A state-of-the-art review on the NRF2 in Hepatitis virus-associated liver cancer.

According to a paper released and submitted to WHO by IARC scientists, there would be 905,700 new cases of liver cancer diagnosed globally in 2020, with 830,200 deaths expected as a direct result. Hepatitis B virus (HBV) hepatitis C virus (HCV), and hepatitis D virus (HDV) all play critical roles in the pathogenesis of hepatocellular carcinoma (HCC), despite the rising prevalence of HCC due to non-infectious causes. Liver cirrhosis and HCC are devastating consequences of HBV and HCV infections, which are widespread worldwide. Associated with a high mortality rate, these infections cause about 1.3 million deaths annually and are the primary cause of HCC globally. In addition to causing insertional mutations due to viral gene integration, epigenetic alterations and inducing chronic immunological dysfunction are all methods by which these viruses turn hepatocytes into cancerous ones. While expanding our knowledge of the illness, identifying these pathways also give possibilities for novel diagnostic and treatment methods. Nuclear factor erythroid 2-related factor 2 (NRF2) activation is gaining popularity as a treatment option for oxidative stress (OS), inflammation, and metabolic abnormalities. Numerous studies have shown that elevated Nrf2 expression is linked to HCC, providing more evidence that Nrf2 is a critical factor in HCC. This aberrant Nrf2 signaling drives cell proliferation, initiates angiogenesis and invasion, and imparts drug resistance. As a result, this master regulator may be a promising treatment target for HCC. In addition, the activation of Nrf2 is a common viral effect that contributes to the pathogenesis, development, and chronicity of virus infection. However, certain viruses suppress Nrf2 activity, which is helpful to the virus in maintaining cellular homeostasis. In this paper, we discussed the influence of Nrf2 deregulation on the viral life cycle and the pathogenesis associated with HBV and HCV. We summed up the mechanisms for the modulation of Nrf2 that are deregulated by these viruses. Moreover, we describe the molecular mechanism by which Nrf2 is modulated in liver cancer, liver cancer stem cells (LCSCs), and liver cancer caused by HBV and HCV. Video Abstract.