Protease and polymerase inhibitors for the treatment of hepatitis C.
Chronic hepatitis C is among the leading causes of chronic liver disease worldwide, with approximately 170 million people infected. The severity of disease varies from asymptomatic chronic infection to cirrhosis and hepatocellular carcinoma. Recently,advances have been made, with the combination of pegylated interferon (PEG-IFN) and ribavirin leading to a sustained virological response (SVR) in approximately 55% of cases. In genotypes 2 or 3, SVR rates reach 80%; in genotype 1 SVR rates is 50%. Furthermore, SVR appears to be long lasting, associated probably with a reduction in the risk of cirrhosis and hepatocellular carcinoma. Despite this progress, treatment failure still occurs in about half of the patients. Furthermore, therapy results in several side effects and high costs. These limitations have led to important development of novel compounds under the name of specifically targeted antiviral therapy for HCV (STAT-C). Also, considering side effects and treatment cost, prediction of virological non-response is mandatory. The management of chronic hepatitis C must include better knowledge of viral cycle and mechanisms of non response. The development of new molecules such as HCV enzyme inhibitors is ongoing. The aim of this review is to summarize results obtained with STATC: protease and polymerase inhibitors.
Asselah
Tarik
T
INSERM, U773, Centre de Recherche Bichat-Beaujon CRB3, Service d'hépatologie, Hôpital Beaujon, Clichy, France. tarik.asselah@bjn.aphp.fr
Benhamou
Yves
Y
Marcellin
Patrick
P
D000998:Antiviral Agents / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011480:Protease Inhibitors / Q000627:therapeutic use*; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use*; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D012324:RNA-Dependent RNA Polymerase
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011092:Polyethylene Glycols; D011480:Protease Inhibitors; D011994:Recombinant Proteins; D012254:Ribavirin; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase; C100416:peginterferon alfa-2a