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Thereafter, using an assay for detecting circulating antibodies identified, approxi-
mately 80% of the infected patients develop chronic infections, and 15% of the
infected patients develop acute infections [ 4 ]. About 5–20% of the chronically
infected patients progress to cirrhosis within 5–20 years, and about 1–2% of the
patients with cirrhosis develop HCC per year [ 5 ]. HCV together with hepatitis B
virus are the predominant cause of HCC all over the world [ 6 ].
HCV is a blood-borne virus and transmits mainly by sharing infected needles,
receiving infected blood by transfusion, or accidental exposure to infected blood,
whereas less efficiently from mother to child or by sexual contact [ 7 ]. There are seven
main HCV genotypes. The HCV genotypes are epidemiologically distinct with dif-
ferent geographical distributions, which may indicate their recent epidemic spread
[ 8 ]. In contrast to HBV that patients who get infected during childhood are prone to
chronic infection [ 9 ], HCV infection at any age can result in chronic infection.
HCV is a positive-sense, single-stranded RNA virus. Its 9.6-kb genome encodes
a single open reading frame that is translated into a polypeptide (Fig. 8.1). The
polyprotein is cleaved into at least ten individual proteins by the host and viral pro-
teinase [ 10 ]. HCV replication takes place in endoplasmic reticulum (ER)-associated
viral-specific double-membrane vesicles (DMVs) [ 11 ].
Although HCV is likely only to replicate within hepatocytes, HCV infection is
commonly associated with extrahepatic manifestations in significant portion of
chronically infected patients. Chronic hepatitis C is also associated with
cryoglobulinemia, lymphoma, insulin resistance, type 2 diabetes, and neurological
disorders [ 12 ].
The discovery of new direct-acting antivirals (DAAs) is a breakthrough for anti-
HCV treatment. Current treatment can obtain a cure rate that exceeds 90% for cer-
tain HCV genotypes [ 13 – 15 ]. Various studies have demonstrated sustained
virological response (SVR) in patients with different stages of liver disease includ-
ing compensated cirrhosis and patients for liver transplantation [ 16 – 20 ]. Anti-HCV
therapy with interferon (IFN) may decrease HCC incidence and HCC recurrence
and benefit patients [ 21 ]. The effect of DAA-based treatment on the HCC incidence
and HCC recurrence needs more clinical studies.
Fig. 8.1 Schematic of HCV genome. The HCV single open reading frame is flanked by the highly
conserved 5′ and 3′ untranslated regions (UTRs). The 5′ UTR contains an internal ribosome entry
site (IRES) to start a cap-independent translation. The 3′ UTR is required for RNA replication. The
structural proteins core protein (C) and envelope glycoproteins (E1 and E2) constitute the virion.
The nonstructural proteins NS3 to NS5B assemble viral replicase for viral replication. NS2 is a
protease. NS3 contains a protease and an RNA helicase domain. NS5B is the viral RNA-dependent
RNA polymerase. The structural proteins are processed by host proteases. HCV NS2 specifically
cleave NS2-3 precursor, whereas NS3 processes the other nonstructural proteins
Z. Yi and Z. Yuan