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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.
This book provides an introduction to the field of biomarkers, how they have been and can be used, and how different approaches can be used to identify, characterize, and monitor biomarkers. The book has chapters on topics including HIV, Cancer, Parkinson’s, vascular injury, environmental exposure. A following section discusses the technologies (diagnostics and assays) to detect biomarkers and authors have emphasized the preclinical and clinical manifestation of the injury/disease process.
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.
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.
This book discusses clinical advances in hepatology, with a focus on metabolic diseases and chronic hepatitis C. The development of direct-acting antiviral (DAA) agents for the treatment of hepatitis C virus (HCV) infection in 2010 has completely transformed the management of this disease. This transformative nature of DAA therapy underpins the goal of the World Health Organization (WHO) to eliminate HCV infection as a public health threat by 2030. The advantages of using these therapies include high efficacy (sustained virological response rate >95%) with minimal side effects, good tolerability, easy drug administration (once-daily oral dosing) and short duration of treatment (8-12 weeks). The commercialization of second-generation DAA agents due to their high effectiveness, few side-effects and pangenotypic action. This transformative nature of DAA therapy underpins the goal of the WHO to eliminate HCV infection as a public health threat by 2030.
This book provides a comprehensive overview of the current limitations and unmet needs in Hepatocellular Carcinoma (HCC) diagnosis, treatment, and prevention. It also provides newly emerging concepts, approaches, and technologies to address challenges. Topics covered include changing landscape of HCC etiologies in association with health disparities, framework of clinical management algorithm, new and experimental modalities of HCC diagnosis and prognostication, multidisciplinary treatment options including rapidly evolving molecular targeted therapies and immune therapies, multi-omics molecular characterization, and clinically relevant experimental models. The book is intended to assist collaboration between the diverse disciplines and facilitate forward and reverse translation between basic and clinical research by providing a comprehensive overview of relevant areas, covering epidemiological trend and population-level patient management strategies, new diagnostic and prognostic tools, recent advances in the standard care and novel therapeutic approaches, and new concepts in pathogenesis and experimental approaches and tools, by experts and opinion leaders in their respective fields. By thoroughly and concisely covering whole aspects of HCC care, Hepatocellular Carcinoma serves as a valuable reference for multidisciplinary readers, and promotes the development of personalized precision care strategies that lead to substantial improvement of disease burden and patient prognosis in HCC.
This book aims to aid the selection of the most appropriate methods for use in early phase (1 and 2) clinical studies of new drugs for diabetes, obesity, non-alcoholic fatty liver disease (NAFLD) and related cardiometabolic disorders. Clinical research methods to assess the pharmacokinetics and pharmacodynamics of new diabetes drugs, e.g. the euglycemic clamp technique, have become well-established in proof-of-mechanism studies. However, selection of the most appropriate techniques is by no means straightforward. Moreover, the application of such methods must conform to the regulatory requirements for new drugs. This book discusses the need for new pharmacotherapies for diabetes, obesity and NAFLD and the molecular targets of drugs currently in development. Emerging technologies including functional imaging, circulating biomarkers and omics are considered together with practical and ethical issues pertaining to early phase clinical trials in subjects with cardiometabolic disorders. Translational Research Methods in Diabetes, Obesity, and Non-Alcoholic Fatty Liver Disease is of interest to biomedical scientists, pharmacologists, academics involved in metabolic research and clinicians practicing in these specialties.