Viral Hepatitis and Hepatocellular Carcinoma: State of the Art

Abstract

Viral hepatitis is one of the main causes leading to hepatocellular carcinoma (HCC). The continued rise in incidence of HCC suggests additional factors following infection may be involved. This review examines recent studies investigating the molecular mechanisms of chronic hepatitis and its association with hepatocarcinogenesis. Hepatitis B virus patients with genotype C display an aggressive disease course leading to HCC more than other genotypes. Furthermore, hepatitis B excretory antigen (HBeAg) seems to be a more sensitive predictive tumor marker exhibiting a six-fold higher relative risk in patients with positive HBsAg and HBeAg than those with HBsAg only. Single or combined mutations of viral genome can predict HCC development in up to 80% of patients. Several mutations in HBx-gene are related with higher HCC incidence. Overexpression of the core protein in HCV leads to hepatocellular lipid accumulation associated with oncogenesis. Reduced number and decreased functionality of natural killer cells in chronic HCV individuals dysregulate their surveillance function in tumor and viral cells resulting in HCC. Furthermore, high T-cell immunoglobulin and mucin 3 levels supress CD8+ T-cells, which lead to immunological dysregulation. Hepatitis D promotes HCC development indirectly via modifications to innate immunity, epigenetic alterations and production of reactive oxygen species with the LHDAg being the most highly associated with HCC development. Summarizing the results, HBV and HCV infection represent the most associated forms of viral hepatitis causing HCC. Further studies are warranted to further improve the prediction of high-risk patients and development of targeted therapeutics preventing the transition from hepatic inflammation–fibrosis to cancer.

Retinoids in the Pathogenesis and Treatment of Liver Diseases

“…The HBV genome has a partially double-stranded DNA genome that gives origin to multiple proteins essential for the virus life cycle. The gene encoding the HBx protein is associated with direct carcinogenic potential, in part because of its ability to integrate into the host genome, its ability to interact with the host cell cycle, transcription factors, and DNA repair, hence, the name ’viral oncoprotein’ [ 182 ]. HCV has a single-stranded RNA genome whose ability to induce carcinogenesis is primarily by promoting accumulation of lipids in the liver via increasing endoplasmic reticulum stress [ 183 , 184 ], and by eliciting a dramatic immune response in the liver [ 185 ].…”

Hepatitis B x (HBx) as a Component of a Functional Cure for Chronic Hepatitis B

“…The immune-mediated pathogenesis of CLD and HCC is associated with ongoing HBV replication, as indicated by the persistence of hepatitis B e antigen (HBeAg) [ 55 , 56 ], which is a surrogate marker of virus replication. However, CLD provides an oxidative environment that activates HBx, which in turn supports virus replication [ 57 ].…”

Resource Management through Artificial Intelligence in Screening Programs—Key for the Successful Elimination of Hepatitis C

“…Untreated, HCV promotes ample changes in the liver, from lipid accumulation to fibrogenesis and liver disfunction [ 5 ]. It is one of the leading causes of liver malignancy worldwide [ 6 , 7 ].…”