Non-invasive biomarkers in chronic liver disease PDF Download

Author: Dr Julie Parkes
Publisher:
ISBN:
Category :
Languages : en
Pages : 263

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Author: Markus Karlsson
Publisher: Linköping University Electronic Press
ISBN: 9179299423
Category :
Languages : en
Pages : 77

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Book Description
There is a large and unmet need for diagnostic tool that can be used to characterize chronic liver diseases (CLD). In the earlier stages of CLD, much of the diagnostics involves performing biopsies, which are evaluated by a histopathologist for the presence of e.g. fat, iron, inflammation, and fibrosis. Performing biopsies, however, have two downsides: i) biopsies are invasive and carries a small but non-negligible risk for serious complications, ii) biopsies only represents a tiny portion of the liver and are thus prone to sampling error. Moreover, in the later stages of CLD, when the disease has progressed far enough, the ability of the liver to perform its basic function will be compromised. In this stage, there is a need for better methods for accurately measuring liver function. Additionally, measures of liver function can also be used when developing new drugs, as biomarkers for drug-induced liver injury (DILI), which is a serious drug-safety issue. Magnetic resonance imaging (MRI) is a non-invasive medical imaging modality, which have shown much promise with regards to characterizing liver disease in all of the abovementioned aspects. The aim of this PhD project was to develop and validate MR-based methods that can be used to non-invasively characterize liver disease. Paper I investigated if R2* mapping, a MR-method for measuring liver iron content, can be confounded by liver fat. The results show fat does affect R2*. The conclusion was therefore that fat must be taken into account when measuring small amounts of liver iron, as a small increase in R2* could be due to either small amounts of iron or large amounts of fat. Paper II examined whether T1 mapping, which is another MR-method, can be used for staging liver fibrosis. The results of previous research have been mixed; some studies have been very promising, whereas other studies have been less promising. Unfortunately, the results in Paper II belongs to the less promising studies. Paper III focused on measuring liver function by dynamic contrast-enhanced MRI (DCEMRI) using a liver specific contrast agent, which is taken up the hepatocytes and excreted to the bile. The purpose of the paper was to extend and validate a method for estimating uptake and efflux rates of the contrast agent. The method had previously only been applied in health volunteers. Paper II showed that the method can be applied to CLD patients and that the uptake of the contrast agent is lower in patients with advanced fibrosis. Paper IV also used studied liver function with DCE-MRI in patients with primary sclerosing cholangitis (PSC). PSC is a CLD where the bile ducts are attacked by the immune system. When diagnosing PSC patients, it is common to use magnetic resonance cholangiopancreatography (MRCP), which is a method for imaging the bile ducts. Paper IV examined if there was any correlation between number and severity of the morphological changes, seen on MRCP, and measures of liver function derived using DCE-MRI. However, the results showed no such correlation. The conclusion was that the results indicates that MRCP should not be used to predict parenchymal function. Paper V developed a method for translating DCE-MRI liver function parameters from rats to humans. This translation could be of value when developing new drugs, as a tool for predicting which drugs might cause drug-induced liver injury. In summary, this thesis has shown that multimodal quantitative MR has a bright future for characterizing liver disease from a range of different aspects.

Author: Victor R. Preedy
Publisher: Springer
ISBN: 9789400776746
Category : Medical
Languages : en
Pages : 0

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In the past decade there has been a major sea change in the way disease is diagnosed and investigated due to the advent of high throughput technologies, such as microarrays, lab on a chip, proteomics, genomics, lipomics, metabolomics etc. These advances have enabled the discovery of new and novel markers of disease relating to autoimmune disorders, cancers, endocrine diseases, genetic disorders, sensory damage, intestinal diseases etc. In many instances these developments have gone hand in hand with the discovery of biomarkers elucidated via traditional or conventional methods, such as histopathology or clinical biochemistry. Together with microprocessor-based data analysis, advanced statistics and bioinformatics these markers have been used to identify individuals with active disease or pathology as well as those who are refractory or have distinguishing pathologies. New analytical methods that have been used to identify markers of disease and is suggested that there may be as many as 40 different platforms. Unfortunately techniques and methods have not been readily transferable to other disease states and sometimes diagnosis still relies on single analytes rather than a cohort of markers. There is thus a demand for a comprehensive and focused evidenced-based text and scientific literature that addresses these issues. Hence the formulation of Biomarkers in Disease The series covers a wide number of areas including for example, nutrition, cancer, endocrinology, cardiology, addictions, immunology, birth defects, genetics, and so on. The chapters are written by national or international experts and specialists.

