Viral and host inflammation-related factors that can predict the prognosis of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC), a malignancy caused mainly by chronic infection with hepatitis B virus (HBV) and/or hepatitis C virus (HCV), is a highly fatal disease. Apart from clinical parameters like venous invasion and multinodularity, viral and host inflammation-related factors are important predictors of HCC prognosis after surgical treatment. The factors of prognostic value can be detected in the specimens of HCC patients. In preoperative peripheral blood, high HBV DNA and the genotypes and mutations of HBV or HCV, high neutrophil-to-lymphocyte ratio and high concentrations of macrophage migration inhibitory factor and osteopontin predict poor prognosis. In tumours, high ratios of neutrophil-to-CD8(+) T cell and Treg-to-CD8(+) T cell, high expression of pro-angiogenic factors such as hypoxia-inducible factor-1α and cell growth/survival factors such as CD24 and activation of inflammatory signalling pathways such as Wnt/β-catenin, nuclear factor-kappa B and signal transducer and activator of transcription 3 predict early recurrence. In peritumoural hepatic tissues, high HBV DNA, HBV mutations, high densities of macrophages, activated stellates and mast cells, high expression of macrophage colony-stimulating factor/its receptor and placental growth factor, Th1/Th2-like cytokine shift, inflammation-related signature and activation of carcinogenesis-related pathways predict late recurrence. Further studies should be focused on the development of a robust strategy by integrating the viral factors, inflammatory factors and clinical factors of complementary prognostic value to ensure high validity of the assessment for postoperative HCC prognosis.