Abstract
Hepatitis C virus (HCV) is a leading cause of liver disease. Direct-acting antivirals have revolutionised management of patients with chronic hepatitis C by increasing viral cure rates while reducing treatment duration and side-effects. 1 Chung RT Baumert TF Curing chronic hepatitis C—the arc of a medical triumph. N Engl J Med. 2014; 370: 1576-1578 Crossref PubMed Scopus (191) Google Scholar However, some limitations remain including direct-acting antiviral failure and resistance in a subset of patients, difficult-to-treat genotypes in patients with cirrhosis, few treatment options for patients with advanced renal insufficiency, limited retreatment options for those who do not respond, and limited access to therapy because of high costs. 2 Pawlotsky JM Hepatitis C drugs: is next generation the last generation?. Gastroenterology. 2016; 151: 587-590 Summary Full Text Full Text PDF PubMed Scopus (20) Google Scholar Next generation direct-acting antivirals and host-targeting agents are in development to further optimise antiviral regimens. 2 Pawlotsky JM Hepatitis C drugs: is next generation the last generation?. Gastroenterology. 2016; 151: 587-590 Summary Full Text Full Text PDF PubMed Scopus (20) Google Scholar , 3 Mailly L Xiao F Lupberger J et al. Clearance of persistent hepatitis C virus infection in humanized mice using a claudin-1-targeting monoclonal antibody. Nature Biotechnol. 2015; 33: 549-554 Crossref PubMed Scopus (105) Google Scholar , 4 Zeisel MB Crouchet E Baumert TF Schuster C Host-targeting agents to prevent and cure hepatitis C virus infection. Viruses. 2015; 7: 5659-5685 Crossref PubMed Scopus (46) Google Scholar MicroRNA-122 (miR-122), a small non-coding RNA highly expressed in hepatocytes, regulates lipid metabolism and acts as a tumour suppressor. 5 Bandiera S Pfeffer S Baumert TF Zeisel MB miR-122—a key factor and therapeutic target in liver disease. J Hepatol. 2015; 62: 448-457 Summary Full Text Full Text PDF PubMed Scopus (415) Google Scholar This agent represents an interesting host target for antiretroviral therapy as HCV usurps miR-122 for its replication. 5 Bandiera S Pfeffer S Baumert TF Zeisel MB miR-122—a key factor and therapeutic target in liver disease. J Hepatol. 2015; 62: 448-457 Summary Full Text Full Text PDF PubMed Scopus (415) Google Scholar The first proof-of-concept study 6 Janssen HL Reesink HW Lawitz EJ et al. Treatment of HCV infection by targeting microRNA. N Engl J Med. 2013; 368: 1685-1694 Crossref PubMed Scopus (1729) Google Scholar has shown that the miR-122 inhibitor miravirsen efficiently reduced viral loads in patients chronically infected with HCV. Safety, tolerability, and antiviral effect of RG-101 in patients with chronic hepatitis C: a phase 1B, double-blind, randomised controlled trialThis study showed that one administration of 2 mg/kg or 4 mg/kg RG-101, a hepatocyte targeted N-acetylgalactosamine conjugated anti-miR-122 oligonucleotide, was well tolerated and resulted in substantial viral load reduction in all treated patients within 4 weeks, and sustained virological response in three patients for 76 weeks. Full-Text PDF
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