Steroids and HCC
Research type
Research Study
Full title
Steroid Hormones, Liver Disease and Hepatocellular Carcinoma
IRAS ID
233716
Contact name
Jeremy Tomlinson
Contact email
Sponsor organisation
University of Oxford, Clinical Trials and Research Governance
Eudract number
2016-003060-40
Duration of Study in the UK
4 years, 3 months, 30 days
Research summary
The liver manifestation of obesity and type 2 diabetes is non-alcoholic fatty liver disease (NAFLD). NAFLD is rapidly becoming the leading cause for cirrhosis and liver transplantation. A devastating consequence of cirrhosis is the development of liver cancer. Liver cancer has an incidence of 2-3% per year in patients with established cirrhosis and currently ranks as the world’s third leading cause of cancer deaths. Despite introduction of new treatments, liver cancer prognosis remains poor.
Early detection and diagnosis of cirrhosis-related liver cancer is important to guide therapy and to improve clinical outcome. Patients will often present without symptoms and current screening strategies are reliant upon serial scans and blood tests that are labour intensive and can miss the diagnosis. There is therefore a clinical need to identify better screening strategies.
The liver represents a major site of natural steroid hormone metabolism and our early results from small numbers of patients suggest that by using a urine test to identify natural steroids we can detect liver cancer as well as identify the severity of underlying liver disease. We now wish to develop and extend these findings, collecting blood and urine samples from patients with liver disease and liver cancer to see if this urine test can be developed and correctly identify those patients with liver cancer. These samples will be collected at the time of the routine NHS clinic appointments for these patients within their dedicated liver follow-up. We are hoping to recruit 480 patients; half will have liver cancer and half will have cirrhosis. We hope to demonstrate that the urine test is able to correctly identify those patients with liver cancer.
Lay summary of study results:
We have recruited 467 patients into the steroids and hepatocellular carcinoma (HCC) study. Using mass spectrometry analysis, we have profiled 19 different steroid metabolites in the urine samples from these patients. The data from these metabolites has been used with a form of machine learning to generate an algorithm to try and predict which patients had cirrhosis and which had cirrhosis+HCC. In patients with alcohol related liver disease, the test was able to identify those patients with HCC with moderate efficacy (area under the curve analysis of the ROC curve = 0.69). Interestingly the analysis of the urine steroid profiles we able to differentiate between patients who had cirrhosis due to hepatitis viruses as opposed to non-alcoholic fatty liver disease of alcohol related liver disease. This suggests that the biology of cirrhosis is different depending upon the underlying liver disease aetiology.REC name
East Midlands - Leicester Central Research Ethics Committee
REC reference
17/EM/0452
Date of REC Opinion
5 Dec 2017
REC opinion
Favourable Opinion