Inflammatory Response in the Pathogenesis and Treatment of Hepatocellular Carcinoma: A Double-Edged Weapon

Abstract

Hepatocellular carcinoma (HCC) is the most frequent among primary liver tumors (90%) and one of the main causes of cancer-related death. It develops usually in a chronically inflamed environment, ranging from compensatory parenchymal regeneration to fibrosis and cirrhosis: carcinogenesis can potentially happen in each of these stages. Inflammation determined by chronic viral infection (hepatitis B, hepatitis C, and hepatitis delta viruses) represents an important risk factor for HCC etiology through both viral direct damage and immune-related mechanisms. The deregulation of the physiological liver immunological network determined by viral infection can lead to carcinogenesis. The recent introduction of immunotherapy as the gold-standard first-line treatment for HCC highlights the role of the immune system and inflammation as a double-edged weapon in both HCC carcinogenesis and treatment. In this review we highlight how the inflammation is the key for the hepatocarcinogenesis in viral, alcohol and metabolic liver diseases.