Potential mechanisms of hepatitis B virus induced liver injury

Abstract

Chronic active hepatitis (CAH) is acknowledged as an imperative risk factor for the development of liver injury and hepatocellular carcinoma. The histological end points of CAH are chronic inflammation, fibrosis and cirrhosis which are coupled with increased DNA synthesis in cirrhotic vs healthy normal livers. The potential mechanism involved in CAH includes a combination of processes leading to liver cell necrosis, inflammation and cytokine production and liver scaring (fibrosis). The severity of liver damage is regulated by Hepatitis B virus genotypes and viral components. The viral and cellular factors that contribute to liver injury are discussed in this article. Liver injury caused by the viral infection affects many cellular processes such as cell signaling, apoptosis, transcription, DNA repair which in turn induce radical effects on cell survival, growth, transformation and maintenance. The consequence of such perturbations is resulted in the alteration of bile secretion, gluconeogenesis, glycolysis, detoxification and metabolism of carbohydrates, proteins, fat and balance of nutrients. The identification and elucidation of the molecular pathways perturbed by the viral proteins are important in order to design effective strategy to minimize and/or restore the hepatocytes injury.

Keywords: Ground squirrel hepatitis virus; Hepatitis B virus; Hepatitis B virus genotype; Hepatocellular carcinoma; Interferon regulatory factor 7; Interleukin-1 receptor-associated kinase 4; Peripheral blood mononuclear cells; TNF receptor-associated factor 3; Woodchuck hepatitis virus.

Figure 1

Mitochondrial, nuclear and cytoplasmic pathways activated by HBx. EMT: Epithelial-mesenchymal transition; TERT: Human telomerase reverse transcriptase; TGFβ: Transforming Growth Factor-β; UPR: Unfolded Protein Response; HDAC: Histone Deacetylase; FN: Fibronectin; ROS: Reactive Oxygen Species; NF-Κb: Nuclear Factor-κB; A2Mα: 2-Macroglobulin; hVDAC: Voltage-Dependent Anion Channel; CDH1: E-cadherin; ER: Endoplasmic reticulum; NF-AT: Nuclear factor of activated T-cells; ATF: Activated transcription factor peroxisome; PPAR-γ: Proliferator-activated receptor gamma; AP: Transcription activitor.