominal ultrasound. The wide variations in general practice in European countries are based on different health care systems but also knowledge of GPs that reflect educational and research policy.

Jaundice as a Diagnostic and Therapeutic Problem: A General Practitioner's Approach.

BACKGROUND: Jaundice is a common clinical finding in clinical practice of hepatologists and general practitioners. It occurs when serum bilirubin levels exceed 3 mg/dL. SUMMARY: In this review, we summarize the pathophysiological mechanism of jaundice, clinical approach to the patient with jaundice, and laboratory and imaging techniques. Clinical presentation of jaundice manifests through yellow skin and sclera coloration. Evaluation of every patient includes detailed medical history and examination. In the laboratory, evaluation of enzymes of hepatic inflammation as well as cholestatic enzymes with serum bilirubin must be included. Additional laboratory analysis and imaging modalities are needed in order to differentiate jaundice etiology. Moreover, imaging is available and needed in further evaluation, and treatment is dependent on the underlying cause. KEY MESSAGES: In this review, we will outline the pathophysiological mechanism of jaundice, clinical approach to the patient with jaundice, and diagnostic and treatment approach to these patients.

Diagnostic Value of Non-invasive Scoring Systems in the Prediction of Esophageal Varices in Patients with Liver Cirrhosis-Single Center Experience.

Background and Objectives: Upper endoscopy is considered the gold standard for screening and diagnosis of esophageal varices (EV). Non-invasive methods for predicting EV have become a research hotspot in recent years. The aim of this study was to assess the role of non-invasive scores in predicting the presence of EV in patients with liver cirrhosis, and to determine the value of these scores in predicting the outcome of patients with cirrhosis presenting with acute variceal bleeding. Materials and Methods: A total of 386 patients with liver cirrhosis were included. The model for end-stage liver disease (MELD), aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (AST/ALT), AST to platelet ratio index (APRI), fibrosis-4-index (FIB-4), fibrosis index (FI), King's Score, albumin-bilirubin (ALBI) score, and platelet-albumin-bilirubin (PALBI) score were calculated. The discriminatory capacities of the examined scores in predicting the presence of esophageal varices were tested using receiver operating characteristic (ROC) curves. Results: The ROC curve analysis showed (area under the curve) AUC values of ALBI and PALBI of 0.603, and 0.606, respectively, for the prediction of EV. APRI, MELD, PALBI, King's, FIB-4, and ALBI scores showed statistically significant correlation with EV bleeding (p < 0.05). AUC of APRI and MELD for predicting EV bleeding were 0.662 and 0.637, respectively. The AUC value of MELD in short-term mortality was 0.761. Conclusions: ALBI and PALBI scores had modest diagnostic accuracy of EVs in liver cirrhosis. APRI and MELD can be used as a reference index for the EV bleeding, and MELD score is best associated with short-term outcome in cirrhotic patients.

Alcohol Use By Women in Serbia-A First Report.

INTRODUCTION: Alcoholism is a growing problem with increasing incidence on in women. The aim of our study was to evaluate drinking habits in women using Alcohol Use Disorders Identification Test (AUDIT), and to look for differences in relations to respondents' demographic, behavioral, and medical characteristics. METHODS: This cross-sectional study included 327 adult women who did not visit a physician due to liver enzymes abnormalities or any other significant health issue. All subjects filled in a questionnaire consisting of socio-demographic survey and the AUDIT. RESULTS: The statistically significant influence of the respondents' age on the answers to the AUDIT was observed in Q1-Q5, Q7, and Q8, and in alcohol use risk groups. It was observed that women with a university degree use alcohol more often, compared to those who have attended primary, or middle school. The effect of responders' employment status demonstrated a statistically significant difference in response to Q3, Q5, Q7, and Q8, and in alcohol use risk groups. We found that marital status contributes to drinking patterns. We found statistically significant difference to the answers on Q1-Q3, Q5, Q7, and Q8. The effect of offspring on the answers on the AUDIT was analyzed and a statistically significant difference was noted in the answers to the Q1-Q3, Q5, Q7, Q8, and in alcohol use risk groups. CONCLUSION: Alcohol use among women is commonly and severely overlooked. Our results showed younger women, the unemployed, those in domestic partnerships, single ones and those with no children deserve increased surveillance.

Relationship between coffee consumption, sleep duration and smoking status with elastographic parameters of liver steatosis and fibrosis; controlled attenuation parameter and liver stiffness measurements.

