Treating Hepatitis C

Current Standard of Care and Emerging Direct-acting Antiviral Agents

F. Poordad; D. Dieterich


J Viral Hepat. 2012;19(7):449-464. 

In This Article

Abstract and Introduction


During the late 1990s and early 2000s, major advances were made in the treatment of patients with chronic hepatitis C virus (HCV) infection. Interferon, combination interferon plus ribavirin (RBV) and pegylated interferon plus RBV increased sustained virologic response (SVR) rates from ~5% to ~40–80%, depending on the genotype of HCV infection. Advances in molecular biology have allowed investigators to begin to understand the mechanisms of HCV infection and replication. Advances in understanding of viral kinetics have provided tools to identify patients who are most likely to attain SVR. With the advances in the science of HCV infection, the first part of the 21st century has seen the development and early introduction of a number of direct-acting antiviral (DAA) drugs. These novel medications interfere with critical steps in HCV replication and have the potential to significantly increase SVR rates. This article will review the key elements of HCV replication and evaluate the various classes of new and investigational DAA that have the potential to create a revolution in the management of patients with chronic hepatitis C.


Globally, at least 170 million people are chronically infected with the hepatitis C virus (HCV), with 9 million infected in the United States and Western Europe.[1,2] The prevalence of the infection varies geographically, from 0.1% to 5%.[3] The highest rates are reported in Africa and the Eastern Mediterranean region.[4] Since 1982, the incidence of acute HCV infection in the United States has fallen from 7.4/100 000 to 0.7/100 000, except in human immunodeficiency virus (HIV) seropositive men who have sex with men (MSM), for whom it is increasing dramatically.[5] This decline is predominantly attributed to HCV screening in transfusion centres, and concerns about HIV infection that have led to institution of universal precautions in healthcare settings and changes in behaviour of injection drug users.[6] Despite the fall in incidence, the number of patients with complications of chronic hepatitis C is increasing.[7] Currently, 40–50% of all liver transplants in the United States are in complications of HCV infection.[8] The reason for this is that chronic HCV infection is usually silent and hepatic fibrosis, cirrhosis, end-stage liver disease and hepatocellular carcinoma develop only after a decade or more of chronic liver injury and hepatic remodelling. The burden of chronic hepatitis C is expected to increase well in the future and continue to be an important cause of premature mortality.[7,9]


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