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World J Hepatol. Dec 28, 2017; 9(36): 1305-1314
Published online Dec 28, 2017. doi: 10.4254/wjh.v9.i36.1305
Molecular basis of hepatocellular carcinoma induced by hepatitis C virus infection
Mohammad Irshad, Priyanka Gupta, Khushboo Irshad
Mohammad Irshad, Priyanka Gupta, Khushboo Irshad, Clinical Biochemistry Division, Department of Laboratory Medicine, All India Institute of Medical Sciences, New Delhi 110029, India
Author contributions: All authors made equal contribution in the preparation of this manuscript and final approval of the version of it to be published.
Conflict-of-interest statement: The authors declare here that there is no conflict of interest related to this study among them.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Mohammad Irshad, Professor, Clinical Biochemistry Division, Department of Laboratory Medicine, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India.
Telephone: +91-11-26594981 Fax: +91-11-26588663
Received: October 9, 2017
Peer-review started: October 10, 2017
First decision: November 7, 2017
Revised: November 8, 2017
Accepted: December 5, 2017
Article in press: December 6, 2017
Published online: December 28, 2017

Present study outlines a comprehensive view of published information about the underlying mechanisms operational for progression of chronic hepatitis C virus (HCV) infection to development of hepatocellular carcinoma (HCC). These reports are based on the results of animal experiments and human based studies. Although, the exact delineated mechanism is not yet established, there are evidences available to emphasize the involvement of HCV induced chronic inflammation, oxidative stress, insulin resistance, endoplasmic reticulum stress, hepato steatosis and liver fibrosis in the progression of HCV chronic disease to HCC. Persistent infection with replicating HCV not only initiates several liver alterations but also creates an environment for development of liver cancer. Various studies have reported that HCV acts both directly as well as indirectly in promoting this process. Whereas HCV related proteins, like HCV core, E1, E2, NS3 and NS5A, modulate signal pathways dysregulating cell cycle and cell metabolism, the chronic infection produces similar changes in an indirect way. HCV is an RNA virus and does not integrate with host genome and therefore, HCV induced hepatocarcinogenesis pursues a totally different mechanism causing imbalance between suppressors and proto-oncogenes and genomic integrity. However, the exact mechanism of HCC inducement still needs a full understanding of various steps involved in this process.

Keywords: Hepatitis C virus, Hepatocellular carcinoma, Fibrosis, Core, NS5A, Inflammation

Core tip: Hepatocellular carcinoma (HCC) is one of the most common cancer occurring in human population all over the world. Chronic hepatitis C virus (HCV) infection is considered as a major cause of producing HCC in developed countries. HCV infection induces chronic inflammation in liver, which initiates several changes including production of oxidative stress, steatosis, progressive fibrosis, cirrhosis and finally HCC. HCV related proteins also interact directly with cellular proteins at various steps of cell signaling disturbing cell cycle and regeneration process. HCC is supposed, now a days, to be the foremost indication for liver transplant.