AIM: our aim was to explore the association between life habits and the controlled attenuation parameter (CAP) and liver stiffness measurements (LSM) as the surrogate markers of liver steatosis and fibrosis in a large cohort of non-alcoholic fatty liver disease (NAFLD) patients. METHODS: In this prospective, cross-sectional study we had analysed 1998 patients with diagnosed NAFLD. Sleeping duration was categorised in three groups: short (S) (<6 hours), moderate (M) (6-8 hours) and long (L) (>8 hours) sleep duration. Coffee drinking was categorized into no (0), moderate (1-2) and frequent (≥3) consumption (in cups/day). Smoking was categorised as yes versus no. RESULTS: Frequent coffee consumers had the lowest prevalence of obesity, hypertension, dyslipidaemia and diabetes. Furthermore, coffee non-consumers had highest values of hepatic enzymes, CAP and LSM. Moderate sleep duration was associated with lower values of CAP and LSM. Coffee consumption was associated with lower CAP in all the multivariate models (CAP unadjusted and model 1, 2 and 3), with largest effect in most frequent coffee consumers (≥3, model 3). Also, most frequent coffee consumers were associated with lower LSM in unadjusted model, model 1 and 2, while this was not the case for model 3 and those who consumed 1-2 cups of coffee per day. Reduced sleeping was confirmed as risk factor for elevated CAP in most of the models (unadjusted and model 1 and 2). Also, negative association of LSM was also confirmed in unadjusted model and model 2. Patients which slept 6-8 hours per day were mostly associated with lower CAP and LSM. Smoking status was not associated with CAP or LSM values. CONCLUSION: Coffee consumption has beneficial effect on CAP and LSM and this effect is dose dependent since and independent of a variety of relevant confounders. We have shown that moderate sleep duration has also beneficial effect on CAP and LSM.

Colonic Diverticulosis and Non-Alcoholic Fatty Liver Disease: Is There a Connection?

Background and Objectives: The development and severity of colonic diverticulosis and non-alcoholic fatty liver disease (NAFLD) has been associated with several components of metabolic syndrome (MetS). Therefore, this study aimed to evaluate a possible connection between NAFLD, colonic diverticulosis, and MetS. Materials and Methods: This retrospective study included patients diagnosed with diverticulosis between January 2017 and December 2019. Data regarding the patient demographics, Diverticular Inflammation and Complication Assessment (DICA) score and category, disease localization, hepatic steatosis, blood pressure, comprehensive metabolic panel, need for colonic surgery, and co-morbidities were collected from medical records. Results: A total of 407 patients with a median age of 68 years (range, 34-89 years) were included (male: 53.81%). The majority was diagnosed with left-sided diverticulosis (n = 367, 90.17%) and an uncomplicated disease course (DICA category 1, n = 347, 85.3%). Concomitant hepatic steatosis was detected in 47.42% (n = 193) of patients. The systolic blood pressure, triglycerides, total cholesterol, C-reactive protein (CRP), and fasting glucose were higher in the NAFLD group (p < 0.001, p < 0.001, p < 0.001, p < 0.001, and p < 0.001, respectively). A higher prevalence of hypertension (HTA), type 2 diabetes mellitus (T2DM), and hypothyroidism was noted in the same group of patients (p < 0.001, p < 0.001, and p = 0.008, respectively). High-density lipoprotein cholesterol was lower in patients with more severe forms of diverticulosis (DICA category 2 and 3), while CRP levels were significantly higher (p = 0.006 and p = 0.015, respectively). HTA and NAFLD were more common in patients with more severe forms of colonic diverticulosis (p = 0.016 and p = 0.025, respectively). Using a multivariate logistic regression, the DICA score, CRP, total cholesterol, HTA, and hypothyroidism were identified as discriminating factors for the presence of hepatic steatosis. Conclusion: Components of metabolic dysregulation were prominent in patients diagnosed with colonic diverticulosis and concomitant hepatic steatosis. HTA, T2DM, and hypothyroidism were more frequently observed in this group. Hepatic steatosis was more commonly detected in more severe forms of colonic diverticulosis.

Leukocytoclastic vasculitis as a rare dermatologic manifestation of Crohn's disease mimicking cellulitis: a case report.

