Sema VURAL, Tuğçin Bora POLAT, Seda Geylani GÜLEÇ, Nafiye URGANCI

Kanser sonrası kronik HCV genotip-1 enfeksiyonu olan çocuklarda tedavi yanıtı

Amaç: Genotip-1b HCV ile enfekte kanserli çocuklarda interferon (INF) ve ribavirin (RBV) ikili tedavisi ile İNF-a tekli tedavisinin yanıt oranlarının karşılaştırılması amaçlandı.Gereç ve Yöntem: 1998-2008 tarihleri arasında Çocuk Gastroenteroloji Bölümü’nde kronik hepatit C tanısı ile izlenen, önceden kanser hastası olup tedavisi kesilmiş ve en az bir yıldır remisyonda olan 27 hasta çalışmaya alındı. 2000 yılından sonra tanı alanlara INF-a 2b ve ağızdan RBV (Grup 1), önce tanı alınanlara INF-a (Grup 2) 12 ay süre ile verildi. Bulgular: Tedavi sonu yanıt oranı (TSY) ve kalıcı virolojik yanıt (KVY) oranı Grup 1’in %75 ve %56 iken, Grup 2’nin %27,2 ve %18,18 idi. İki grup arasındaki TSY anlamlı olup (p0,05). Tedavi öncesi enfeksiyon süresi Grup 1’de Grup 2’dekilere göre anlamlı derecede düşük bulundu (p=0,001). Çıkarımlar: Çalışmamızda ikili tedavinin tekli tedaviye göre daha iyi yanıt sağladığı saptandı. İkili tedavideki yüksek tedavi yanıtının, tedavi öncesi enfeksiyon süresinin kısalığı ile de ilişkili olabileceği düşünüldü.

Therapeutic response in children with post malignancy chronic HCV genotype 1infection

Aim: The aim of this study was to assess and compare the efficacy of interferon (INF) and its combination with ribavirin (RBV) treatment in children infected with Genotype-1b HCV. Material and Method: Twenty-seven children who had malignancy in remission for at least 12 months and were followed up for chronic hepatitis C infection between the years 1998 and 2000 were included. Patients diagnosed after the year 2000 were given INF-a 2b plus RBV in oral form (Group 1) and patients diagnosed before the year 2000 were given INF-a (Group 2) for twelve months respectively. Results: In Group 1, end of treatment response and sustained virological response (SVR) rates were 75% and 56%, respectively. In Group 2, the rates were 27.2% and 18.18 %, respectively. The difference in the end of treatment response rates between the two groups were statistically significant (p0.05). Duration of infection before treatment in Group 1 was significantly lower than in Group 2 (p=0.001). Conclusions: Better response rates were observed with combined therapy as compared to mono therapy. Higher response rate of combination therapy may be related to shorter initial infection period.

