Innate and Adaptive Immunopathogeneses in Viral Hepatitis; Crucial Determinants of Hepatocellular Carcinoma

SIMPLE SUMMARY: Infections with Hepatitis B and Hepatitis C viruses are usually asymptomatic and although some patients undergo resolution of infection, the majority do not. Chronic hepatitis leads to continuous cycles of inflammation that can cause complications including liver fibrosis, cirrhosis, and eventually liver cancer. This review summarizes the changes in liver immunity in acute and chronic Hepatitis B and C infections, as well as in liver cancer patients who developed their malignancy within a viral hepatitis background, aiming to better understand the disease biology. This review provides researchers in the field of chronic liver diseases with immune insights into viral hepatitis and hopes to be of help in developing better prophylactic approaches for cancer management. ABSTRACT: Viral hepatitis B (HBV) and hepatitis C (HCV) infections remain the most common risk factors for the development of hepatocellular carcinoma (HCC), and their heterogeneous distribution influences the global prevalence of this common type of liver cancer. Typical hepatitis infection elicits various immune responses within the liver microenvironment, and viral persistence induces chronic liver inflammation and carcinogenesis. HBV is directly mutagenic but can also cause low-grade liver inflammation characterized by episodes of intermittent high-grade liver inflammation, liver fibrosis, and cirrhosis, which can progress to decompensated liver disease and HCC. Equally, the absence of key innate and adaptive immune responses in chronic HCV infection dampens viral eradication and induces an exhausted and immunosuppressive liver niche that favors HCC development and progression. The objectives of this review are to (i) discuss the epidemiological pattern of HBV and HCV infections, (ii) understand the host immune response to acute and chronic viral hepatitis, and (iii) explore the link between this diseased immune environment and the development and progression of HCC in preclinical models and HCC patients.