BACKGROUND: Leukocytoclastic vasculitis (LCV) is an immune-complex mediated vasculitis characterized by neutrophilic inflammation and nuclear debris in post capillary venules. LCV is a rare dermatologic manifestation of Crohn's disease (CD) and may occur with the onset of the disease or any time after the diagnosis including the period of exacerbation. CASE PRESENTATION: We present a 70 year old woman with history of psoriasis and treatment refractory CD requiring monoclonal antibody therapy with ustekinumab. One month prior to the current admission, she developed abdominal pain, worsening diarrhea and was diagnosed with CD exacerbation for which she was given ustekinumab. While her abdominal symptoms mildly improved with ustekinumab, she developed new bilateral lower extremity rash initially treated with levofloxacin for presumed cellulitis. The rash consisted of mild erythematous, non-scaling patches with scattered non-palpable petechiae on the lower extremities with subsequent involvement of abdomen, lower back and buttocks. Abdominal exam showed diffuse tenderness without mass, guarding or rebound while reminder of physical exam was unremarkable. Following the failure of antimicrobial therapy, she was diagnosed with LCV by skin biopsy. Complete work up was negative for infectious, malignant and inflammatory etiologies of LCV. Patient improved with increased dose of budesonide and subsequently continued to tolerate ustekinumab without recurrence of LCV. DISCUSSION AND CONCLUSION: LCV is a rare form of vasculitis and one of the rarest dermatologic manifestations of CD, appearing at any stage of the disease. LCV has been associated with autoimmune diseases, infections, specific drugs (levofloxacin, ustekinumab), and malignancy. Clinical presentation of LCV is variable and frequently mistaken for cellulitis. LCV should be considered in differential diagnosis of bilateral lower extremity rash in patients with CD after infectious, malignant and auto-immune/inflammatory etiologies are excluded. Unlike erythema nodosum (EN) and pyoderma gangrenosum (PG), LCV requires biopsy for diagnosis. Most patients respond well to steroids without scarring.

Quality of Life in Patients with Primary Biliary Cholangitis: A Single-Center Experience in Serbia.

BACKGROUND: Primary biliary cholangitis (PBC) is a chronic cholestatic autoimmune disease, predominantly affecting middle-aged women, which may progress to end-stage liver disease. We aimed to assess the quality of life (QoL) in patients with PBC given that social, economic, and geographical factor also influence QoL. METHODS: This study included patients with diagnosed PBC according to the European Association for the Study of the Liver guidelines, who were treated for at least 6 months in order to allow adequate time for the initial burden of symptoms to subside. We used the PBC-40 questionnaire validated in the Serbian language. RESULTS: The mean total PBC-40 score was 89.4 ± 29.3. The overall frequency of moderate and severe involvement in each domain was as follows: 84.9% (n = 107) in "Symptoms," 29.3% (n = 36) in "Itch," 76.4% (n = 97) in "Fatigue," 58.1% (n = 72) in "Cognitive," 77.2% (n = 98) in "Social," and 70.9% (n = 90) in "Emotional." There was a statistically significant negative correlation of disease duration and albumin score with the Emotional domain score. Furthermore, this domain showed a significant positive correlation with the Mayo score. CONCLUSION: The present study demonstrates that patients with PBC have significant impairment in QoL with fatigue being the most prevalent symptom. The Social and Emotional domains were also significantly affected in these individuals, particularly in patients with peripheral edema who exhibited worse QoL that those who were euvolemic.

Epidemiology and risk factors for multi-drug resistant hospital-acquired urinary tract infection in patients with liver cirrhosis: single center experience in Serbia.

BACKGROUND: Cirrhosis-associated immune dysfunction syndrome (CAIDS) has been identified in patients with liver cirrhosis (LC), predisposing them to a wide variety of infections. In patients with LC, healthcare-associated infections involving multi-drug resistant (MDR) bacteria have increased significantly over the last decades. Among them, hospital-acquired urinary tract infections (HA-UTI) are the most common. This study aimed to investigate the rates of antimicrobial resistance among patients with LC and HA-UTI and to determine risk factors associated with their development among patients hospitalized in tertiary care facility in Serbia. METHODS: This retrospective study included 65 hospitalized patients with LC who had developed HA-UTI. We examined the epidemiology of these infections concerning resistance to the most commonly used antimicrobials and patient-specific risk factors associated with HA-UTI development by MDR pathogens. RESULTS: The most frequently isolated organisms were Enterococcus spp. (n = 34, 52.3%), Klebsiella spp. (n = 10, 15.4%), and E.coli (n = 6, 9.2%). Thirty-five isolates (53.8%) were identified as MDR, and 30 (46.2%) were non-MDR.We found a statistically significant difference in the distribution of MDR and non-MDR strains, based on Gram staining, with the majority of Gram-negative pathogens being MDR (p = 0.005). We identified age ≥ 65 years (p = 0.007), previous use of cephalosporins as empiric therapy (p = 0.042), and the presence of hepatic encephalopathy (p = 0.011) as independent risk factors for the development of MDR UTIs. CONCLUSION: This is the first study from Serbia and the Balkans concerning the changing epidemiology of MDR UTI in patients with LC. Our study showed that more than half of HA-UTI was caused by MDR and the most common pathogen was Enterococcus spp. The overall resistance to ceftriaxone was 92%. Our findings underscore the need for institutions to individualize protocols for treatment of hospital-acquired infections, particularly in immunocompromised populations.

