© Springer Nature Singapore Pte Ltd. 2017 129
Q. Cai et al. (eds.), Infectious Agents Associated Cancers: Epidemiology
and Molecular Biology, Advances in Experimental Medicine and Biology 1018,
DOI 10.1007/978-981-10-5765-6_8
Chapter 8
Hepatitis C Virus-Associated Cancers
Zhigang Yi and Zhenghong Yuan
Abstract Most hepatitis C virus (HCV) infection results in persistent infection.
Significant portion of chronic HCV-infected patients develop hepatocellular carci-
noma (HCC). Chronic hepatitis C is also associated with extrahepatic manifesta-
tions, including cryoglobulinemia, lymphoma, insulin resistance, type 2 diabetes,
and neurological disorders. The molecular mechanisms of how HCV infection
causes liver cancer are largely unknown. HCV replication or viral proteins may per-
turb cellular hemostasis and induce the generation of reactive oxygen species (ROS);
viral components or viral replication products act as agonist to trigger innate immune
response and cause chronic inflammation. Within the liver, non- hepatocytes such as
hepatic stellate cell (HSC) are activated upon HCV infection to provide the major
source of extracellular proteins and play important roles in fibrogenesis. With the
great achievements of HCV treatment, especially the direct-acting antivirals (DAAs)
against HCV, HCV eradication is possible. However, until now there are only very
limited data on the effect of DAA-based anti-HCV treatment on HCC patients.
Keywords Hepatitis C virus • Chronic infection • Direct-acting antivirals •
Hepatocellular carcinoma • Fibrogenesis • Steatosis • Inflammation • Hepatic stel-
late cells • Transforming growth factor • Reactive oxygen species
8.1 Introduction
Hepatitis C virus (HCV), a member of the genus Hepacivirus within the Flaviviridae
family, chronically infects approximately 160 million people worldwide and causes
hepatocellular carcinoma (HCC) in a significant proportion of the chronically
infected population [ 1 ]. HCC represents the leading cause of death from cancer
worldwide and is the most common cause of death in patients with cirrhosis [ 2 ].
HCV was discovered as the etiologic agent of non-A, non-B hepatitis in 1989 [ 3 ].
Z. Yi () • Z. Yuan ()
Key Laboratory of Medical Molecular Virology (Ministries of Education and Health),
School of Basic Medical Sciences, Fudan University, Shanghai 200032,
People’s Republic of China
e-mail: [email protected]; [email protected]