C형간염바이러스 유전자형 1b에 감염된 한국인 환자에서 인터페론 감수성 결정 영역의 유전자 돌연변이 양상
Mutations within the interferon sensitivity determining region in Korean patients infected with hepatitis C virus genotype 1b
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목적: C형간염바이러스의 유전형-1b에 감염된 환자에 있어 인터페론 감수성 결정 영역(ISDR)에 따라 인터페론 치료 반응이 달라질 수 있다고 알려져 있다. 이에 저자 등은 HCV 유전형-1b에 감염된 만성 C형간염 또는 간경변증 환자에서 ISDR 영역의 돌연변이 양상을 분석하고, 아미노산 치환 돌연변이의 개수가 페그인터페론 및 리바비린에 대한 치료 반응에 미치는 영향을 분석하고자 하였다. 대상 및 방법: 2006년 1월부터 2008년 12월까지 서울아산병원과 분당서울대학교병원에서 혈청이 보관되어 있고 페그인터페론 알파 2a(n=37) 또는 2b(n=15)와 리바비린 병합치료를 받았던 HCV 유전자형 1b에 감염된 52명의 환자를 대상으로 했다. 그리고 초기 바이러스 반응(EVR), 치료 종료 반응(ETR) 및 지속적 바이러스 반응(SVR)을 후향적으로 분석하였고 직접 염기서열 방법을 통해 ISDR을 분석하였다. 결과: 총 52명의 환자의 치료 전 혈청에서 시행한 ISDR 영역의 돌연변이 분석 결과 야생형(아미노산 치환 변이 수: 0개), 중간형(변이 수: 1～3개), 변이형(변이 수: 4개 이상)의 비율은 각각 50%(26/52), 42.3%(22/52), 7.7%(4/52)였다. 야생형, 중간형, 변이형 환자들에서 SVR은 각각 63%, 50%, 67%였고, 변이 수(<2 vs. ≥2)에 따른 SVR 환자 비율은 각각 59.4%, 50%로 변이 수에 따른 SVR의 차이는 없었다. 단변량 분석에서 치료 전 SVR을 예측하는 인자에는 연령이 유일한 인자였고(P=0.016) 치료 전의 HCV RNA 수치는 통계적인 유의성은 없었지만 치료 전의 수치가 높을수록 SVR이 낮은 경향을 보였다(P=0.069). 결론: 본 연구에서는 HCV 유전자형-1b에 감염된 한국인 환자에서 ISDR 아미노산 치환 변이는 낮은 빈도로 관찰되었고, 돌연변이에 따른 페그인터페론 및 리바비린 병합치료에 대한 반응의 차이는 관찰할 수 없었다. 추후 전국적 단위의 환자를 대상으로 추가 연구가 필요할 것으로 판단된다.
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 (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 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.
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