Terapija hronične HCV infekcije - povezanost prediktivnih faktora i virusološkog odgovora
Sažetak
Sažetak
Uvod/Cilj. Na ishod terapije hronične HCV infekcije utiču brojni faktori domaćina (starost, pol, stadijum fibroze, imunski odgovor), i virusa (visina viremije, genotip, razvoj virusnih kvazi specijesa). Cilj rada bio je da se utvrdi povezanost najznačajnijih prediktivnih faktora i odgovora na terapiju kod pacijenata sa hroničnom HCV infekcijom.
Metode. Ispitivanjem je bilo obuhvaćeno 76 bolesnika sa hroničnim HCV hepatitisom, koji su lečeni u periodu od 2007 do 2010. godine na Infektivnoj Klinici Kliničkog centra Kragujevac. Lečenje je sprovedeno tokom 24/48 nedelja u zavisnosti od genotipa virusa.
Rezultati. HCV infekcija je češća kod muškaraca, ali polne, kao ni starosne karakteristike ne utiču na ishod infekcije. Najčešći faktor rizika u grupi pacijenata sa povoljnim odgovorom (SVR i ETR) je intravenska upotreba psihoaktivnih supstanci, dok su transfuzija krvi i dijaliza vodeći faktor rizika za bolesnike sa nepovoljnim odgovorom (NR/RR). Serumske vrednosti aminotransferaza i alkalne fosfataze su niže u SVR i ETR grupi pacijenata. Najmanji broj virusnih čestica registrovan je u grupi bolesnika sa trajnim virusološkim odgovorom, dok je najveći broj registrovan u grupi bolesnika sa nepovoljnijim odgovorom. Najčešći genotip HCV virusa je genotip 1 koji je u visokom procentu zastupljen kako kod bolesnika sa povoljnim, tako i kod bolesnika sa nepovoljnim odgovorom na terapiju. Prisustvo HCV virusa genotipa 2 zabeleženo je samo kod pacijenata sa nepovoljnim odgovorom na terapiju. Najveći procenat bolesnika sa odsustvom fibroze se nalazi u grupi bolesnika sa povoljnim odgovorom.
Zaključak. Rezultati ove studije pokazuju da je pozitivan odgovor na terapiju postignut u gotovo 90% pacijenata sa hroničnom HCV infekcijom. Bazalni nivo virusa, genotip i stadijum fibroze su povezani sa ishodom lečenja hronične HCV. Naša studija nije potvrdila asocijaciju između starosti, pola pacijenata i biohemijskih parametara i ishoda terapije.
Ključne reči: HCV, lečenje, AST, broj virusnih čestica, genotip, fibroza
Reference
Сhоо QL, Kuo G, Weiner AJ, et al. Isolation of a c DNA clone derived from a blood born non- A, non- B viral hepatitis genome 1989; 244: 359-62.
Bradley D. Virology, molecular biology and serology of hepatitis C virus. Transfus Med Rev 1992; 5: 93–102.
Cuthbert JA. Hepatitis C: progress and problems. Clin Microbiol Rev 1994; 7: 505–32.
Esteban Ji, Sauleda S, Quer J. The changing epidemiology of hepatitis C virus infection in Europe. J Hepatol 2008; 48: 148-62.
Bacon BR, Mchutchison JG. Into the light: Strategies for battling hepatitis C. Am J Manag Care, 2007; 13: 319-26.
Кyong-Mi Chang, Rehermann B, Francis V. Chisari. Immunopatology of hepatitis C. Springer Semin Immunopathol 1997; 19: 57-68.
Cerny A.,Chisari F.V. Pathogenesis of chronic hepatitis C: Immunological features of hepatic injury and viral persistence. Hepatology, 1999; 30 (3): 595-601.
Deuffic-Burban S, Babany G, Lonjon-Domanec I, et al. Impact of pegylated interferon and ribavirin on morbidity and mortality in patients with chronic hepatitis C and normal aminotransferases in France. Hepatology 2009; 50: 1351–55.
Vermehren J, Kau A, Gartner BC, Gobel R, Zeuzem S, Sarrazin C. Differences between two real-time PCR-based hepatitis C virus (HCV) assays (RealTime HCV and Cobas AmpliPrep / Cobas Taq Man) and one signal amplification assay (Versant HCV RNA 3.0) for RNA detection and quantification. J Clin Microbiol 2008; 46: 3880–91.