Author: Gabriela Gutierrez-Reyes
Publisher:
ISBN:
Category : Electronic books
Languages : en
Pages : 0

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The clinical importance of monitoring liver fibrosis lies in the morbidity and mortality of the chronic liver diseases in relation to the stage and progression of fibrosis. Whether the fibrosis stabilizes or regresses depends on the specific treatment. Liver biopsy, the current standard for the diagnosis, has implicit limitations due to sampling heterogeneity. There are noninvasive imaging methods, such as transient elastography that measures the stiffness of the liver, but it has some limitations (feasibility and unreliability), particularly in obese patients. FibroTest is the most widely used noninvasive serological method worldwide which is efficacious in the extreme stages of fibrosis, but these methods cannot discern intermediate stages. Liver fibrosis is a dynamic response that involves multiple cellular and molecular events with an excessive deposit of extracellular matrix. Even though there is much information on the pathophysiology of fibrosis, that knowledge is still incomplete, greatly hindering the development of both an accurate treatment and a noninvasive diagnostic method with adequate sensitivity for all the stages of fibrosis. It is known that IGFBP participates in liver homeostasis, and thus these proteins can be used as serum biomarkers during the progression of liver fibrosis in chronic hepatitis C.

Author: Manuel Romero-Gomez
Publisher: Springer Nature
ISBN: 3030371735
Category : Medical
Languages : en
Pages : 239

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Book Description
This book provides a comprehensive overview of the diagnosis and management of Non-alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatis (NASH). Basic principles of disease progression, the genetic and nutritional basis of NAFLD and NASH are explained along with the proteomic principles underlying biomarker development. Chapters cover both biochemical and imaging biomarkers used in elastrography and ultrasound and discuss how these are applicable to early diagnosis and monitoring of NASH and NAFLD. This is a useful resource for hepatologists, primary care providers with an interest in metabolic disease, diabetologists and endocrinologists in their daily clinical practice.

Author: Georgios Tsoulfas
Publisher: BoD – Books on Demand
ISBN: 9535133098
Category : Medical
Languages : en
Pages : 304

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Book Description
Liver cirrhosis represents one of the major challenges for most physicians and surgeons on a global scale. This book provides practicing hepatologists, gastroenterologists and liver surgeons with a valuable tool in their efforts to understand the (molecular) mechanisms involved, be updated regarding the newest and less invasive diagnostic methods, and educate themselves about the challenges involved in the management of liver cirrhosis and its complications. The authors of this book represent a team of true global experts on the topic. In addition to the knowledge shared, the authors provide their personal clinical experience on a variety of different aspects of liver cirrhosis, giving us a well-rounded overview.

Author: Mikael Forsgren
Publisher: Linköping University Electronic Press
ISBN: 9176855724
Category :
Languages : en
Pages : 126

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Book Description
The liver is one of the largest organs within the human body and it handles many vital tasks such as nutrient processing, toxin removal, and synthesis of important proteins. The number of people suffering from chronic liver disease is on the rise, likely due to the present ‘western’ lifestyle. As disease develops in the liver there are pathophysiological manifestations within the liver parenchyma that are both common and important to monitor. These manifestations include inflammation, fatty infiltration (steatosis), excessive scar tissue formation (fibrosis and cirrhosis), and iron loading. Importantly, as the disease progresses there is concurrent loss of liver function. Furthermore, postoperative liver function insufficiency is an important concern when planning surgical treatment of the liver, because it is associated with both morbidity and mortality. Liver function can also be hampered due to drug-induced injuries, an important aspect to consider in drug-development. Currently, an invasive liver needle biopsy is required to determine the aetiology and to stage or grade the pathophysiological manifestations. There are important limitations with the biopsy, which include, risk of serious complications, mortality, morbidity, inter- and intra-observer variability, sampling error, and sampling variability. Cleary, it would be beneficial to be able investigate the pathophysiological manifestations accurately, non-invasively, and on regional level. Current available laboratory liver function blood panels are typically insufficient and often only indicate damage at a late stage. Thus, it would be beneficial to have access to biomarkers that are both sensitive and responds to early changes in liver function in both clinical settings and for the pharmaceutical industry and regulatory agencies. The main aim of this thesis was to develop and evaluate methods that can be used for a ‘non-invasive liver biopsy’ using magnetic resonance (MR). We also aimed to develop sensitive methods for measure liver function based on gadoxetate-enhanced MR imaging (MRI). The presented work is primarily based on a prospective study on c. 100 patients suffering from chronic liver disease of varying aetiologies recruited due to elevated liver enzyme levels, without clear signs of decompensated cirrhosis. Our results show that the commonly used liver fat cut-off for diagnosing steatosis should be lowered from 5% to 3% when using MR proton-density fat fraction (PDFF). We also show that MR elastography (MRE) is superior in staging fibrosis. Finally we presented a framework for quantifying liver function based on gadoxetate-enhanced MRI. The method is based on clinical images and a clinical approved contrast agent (gadoxetate). The framework consists of; state-of the-art image reconstruction and correction methods, a mathematical model, and a precise model parametrization method. The model was developed and validated on healthy subjects. Thereafter the model was found applicable on the chronic liver disease cohort as well as validated using gadoxetate levels in biopsy samples and blood samples. The liver function parameters correlated with clinical markers for liver function and liver fibrosis (used as a surrogate marker for liver function). In summary, it should be possible to perform a non-invasive liver biopsy using: MRI-PDFF for liver fat and iron loading, MRE for liver fibrosis and possibly also inflammation, and measure liver function using the presented framework for analysing gadoxetate-enhanced MRI. With the exception of an MREtransducer no additional hardware is required on the MR scanner. The liver function method is likely to be useful both in a clinical setting and in pharmaceutical trials.

