The Korean Journal of Medicine

  • 제79권6호
  • /
  • Pages.652-660
  • /
  • 2010
  • /
  • 1738-9364(pISSN)
  • /
  • 2289-0769(eISSN)
대한내과학회 (The Korean Association of Internal Medicine)
권호 표지

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

  • 이영선 (고려대학교 의과대학 내과학교실) ;
  • 김지훈 (고려대학교 의과대학 내과학교실) ;
  • 이현정 (고려대학교 의과대학 내과학교실) ;
  • 윤아일린 (고려대학교 의과대학 내과학교실) ;
  • 김태형 (고려대학교 의과대학 내과학교실) ;
  • 고진성 (고려대학교 의과대학 내과학교실) ;
  • 김선원 (고려대학교 의과대학 내과학교실) ;
  • 임상아 (고려대학교 의과대학 내과학교실) ;
  • 이준영 (고려대학교 의과대학 내과학교실) ;
  • 이범재 (고려대학교 의과대학 내과학교실) ;
  • 연종은 (고려대학교 의과대학 내과학교실) ;
  • 박종재 (고려대학교 의과대학 내과학교실) ;
  • 김재선 (고려대학교 의과대학 내과학교실) ;
  • 박영태 (고려대학교 의과대학 내과학교실) ;
  • 변관수 (고려대학교 의과대학 내과학교실)
  • Lee, Young-Sun (Department of Internal Medicine, Korea University College of Medicine) ;
  • Kim, Ji-Hoon (Department of Internal Medicine, Korea University College of Medicine) ;
  • Lee, Hyun-Jung (Department of Internal Medicine, Korea University College of Medicine) ;
  • Yoon, Eileen L. (Department of Internal Medicine, Korea University College of Medicine) ;
  • Kim, Tae-Hyung (Department of Internal Medicine, Korea University College of Medicine) ;
  • Koh, Jin-Sung (Department of Internal Medicine, Korea University College of Medicine) ;
  • Kim, Sun-Won (Department of Internal Medicine, Korea University College of Medicine) ;
  • Lim, Sang-Ah (Department of Internal Medicine, Korea University College of Medicine) ;
  • Lee, Joon-Young (Department of Internal Medicine, Korea University College of Medicine) ;
  • Lee, Beom-Jae (Department of Internal Medicine, Korea University College of Medicine) ;
  • Yoen, Jong-Eun (Department of Internal Medicine, Korea University College of Medicine) ;
  • Park, Jong-Jae (Department of Internal Medicine, Korea University College of Medicine) ;
  • Kim, Jae-Seon (Department of Internal Medicine, Korea University College of Medicine) ;
  • Bak, Young-Tae (Department of Internal Medicine, Korea University College of Medicine) ;
  • Byun, Kwan-Soo (Department of Internal Medicine, Korea University College of Medicine)
  • 투고 : 2010.07.21
  • 심사 : 2010.10.11
  • 발행 : 2010.12.01
⟨ 이전 논문 다음 논문 ⟩

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 $53.5{\pm}10$세이고, 21명(58%)이 남자였으며, 치료 전 HCV RNA의 평균은 $5.7{\pm}0.9$ log10 IU/mL 이었고, IP-10 정량 결과는 평균 $432.2{\pm}343.7$ 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 $432.2{\pm}343.7$ pg/mL이었고, 치료 1개월 후의 IP-10의 평균값은 $306.5{\pm}246.1$ 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.

Background/Aims: Recent studies have shown that serum interferon ${\gamma}$-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.

