Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD), Hepatocellular Carcinoma (HCC), Primary Biliary Cholangitis (PBC), Auto immune hepatitis (AIH) and the mechanisms behind these three conditions are the main areas that the theme is studying to find treatments that can improve the quality of life for those diagnosed.
Hepatocellular carcinoma, commonly known as HCC, is the most common cause of primary liver cancer. HCC arises from cells in the liver called hepatocytes. The majority of HCCs arise in people who already have chronic liver disease or cirrhosis.
Here are insights into current research studies on Hepatocellular carcinoma (HCC) that are being conducted with support from the NIHR Newcastle BRC:
Hepatocellular carcinoma (HCC) is a type of liver cancer that significantly impacts health globally. Despite recent advances in treatment, particularly with immunotherapy, the majority of patients with HCC do not respond effectively to these treatments. This research aims to delve into why only a few patients benefit from immunotherapy and to find ways to predict who these responders might be.
Immunotherapy uses the body's immune system to fight cancer and has been a groundbreaking advancement in cancer treatment. This research focuses on understanding the differences between patients who respond to immunotherapy and those who do not. The goal is to identify specific markers or signs within the cancerous tissues that could help predict a patient's response to treatment.
We propose to use a cutting-edge technique called imaging mass cytometry (IMC). This method allows for an in-depth analysis of cancer tissues at a cellular level. By examining both the cancerous and surrounding non-cancerous tissues from patients who have undergone immunotherapy, the team aims to identify patterns or combinations of biological markers associated with a positive response to treatment.
This study is significant because it could lead to a more personalised approach to treating liver cancer. By understanding which patients are likely to respond to immunotherapy, doctors could tailor treatments more effectively, potentially improving outcomes and reducing unnecessary side effects. Additionally, this research could provide valuable insights into the biological mechanisms of how and why immunotherapy works in certain cases of HCC, leading to advancements in cancer treatment strategies.
In summary, this research aims to enhance our understanding of liver cancer treatment, specifically in predicting and improving patient response to immunotherapy. The findings from this study could have a profound impact on the treatment of liver cancer, offering hope for more effective and personalised care for patients.
Fatty liver disease is common as we get older, affecting over a billion people worldwide. Around 25% are at risk of developing an inflammatory response that leads to scarring. End stage scarring is called cirrhosis, with patients at risk of liver failure but also liver cancer. Liver cancer (called Hepatocellular Carcinoma or HCC) is the 4th commonest cause of cancer death globally.
Poor liver function and age-related conditions often limit treatment options – especially for cancer detected at a late stage. Patients with cirrhosis have a very high risk of cancer development, so they have liver cancer screening, with 6 monthly ultrasound scans. However, patients without cirrhosis can also develop cancers, but they do not have regular scans, because the numbers ‘at risk’ is huge with <1 in a thousand ever getting cancer – so ultrasound is not cost-effective. This is unfortunate, as these patients generally have good liver function, with less risk from curative treatments if detected early. So there is a pressing need to develop better cost-effective screening tests for patients with FLD to detect HCC – particularly in the absence of cirrhosis.
The liver cells release extracellular vesicles (EV) – little parcels – into the blood all the time. These carry molecules like DNA, RNA and proteins, that help carry out normal liver functions and communicate with other parts of the body. These can change when cancers develop. We want to develop methods to study EV-encapsulated RNA, in patients with fatty liver disease with and without cancers. This will be the start of developing specific tests to support early detection of progression to cancer. In future, we will employ this methodology to explore exRNA and develop blood tests that help us choose the right treatments for our patients with cancer too.
Liver cancer is a very difficult disease to treat and many people die from the disease. One problem is that the majority of people with liver cancer have it diagnosed when it is advanced and cannot be cured with surgery. Another problem is that it is difficult to treat with drugs, as the cancers aren’t sensitive to them, or sometimes the side effects are just too great.
Recently a new drug regime called ‘atezo/bev’ has proved to be very successful for around 25% of those treated, but at the expense of 75% of people, who don’t benefit and experience adverse side effects. Atezo/bev can awaken the immune system and damage blood vessel formation in the tumours and we think that it is the types of immune cells in the tumour that determine if a person will respond to atezo/bev, but we don’t like to biopsy tumours as they can bleed. However, we have shown that a protein called interleukin-8, released from these tumour immune cells, is much higher in some patients with advanced cancers.
Many of our patients, receiving different kinds of treatments, have donated their blood samples for research. We know what treatment they had and how they have done it. We want to test if it can also be a blood test that will help us identify those who atezo/bev will benefit, and those where it will do more harm than good.
One of the priorities within the Newcastle BRC is improving access to research irrespective of age and socioeconomic factors; to move towards a situation where all patients feel empowered to participate in research. There are increasing opportunities for patients to take part in research which is entirely IT-based without any paper documents being used. Not all patients are confident with using technology, particularly in settings (such as research) where they have no or limited experience. Having access to electronic research platforms with tablets being readily accessible to patients in both inpatient and outpatient settings will be invaluable.
The BRC has funded 10 tablets for use at the main outpatient department at the Freeman Hospital and the outpatient clinic at the Centre for Aging and Vitality to aid information dissemination, enable team members to support patients with less IT experience to participate in studies and collect feedback from patients about their participation in research. It may also help us to understand why there are some patient groups who are particularly ‘research active’ and why some are less so.
Whilst these new technology solutions are exciting we need to ensure we support patients with their use, particularly in under-served groups. We believe the impact of having these tablets available will be increasing participation in inpatient and outpatient studies across the research portfolio in the Newcastle BRC.
Higher levels of physical activity before a hepatocellular carcinoma (HCC) diagnosis is associated with a reduced risk of HCC-specific death. Evidence in other cancer types, and our own preclinical studies, shows that physical activity after a diagnosis is associated with improved overall survival and may improve HCC outcomes in people with chronic liver disease.
Newcastle BRC is funding a PhD studentship which aim to determine the association between postdiagnosis physical activity and HCC outcomes (progression-free survival, overall survival, fitness for second-line therapy). This studentship will also explore the association between attributes of walking (frequency, volume, pattern, variability) and HCC outcomes. It will also assess the agreement between device-based physical activity and self-reported physical activity.
Physical activity will be assessed with a state-of-the-art Inertial Measurement Unit worn continuously for seven days and self-reported physical activity will be assessed with the International Physical Activity Questionnaire.
The findings may support the delivery of physical activity as an adjuvant intervention to improve outcomes and prolong survival in patients treated for HCC. This would bring huge benefits to a patient group with significant unmet needs.
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