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Non-alcoholic fatty liver disease and obesity: Biochemical, metabolic and clinical presentations

World Journal of Gastroenterology 2014年第28期20卷 9330-9337页

作者： sandra milic Davorka Lulic Davor Stimac Division of Gastroenterology Department of Internal MedicineUniversity Hospital Rijeka

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world. Presentation of the disease ranges from simple steatosis to non-alcoholic steatohepatitis (NASH). NAFLD is a hepatic manifestation of metabolic syndrome that includes central abdominal obesity along with other components. Up to 80% of patients with NAFLD are obese, defined as a body mass index (BMI) > 30 kg/m2. However, the distribution of fat tissue plays a greater role in insulin resistance than the BMI. The large amount of visceral adipose tissue (VAT) in morbidly obese (BMI > 40 kg/m2) individuals contributes to a high prevalence of NAFLD. Free fatty acids derived from VAT tissue, as well as from dietary sources and de novo lipogenesis, are released to the portal venous system. Excess free fatty acids and chronic low-grade inflammation from VAT are considered to be two of the most important factors contributing to liver injury progression in NAFLD. In addition, secretion of adipokines from VAT as well as lipid accumulation in the liver further promotes inflammation through nuclear factor kappa B signaling pathways, which are also activated by free fatty acids, and contribute to insulin resistance. Most NAFLD patients are asymptomatic on clinical presentation, even though some may present with fatigue, dyspepsia, dull pain in the liver and hepatosplenomegaly. Treatment for NAFLD and NASH involves weight reduction through lifestyle modifications, anti-obesity medication and bariatric surgery. This article reviews the available information on the biochemical and metabolic phenotypes associated with obesity and fatty liver disease. The relative contribution of visceral and liver fat to insulin resistance is discussed, and recommendations for clinical evaluation of affected individuals is provided.

关键词： Fatty liver Insulin resistance Intra-abdominal fat Metabolism Non-alcoholic fatty liver disease Obesity

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Advances in diagnosis of chronic liver diseases in pediatric patients

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World Journal of Pediatrics 2018年第6期14卷 541-547页

作者： Lucija Ruzman Ivana Mikolasevic Kristina Baraba Dekanic sandra milic Goran Palcevski Pediatric Clinic UHC RijekaIstarska 4351000 RijekaCroatia Department of Gastroenterology UHC RijekaRijekaCroatia Pediatric Clinic Department of GastroenterologyUHC RijekaRijekaCroatia

Background Chronic liver diseases (CLD) present important clinical problem in children with various age-dependent causes. Nonalcoholic fatty liver disease (NAFLD) with its increasing prevalence is a major problem with regard to its timely recog-nition and the need for long-term disease monitoring. At present, a perfect non-invasive method for the evaluation of liver fibrosis is not available. Methods A non-systematic literature search was performed to summarize the current knowledge about transient elastog-raphy (TE) with controlled attenuation parameter (CAP) in children with CLD. Ovid MEDLINE, Ovid EMBASE, Google scholar, and The Cochrane Library databases were searched for relevant articles evaluating TE in the pediatric population. Results Normal values of liver stiffness measurements (LSM) according to the age are given, as well as the advantages and disadvantages of the method. The utility of TE in specific liver disease in pediatric population is summarized. Conclusions TE with CAP is a valuable non-invasive method for the liver-damage assessment. Clinical interpretation of TE results should be made in parallel with the assessment of the patient's demographics, disease etiology, and essential laboratory parameters.

关键词： Child Liver disease Liver stiffness Pediatric Transient elastography

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Transient elastography(Fibro Scan~?) with controlled attenuation parameter in the assessment of liver steatosis and fibrosis in patients with nonalcoholic fatty liver disease- Where do we stand?

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World Journal of Gastroenterology 2016年第32期22卷 7236-7251页

作者： Ivana Mikolasevic Lidija Orlic Neven Franjic Goran Hauser Davor Stimac sandra milic Department of Gastroenterology UHC Rijeka Department of Nephrology Dialysis and Kidney Transplantation UHC Rijeka

Non-alcoholic fatty liver disease(NAFLD) is the most common cause of chronic liver disease worldwide. Currently, the routinely used modalities are unable to adequately determine the levels of steatosis and fibrosis(laboratory tests and ultrasonography) or cannot be applied as a screening procedure(liver biopsy). Among the non-invasive tests, transient elastography(Fibro Scan?, TE) with controlled attenuation parameter(CAP) has demonstrated good accuracy in quantifying the levels of liver steatosis and fibrosis in patients with NAFLD, the factors associated with the diagnosis and NAFLD progression. The method is fast, reliable and reproducible, with good intra- and interobserver levels of agreement, thus allowing for population-wide screening and disease follow-up. The initial inability of the procedure to accurately determine fibrosis and steatosis in obese patients has been addressed with the development of the obese-specific XL probe. TE with CAP is a viable alternative to ultrasonography, both as an initial assessment and during follow-up of patients with NAFLD. Its ability to exclude patients with advanced fibrosis may be used to identify low-risk NAFLD patients in whom liver biopsy is not needed, therefore reducing the risk of complications and the financial costs.

