Sanja Stojsavljević

Bio: Sanja Stojsavljević is an academic researcher from University of Zagreb. The author has contributed to research in topics: Insulin resistance & Metabolic syndrome. The author has an hindex of 5, co-authored 12 publications receiving 331 citations.

Adipokines and proinflammatory cytokines, the key mediators in the pathogenesis of nonalcoholic fatty liver disease

Abstract: Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat accumulates in the liver of a patient with no history of alcohol abuse or other causes for secondary hepatic steatosis. The pathogenesis of NAFLD and nonalcoholic steatohepatitis (NASH) has not been fully elucidated. The “two-hit“ hypothesis is probably a too simplified model to elaborate complex pathogenetic events occurring in patients with NASH. It should be better regarded as a multiple step process, with accumulation of liver fat being the first step, followed by the development of necroinflammation and fibrosis. Adipose tissue, which has emerged as an endocrine organ with a key role in energy homeostasis, is responsive to both central and peripheral metabolic signals and is itself capable of secreting a number of proteins. These adipocyte-specific or enriched proteins, termed adipokines, have been shown to have a variety of local, peripheral, and central effects. In the current review, we explore the role of adipocytokines and proinflammatory cytokines in the pathogenesis of NAFLD. We particularly focus on adiponectin, leptin and ghrelin, with a brief mention of resistin, visfatin and retinol-binding protein 4 among adipokines, and tumor necrosis factor-α, interleukin (IL)-6, IL-1, and briefly IL-18 among proinflammatory cytokines. We update their role in NAFLD, as elucidated in experimental models and clinical practice.

Hepatitis C Virus, Insulin Resistance, and Steatosis

Abstract: Hepatitis C virus (HCV) is one of the main causes of liver disease worldwide. Liver steatosis is a common finding in many hepatic and extrahepatic disorders, the most common being metabolic syndrome (MS). Over time, it has been shown that the frequent coexistence of these two conditions is not coincidental, since many epidemiological, clinical, and experimental studies have indicated HCV to be strongly associated with liver steatosis and numerous metabolic derangements. Here, we present an overview of publications that provide clinical evidence of the metabolic effects of HCV and summarize the available data on the pathogenetic mechanisms of this association. It has been shown that HCV infection can induce insulin resistance (IR) in the liver and peripheral tissues through multiple mechanisms. Substantial research has suggested that HCV interferes with insulin signaling both directly and indirectly, inducing the production of several proinflammatory cytokines. HCV replication, assembly, and release from hepatocytes require close interactions with lipid droplets and host lipoproteins. This modulation of lipid metabolism in host cells can induce hepatic steatosis, which is more pronounced in patients with HCV genotype 3. The risk of steatosis depends on several viral factors (including genotype, viral load, and gene mutations) and host features (visceral obesity, type 2 diabetes mellitus, genetic predisposition, medication use, and alcohol consumption). HCV-related IR and steatosis have been shown to have a remarkable clinical impact on the prognosis of HCV infection and quality of life, due to their association with resistance to antiviral therapy, progression of hepatic fibrosis, and development of hepatocellular carcinoma. Finally, HCV-induced IR, oxidative stress, and changes in lipid and iron metabolism lead to glucose intolerance, arterial hypertension, hyperuricemia, and atherosclerosis, resulting in increased cardiovascular mortality.

Scoring systems for peptic ulcer bleeding: Which one to use?

Abstract: Aim To compare the Glasgow-Blatchford score (GBS), Rockall score (RS) and Baylor bleeding score (BBS) in predicting clinical outcomes and need for interventions in patients with bleeding peptic ulcers. Methods Between January 2008 and December 2013, 1012 consecutive patients admitted with peptic ulcer bleeding (PUB) were prospectively followed. The pre-endoscopic RS, BBS and GBS, as well as the post-endoscopic diagnostic scores (RS and BBS) were calculated for all patients according to their urgent upper endoscopy findings. Area under the receiver-operating characteristics (AUROC) curves were calculated for the prediction of lethal outcome, rebleeding, needs for blood transfusion and/or surgical intervention, and the optimal cutoff values were evaluated. Results PUB accounted for 41.9% of all upper gastrointestinal tract bleeding, 5.2% patients died and 5.4% patients underwent surgery. By comparing the AUROC curves of the aforementioned pre-endoscopic scores, the RS best predicted lethal outcome (AUROC 0.82 vs 0.67 vs 0.63, respectively), but the GBS best predicted need for hospital-based intervention or 30-d mortality (AUROC 0.84 vs 0.57 vs 0.64), rebleeding (AUROC 0.75 vs 0.61 vs 0.53), need for blood transfusion (AUROC 0.83 vs 0.63 vs 0.58) and surgical intervention (0.82 vs 0.63 vs 0.52) The post-endoscopic RS was also better than the post-endoscopic BBS in predicting lethal outcome (AUROC 0.82 vs 0.69, respectively). Conclusion The RS is the best predictor of mortality and the GBS is the best predictor of rebleeding, need for blood transfusion and/or surgical intervention in patients with PUB. There is no one 'perfect score' and we suggest that these two tests be used concomitantly.