Diagnosis of Eosinophilic Esophagitis in Children: A Serbian Single-Center Experience from 2010 to 2017.

OBJECTIVES: The aim of this study was to assess the epidemiological, clinical, endoscopic, and pathohistological characteristics of pediatric eosinophilic esophagitis (EoE) in Serbia. METHOD: All children aged 0-18 years diagnosed with EoE in the period between 2010 and 2017 at the University Children's Hospital in Belgrade, Serbia, were retrospectively enrolled. RESULTS: EoE was diagnosed in 35 children (12.45 ± 3.77 years) with a male predominance (74%). The median incidence rate was estimated to be 0.85 per 100,000 children per year with the highest rate estimated at 3.17 per 100,000 children in 2017. Dysphagia (71.4%) and food impaction (40%) were dominant symptoms. Inflammatory endoscopic changes were found in 74.3% and fibrostenotic changes in 62.9% of the children. The esophageal biopsy rate was low (6.8%), especially in children with reflux and nonspecific symptoms. Subepithelial fibrosis was found in only 20% of the patients. Since 2016, the number of biopsy samples has increased, but the sampling rate of lamina propria is still low (<50%). The correlation between the number of biopsies and lamina propria acquisition was strong (rs = 0.773, p < 0.05). In 2 immunocompetent adolescents, EoE was diagnosed after successful treatment of infectious esophagitis. CONCLUSIONS: An increase in the incidence of EoE in Serbian children is evident. The biopsy rate in children with nonspecific and reflux symptoms should be increased, as well as the number of biopsy samples for the detection of subepithelial fibrosis. In immunocompetent children with infectious esophagitis, EoE should be suspected and endoscopy may be recommended after successful treatment of infection.

Ultrasonographic Evaluation of Fatty Pancreas in Serbian Patients with Non Alcoholic Fatty Liver Disease-A Cross Sectional Study.

Background and Objectives: The aim of the study was to determine the association between presences of fatty pancreas (FP) with the features of metabolic syndrome (MeS) in patients with non-alcoholic fatty liver disease (NAFLD) and to establish a new noninvasive scoring system for the prediction of FP in patients with NAFLD. Material and Methods: 143 patients with NAFLD were classified according to FP severity grade into the two groups and evaluated for diagnostic criteria of MeS. All patients underwent sonographic examination with adiposity measurements and the liver biopsy. Liver fibrosis was evaluated semi-quantitatively according to the METAVIR scoring system and using non-invasive markers of hepatic fibrosis. Results: Waist circumference (WC) was predictive for increased risk of FP in NAFLD patients. Elevated fasting plasma glucose, total cholesterol, serum amylase and lipase levels were associated with presence of severe FP (p value = 0.052, p value = 0.007, p value = 0.014; p value = 0.024, respectively). Presence of increased amounts of mesenteric fat was associated with severe FP (p value = 0.013). The results of this study demonstrated highly significant association between NAFLD and presence of FP. The model for predicting the presence of FP was designed with probability value above 6.5. Conclusion: Pancreatic fat accumulation leads to worsening of pancreatic function which in turns exacerbates severity of metabolic syndrome associated with both, NAFLD and NAFPD.

Intrahepatic Cholestasis of Pregnancy: A Case Study of the Rare Onset in the First Trimester.

Intrahepatic cholestasis of pregnancy (ICP) is a gestation-specific liver disorder, defined most often as the onset of pruritus, usually from the third trimester of pregnancy, associated with abnormal liver test results and/or increased total serum bile acids and spontaneous relief after delivery. The 21-year-old patient was admitted to our ward in the 11th week of pregnancy due to raised liver enzymes. The first onset of pruritus and jaundice appeared a month before hospitalization. Immunology tests and Toxoplasma gondii were negative. We excluded viral etiology, while alpha-1-antitrypsin, serum and urine copper levels, and thyroid hormones were within the reference values. The patient denied she had taken any medicines and herbal preparations before and during pregnancy. Total bile acids in the serum were significantly elevated (242 µmol/L). The abdominal ultrasound revealed a regular finding. Liver biopsy suggested a cholestatic liver disorder. After a presentation of all risks, the patient decided to stop the pregnancy. After a month, the hepatogram was within the reference values. Very rarely an ICP can occur in early pregnancy (first trimester), which calls for close monitoring. The risk of serious adverse fetal outcomes and spontaneous preterm delivery is proportional with increased levels of maternal serum bile acid.

