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incidence of HCC or lower recurrence of HCC in HCV-infected patients who receive
IFN-based therapy is only observed in more than 5-year follow-up studies. Overall
IFN-based therapies significantly benefit HCC patients after curative HCC therapy,
which is probably due to the additional inhibitory effects of IFN on liver cancer
rather than antiviral effect [ 21 ].
8.4.2 Anti-HCV Treatment with Direct-Acting
Antivirals (DAAs)
The discovery of new direct-acting antivirals (DAAs) is a breakthrough for HCV
treatment. Anti-HCV treatment with DAA can yield sustained virological response
(SVR) exceeding 95% in patients with genotype 1 HCV infection and compensated
cirrhosis within 12 weeks [ 18 ]. Administration of combination of HCV NS5A
inhibitor, the nucleotide polymerase inhibitor, and ribavirin to patients with
advanced liver disease or post-liver transplantation recurrence produces high rates
of SVR12 exceeding 80% [ 19 , 20 ]. In real-world patients with HCV genotype 1
infection, treatment with NS3/4A protease inhibitor simeprevir and nucleotide
polymerase inhibitor sofosbuvir yields overall SVR rate of 84% [ 15 ].
Eradication of viral infection by DAA theoretically removes the oncogenic agentand may, like IFN-based therapy, decrease HCC incidence or benefit HCC patients.
However a recent study enrolled HCV-related HCC patients who have been success-
fully treated before for their cancer to receive DAA treatment. After a follow-up of
5.7 months, there is unexpected high rate of tumor recurrence in some patients with
HCV eradication [ 110 ]. This may be attributed to the sudden elimination of inflam-
mation signals from viral replication and following reduction of immune surveil-
lance [ 110 ]. More studies are needed to assess the effect of IFN-free DAA treatment
on HCC incidence and recurrence.
8.5 Conclusion and Perspectives
As a cytoplasmic RNA virus, it is possible to eradicate HCV infection in patients by
antiviral therapy. The discovery of DAAs makes it possible to successfully cure
HCV patients with IFN-free DAA therapies within a short time. Clearance of virus
and viral antigens may significantly decrease the incidence of HCC and relieve
other extrahepatic manifestations. However, the long-term effect of DAA treatment
on HCC incidence and recurrence needs more cohort studies.
Chronic HCV infection induces local inflammations within the liver; HCV infec-tion induces reactive oxygen species and interferes with functions of maintaining
host genomic stability; these may generate a microenvironment for aberrant hepato-
cellular proliferation and help develop hepatocellular carcinoma. The molecular
mechanism of how HCV infection induces HCC is still not well understood. If there
Z. Yi and Z. Yuan