关键词： Non-alcoholic fatty liver disease Transient elastography Controlled attenuation parameter

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Nonalcoholic fatty liver disease-A multisystem disease?

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World Journal of Gastroenterology 2016年第43期22卷 9488-9505页

作者： Ivana Mikolasevic sandra milic Tamara Turk Wensveen Ivana Grgic Ivan Jakopcic Davor Stimac Felix Wensveen Lidija Orlic Department of Gastroenterology UHC Rijeka51000 Rijeka Croatia Department of Endocrinology Diabetes and Metabolic Diseases UHC Rijeka51000 Rijeka Croatia Department of Cardiology UHC Rijeka51000 Rijeka Croatia School of Medicine 51000 Rijeka Croatia Department of Histology and Embryology School of Medicine51000 Rijeka Croatia Department of Nephrology Dialysis and Kidney Transplantation UHC Rijeka51000 Rijeka Croatia

Non-alcoholic fatty liver disease(NAFLD) is one of the most common comorbidities associated with overweight and metabolic syndrome(Met S). Importantly, NAFLD is one of its most dangerous complications because it can lead to severe liver pathologies, including fibrosis, cirrhosis and hepatic cellular carcinoma. Given the increasing worldwide prevalence of obesity, NAFLD has become the most common cause of chronic liver disease and therefore is a major global health problem. Currently, NAFLD is predominantly regarded as a hepatic manifestation of Met S. However, accumulating evidence indicates that the effects of NAFLD extend beyond the liver and are negatively associated with a range of chronic diseases, most notably cardiovascular disease(CVD), diabetes mellitus type 2(T2DM) and chronic kidney disease(CKD). It is becoming increasingly clear that these diseases are the result of the same underlying pathophysiological processes associated with Met S, such as insulin resistance, chronic systemic inflammation and dyslipidemia. As a result, they have been shown to be independent reciprocal risk factors. In addition, recent data have shown that NAFLD actively contributes to aggravation of the pathophysiology of CVD, T2 DM, and CKD, as well as several other pathologies. Thus, NAFLD is a direct cause of many chronic diseases associated with MetS, and better detection and treatment of fatty liver disease is therefore urgently needed. As non-invasive screening methods for liver disease become increasingly available, detection and treatment of NAFLD in patients with MetS should therefore be considered by both(sub-) specialists and primary care physicians.

关键词： Nonalcoholic fatty liver disease Metabolic syndrome Diabetes mellitus type 2 Cardiovascular disease Chronic kidney disease Multisystem disease

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Nonalcoholic fatty liver disease and liver transplantation-Where do we stand?

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World Journal of Gastroenterology 2018年第14期24卷 1491-1506页

作者： Ivana Mikolasevic Tajana Filipec-Kanizaj Maja Mijic Ivan Jakopcic sandra milic Irena Hrstic Nikola Sobocan Davor Stimac Patrizia Burra Department of Gastroenterology UHC Rijeka School of Medicine University of Rijeka Department of Gastroenterology University Hospital MerkurSchool of Medicine University of Zagreb Department of Internal medicine General Hospital Pula Pula School of Medicine University of Rijeka and Zagreb Multivisceral Transplant Unit Department of Surgery Oncology and Gastroenterology Padua University Hospital

Nonalcoholic fatty liver disease/nonalcoholic steatohepatitis(NAFLD/NASH) is a challenging and multisystem disease that has a high socioeconomic impact. NAFLD/NASH is a main cause of macrovesicular steatosis and has multiple impacts on liver transplantation(LT), on patients on the waiting list for transplant, on posttransplant setting as well as on organ donors. Current data indicate new trends in the area of chronic liver disease. Due to the increased incidence of metabolic syndrome(Met S) and its components, NASH cirrhosis and hepatocellular carcinoma caused by NASH will soon become a major indication for LT. Furthermore, due to an increasing incidence of Met S and, consequently, NAFLD, there will be more steatotic donor livers and less high quality organs available for LT, in addition to a lack of available liver allografts. Patients who have NASH and are candidates for LT have multiple comorbidities and are unique LT candidates. Finally, we discuss long-term grafts and patient survival after LT, the recurrence of NASH and NASH appearing de novo after transplantation. In addition, we suggest topics and areas that require more research for improving the health care of this increasing patient population.

关键词： nonalcoholic steatohepatitis chronic liver disease liver transplantation nonalcoholic fatty liver disease outcome

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Liver disease in the era of COVID-19: Is the worst yet to come?

