title: The Path to Cancer and Back: Immune Modulation During Hepatitis C Virus Infection, Progression to Fibrosis and Cancer, and Unexpected Roles of New Antivirals.
abstract: Hepatitis C virus (HCV) infection affects over 130 million individuals worldwide, and it is the number 1 reason for liver transplantation in the United States. HCV infection progresses in a slow chronic fashion eliciting a strong but ineffective immune response, mainly characterized by NK cell dysfunction and T cell exhaustion. The chronic hepatic inflammation leads to liver fibrosis, cirrhosis, and cancer in a significant number of patients. In recent years, groundbreaking research has led to the discovery of new HCV-specific direct-acting antivirals (DAAs), which have an unprecedented efficacy to clear the virus, and establish a sustained virological response. Indeed, curing HCV infection with an oral medication is now reality. The effects of DAAs in mitigating the HCV-related complications of liver fibrosis and cancer are yet largely unknown. Nonetheless, recent controversial reports suggest a potential increase in liver cancer recurrence upon use of DAAs. In the current article, we review the most important immune-mediated mechanisms underlying HCV chronicity and the development of liver fibrosis and cancer. Furthermore, we discuss recent concern on use of the new agents.
authors.affiliation: 1 Department of Medicine, University of Minnesota, Minneapolis, MN. 2 Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, The Netherlands.
authors.forename: Jose D
authors.initials: JD
authors.lastname: Debes
authors.forename: Robert J
authors.initials: RJ
authors.lastname: de Knegt
authors.forename: Andre
authors.initials: A
authors.lastname: Boonstra
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000473:pathology / Q000821:virology*; D018450:Disease Progression; D019698:Hepatitis C, Chronic / Q000150:complications / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007107:Immune System / Q000187:drug effects*; D008103:Liver Cirrhosis / Q000276:immunology / Q000473:pathology / Q000821:virology*; D008113:Liver Neoplasms / Q000276:immunology / Q000473:pathology / Q000821:virology*; D009364:Neoplasm Recurrence, Local / Q000276:immunology*
chemical_list: D000998:Antiviral Agents