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Title: Primary liver cancer : epidemiological and biomarker discovery studies
Author: Ladep, Nimzing
ISNI:       0000 0004 5348 5697
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2014
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With previous reports indicating changes in mortality, risk factors and management of primary liver cancer (PLC), evaluation of current trends in the incidence and mortality rates was indicated. Late diagnosis has been implicated to be a major contributor to the high fatality rates of PLC. This work aimed at: • studying trends of PLC by subcategories globally in general, and in England and Wales, in particular; • investigating liver-related morbidities of HIV infected patients in an African setting; and • discovering urinary biomarkers of hepatocellular carcinoma. The World Health Organisation (WHO) and Small Area Health Statistics Unit (SAHSU) databases were interrogated respectively, in order to achieve the first aim. The second aim was achieved through utilisation of databases of an African-based HIV treatment programme- AIDS Prevention Initiative in Nigeria (APIN), located in Jos, Nigeria. The European Union-funded Prevention of Liver Fibrosis and Cancer in Africa (PROLIFICA) case-control study in three West African countries was the platform through which urinary metabolic profiling was accomplished. Proton nuclear magnetic resonance spectroscopy (NMR) and parallel ultra-performance liquid chromatography mass spectrometry (UPLC-MS) were used for biomarker discovery studies. Mortality rates of intrahepatic bile duct carcinoma (IHBD) increased in all countries that were studied. Misclassification of hilar cholangiocarcinoma accounted for only a small increase in the rate of IHBD in England and Wales. With over 90% screening rate for viral hepatitides, the rates of hepatitis B (HBV), hepatitis C (HCV) and HBV/HCV in HIV-infected patients in the APIN programme were 17.8%, 11.3% and 2.5% respectively. There was attenuated immune response as well as significantly lower survival observed in HBV/HIV co-infection, relative to HIV mono-infected patients (p=0.0097). Whereas single urinary metabolites, including acetylcarnitine, N-acetylglutamate, betaine aldehyde, 3'-sialyllactose, methionine among others possessed high discriminatory power to diagnose HCC, a combination of three metabolites: 3'-sialyllactose, methionine and 9-decenoylcarnitine significantly outperformed serum alpha-fetoprotein (AFP) in the diagnosis of HCC in a cirrhosis population (area under the receiver operating characteristic curve; [urinary panel= 0.96] compared to [AFP = 0.64]). This work informs a critical assessment of current control strategies in the prevention of HCC, and potentially assists in the development of more affordable means of early detection of PLC for most affected regions of the world.
Supervisor: Taylor-Robinson, Simon; Khan, Shahid; Toledano, Mireille Sponsor: The London Clinic
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available