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World J Gastroenterol. Sep 21, 2014; 20(35): 12462-12472
Published online Sep 21, 2014. doi: 10.3748/wjg.v20.i35.12462
Potential mechanisms of hepatitis B virus induced liver injury
Mohd Suhail, Hany Abdel-Hafiz, Ashraf Ali, Kaneez Fatima, Ghazi A Damanhouri, Esam Azhar, Adeel GA Chaudhary, Ishtiaq Qadri
Mohd Suhail, Ashraf Ali, Ghazi A Damanhouri, Adeel GA Chaudhary, Ishtiaq Qadri, King Fahd Medical Research Center, King Abdul Aziz University, Jeddah 21589, Saudi Arabia
Hany Abdel-Hafiz, Department of Medicine, University of Colorado Health Sciences Center at Fitzsimons, Aurora, CO 80309, United States
Kaneez Fatima, IQ Institute of Infection and Immunity, Lahore 54000, Pakistan
Esam Azhar, Special Infectious Agents Unit-Biosafety Level 3, King Fahd Medical Research Center, King Abdul Aziz University, Jeddah 22254, Saudi Arabia
Esam Azhar, Medical Laboratory Technology Department, Faculty of Applied Medical Sciences King Abdul Aziz University, Jeddah 22254, Saudi Arabia
Author contributions: All authors contributed to the manuscript.
Correspondence to: Dr. Ishtiaq Qadri, King Fahd Medical Research Center, King Abdul Aziz University, PO Box 80216, Jeddah 21589, Saudi Arabia. ishtiaq80262@yahoo.com
Telephone: +96-65-35168434 Fax: +96-62-6952076
Received: February 23, 2014
Revised: March 25, 2014
Accepted: May 19, 2014
Published online: September 21, 2014
Processing time: 208 Days and 4.3 Hours
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: Hepatitis B virus; Hepatitis B virus genotype; Hepatocellular carcinoma; Woodchuck hepatitis virus; Ground squirrel hepatitis virus; Peripheral blood mononuclear cells; Interferon regulatory factor 7; Interleukin-1 receptor-associated kinase 4; TNF receptor-associated factor 3

Core tip: There are over 400 million people infected with hepatitis B virus worldwide and chronic active hepatitis is recognized as an important risk factor for liver injury and hepatocellular carcinoma. Cirrhosis is the histological end point of this chronic inflammatory and fibrotic process and is coupled with increased DNA synthesis in cirrhotic as compared to normal livers. The potential mechanism(s) involved in chronic active hepatitis include a combination of processed leading to liver cell necrosis, inflammation and cytokine synthesis and 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 process 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 dictated in bile secretion, gluconeogenesis, glycolysis, detoxification and metabolism of carbohydrates, proteins, and fat and balance of nutrients. The identification and elucidation of the molecular pathways perturbed by the viral protein(s) are important in order to design effective strategy to minimize and/or restore the hepatocyte injury.