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

Research output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
Pages (from-to)1154-1158
Number of pages5
JournalJournal of the Korean Medical Association
Volume58
Issue number12
DOIs
StatePublished - 1 Dec 2015

Fingerprint

Chronic Hepatitis C
Antiviral Agents
Genotype
Hepacivirus
Therapeutics
Ribavirin
Interferons
Galectin 3
Republic of Korea
Virus Diseases
Korea
Drug Interactions
Interferon-alpha
Codon
Genome
RNA
Costs and Cost Analysis

Keywords

  • Asunaprevir
  • Daclatasvir
  • HCV
  • Resistance-associated variant
  • Sofosbuvir

Cite this

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title = "New direct-acting antivirals for the treatment of chronic hepatitis C",
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.",
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New direct-acting antivirals for the treatment of chronic hepatitis C. / Jeong, Sook Hyang.

In: Journal of the Korean Medical Association, Vol. 58, No. 12, 01.12.2015, p. 1154-1158.

Research output: Contribution to journalArticleResearchpeer-review

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