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Hepatocellular carcinoma is the most common type of primary liver cancer and constitutes about 90-95% of all hepatic malignancies. It is the second and fastest-growing cause of cancer-related mortality worldwide. Although there is multiplicity in the etiology of hepatocellular carcinoma, accumulating evidence shows that non-alcoholic fatty liver disease has risen to become the top etiological factor for hepatocellular carcinoma in the United States and other developed nations, mainly because of the metabolic disturbances from obesity, a western epidemic. Non-alcoholic fatty liver disease comprises a spectrum of hepatic pathologies, ranging from simple steatosis to its inflammatory form, non-alcoholic steatohepatitis. With its concomitant increasing liver collagen deposition, non-alcoholic steatohepatitis paves the pathway for hepatocellular carcinoma development, which may occur with or without established cirrhosis. This chapter focuses on the current knowledge related to the epidemiology and cellular mechanisms that underpin the progression of non-alcoholic fatty liver disease to malignancy. Furthermore, it gives insight into the diagnosis, treatment options, and future directions for non-alcoholic steatohepatitis-related tumorigenesis.
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