Sufficient evidence has accumulated that chronic infection with HCV substantially increases the risk of HCC, particularly in the presence of cirrhosis. HCV appears to represent a major underlying cause of HCC in southern Europe and Japan, regions where HCC incidence is intermediate, whereas its impact is smaller in sub-Saharan Africa and China, where HBV-related HCC predominates, and in the developed western world, where the majority of cases of HCC are associated with cirrhosis of unknown etiology.