키워드

참고문헌

  1. Liang TJ, Rehermann B, Seeff LB, Hoofnagle JH. Pathogenesis, natural history, treatment, and prevention of hepatitis C. Ann Intern Med 132:296-305, 2000 https://doi.org/10.7326/0003-4819-132-4-200002150-00008
  2. Kim YS, Pai CH, Chi HS, Kim DW, Min YI, Ahn YO. Prevalence of hepatitis C virus antibody among Korean adults. J Korean Med Sci 7:333-336, 1992 https://doi.org/10.3346/jkms.1992.7.4.333
  3. Kim BS, Park YM. Prevalence of hepatitis C virus related to liver diseases in Korea. Gastroenterol Jpn 28(Suppl 5):S17-S22, 1993 https://doi.org/10.1007/BF02989198
  4. Strader DB, Wright T, Thomas DL, Seeff LB. Diagnosis, management, and treatment of hepatitis C. Hepatology 39:1147-1171, 2004 https://doi.org/10.1002/hep.20119
  5. Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Goncales FL Jr, Häussinger D, Diago M, Carosi G, Dhumeaux D, Craxi A, Lin A, Hoffman J, Yu J. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 347:975-982, 2002 https://doi.org/10.1056/NEJMoa020047
  6. Hadziyannis SJ, Sette H Jr, Morgan TR, Balan V, Diago M, Marcellin P, Ramadori G, Bodenheimer H Jr, Bernstein D, Rizzetto M, Zeuzem S, Pockros PJ, Lin A, Ackrill AM. Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med 140:346-355, 2004 https://doi.org/10.7326/0003-4819-140-5-200403020-00010
  7. Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, Goodman ZD, Koury K, Ling M, Albrecht JK. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 358:958-965, 2001 https://doi.org/10.1016/S0140-6736(01)06102-5
  8. Gao B, Hong F, Radaeva S. Host factors and failure of interferon-alpha treatment in hepatitis C virus. Hepatology 39:880-890, 2004 https://doi.org/10.1002/hep.20139
  9. Pawlotsky JM. Mechanisms of antiviral treatment efficacy and failure in chronic hepatitis C. Antiviral Res 59:1-11, 2003 https://doi.org/10.1016/S0166-3542(03)00088-3
  10. Ferenci P. Predicting the therapeutic response in patients with chronic hepatitis C: the role of viral kinetic studies. J Antimicrob Chemother 53:15-18, 2004
  11. Pawlotsky JM, Roudot-Thoraval F, Bastie A, Darthuy F, Remire J, Metreau JM, Zafrani ES, Duval J, Dhumeaux D. Factors affecting treatment responses to interferon-alpha in chronic hepatitis C. J Infect Dis 174:1-7, 1996 https://doi.org/10.1093/infdis/174.1.1
  12. Larrea E, Garcia N, Qian C, Civeira MP, Prieto J. Tumor necrosis factor alpha gene expression and the response to interferon in chronic hepatitis C. Hepatology 23:210-217, 1996
  13. Kishihara Y, Hayashi J, Yoshimura E, Yamaji K, Nakashima K, Kashiwagi S. 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 41:315-321, 1996 https://doi.org/10.1007/BF02093821
  14. Cramp ME, Rossol S, Chokshi S, Carucci P, Williams R, Naoumov NV. Hepatitis C virus-specific T-cell reactivity during interferon and ribavirin treatment in chronic hepatitis C. Gastroenterology 118:346-355, 2000 https://doi.org/10.1016/S0016-5085(00)70217-4
  15. Zeremski M, Petrovic LM, Talal AH. The role of chemokines as inflammatory mediators in chronic hepatitis C virus infection. J Viral Hepat 14:675-687, 2007
  16. Apolinario A, Diago M, Lo Iacono O, Lorente R, Perez C, Majano PL, Clemente G, Garcia-Monzon C. 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 19:551-562, 2004 https://doi.org/10.1111/j.1365-2036.2004.01872.x
  17. Diago M, Castellano G, Garcia-Samaniego J, Perez C, Fernandez I, Romero M, Iacono OL, Garcia-Monzon C. 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 55:374-379, 2006 https://doi.org/10.1136/gut.2005.074062
  18. Lagging M, Romero AI, Westin J, Norkrans G, Dhillon AP, Pawlotsky JM, Zeuzem S, von Wagner M, Negro F, Schalm SW, Haagmans BL, Ferrari C, Missale G, Neumann AU, Verheij-Hart E, Hellstrand K. IP-10 predicts viral response and therapeutic outcome in difficult-to-treat patients with HCV genotype 1 infection. Hepatology 44:1617-1625, 2006 https://doi.org/10.1002/hep.21407
  19. Lai MY, Kao JH, Yang PM, Wang JT, Chen PJ, Chan KW, Chu JS, Chen DS. Long-term efficacy of ribavirin plus interferon alfa in the treatment of chronic hepatitis C. Gastroenterology 111:1307-1312, 1996 https://doi.org/10.1053/gast.1996.v111.pm8898645
  20. Reiberger T, Aberle JH, Kundi M, Kohrgruber N, Rieger A, Gangl A, Holzmann H, Peck-Radosavljevic M. 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 13:969-976, 2008
  21. Apolinario A, Majano PL, Lorente R, Nunez O, Clemente G, Garcia-Monzon C. 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 12:27-37, 2005 https://doi.org/10.1111/j.1365-2893.2005.00540.x
  22. McHutchison JG, Lawitz EJ, Shiffman ML, Muir AJ, Galler GW, McCone J, Nyberg LM, Lee WM, Ghalib RH, Schiff ER, Galati JS, Bacon BR, Davis MN, Mukhopadhyay P, Koury K, Noviello S, Pedicone LD, Brass CA, Albrecht JK, Sulkowski MS. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med 361:580-593, 2009 https://doi.org/10.1056/NEJMoa0808010
  23. Rumi MG, Aghemo A, Prati GM, D'Ambrosio R, Donato MF, Soffredini R, Del Ninno E, Russo A, Colombo M. Randomized study of peginterferon-alpha2a plus ribavirin vs peginterferon-alpha2b plus ribavirin in chronic hepatitis C. Gastroenterology 138:108-115, 2010 https://doi.org/10.1053/j.gastro.2009.08.071
  24. Ascione A, De Luca M, Tartaglione MT, Lampasi F, Di Costanzo GG, Lanza AG, Picciotto FP, Marino-Marsilia G, Fontanella L, Leandro G. Peginterferon alfa-2a plus ribavirin is more effective than peginterferon alfa-2b plus ribavirin for treating chronic hepatitis C virus infection. Gastroenterology 138:116-122, 2010 https://doi.org/10.1053/j.gastro.2009.10.005