유전자형 1형 만성 C형 간염 환자에서 혈청 인터페론감마유도단백질-10의 의미
The clinical significance of interferon inducible protein-10 in patients having chronic hepatitis C with genotype I
0
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
목적: 최근 1형 만성 C형 간염 환자에서 CXC 케모카인 중 하나인 IP-10의 치료 전 혈중 농도가 지속적 바이러스 반응을 예측할 수 있는 주요한 인자일 수 있다는 보고들이 있었다. 이에 본 연구에서는 국내의 1형 만성 C형 간염 환자에서 페그인터페론과 리바비린 병용 투여 시 T 림프구 특이성 케모카인인 IP-10의 혈중 농도 변화와 이들과 여러 바이러스 반응들 간의 연관성을 알아보고자 하였다. 방법: 유전자형 1형 만성 C형 간염으로 진단받고 초 치료로써 페그인터페론과 리바비린 병용 치료를 받은 환자 36명을 대상으로 진행하였다. 보관되어 있는 환자 혈청을 이용하여 치료 시작 1개월 전과 1개월 후의 IP-10 수치를 각각 측정하였으며, 치료 전 IP-10 수치와 여러 바이러스 반응과의 관계 및 치료 전과 치료 후의 IP-10 수치 변화와 여러 바이러스 반응과의 관계에 대하여 연구하였다. 결과: 환자의 나이는 평균 53.5±10세이고, 21명(58%)이 남자였으며, 치료 전 HCV RNA의 평균은 5.7±0.9 log10 IU/mL이었고, IP-10 정량 결과는 평균 432.2±343.7 pg/mL이었다. 치료 전 환자의 IP-10 정량 값과 HCV RNA 정량 값은 양의 상관관계를 나타내었으나, 통계적으로는 유의하지 않았다. 치료 전 환자의 IP-10의 평균값은 432.2±343.7 pg/mL이었고, 치료 1개월 후의 IP-10의 평균값은 306.5±246.1 pg/mL로 그 감소 정도는 유의하였다(p=0.033). 여러 바이러스 반응과 치료 전 IP-10치의 관계에 대한 분석에서 바이러스 반응 유무에 따른 치료 전 IP-10 값에는 유의한 차이를 발견할 수 없었다. 각각의 바이러스 반응을 보인 군과 그렇지 않은 군에서 치료 전과 치료 후의 IP-10의 변화를 확인해 본 결과 바이러스 반응의 유무에 관계없이 전반적으로 치료 후 IP-10 값은 감소하는 모습이었으나 대체로 통계적으로 유의한 수준은 아니었다. 결론: 치료 전 IP-10 수치와 치료 한 달 전과 한 달 후의 IP-10 수치의 변화는 지속적 바이러스 반응의 예측인자는 아니었다. 하지만 더 큰 규모의 연구를 통하여 IP-10 수치와 바이러스 반응과의 관계를 규명하는 것이 필요하겠다.
Abstract
Background/Aims: Recent studies have shown that serum interferon γ-inducible protein-10 (IP-10) concentration decreased after pegylated interferon and ribavirin therapy, and was associated with a sustained virologic response (SVR). The aim of this study was to investigate the clinical significance of the pretreatment IP-10 level and change in serum IP-10 level between 1 month before and after treatment and its association with various virologic responses in patients having chronic hepatitis C (CHC) with genotype 1 undergoing pegylated interferon and ribavirin therapy. Methods: Thirty-six patients having CHC with genotype I undergoing pegylated interferon and ribavirin therapy who had available stored sera 1 month before and after treatment were enrolled retrospectively. Serum IP-10 levels were measured by ELISA. Serum HCV RNA was measured by RT-PCR (detection limit<50 IU/mL). Results: The mean age of patients (n=36; 21 men) was 53.5 years, and the mean of pretreatment HCV RNA levels was 5.7 log10 IU/mL. The serum IP-10 level at 1 month after treatment significantly decreased from 432.2 to 306.5 pg/mL (p=0.033). The rate of rapid virologic response (RVR), early virologic response (EVR), end-of-treatment response (ETR), and SVR were 58%, 83%, 74%, and 57%, respectively. No significant difference in pretreatment IP-10 levels was observed between the patients with (RVR, EVR, ETR, and SVR) and without various virologic responses (p>0.05). The change in serum IP-10 between 1 month before and after treatment had no clinical meaning based on various virologic responses (p>0.05). Conclusions: The level of pretreatment IP-10 and change in IP-10 level between 1 month before and after treatment were not predictive factors of a SVR. Additional large-scale studies to determine the SVR-predicting role of serum IP-10 levels in patients with CHC are needed.
