PhD defence J.D. (Jose) Debes

This thesis argues that as underlying liver disease defines occurrence and prognosis of HCC, the area of the world where a patient is born or lives is of importance when considering screening or treatment. Indeed, the thesis shows that hepatitis B-related HCC can occur at early ages in South America, exposing consideration for early screening in this region. It also argues that even in a relatively homogenous area like South America, the main risk factors for HCC do vary country by country. The prevention section focuses of hepatitis B-related HCC (the most common risk factor worldwide) and explores new rapid tests for hepatitis B, arguing that easy diagnosis of the disease is the ultimate approach to implement screening for HCC in this population. Moreover, it proposes a novel approach of using emergency department visits as platforms to test young people for hepatitis B, a concept that could have considerable success in resourcelimited areas where primary care establishment is not as strong as in resource-rich areas. Mechanistically wise, this thesis shows for the first time that a differential gene expression in sorted hepatocytes of the liver (increase in oncogenes and decrease in tumor suppressor genes) is present in individuals infected with hepatitis C, the most
frequent risk factor for HCC in western countries, even at very early fibrosis levels. Suggesting that the path to hepatocarcinogenesis in these individuals is already present before the development of liver cirrhosis. This section also provides evidence that immune markers detected in peripheral blood can predict the development of HCC in individuals with hepatitis C. A certainly novel approach to screening. Whether this is applicable or not to HCC from other causes is discussed below. Finally, the thesis explores the different treatments used for HCC in areas of South America and Africa. It brings to light the low number of individuals that get treated via liver transplantation, the ultimate treatment for HCC and highlights the large number patients that can only receive palliative therapy. It also assesses the use of sorafenib, one of the few systemic therapies for HCC, in these parts of the world, providing insight into survival in different HCC groups as well as proposing a new score to predict survival, that could benefit resource-limited areas.

The public defence will take place at the Prof. Andries Queridoroom, 3rd floor Education Center, Erasmus MC. The ceremony will begin exactly at 15.30 PM. In light of the solemn nature of the ceremony, we recommend that you do not take children under the age of 6 to the first part of the ceremony.