Mechanisms and clinical behavior of hepatocellular carcinoma in HBV and HCV infection and alcoholic and non-alcoholic fatty liver disease

Hepatocellular carcinoma (HCC) is the main tumor of the liver and is the sixth most frequently diagnosed tumor in the world. It is the evolution of chronic hepatic injury secondary to different etiologies. Chronic HBV and HCV infection, chronic alcoholic hepatitis, as well as non-alcoholic fatty liver disease are the most common causes behind the development of HCC. The introduction of effective prophylaxis and treatment against hepatitis B, the recent use of highly effective hepatitis C treatments, as well as lifestyle changes observed in recent decades in the general population causing an increase in obesity and metabolic syndrome have led to significant epidemiological change in HCC in relation to the changed etiologic prevalence of liver injury. An increasing number of evidences are emerging, emphasizing how the development of HCC is a complex and multifactorial process. The knowledge of the molecular mechanisms involved is of great importance to understand the bases of the development of hepatocarcinogenesis and of possible therapeutic approaches. Several pathogenic mechanisms and clinical expression of HCC occur in relation to the different etiologies of the underlying liver disease. The different clinical behavior of HCC often makes diagnosis difficult at an early stage that is necessary for an effective therapeutic approach. This review analyzes the possible different pathogenic mechanisms involved in the development of HCC and emphasizes the different epidemiological and clinical behavior of HCC observed in the most common forms of liver diseases of viral and non-viral origin.