Korean J Hepatol.  2010 Jun;16(2):158-167. 10.3350/kjhep.2010.16.2.158.

Mutations within the interferon sensitivity determining region in Korean patients infected with hepatitis C virus genotype 1b

• Jin YJ
• Park YK
• Yun GJ
• Lee HC
• Jeong SH
• Kim GM
• Lim YS
• Chung YH
• Lee YS
• Suh DJ

• KMID: 1792594
• DOI: http://doi.org/10.3350/kjhep.2010.16.2.158

Abstract

BACKGROUND/AIMS
The treatment response to interferon could differ with mutations in the interferon-sensitivity-determining region (ISDR) in patients infected with hepatitis C virus (HCV) genotype-1b (HCV-Ib). We examined the pattern of ISDR mutations and analyzed whether the number of amino acid substitutions influences the treatment response to peginterferon plus ribavirin in chronic hepatitis or cirrhotic patients infected with HCV-Ib.
METHODS
The study population comprised 52 patients who visited Seoul Asan Medical Center and Seoul National University Bundang Hospital from January 2006 to December 2008 and who received peginterferon alpha-2a (n=37) or -2b (n=15) plus ribavirin, and whose serum was stored. We analyzed the early virologic response, end-of-treatment response, and sustained virologic response (SVR), and examined the ISDR using direct sequencing.
RESULTS
The proportions of patients with ISDR mutation types of wild (0 mutations), intermediate (1-3 mutations), and mutant (> or =4 mutations) were 50.0%, 42.3%, and 7.7%, respectively, and the corresponding SVR rates were 63%, 50%, and 67% (p>0.05). The SVR rates were 59.4% and 50.0% in patients with <2 and > or =2 mutations, respectively (p>0.05). On univariate analysis, age was the only predictive factor for SVR (p=0.016). The pretreatment HCV RNA titer tended to be lower in those with SVR, but without statistical significance (p=0.069).
CONCLUSIONS
The frequency of ISDR mutations was low in our cohort of Korean patients infected with HCV-Ib. Therefore, ISDR mutations might not contribute to the response to treatment with peginterferon plus ribavirin.

Keyword

Hepatitis C virus genotype-1b; Interferon sensitivity determining region; Early virologic response; End of treatment response; Sustained virologic response

MeSH Terms

Adult
Aged
Amino Acid Sequence
Antiviral Agents/*therapeutic use
Drug Resistance, Viral/genetics
Drug Therapy, Combination
Female
Genotype
Hepacivirus/*genetics
Hepatitis C, Chronic/*drug therapy/virology
Humans
Interferon Alfa-2a/*therapeutic use
Interferon Alfa-2b/*therapeutic use
Male
Middle Aged
Molecular Sequence Data
*Mutation
Polyethylene Glycols/*therapeutic use
Republic of Korea
Ribavirin/therapeutic use