Author: Catherine Emer Fitzpatrick
Publisher:
ISBN:
Category : Biochemical markers
Languages : en
Pages : 416

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Book Description
Prevalence of nonalcoholic fatty liver disease (NAFLD) in children is rising exponentially, mirroring the increase in paediatric obesity. The spectrum ranges from simple steatosis to inflammation and fibrosis (nonalcoholic steatohepatitis/NASH). A third of those with NASH may develop cirrhosis and/or hepatocellular carcinoma. Liver biopsy is the standard for establishing the diagnosis and assessing severity, but is limited by the potential risks. There is a real need for noninvasive methods of screening, stratifying disease severity and following disease progression over time. This thesis explores and evaluates noninvasive biomarkers of disease in children with NAFLD. -- An initial pilot study (n=45) evaluated serum markers of apoptosis, inflammation and fibrogenesis. CK18-M30 and leptin concentrations were found to be valuable markers of NAFLD activity. Following this, a panel of adipokines was investigated in a cohort of children with NAFLD (n=40). Plasminogen activator inhibitor, monocyte chemoattractant protein 1 and resistin were useful markers of disease. A prospective study (n=101) then combined transient elastography (TE) and blood biomarkers in children with various forms of chronic liver disease (including NAFLD). TE was the best predictor of fibrosis severity (AUROC 0.96 for cirrhosis). -- Proteomic studies suggest that the glycoprotein, lumican, may be a potential biomarker of NAFLD. Expression of lumican in liver tissue of children with NAFLD was quantified using histomorphometry and molecular biology. Lumican was found to be overexpressed at protein level (by 215%) and upregulated at pre-translational level (15x) with more severe disease. Finally, the role of glycosylation in NAFLD was evaluated by characterising the glycomic profile in serum of 51 paediatric patients. -- In conclusion, this thesis describes and evaluates a variety of noninvasive biomarkers of paediatric NAFLD.

Author: Annalisa Berzigotti
Publisher: Springer
ISBN: 3319726285
Category : Medical
Languages : en
Pages : 337

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Book Description
This book provides a unique up-to-date and comprehensive overview of the most important diagnostic methods available for assessing liver cirrhosis and portal hypertension. The book covers all the significant advances made in the last 10 years in HVPG and biopsy interpretation, imaging and elastography. This is a unique and well structured book authored by senior experts in the field aimed at providing updated knowledge to the hepatology specialist and to the physicians interested in chronic liver disease. The book starts by giving an overview of the disease, outlining the clinical needs in this field; this is followed by detailed information both on the invasive gold-standard methods (HVPG measurement, liver biopsy, endoscopy), and on the standard and emerging non-invasive methods, including serum markers of fibrosis, ultrasound-elastography, magnetic resonance elastography, ultrasound, contrast-enhanced ultrasound, CT, magnetic resonance and derived methods (dynamic flow assessment). The final part of the book is devoted to diagnostic tests in non-cirrhotic causes of portal hypertension (Budd-Chiari Syndrome, Portal vein thrombosis, idiopathic portal hypertension, etc), and in pediatric portal hypertension. Written by a team of worldwide opinion leaders this book pays special attention to the most promising novel non-invasive methods in the field.

Author: Florentina Radu-Ionita
Publisher: Springer Nature
ISBN: 3030244326
Category : Medical
Languages : en
Pages : 806

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Book Description
This book provides an in-depth coverage not only of liver pathology but also of diagnosis of the numerous types of liver disease, placing specific emphasis on current treatments of liver pathology including the most up-to-date information on liver transplantation. The first part of provides an in-depth account of the liver pathology in different conditions such as Hepatits, liver ischaemia reperfusion injury, Lyme disease, cirrhotic cardiomyopathy and hepatocellular carcinoma. The second part provides a comprehensive overview of diagnostic methods. Of particular interest are chapters on the latest techniques in Patient-specific 3D printing and transient elastography (FibroScan). The final part focuses on treatment and provides a step-by step guide to the therapeutic management of liver diseases starting with pharmacological treatment and techniques including surgery and liver transplantation. This is an invaluable book for clinicians, practitioners including academics, scientists/researchers and postgraduates to provide the newest knowledge in the field of liver pathogenesis. It is written by a multidisciplinary team of experts in hepathology, gastroenterology, and surgery especially from liver transplantation.