Microvascular alterations in the pathophysiology of non-alcoholic fatty liver disease (NAFLD) and micro-environmental factors of NAFLD-induced hepatocellular carcinoma.

The research will be performed in close collaboration with the Edwin L. Steele Laboratories in Boston (MA; United States of America). Non-alcoholic fatty liver disease (NAFLD) is defined by excessive fat accumulation in the liver and encompasses a spectrum ranging from non-alcoholic fatty liver (NAFL, also known as simple steatosis), via non-alcoholic steatohepatitis (NASH), in which there is accompanying liver cell injury and inflammation, to advanced fibrosis and cirrhosis at the end of the spectrum. The aetiopathogeneis of NAFLD and its progressions is not fully understood yet. NAFLD has become one of the major chronic liver diseases in the Western societies, and is expected to increase even further.Previous data from our laboratory indicate that alterations of the intrahepatic vascular resistance are an early event in NAFLD and hence might significantly contribute to the pathogenesis and progression of the disease. Further and detailed research is necessary and will be executed in close collaboration with the E.L. Steele laboratories in Boston, USA. Hepatocellular carcinoma (HCC) is a major cause of liver death and occurs classically in cirrhosis, so in NAFLD. Recent data, however, point towards an increasing prevalence of HCC in NAFLD even before the development of advanced fibrosis. Further elucidating of potential driving forces behind HCC development will significantly contribute towards knowledge of HCC (independent of its aetiology) and might guide potential therapeutic targets. The longstanding expertise in tumourigenesis and tumour micro-environment offers an opportunity for in depth analysis of NAFLD-induced HCC, which has not been performed thus far.

Keywords:LIVER DISEASE, PATHOPHYSIOLOGY

Disciplines:Gastro-enterology and hepatology