Chevaliez S, Bouvier-Alias M, Brillet R, Pawlotsky JM. Hepatitis C virus (HCV) genotype 1 subtype identification in new HCV drug development and future clinical practice. PLoS One. 2009 Dec 8; 4(12): e8209. doi: 10.1371/journal.pone.0008209.
Alter M J Prevention of spread of hepatitis C. Hepatology 2002; 36: 93-98.
Buckton AJ, Ngui, SL, Arnold, C, et al. Multitypic Hepatitis C virus infection identified by real-time nucleotide sequencing of minority genotypes. Journal of Clinical Microbiology, 2006; 44 (8): 2779.
Hwang SY, Lee HJ, Park KT, et al. Effectiveness and complications of combination therapy with interferon alpha and ribavirin in patients with chronic hepatitis C. Korean J Gastroenterol, 2007; 49(3): 166-72.
Ayaz C, Celen MK, Yuce UN, Geyik MF. Efficacy and safety of pegylated-interferon a-2a in hemodialysis patients with chronic hepatitis C. World Journal of Gastroenterology, 2008 14(2): 255.
Bedossa P. Liver biopsy. Gastroenterol Clin Biol 2008; 32: 4–7.
Kleiner DE. The liver biopsy in chronic hepatitis C: a view from the other side of the microscope. Semin Liver Dis 2005; 25: 52-64
Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 2002; 347: 975-82.
Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 2001; 358: 958-65.
Ghany MG, Strader DB, Thomas DL, Seeff LB. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology 2009; 49: 1335–74.
McCaughan GW. Asian Pacific Association for the Study of the Liver consensus statements on the diagnosis, management and treatment of hepatitis C virus infection. J Gastroenterol Hepatol 2007; 22: 615–33.
Bruijne J, Buster EHCJ, Gelderblom HC, et al. Treatment of chronic hepatitis C virus infection – Dutch national guidelines. Netherlands J Med 2008; 66: 311–22.
Sarrazin C, Berg T, Ross RS, et al. Prophylaxis, diagnosis and therapy of hepatitis C virus (HCV) infection: the German guidelines on the management of HCV infection. Z Gastroenterol 2010; 48: 289–351.
McHutchison JG, Lawitz EJ, Shiffman ML, et al. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. New Engl J Med 2009; 361: 580–93.
Jensen DM, Morgan TR, Marcellin P, et al. Early identification of HCV genotype 1 patients responding to 24 weeks peginterferon alpha-2a (40 kD)/ribavirin therapy. Hepatology 2006; 43: 954–60.
Ferenci P, Laferl H, Scherzer TM, et al. Peginterferon alfa-2a and ribavirin for 24 weeks in hepatitis C type 1 and 4 patients with rapid virological response. Gastroenterology 2008; 135: 451–58.
Zeuzem S, Buti M, Ferenci P, et al. Efficacy of 24 weeks treatment with peginterferon alfa- 2b plus ribavirin in patients with chronic hepatitis C infected with genotype 1 and low pretreatment viremia. J Hepatol 2006; 44: 97–103.
Moreno C, Deltenre P, Pawlotsky JM, Henrion J, Adler M, Mathurin P. Shortened treatment duration in treatment-naive genotype 1 HCV patients with rapid virological response: a meta-analysis. J Hepatol 2010; 52: 25–31.
Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 2002; 347: 975-82.
Jensen DM, Morgan TR, Marcellin P, Pockros PJ, Reddy KR, Hadziyannis SJ, et al. Early identification of HCV genotype 1 patients responding to 24 weeks peginterferon alpha-2a (40 kd) / ribavirin therapy. Hepatology 2006; 43: 954-60.
Davis GL, Wong JB, McHutchison JG, Manns MP, Harvey J, Albrecht J. Early virologic response to treatment with peginterferon alfa-2b plus ribavirin in patients with chronic hepatitis C. Hepatology 2003;38: 645-52.
Hadziyannis SJ, Sette H, Morgan TR et al. Peginterferon alfa2a and ribavirin combination therapy in treatment of chronic hepatitis C: randomised study of treatment duration and ribavirin dose. Ann. Inter. Med 2004; 140: 346-55.
Pawlotsky JM. Therapy of hepatitis C: from empiricism to eradiction Hepatology 2006; 43: 397-408.
