Rewiring Host Signaling: Hepatitis C Virus in Liver Pathogenesis

Cold Spring Harb Perspect Med. 2020 Jan 2;10(1):a037366. doi: 10.1101/cshperspect.a037366.


Hepatitis C virus (HCV) is a major cause of liver disease including metabolic disease, fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). HCV induces and promotes liver disease progression by perturbing a range of survival, proliferative, and metabolic pathways within the proinflammatory cellular microenvironment. The recent breakthrough in antiviral therapy using direct-acting antivirals (DAAs) can cure >90% of HCV patients. However, viral cure cannot fully eliminate the HCC risk, especially in patients with advanced liver disease or comorbidities. HCV induces an epigenetic viral footprint that promotes a pro-oncogenic hepatic signature, which persists after DAA cure. In this review, we summarize the main signaling pathways deregulated by HCV infection, with potential impact on liver pathogenesis. HCV-induced persistent signaling patterns may serve as biomarkers for the stratification of HCV-cured patients at high risk of developing HCC. Moreover, these signaling pathways are potential targets for novel chemopreventive strategies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Antiviral Agents / therapeutic use
  • Biomarkers / analysis
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / virology*
  • Hepacivirus / drug effects
  • Hepacivirus / pathogenicity*
  • Hepatitis C / drug therapy
  • Hepatitis C / genetics
  • Hepatitis C / virology
  • Hepatitis C, Chronic / pathology
  • Hepatitis C, Chronic / virology*
  • Humans
  • Liver Cirrhosis / pathology
  • Liver Cirrhosis / virology*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / pathology
  • Liver Neoplasms / virology*
  • Oncogenes
  • Signal Transduction
  • Tumor Microenvironment


  • Antiviral Agents
  • Biomarkers