The pathogenesis of hepatocellular carcinoma is multifactorial event. Novel immunological treatment in prospect.

ABSTRACT

PURPOSE: To discuss exhanstively complex molecular and cellular mechanism in Hepatocellular Carcinoma (HCC); effect of chronic inflammation and cirrhosis, accompained by regenerative process, on the development of HCC; genetic instability of liver cells of regenerating nodules; the relative role of hepatitis C virus (HCV) and hepatitis B virus (HBV) in hepatocarcinogenesis; tumorigenicity of aflatoxin B1 (AFB1); gene expression profiles in HCC; liver tumors and host defense; future perspectives of HCC treatment. DESIGN: We reviewed the most important studies on HCV. RESULTS: HCC is an aggressive malignancy with poor prognosis and is one of the most common tumor in the world. In the majority of cases, HCC is found in conjunction with cirrhosis of the liver. Chronic inflammation and cirrhosis, accompagnied by regenerative process, function as a tumor promoter, providing a common pathway from chronic HBV or HCV infection to HCC. The direct etiologic role of HBV and HCV for HCC is obscure. Tumor progression may be brought about in HCC by mutation of the p53 tumor suppressor gene. The prevalences of p53 mutations is similar in HBV-associated and HCV-associated HCCs. Another mechanisms of host defense are the production of transforming growth factor beta1 (TGFbeta1), and the induction of cytotoxic T lymphocytes; the failure of there mechanisms permits the process of hepatocarcinogenesis. Treatment with alpha interferon of chronic hepatitis is necessary to delary or prevent the progression to liver cirrhosis and development of HCC. Various therapies, such radical operation, intra-arterial chemoembolization, percutaneous intratumoral ethanol injection, radio-frequency ablation, have been employed, but there is still non satisfactory treatment. Recent advances in recombinant and gene delivery thechnologies suggest that gene therapy may be a promising alternative to explore. Furthemore, immunotherapy may become a modality for patients with HCC. Clinical application of vaccine immunotherapy with NY-ESO-1 derived peptides in HLA-A2 positive HCC patients will be possible.