Ferenci P, Fried MW, Shiffman ML, et al. Predicting sustained virological responses in chronic hepatitis C patients treated with peginterferon alfa-2a (40 KD)/ribavirin. J Hepatol 2005; 43: 425-33.
Kobayashi S, Takeda T, Enomoto M, et al. Development of hepatocellular carcinoma in patients with chronic hepatitis C who had a sustained virological response to interferon therapy: a multicenter, retrospective cohort study of 1124 patients. Liver Int 2007; 27: 186-91.
Yu JW, Wang GQ, Sun LJ, Li XG, Li SC. Predictive value of rapid virological response and early virological response on sustained virological response in HCV patients treated with pegylated interferon alpha-2a and ribavirin. J Gastroenterol Hepatol 2007; 22: 832-36.
Liang TJ. Pathogenesis, natural history, treatment and prevention of hepatitis C. Ann Intern Med 2000;132: 296-305.
Kamal SM. Peginterferon alone or with ribavirin enahnces HCVspecific CD4 T-helper 1 responses in patients with chronic hepatitis C. Gastroenterology 2002; 123: 1070-83.
Lauer GM, Walker BD. Hepatitis C virus infection. N Engl. J Med 2001; 345:41-52.
Knodell R, Ishak K, Black W, et al. Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology 1981; 1: 431-35.
Lavanchy D. The global burden of hepatitis C. Liver Int 2009; 29: 74-81.
Shepard CW, Finelli L, Alter MJ. Global epidemiology of hepatitis C infection. Lancet Infect Dis 2005; 5: 558-67.
Farnik H, Lange CM, Sarrazin C, Kronenberger B, Zeuzem S, Herrmann E. Meta-analysis shows extended therapy improves response of patients with chronic hepatitis C virus genotype 1 infection. Clin Gastroenterol Hepatol 2010; 8: 884–90.
Kau A, Vermehren J, Sarrazin C. Treatment predictors of a sustained virologic response in hepatitis B and C. J Hepatol 49 (2008; 49: 634–51.
Idrees M, Riazuddin S. A study of best positive predictors for sustained virologic response to interferon alpha plus ribavirin therapy in naïve chronic hepatitis C patients. BMC Gastroenterol 2009; 9: 5. doi:10.1186/1471-230X-9-5.
Kostić V, Ðorđević M, Popović L, Kostić E, Ðorđević J, Paunović K. Hronična bubrežna insuficijencija udružena sa virusnima hepatitisa B i C kao terapijski problem. Acta Medica Medianae 2008; 47(3): 5-8.
Wang YH, Guy R, Hellard M. The Victorian hepatitis C education program for GPs—an evaluation. Aust Farm Physician 2009; 38(9):749-52.
Kuljić-Kapuljica N, Jovanović D, Savić D, et al. Terapija hroničnog hepatitisa C–praćenje virusološkog odgovora, Vojnosanitetski pregled 2010; 67(11): 923–27.
Mijailović Ž, Čanović P, Gajović O, et al. Faktori rizika za nastanak hepatitis C virusne infekcije, Medicinski pregled, 2003; vol. 56, br. 11-12: 511-15.
Manns MP, Wedemeyer H, Cornberg HM. Treating viral hepatitis C: efficacy, side effects, and complications. Gut 2006; 55: 1350–59.
Simmonds P, Bukh J, Combet C, et al. Consensus proposals for a unified system of nomenclature of hepatitis C virus genotypes. Hepatology 2005; 42(4): 962-73.
Zein N.N, J. Rakela, E.L. Krawitt, K.R. Reddy, T.Tominaga and D.H. Persing. Hepatitis C virus genotypes in the United States: Epidemiology, pathogenicity and response to interferon therapy. Collaborative Study Group. Ann Intern Med 1996; 125: 634-39.
Attaullah S, Khan S, Ijaz A. Hepatitis C virus genotypes in Pakistan: a systemic review Virology J. 2011; 8: 433.
Innes HA, Hutchinson SJ, Allen S, et al. Ranking predictors of a sustained viral response for patients with chronic hepatitis C treated with pegylated interferon and ribavirin in Scotland. Eur J Gastroenterol Hepatol 2012; 24(6): 646-55.
Cescon M, Grazi GL, Cucchetti A, et al. Predictors of sustained virological response after antiviral treatment for hepatitis C recurrence following liver transplantation. Liver Transpl 2009; 15(7): 782-89.