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World Journal of Gastroenterology 2021年第36期27卷 6039-6052页

作者： Ivana Mikolasevic Dorotea Bozic Tajana Pavić Alen Ruzic Goran Hauser Marija Radic Delfa Radic-Kristo Melanija Razov-Radas Zeljko Puljiz sandra milic Department of Gastroenterology Clinical Hospital Center RijekaRijeka 51000Croatia Department of Gastroenterology University Hospital MerkurZagreb 10000Croatia Faculty of Medicine University of RijekaRijeka 51000Croatia Department for Gastroenterology and Hepatology University Hospital Center SplitSplit 21000Croatia Department of Gastroenterology and Hepatology Faculty of MedicineSestre Milosrdnice University Hospital CenterZagreb 10000Croatia Clinic for Cardiology University Hospital Center RijekaRijeka 51000Croatia Faculty of Health Studies University of RijekaRijeka 51000Croatia Faculty of Medicine Zagreb 10000Croatia Department of Hematology University Hospital MerkurZagreb 10000Croatia Division of Gastroenterology General Hospital ZadarZadar 23000Croatia University of Split School of MedicineSplit 21000Croatia

The global social,economic and political crises related to coronavirus disease 2019(COVID-19)presumably had more indirect than direct negative impacts on health *** lifestyle changes,social isolation and distancing,and individual and global financial crises resulted in robust populations forfeiting healthy habits and seeking comfort in alcoholic beverages,drugs and unhealthy *** inevitable consequences are increases in the incidence of nonalcoholic fatty liver disease,viral hepatitis,acute alcoholic hepatitis,liver cirrhosis decompensation and ultimately liver-related *** inaccessibility of regular clinical and sonographic monitoring systems has caused difficulties in the treatment of patients with chronic liver disease(CLD)and has prevented prompt hepatocellular carcinoma detection and treatment.A dramatic reduction in the number of liver donors and the transformation of numerous transplantation centers into COVID-19 units drastically decreased the rate of orthotopic liver *** indirect,unavoidable effects of the COVID-19 pandemic in the following years have yet to be *** efforts in the management of patients with liver disease in order to overcome the inevitable COVID-19-related morbidity and mortality that will follow have yet to be *** questions regarding the impact of the COVID-19 pandemic on liver disease *** most important question for general CLD patients is:How will the modification of clinical practice during this pandemic affect the outcomes of CLD patients?This article reviews the influence of COVID-19 on patients with liver disease during the pandemic,with particular emphasis on the disease course associated with pandemic resolution.

关键词： COVID-19 Pandemic Chronic liver disease Management Impact Liverrelated mortality

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Assessment of food supplementation and surveillance as techniques to reduce damage caused by black capuchin monkeys Sapajus nigritus to forest plantations

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Current Zoology 2014年第5期60卷 581-590页

作者： sandra Bos MIKICH Laboratory of Ecology (Laborat6rio de Ecologia) Embrapa Florestas Caixa Postal 319 CEP 83411-000 Colombo PR Brazil Black Capuchin Monkey Program (Programa Macaco-prego) National Fund for the Control of Forest Pests (Fundo Nacional de Controle de Pragas Florestais) Dieter Liebsch Environmental Consulting (Dieter Liebsch Consultoria Ambiental) Curitiba PR Brazil dieterliebsch@yahoo.com.br

Black capuchin monkeys Sapajus nigritus are among several mammalian species that damage forest plantations, pri- marily plantations of pine trees （Pinus spp.） in South Brazil. Management practices to reduce these damages include supplemen- tary food offerings and plantation surveillance. To assess the efficiency of these techniques, four treatments were evaluated： feeding （F, with supplementary bananas and maize）, surveillance （S, in situ, wherein men patrolled the plantations, deterring the monkeys）, feeding ＋ surveillance （FS） and control （no procedures）（C）. The efficiency assessment of each treatment involved the number of recorded primate sightings in the treatments with the presence of guards （S and FS） and a damage inventory of the outskirts of the experimental points immediately before and after the experiment. These data were complemented by a simulta- neous study of the availability of fruit, the primary item in the diet of this primate species, in the remnant native forest in the study area. Most sightings of S. nigritus occurred early in the morning, and in general, sightings were inversely proportional to the availability of native fruits. This trend was most evident in treatment FS, most likely due to the presence of food. Treatments F and FS exhibited higher percentages of damage, indicating that these are inefficient management techniques. Treatment S exhi- bited the lowest damage rate, but at a high cost, making this technique difficult to apply over large expanses. The development of other management techniques, such as environmental enrichment and the use of deterrents, is recommended to minimize the damage caused by capuchins in forest plantations [Current Zoology 60 （5）： 581-590, 2014].

