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World J Gastroenterol. May 28, 2014; 20(20): 5951-5961
Published online May 28, 2014. doi: 10.3748/wjg.v20.i20.5951
Occult hepatitis B virus and hepatocellular carcinoma
Teresa Pollicino, Carlo Saitta
Teresa Pollicino, Department of Pediatric, Gynecologic, Microbiological, and Biomedical Sciences, University Hospital of Messina, 98124 Messina, Italy
Carlo Saitta, Department of Clinical and Experimental Medicine, University Hospital of Messina, 98124 Messina, Italy
Author contributions: Saitta C collected the data and wrote the initial draft; Pollicino T reviewed the data, and finalized the paper; both authors revised and approved the final manuscript before submission.
Correspondence to: Teresa Pollicino, MD, Department of Pediatric, Gynecologic, Microbiological, and Biomedical Sciences, University Hospital of Messina, Via Consolare Valeria, 98124 Messina, Italy. tpollicino@unime.it
Telephone: +39-90-2217070 Fax: +39-90-2213594
Received: November 1, 2013
Revised: February 16, 2014
Accepted: April 15, 2014
Published online: May 28, 2014
Abstract

Occult hepatitis B virus (HBV) infection (OBI) is a challenging pathobiological and clinical issue that has been widely debated for several decades. By definition, OBI is characterized by the persistence of HBV DNA in the liver tissue (and in some cases also in the serum) in the absence of circulating HBV surface antigen (HBsAg). Many epidemiological and molecular studies have indicated that OBI is an important risk factor for hepatocellular carcinoma (HCC) development. OBI may exert direct pro-oncogenic effects through the activation of the same oncogenic mechanisms that are activated in the course of an HBsAg-positive infection. Indeed, in OBI as in HBV-positive infection, HBV DNA can persist in the hepatocytes both integrated into the host genome as well as free episome, and may maintain the capacity to produce proteins-mainly X protein and truncated preS-S protein - provided with potential transforming properties. Furthermore, OBI may indirectly favor HCC development. It has been shown that the persistence of very low viral replicative activity during OBI may induce mild liver necro-inflammation continuing for life, and substantial clinical evidence indicates that OBI can accelerate the progression of liver disease towards cirrhosis that is considered the most important risk factor for HCC development.

Keywords: Hepatitis B virus, Hepatitis B virus surface antigen, Hepatitis B virus DNA, HBx protein, Hepatocellular carcinoma, Occult hepatitis B virus infection

Core tip: Accumulating evidence indicates that occult hepatitis B virus (HBV) infection (OBI) is an important risk factor for hepatocellular carcinoma (HCC) development both in hepatitis C virus (HCV)-infected and HCV-negative patients with chronic liver disease. Data form humans and animal models have shown that OBI may contribute to hepatocellular transformation through the same direct and indirect mechanisms that subtend HCC development in overt HBV infection. In this review, we aimed at revising the current epidemiological, clinical and molecular data linking OBI to HCC development.