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.

New Therapeutic Approaches for the Treatment of Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and Increased Cardiovascular Risk.

Metabolic dysfunction-associated steatotic liver disease (MASLD) was previously known as nonalcoholic fatty liver disease (NAFLD). The main characteristic of the disease is the process of long-term liver inflammation, which leads to hepatocyte damage followed by liver fibrosis and eventually cirrhosis. Additionally, these patients are at a greater risk for developing cardiovascular diseases (CVD). They have several pathophysiological mechanisms in common, primarily lipid metabolism disorders and lipotoxicity. Lipotoxicity is a factor that leads to the occurrence of heart disease and the occurrence and progression of atherosclerosis. Atherosclerosis, as a multifactorial disease, is one of the predominant risk factors for the development of ischemic heart disease. Therefore, CVD are one of the most significant carriers of mortality in patients with metabolic syndrome. So far, no pharmacotherapy has been established for the treatment of MASLD, but patients are advised to reduce their body weight and change their lifestyle. In recent years, several trials of different drugs, whose basic therapeutic indications include other diseases, have been conducted. Because it has been concluded that they can have beneficial effects in the treatment of these conditions as well, in this paper, the most significant results of these studies will be presented.

Therapeutic Potential of Palmitoylethanolamide in Gastrointestinal Disorders.

Palmitoylethanolamide (PEA) is an endocannabinoid-like bioactive lipid mediator belonging to the family of N-acylethanolamines, most abundantly found in peanuts and egg yolk. When the gastrointestinal (GI) effects of PEA are discussed, it must be pointed out that it affects intestinal motility but also modulates gut microbiota. This is due to anti-inflammatory, antioxidant, analgesic, antimicrobial, and immunomodulatory features. Additionally, PEA has shown beneficial effects in several GI diseases, particularly irritable bowel syndrome and inflammatory bowel diseases, as various studies have shown, and it is important to emphasize its relative lack of toxicity, even at high dosages. Unfortunately, there is not enough endogenous PEA to treat disturbed gut homeostasis, even though it is produced in the GI tract in response to inflammatory stimuli, so exogenous intake is mandatory to achieve homeostasis. Intake of PEA could be through animal and/or vegetable food, but bearing in mind that a high dosage is needed to achieve a therapeutic effect, it must be compensated through dietary supplements. There are still open questions pending to be answered, so further studies investigating PEA's effects and mechanisms of action, especially in humans, are crucial to implementing PEA in everyday clinical practice.

Clinical Manifestations of Leukocytoclastic Vasculitis, Treatment, and Outcome in Patients with Ulcerative Colitis: A Systematic Review of the Literature.

Leukocytoclastic vasculitis (LCV) is a rare extraintestinal manifestation (EIM) of ulcerative colitis (UC). Observations about its association with UC stem from case reports and small case series. Due to its rarity, more rigorous cross-sectional studies are scarce and difficult to conduct. The aim of this systematic review was to synthetize the knowledge on this association by reviewing published literature in the form of both case reports and case series; and report the findings according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. In contrast to LCV in Chron disease (CD), which occurs secondary to biologic therapies used for its treatment, LCV in UC is a true reactive skin manifestation. Both genders are equally affected. Palpable purpura (41%) and erythematous plaques (27%) are the most common clinical manifestations. In 41% of patients, the rash is painful, and the lower extremities are most commonly involved (73%). Systemic symptoms such as fever, arthralgias, fatigue, and malaise are seen in 60% of patients. Unlike previous reports, we found that LCV more commonly occurs after the UC diagnosis (59%), and 68% of patients have active intestinal disease at the time of LCV diagnosis. Antineutrophil cytoplasmic antibody (ANCA) is positive in 41% of patients, and 36% of patients have other EIMs present concomitantly with LCV. The majority of patients were treated with corticosteroids (77%), and two (10%) required colectomy to control UC and LCV symptoms. Aside from one patient who died from unrelated causes, all others survived with their rash typically resolving without scarring (82%).