关键词： Cebus Damage control Wildlife management Pinus Food provisioning

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Pork Meat Quality of Preto Alentejano and Commercial Largewhite Landrace Cross

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Journal of Integrative Agriculture 2013年第11期12卷 1961-1971页

作者： Alfredo Teixeira sandra Rodrigues Veterinary and Animal Reserch Centre (CECAV) Agrarian School of Polytechnic Institute of BraganaCampus Sta Apolónia Apt.1172Bragan a 5301-855Portugal Mountain Research Centre(CIMO) Agrarian School of Polytechnic Institute of BraganaCampus Sta Apolónia Apt.1172Bragan a 5301-855Portugal

This work aimed to evaluate the physical-chemical characteristics of pork from a local breed （Portuguese black pork called Preto Alentejano） and a commercial breed. Sixteen animals were used, 4 females and 4 males from each breed. Animals had 80-100 kg of live weight. The longissimus muscle between the 5th thoracic vertebra and the 10th lumbar vertebra was used in the analysis. Samples were analysed for protein, fat, pigments, ashes, dry mater, water-holding capacity, and texture. Results of fat and pigments contents indicate signiifcant （P〈0.05 and P〈0.01） differences for all treatments. For protein, ashes, dry mater, water-holding capacity and texture, no signiifcant differences were found for sex. In the analysis of fatty acids composition, ten were detected, being the main ones C16：0, C18：0, C16：1, C18：1, C18：2. There was a predominance of monounsaturated fatty acids （MUFA）, followed by saturated （SFA） and polyunsaturated （PUFA）. Differences were signiifcant for sex （P〈0.01） and breed （P〈0.01）. Preto Alentejano breed and females presented the higher percentages of SFA （P〈0.01） and MUFA （P〈0.001） fatty acids. Differences between breeds might be due to breed production system and feed differences.

关键词： breed sex pork meat quality

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Catalytic domain of PDC-E2 contains epitopes recognized by antimitochondrial antibodies in primary biliary cirrhosis

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World Journal of Gastroenterology 2010年第8期16卷 973-981页

作者： sandra Braun Christoph Berg sandra Buck Michael Gregor Reinhild Klein Department of Internal Medicine University of Tuebingen Department of Internal Medicine University of Tuebingen

AIM:To search for further immunodominant peptides of the pyruvate dehydrogenase complex E2-component (PDC-E2) recognized by antimitochondrial antibodies (AMA) in primary biliary cirrhosis (PBC). METHODS:Sera from 95 patients with PBC were tested by enzyme-linked immunosorbent assay against 33 synthetic overlapping peptides (25 amino acids; aa) covering the entire length of the E2-subunit of PDC-E2. Furthermore,the inner lipoyl peptide 167-184 was used in an unlip oylated and a lipoylated form as well as coupled to ovalbumin. Sera from 11 AMA negative/ANA posit ive PBC patients,63 patients with other liver disorders and 22 healthy blood donors served as ***:Of the 95 PBC-sera,74% reacted with the peptide 475-499 and 58% with the pept ide 407-431 located within the catalytic domain of PDC-E2. Patients with other disorders or healthy controls were positive in only up to 18%. Antibodies to the unlipoylatedand lip oylated pept ide 167-184 within the inner lipoyl domain were found in only 5% and 11% of the PBC sera,respectively; using ovalbumin-coupled peptides,the incidence increased up to 57% (unlipoylated form). CONCLUSION:Peptides within the catalytic site of PDC-E2 rather than the previously reported lipoyl binding peptide 167-184 may represent major immunodomin ant epitopes recognized by AMA in PBC.

关键词： Anti-M2 Epitope mapping E2-subunit Pyruvate dehydrogenase complex Inner lipoyl domain Active site Catalytic domain Primary biliary cirrhosis

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Hyper-chaos encryption using convolutional masking and model free unmasking

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Chinese Physics B 2014年第5期23卷 161-166页

作者：齐国元 sandra Bazebo Matondo Department of Electrical Engineerin Tshwane University of Technology Pretoria

In this paper, during the masking process the encrypted message is convolved and embedded into a Qi hyper-chaotic system characterizing a high disorder degree. The masking scheme was tested using both Qi hyper-chaos and Lorenz chaos and indicated that Qi hyper-chaos based masking can resist attacks of the filtering and power spectrum analysis, while the Lorenz based scheme fails for high amplitude data. To unmask the message at the receiving end, two methods are proposed. In the first method, a model-free synchronizer, i.e. a multivariable higher-order differential feedback controller between the transmitter and receiver is employed to de-convolve the message embedded in the receiving signal. In the second method, no synchronization is required since the message is de-convolved using the information of the estimated derivative.

关键词： Qi hyper-chaos masking high-order differentiator chaos-based encryption

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