Magnetic resonance characterisation of developing hepatocellular carcinoma in a diet induced model of liver cancer in the rat

Abstract

Non-alcoholic fatty liver disease (NAFLD), a disorder associated with abnormal lipid accumulation within hepatocytes, is considered benign disorder in nature. However, in some cases it may progress to inflammation, nonalcoholic steatohepatitis (NASH), then cirrhosis, precancerous nodules and finally to hepatocellular carcinoma (HCC). NAFLD and NASH are both reversible with appropriate clinical intervention and lifestyle changes. In developed countries, the non-alcoholic fatty liver disease (NAFLD) is becoming one of the most common causes of precancerous and HCC lesions [1]. Unfortunately, most nodular lesions are detected too late with a poor prognosis. The discovery of markers that can predict which livers may progress to HCC would allow early intervention and potentially halting progress to HCC. This would be of great benefit at any stage up to precancerous lesions, however the earlier the better.Development of end stage liver malignancy would be decreased, resulting in decreased mortality from this disease.Histology is considered the reference standard for the assessment of fatty disease and nodular lesion in liver. However, there are significant drawbacks including invasiveness, small sample size and observer-dependence which limits its usefulness in evaluating liver disease.Magnetic resonance imaging is a non-invasive modality that can provide information on anatomical and physiological changes in the liver (e.g. fatty liver disease and HCC). MRI images are primarily assessed visually by expert radiologists looking for anatomical and contrast changes in the images compared to normal tissue. This qualitative method requires inspection of all datasets for abnormalities. Visual interpretation is subjective, labour intensive, and depends on the experience of the radiologist. This can introduce inter-observer variation and is suitable only when the pathology leads to sufficient contrast changes in the images acquired.MRI also allows the calculation of quantitative parameters like T1, T2 and diffusion values. These parameters are dependent on physical, chemical and microstructural properties of the tissue. When standard protocols are used, the calculation of these parameters should be independent of the observer. This has the potential for more precise characterization of changes that occur over time. Clinically, here has been limited utilization of these methods, as they generally require longer acquisition times and significant post processing of the images. Declaration by authorThis thesis is composed of my original work, and contains no material previously published or written by another person except where due reference has been made in the text.

Retraction Statement: Inhibition of miR‐499‐5p expression improves nonalcoholic fatty liver disease

“…Nonalcoholic fatty liver disease (NAFLD) is a disease associated with abnormal lipid accumulation in hepatocytes, which might develop into fibrosis, cirrhosis, and even canceration under certain circumstances (Alghamdi, 2017;Atarashi et al, 2018). Steatosis (accumulation of fat droplets in hepatocytes), inflammation, balloon damage, fibrosis, and cirrhosis are the pathological features of NAFLD (Bedossa & Kleiner, 2016).…”

Inhibition of miR-499-5p expression improves nonalcoholic fatty liver disease

“…Non-alcoholic fatty liver disease (NAFLD) is a disease associated with abnormal lipid accumulation in hepatocytes, which might develop into fibrosis, cirrhosis and even canceration under certain circumstances [1,2]. Steatosis (accumulation of fat droplets in hepatocytes), inflammation, balloon damage, fibrosis and cirrhosis are the pathological features of NAFLD [3].…”