Acid inhibition and the acid rebound effect.

Abstract: Acid secretion from gastric parietal cells is a result of a complex interaction between different stimulatory and inhibitory mediators. One of the most important mediators is gastrin, which stimulates gastric acid secretion from parietal cells mostly indirectly, by the release of histamine from enterochromaffin-like (ECL) cells. Therapy with antisecretory agents leads to hypergastrinemia, mucosal hyperplasia and increased ECL cell mass, which results in increase of gastric acid secretion capacity. This increased secretion capacity has been shown to manifest itself after antisecretory therapy withdrawal as rebound acid hypersecretion (RAH). Various studies have quantified acid hypersecretion after the cessation of therapy with H(2) antagonists and proton-pump inhibitors (PPIs). While most of those studies had small patient numbers, the findings generally demonstrate that RAH after H(2) antagonist therapy is of low magnitude, short duration, and has questionable clinical significance. On the contrary, acid hypersecretion after PPI therapy is more pronounced, lasts longer, and could possibly be the cause of acid-related symptoms. Potential for causing symptoms has recently been confirmed in two randomized placebo-controlled studies, and while we witness the increasing use of PPIs, RAH could become a proven cause of failure to withdraw therapy in a proportion of patients with reflux or dyspeptic symptoms.

Nutritional Screening Model in Tertiary Medical Unit in Croatia

Abstract: Background/Aims: Malnutrition of hospitalized patients is often undetected and untreated due to poor awareness and insufficient knowledge of the attending hospita

Non-alcoholic fatty liver disease and dyslipidemia: An update

Abstract: Non-alcoholic fatty liver (NAFLD) is the most common liver disease worldwide, progressing from simple steatosis to necroinflammation and fibrosis (leading to non-alcoholic steatohepatitis, NASH), and in some cases to cirrhosis and hepatocellular carcinoma Inflammation, oxidative stress and insulin resistance are involved in NAFLD development and progression NAFLD has been associated with several cardiovascular (CV) risk factors including obesity, dyslipidemia, hyperglycemia, hypertension and smoking NAFLD is also characterized by atherogenic dyslipidemia, postprandial lipemia and high-density lipoprotein (HDL) dysfunction Most importantly, NAFLD patients have an increased risk for both liver and CV disease (CVD) morbidity and mortality In this narrative review, the associations between NAFLD, dyslipidemia and vascular disease in NAFLD patients are discussed NAFLD treatment is also reviewed with a focus on lipid-lowering drugs Finally, future perspectives in terms of both NAFLD diagnostic biomarkers and therapeutic targets are considered

Animal models of non-alcoholic fatty liver disease: current perspectives and recent advances.

Abstract: Non-alcoholic fatty liver disease (NAFLD) is a continuous spectrum of diseases characterized by excessive lipid accumulation in hepatocytes. NAFLD progresses from simple liver steatosis to non-alcoholic steatohepatitis and, in more severe cases, to liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Because of its growing worldwide prevalence, various animal models that mirror both the histopathology and the pathophysiology of each stage of human NAFLD have been developed. The selection of appropriate animal models continues to be one of the key questions faced in this field. This review presents a critical analysis of the histopathology and pathogenesis of NAFLD, the most frequently used and recently developed animal models for each stage of NAFLD and NAFLD-induced HCC, the main mechanisms involved in the experimental pathogenesis of NAFLD in different animal models, and a brief summary of recent therapeutic targets found by the use of animal models. Integrating the data from human disease with those from animal studies indicates that, although current animal models provide critical guidance in understanding specific stages of NAFLD pathogenesis and progression, further research is necessary to develop more accurate models that better mimic the disease spectrum, in order to provide both increased mechanistic understanding and identification/testing of novel therapeutic approaches. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Adipokines in nonalcoholic fatty liver disease.

Abstract: Since the discovery of adipose tissue as a higly active endocrine tissue, adipokines, peptides produced by adipose tissue and exerting autocrine, paracrine and endocrine function, have gained increasing interest in various obesity-related diseases, including nonalcoholic fatty liver disease (NAFLD). Data regarding the association between NAFLD and circulating leptin and adiponectin levels are generally well documented: leptin levels increase, whereas adiponectin levels decrease, by increasing the severity of NAFLD. Data regarding other adipokines in histologically confirmed NAFLD populations are inconclusive (e.g., resistin, visfatin, retinol-binding protein-4, chemerin) or limited (e.g., adipsin, obestatin, omentin, vaspin etc.). This review summarizes evidence on the association between adipokines and NAFLD. The first part of the review provides general consideration on the interplay between adipokines and NAFLD, and the second part provides evidence on specific adipokines possibly involved in NAFLD pathogenesis. A thorough insight into the pathophysiologic mechanisms linking adipokines with NAFLD may result in the design of studies investigating the combined adipokine use as noninvasive diagnostic markers of NAFLD and new clinical trials targeting the treatment of NAFLD.