참고문헌 (24)
- Liang TJ, "Pathogenesis, natural history, treatment, and prevention of hepatitis C", Ann Intern Med, 132, pp.296~305 (2000)
- Kim YS, "Prevalence of hepatitis C virus antibody among Korean adults", J Korean Med Sci, 7, pp.333~336 (1992)
- Kim BS, "Prevalence of hepatitis C virus related to liver diseases in Korea", Gastroenterol Jpn, 28(Suppl 5), pp.S17~S22 (1993)
- Strader DB, "Diagnosis, management, and treatment of hepatitis C", Hepatology, 39, pp.1147~1171 (2004)
- Fried MW, "Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection", N Engl J Med, 347, pp.975~982 (2002)
- Hadziyannis SJ, "Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose", Ann Intern Med, 140, pp.346~355 (2004)
- Manns MP, "Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial", Lancet, 358, pp.958~965 (2001)
- Gao B, "Host factors and failure of interferonalpha treatment in hepatitis C virus", Hepatology, 39, pp.880~890 (2004)
- Pawlotsky JM, "Mechanisms of antiviral treatment efficacy and failure in chronic hepatitis C", Antiviral Res, 59, pp.1~11 (2003)
- Ferenci P, "Predicting the therapeutic response in patients with chronic hepatitis C: the role of viral kinetic studies", J Antimicrob Chemother, 53, pp.15~18 (2004)
- Pawlotsky JM, "Factors affecting treatment responses to interferon-alpha in chronic hepatitis C", J Infect Dis, 174, pp.1~7 (1996)
- Larrea E, "Tumor necrosis factor alpha gene expression and the response to interferon in chronic hepatitis C", Hepatology, 23, pp.210~217 (1996)
- Kishihara Y, "IL-1 beta and TNF-alpha produced by peripheral blood mononuclear cells before and during interferon therapy in patients with chronic hepatitis C", Dig Dis Sci, 41, pp.315~321 (1996)
- Cramp ME, "Hepatitis C virus-specific T-cell reactivity during interferon and ribavirin treatment in chronic hepatitis C", Gastroenterology, 118, pp.346~355 (2000)
- Zeremski M, "The role of chemokines as inflammatory mediators in chronic hepatitis C virus infection", J Viral Hepat, 14, pp.675~687 (2007)
- Apolinario A, "Increased circulating and intrahepatic T-cell-specific chemokines in chronic hepatitis C: relationship with the type of virological response to peginterferon plus ribavirin combination therapy", Aliment Pharmacol Ther, 19, pp.551~562 (2004)
- Diago M, "Association of pretreatment serum interferon gamma inducible protein 10 levels with sustained virological response to peginterferon plus ribavirin therapy in genotype 1 infected patients with chronic hepatitis C", Gut, 55, pp.374~379 (2006)
- Lagging M, "IP-10 predicts viral response and therapeutic outcome in difficult-to-treat patients with HCV genotype 1 infection", Hepatology, 44, pp.1617~1625 (2006)
- Lai MY, "Long-term efficacy of ribavirin plus interferon alfa in the treatment of chronic hepatitis C", Gastroenterology, 111, pp.1307~1312 (1996)
- Reiberger T, "IP-10 correlates with hepatitis C viral load, hepatic inflammation and fibrosis and predicts hepatitis C virus relapse or non-response in HIV-HCV coinfection", Antivir Ther, 13, pp.969~976 (2008)
- Apolinario A, "Gene expression profile of T-cell-specific chemokines in human hepatocyte-derived cells: evidence for a synergistic inducer effect of cytokines and hepatitis C virus proteins", J Viral Hepat, 12, pp.27~37 (2005)
- McHutchison JG, "Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection", N Engl J Med, 361, pp.580~593 (2009)
- Rumi MG, "Randomized study of peginterferon-alpha2a plus ribavirin vs peginterferonalpha2b plus ribavirin in chronic hepatitis C", Gastroenterology, 138, pp.108~115 (2010)
- Ascione A, "Peginterferon alfa-2a plus ribavirin is more effective than peginterferon alfa-2b plus ribavirin for treating chronic hepatitis C virus infection", Gastroenterology, 138, pp.116~122 (2010)