PDF

___

1. Choo QL, Kuo G, Weiner AJ, Overby LR, Bradley DW, Houghton M. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science 1989; 244: 359-62.
2. Weiner AJ, Kuo G, Bradley DW. Detection of hepatitis C viral sequences in non-A, non-B hepatitis. Lancet 1990; 335: 1-3.
3. Cesaro S, Petris MG, Rossetti F. Chronic hepatitis C virus infection after treatment for pediatric malignancy. Blood 1997; 90: 1315-20.
4. Fink FM, Höcker-Schulz S, Mor W. Association of hepatitis C virus infection with chronic liver disease in paediatric cancer patients. Eur J Pediatr 1993; 152: 490-2.
5. Paul IM, Sanders J, Ruggiero F, Andrews T, Ungar D, Eyster ME. Chronic hepatitis C virus infections in leukemia survivors: prevalence, viral load, and severity of liver disease. Blood 1999; 93: 3672-7.
6. Januszkiewicz D, Wysocki J, Nowak J. Hepatitis B and C virus infection in Polish children with malignancies. Eur J Pediatr 1997; 156: 454-6.
7. Fujisawa T, Komatsu H, Inui A. Spontaneous remission of chronic hepatitis C in children. Eur J Pediatr 1997; 156: 773-6.
8. Ruiz-Moreno M, Rua MJ, Castillo I. Treatment of children with chronic hepatitis C with recombinant interferon-a: a pilot study. Hepatology 1992; 16: 882-5.
9. Cesaro S, Rossetti F, De Moliner L, Crivellaro C, Zanesco L, Bortolotti F. Interferon for chronic hepatitis C in patients cured of malignancy. Eur J Pediatr 1994; 153: 659-62.
10. Fujisawa T, Inui A, Ohkawa T, Komatsu H, Miyakawa Y, Onoue M. Response to interferon therapy in children with chronic hepatitis C. J Pediatr 1995; 127: 660-2.
11. Bortolotti F, Giacchino R, Vajro P. Recombinant interferon- therapy in children with chronic hepatitis C. Hepatology 1995; 22: 1623-7.
12. Komatsu H, Fujisawa T, Inui A. Efficacy of interferon in treating chronic hepatitis C in children with a history of acute leukemia. Blood 1996; 87: 4072-5.
13. Reichard O, Schvarcz R, Weiland O. Therapy of hepatitis C: alpha interferon and ribavirin. Hepatology 1997; 26: 108-11.
14. Reichard O, Norkrans G, Frydén A, Braconier JH, Sönnerborg A, Weiland O. Randomised, double-blind, placebo-controlled trial of interferona-2b with and without ribavirin for chronic hepatitis C. Lancet 1998; 351: 83-7.
15. McHutchison JG, Gordon SC, Schiff ER. Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. N Engl J Med 1998; 339: 1485-92.
16. Hartman C, Berkowitz D, Rimon N, Shamir R. The effect of early treatment in children with chronic hepatitis. J Pediatr Gastroenterol Nutr 2003; 37: 252-7.
17. Simmonds P, Holmes EC, Cha TA, et al. Classification of hepatitis C virus in six major genotypes and a series subtypes by phylogenetic analysis of the NS-5 region. J Gen Virol 1993; 74: 2391-9.
18. Knodell RG, Ishak KG, Black WC, et al. Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology 1981; 1: 431-5.
19. Desmet VJ, Gerber M, Hoofnagle JH, Manns M, Scheuer PJ. Classification of chronic hepatitis: diagnosis, grading and staging. Hepatology 1994; 19: 1513-20.
20. Craxi A, Camma C, Giunata M. Definition of response to antiviral therapy in chronic hepatitis C. J Hepatol 1999; 31: (suppl 1): 160-7.
21. Locasciulli A, Gornati G, Tagger A, et al. Hepatitis C virus infection and chronic liver disease in children with leukemia in long term remission. Blood 1991; 78: 1619-22.
22 Chang MH. Treatment of chronic hepatitis C virus infection in children. Baillieres Best Pract Res Clin Gastroenterol 2000; 14: 341-50.
23. Poynard T, Marcellin P, Lee SS, et al. Randomised trial of interferon alfa-2b plus ribavirin for 48 weeks or for 24 weeks versus interferon alfa-2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus. International Hepatitis Interventional Therapy Group (IHIT). Lancet 1998; 352: 1426-32.
24. Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Eng J Med 2002; 347: 975 82.
25. Hadziyannis SJ, Sette H Jr, Morgan TR, et al. Peginterferon- alfa-2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med 2004; 140: 346 55.
26. 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.
27. Deutsch M, Hadziyannis SJ. Old and emerging therapies in chronic hepatitis C: an update. J Viral Hepatitis 2008; 15: 2-11.
28. Pensati P, Iorio R, Botta S. Low virological response to interferon in children with chronic hepatitis C. J Hepatol 1999; 31: 604-11.
29. Jacobson KR, Murray K, Zellos A, Schwarz KB. An analysis of published trials of interferon monotherapy in children with chronic hepatitis C. J Pediatr Gastroenterol Nutr 2002; 34: 52-8.
30. Iorio R, Giannattasio A, Sepe A, Terracciano LM, Vecchione R, Vegnente A. Chronic hepatitis C in childhood: an 18 year experience. Clin Infect Dis 2005; 41: 1431-7.
31. Lackner H, Moser A, Deutsch J, et al. Interferon-alpha and ribavirin in treating children and young adults with chronic hepatitis C after malignancy. Pediatrics 2000; 106: 1-4.
32. Suoglu OD, Elkabes B, Sokucu S, Saner G. Does interferon and ribavirin combination therapy increase the rate of treatment response in children with hepatitis C. J Pediatr Gastroenterol Nutr 2002; 34:199-206.
33. Christensson B, Wiebe T, Akesson A, Widell A. Interferon-a and ribavirin treatment of hepatitis C in children with malignancy in remission. Clin Infect Dis 2000; 30: 585-6.
34. Di Marco V, Ferraro D, Almasio P, et al. Early viral clearance and sustained response in chronic hepatitis C: a controlled trial of interferon and ribavirin after high-dose interferon induction. J Viral Hepatitis 2002; 9: 354-9.
35. Weiland O. Treatment of naive patients with chronic hepatitis C. J Hepatol 1999; 31: (suppl 1): 168-73.
36. Davis GL, Esteban-Mur R, Rustgi V, et al. Interferon alfa 2b alone or in combination with ribavirin for the treatment of relapse of chronic hepatitis C. N Engl J Med 1998; 339: 1493-9.
37. Garcia-Monzon C, Jara P, Fernandez-Bermejo M, et al. Chronic hepatitis C in children: a clinical and immunohistochemical comparative study with adult patients. Hepatology 1998; 28: 1696-701.
38. Locasciulli A, Testa M, Pontisso P, et al. Prevalence and natural history of hepatitis C infection in patients cured of childhood leukemia. Blood 1997; 90: 4628-33.
39. Hoshiyama A, Kimura A, Fujisawa T, Kage M, Kato H. Clinical and histologic features of chronic hepatitis C virus infection after blood transfusion in Japanese children. Pediatrics 2000; 105: 62-5.
40. Badizadegan K, Jonas MM, Ott MJ, Nelson SP, Perez-Atayde AR. Histopathology of the liver in children with chronic hepatitis C viral infection. Hepatology 1998; 28: 1416-23.
41. Hardikar W. Hepatitis C in childhood. J Gastroenterol and Hepatol 2002; 17: 476-81.