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Page 4 of 11 Puoti. Hepatoma Res 2018;4:57 I http://dx.doi.org/10.20517/2394-5079.2018.67

HCC incidence; and (4) maintained HBV DNA suppression does not fully eliminate the risk of HCC in
[19]
patients with pre-existing cirrhosis .

Several prediction models of hepatocellular carcinoma development in chronic HBV patients have been
[20]
proposed. The PAGE-B score has been suggested for assessing HCC risk in HBV afflicted patients .

HCV AND HCC
For whom it concerns the natural history of HCV-related cirrhosis, it has been clearly showed that the
progression of chronic HCV hepatitis to cirrhosis is greatly influenced by the age of the patients: 5% of
patients under 40 years and 20% of those over 40 years progress to cirrhosis in less than 20 years [20,22] .
HCC risk in chronic HCV patients depends on the severity of fibrosis stage and the rate of progression is
approximately 2%-6% per year. It has been established that HCV infected patients have a 15-20 fold risk of
[22]
developing HCC compared with HCV negative patients .

Previous papers reported that HCV patients achieving sustained virological response (SVR) have a
significant reduction of life-threatening complications, such as liver failure and HCC. Cardoso et al. [23]
reported the cumulative incidence of HCC and of liver-related complications stratified according to the
response to interferon (IFN) treatment, thus confirming that patients with SVR had a paramount reduction
[24]
of the incidence of HCC with respect to those without SVR. These data were confirmed by Singal et al. .

The recent development and widespread availability of the new DAAs of II generation have increased the rate
of SVR up to 90%-95%, rapidly decreasing the prevalence of HCV infection. Due to the lack of significant
side effects, on the contrary of previous treatment with IFN plus ribavirin, also HCV patients with advanced
liver disease or contraindications to IFN might receive this therapy. Although no adequate long-term follow-
ups are to date available, it is possible to predict that the incidence of HCC in HCV cirrhotic patients with
[25]
stable viral eradication will greatly decrease in the next future .

Development of HCV-related HCC in subjects with normal liver has been rarely reported [26,27] .

In conclusion, it is possible to affirm that: (1) in patients with chronic C hepatitis and cirrhosis no correlation
exists between serum HCV RNA levels and the severity of the disease, in contrast with HBV-related
[28]
disease ; (2) in patients with HCV cirrhosis, HCC development is significantly reduced in SVR, while no
[23]
differences are seen between non responders and untreated people ; (3) prevention of HCC is not achieved
in the absence of SVR [29-31] ; (4) due to the paramount virological efficacy of the new DAAs it is possible to
[32]
predict that in the next years the incidence in HCV cirrhosis will be dramatically reduced .

LIVER STEATOSIS AND HCC
Fatty liver (NAFLD/NASH) and obesity at present represent the leading cause of HCC, at least in
developed countries, probably becoming in the next future the main cause for developing HCC [1-4,33] . In
comparison with the lot of papers on the prevalence of HCC in patients with HBV/HCV chronic infections,
epidemiological data regarding the prevalence and incidence of HCC in patients with fatty liver are relatively
[34]
scarce. A systematic review reported a prevalence of 0%-3% on a follow-up period between 5.6 and 21
[6]
years in the whole population of NAFLD/NASH people . When only patients with steato-cirrhosis were
considered, the incidence raise to 2.4% within a follow-up period of 7.2 years and 12.8% with a 3.2-year
[34]
follow-up .
In a study of HCC management in a realworld setting, including 18,031 patients with HCC in 14 countries
[35]
(2005-2012), NAFLD accounted for 10%-12% of underlying liver diseases in Europe and North America .