Emerging therapies for hepatitis C virus.
BACKGROUND
Currently, 170 million people worldwide are affected by the HCV. Chronic HCV infection is amongst the leading causes of chronic liver disease and its complications such as cirrhosis and hepatocellular carcinoma, making it the most common reason for liver transplantation. The current standard of treatment for HCV is pegylated IFN-α plus ribavirin. This treatment, when administered for the standard duration, allows sustained virological response (SVR) in ∼ 50% of patients infected with HCV and about 40% for HCV genotype 1, the most prevalent form of HCV in the US. SVR rates for populations with co-morbidities (patients with chronic renal disease) and certain ethnic backgrounds (African Americans and Hispanics) are lower. Given the high prevalence and relatively low cure rates of current antiviral therapy, the burden of HCV is enormous.


METHODS
Faced with this urgent and growing medical need, research into novel therapeutic compounds for the treatment of HCV is a rapidly growing industry. Several novel compounds are in advanced stages of clinical development, such as HCV protease inhibitors (particularly those against NS3-4A protease), HCV polymerase inhibitors (including both nucleoside and non-nucleoside analogs) and cyclophilin inhibitors.


RESULTS
HCV treatment has seen many advances in the last decade and the discovery process has been fraught with both successes and disappointments. Through a process of rigorous research, the current late stage novel HCV therapeutics seem to have overcome some of the obstacles met by their early predecessors and offer the promise of meeting the shortfalls of the current standard of treatment.


CONCLUSIONS
Data from clinical trials are encouraging and suggest that combination therapies of these novel agents may have the potential to shorten treatment duration and increase viral clearance when used in conjunction with pegylated IFN-α and ribavirin.
Birerdinc
Aybike
A
Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA.
Younossi
Zobair M
ZM
D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D015195:Drug Design; D004359:Drug Therapy, Combination; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016896:Treatment Outcome
D000998:Antiviral Agents