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and esophageal variceal bleeding, ultimately explaining Studies on the natural history of chronic HBV infection
why HBV and HCV infection are currently the leading have shown that active HBV replication contributes
causes of liver-related death and the main indication for to the development of acute hepatitis flare, hepatic
[17]
[2]
liver transplantation in developed countries. There is no decompensation, cirrhosis, and HCC. A prospective
clear evidence about the role of antiviral therapies in HCC cohort study with 11 years of follow-up observed that
prevention in patients with chronic hepatitis B (CHB) and there was a significant increase in HCC-related mortality
hepatitis C. [3] across viral load categories, with a relative risk (RR) for HCC
mortality in the low viral load group of 1.7 [95% confidence
Reanalysis of studies with antivirals suggested that virus- interval (CI): 0.5-5.7] when compared with 11.2 (3.6-35.0)
induced HCC was more likely to be prevented in younger in the high viral load group. In the REVEAL-HBV study,
[18]
patients with mild liver inflammation rather than in older serum HBV DNA levels, and HCC risk correlate in a linear
patients with advanced liver fibrosis or cirrhosis, who in relationship, independently of hepatitis B early antigen
fact, were at higher risk of developing liver cancer. In (HBeAg) status, serum alanine aminotransferase level, and
[4]
[19]
this review, we will address the possible role of antiviral the presence or absence of liver cirrhosis. In addition to
therapy in reducing the risk of HCC in patients affected by these viral factors, older age, male gender, heavy alcohol
HBV and HCV. consumption, and exposure to carcinogens such as
aflatoxin B, a family history of HCC, and more recently, the
We reviewed in PubMed database reports published in elevated levels of quantitative hepatitis B surface antigen,
English language up to January 2015, using the following as well as metabolic syndrome, associated with obesity
keywords: “HCC”, “hepatocellular carcinoma”, “hepatitis and diabetes mellitus have been established as the risk
B”, “HBV”, “hepatitis C”, “HCV”, “antiviral therapy”, and factors for HBV-related HCC. [17,20-22]
“cirrhosis”. We selected the pivotal randomized controlled
trials (RCTs) and meta-analysis on this issue. In addition, a The primary prevention of HBV-related HCC concerns
manual search for American Association for the Study of in the prevention of the population exposure to HBV,
Liver Diseases and European Association for the Study of treatment of HBV infection itself, elimination of those
the Liver 2012-2014 conference abstracts were performed factors which contribute to the progression of liver
using the same search terms. disease and risk scores have also been established to
estimate the risk of developing HCC in < 10 years after
HBV presentation. Such scores based on age, gender, HBV
DNA levels, core promoter mutations, and cirrhosis, can
HBV is one of the most etiologic agent of HCC in the be used to identify high-risk patients. [23-25] However, these
world, in particular, in areas prevalent for HBV infection models were found lacking accuracy for the prediction
such as Asia, Africa, Southern part of Eastern and Central of HCC in Caucasian patients, for whom different models
Europe, and the Middle East. A report published in 2006 are, therefore, deemed necessary. The implementation
[5]
[26]
showed that HBV infection accounted for about 60% of the of universal hepatitis B vaccination program has reduced
total liver cancer occurrence in developing countries and the incidence rates of childhood HCC in several countries
about 23% in developed countries. [6] including Taiwan. Prompt treatment is the only strategy
[11]
to prevent end-stage liver disease, incidence, and mortality
There are viral and host factors that are associated with for HCC in unvaccinated adults with chronic HBV infection.
an increased risk of HCC among patients with HBV.
[7]
Although a majority of liver cancers develop from cirrhotic Current therapeutic options for patients with CHB
livers, a significant fraction of HBV-related HCCs occurs in infection are treatment with interferon-alpha (IFN-α),
a background of CHB in the absence of liver cirrhosis. The pegylated interferon-alpha (Peg-IFN-α), lamivudine,
lower rate of underlying cirrhosis in HBV-related HCCs as adefovir, entecavir, telbivudine, and tenofovir. IFN-α has
compared to other etiologies argues for a more direct role antiviral, immunomodulatory and perhaps antitumoral
of HBV in the oncogenetic process. [8] activities. It has been used in the treatment of CHB for
decades and beneficial effects, including HBeAg/HBV-
The molecular and genetic features of HBV chronic infection DNA, clearance the reduction of HCC development, and
involving cancer development could be summarized into better complication free survival have been documented.
(1) Pre-core and basal core promoter mutations, genotype However, the effect on the prevention of cirrhosis and HCC
B and C [9-13] and (2) integration of HBV DNA into the host development was controversial. Colombo and Iavarone
[3]
genome and the expression of HBV proteins such as have recently reviewed the six meta-analysis published to
surface proteins and the X protein. [14-16] date: The administration of IFN decreased the rate of HCC

Hepatoma Research | Volume 2 | Issue 1 | January 15, 2016 11