J Korean Med Assoc.  2015 Dec;58(12):1154-1158. 10.5124/jkma.2015.58.12.1154.

New direct-acting antivirals for the treatment of chronic hepatitis C

• Jeong SH

• KMID: 2195144
• DOI: http://doi.org/10.5124/jkma.2015.58.12.1154

Abstract

The successful development of direct-acting antivirals (DAA) represents a breakthrough in the treatment of hepatitis C virus (HCV) infection. Pegylated interferon alpha and ribavirin combination therapy for 24-48 weeks was a longstanding standard therapy despite high rate of adverse events and relatively low efficacy, with a sustained virological response (SVR) rate of 60% in genotype 1 and 80% in genotype 2 HCV infected patients in South Korea. However, the treatment paradigm is rapidly shifting from interferon-based therapy to interferon-free, all-oral DAA combination therapy, which leads to SVR rates of 90% with minimal adverse events and a shorter duration of treatment (12-24 weeks). Quantitation of serum HCV RNA and genotyping of HCV are essential tests for treatment with DAA agents, and genotype 1b and genotype 2 are the two most common genotypes in Korea. The first DAA treatment approved in 2015 was daclatasvir and asunaprevir combination therapy for 24 weeks, which carries an expected SVR rate of 80-90%. It is indicated for genotype 1b patients in whom resistance-associated mutation is not detected in the NS5A region of the HCV genome (L31 or Y93 codon). The next treatment approved was the ledipasvir/sofosbuvir fixed dose combination for genotype 1 patients, with an expected SVR rate of 90%-99% using the 12-24 week regimen. For genotype 2 infection, sofosbuvir and ribavirin combination for 12-16 weeks is recommended, with an expected SVR rate of 95%. However, the high cost of DAA therapy, drug-drug interactions, and the development of resistance-associated mutants remain as problems to overcome.

Keyword

HCV; daclatasvir; asunaprevir; sofosbuvir; resistance-associated variant

MeSH Terms

Antiviral Agents*
Genome
Genotype
Hepacivirus
Hepatitis C, Chronic*
Hepatitis, Chronic*
Humans
Interferon-alpha
Korea
Nicardipine
Ribavirin
RNA
Antiviral Agents
Interferon-alpha
Nicardipine
RNA
Ribavirin

Figure

• 

  Figure 1 Hepatitis C virus genome and its translated polyprotein indicating 3 drug targets. The hepatitis C virus genome is translated as a polyprotein which is cleaved into structural proteins (core, envelope protein 1 and 2), and nonstructural protein (NS) 2, 3, 4A, 4B, 5A, and 5B. Direct acting antivirals inhibit the NS3 protease, the NS5A replication complex, and the NS5B polymerase. UTR, untranslated region.

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