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. 2001 Feb;10(1):37–41. doi: 10.1080/09629350124104

Recurrence of hepatitis C after liver transplantation is associated with increased systemic IL-10 levels.

P A Sheiner 1, S S Florman 1, S Emre 1, T Fishbein 1, M E Schwartz 1, C M Miller 1, P Boros 1
PMCID: PMC1781689  PMID: 11324903

Abstract

BACKGROUND: Recurrence of hepatitis C after liver transplantation is an almost universal occurrence. T-cell derived cytokines have an important role in the development of liver damage associated with chronic hepatitis C, their post-transplant levels, however, have not been correlated with histologic recurrence of the disease. AIMS: We sought to analyze levels of TNF-alpha, soluble IL-2 receptor, IL-4 and IL-10 at 1 month, 6 months and 1 year after transplantation in 27 patients undergoing transplantation for hepatitis C related end-stage liver disease. METHODS: HCV RNA levels were monitored by a branched-chain DNA signal amplification assay. Diagnosis of recurrent hepatitis was based on 1-year protocol biopsies and on biopsies performed for liver enzyme elevations. RESULTS: Recurrent hepatitis C was detected in 52% (n=14) of the 27 patients. HCV RNA levels rose over time in all patients regardless of histologic recurrence. TNF-alpha, and IL-4 levels, although elevated, did not show specific patterns over time or in correlation with recurrence. Similarly, the early elevation followed by a gradual decrease over the first year in the amount of soluble IL-2 receptor was not related to histologic recurrence. We observed a significant increase in circulating IL-10 levels over the first year in patients with biopsy-proven recurrence, while patients with no signs of histologic recurrence displayed increased, but steady levels. CONCLUSIONS: These results suggest that while these cytokines are associated with post-transplant recurrence of hepatitis C, their production may be altered by additional factors.

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Selected References

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  1. Alberti A., Chemello L., Fattovich G., Pontisso P., Semenzato G., Colletta C., Vinante F., Pizzolo G. Serum levels of soluble interleukin-2 receptors in acute and chronic viral hepatitis. Dig Dis Sci. 1989 Oct;34(10):1559–1563. doi: 10.1007/BF01537110. [DOI] [PubMed] [Google Scholar]
  2. Alter M. J., Margolis H. S., Krawczynski K., Judson F. N., Mares A., Alexander W. J., Hu P. Y., Miller J. K., Gerber M. A., Sampliner R. E. The natural history of community-acquired hepatitis C in the United States. The Sentinel Counties Chronic non-A, non-B Hepatitis Study Team. N Engl J Med. 1992 Dec 31;327(27):1899–1905. doi: 10.1056/NEJM199212313272702. [DOI] [PubMed] [Google Scholar]
  3. Bertoletti A., D'Elios M. M., Boni C., De Carli M., Zignego A. L., Durazzo M., Missale G., Penna A., Fiaccadori F., Del Prete G. Different cytokine profiles of intraphepatic T cells in chronic hepatitis B and hepatitis C virus infections. Gastroenterology. 1997 Jan;112(1):193–199. doi: 10.1016/s0016-5085(97)70235-x. [DOI] [PubMed] [Google Scholar]
  4. Boros P., Suehiro T., Curtiss S., Sheiner P., Emre S., Guy S., Schwartz M. E., Miller C. M. Differential contribution of graft and recipient to perioperative TNF-alpha, IL-1 beta, IL-6 and IL-8 levels and correlation with early graft function in clinical liver transplantation. Clin Transplant. 1997 Dec;11(6):588–592. [PubMed] [Google Scholar]
  5. Cacciarelli T. V., Martinez O. M., Gish R. G., Villanueva J. C., Krams S. M. Immunoregulatory cytokines in chronic hepatitis C virus infection: pre- and posttreatment with interferon alfa. Hepatology. 1996 Jul;24(1):6–9. doi: 10.1002/hep.510240102. [DOI] [PubMed] [Google Scholar]
  6. Del Prete G. The concept of type-1 and type-2 helper T cells and their cytokines in humans. Int Rev Immunol. 1998;16(3-4):427–455. doi: 10.3109/08830189809043004. [DOI] [PubMed] [Google Scholar]
  7. Dienstag J. L. Non-A, non-B hepatitis. I. Recognition, epidemiology, and clinical features. Gastroenterology. 1983 Aug;85(2):439–462. [PubMed] [Google Scholar]
  8. Dumoulin F. L., Bach A., Leifeld L., El-Bakri M., Fischer H. P., Sauerbruch T., Spengler U. Semiquantitative analysis of intrahepatic cytokine mRNAs in chronic hepatitis C. J Infect Dis. 1997 Mar;175(3):681–685. doi: 10.1093/infdis/175.3.681. [DOI] [PubMed] [Google Scholar]
  9. Fiorentino D. F., Zlotnik A., Vieira P., Mosmann T. R., Howard M., Moore K. W., O'Garra A. IL-10 acts on the antigen-presenting cell to inhibit cytokine production by Th1 cells. J Immunol. 1991 May 15;146(10):3444–3451. [PubMed] [Google Scholar]
  10. Féray C., Gigou M., Samuel D., Paradis V., Mishiro S., Maertens G., Reynés M., Okamoto H., Bismuth H., Bréchot C. Influence of the genotypes of hepatitis C virus on the severity of recurrent liver disease after liver transplantation. Gastroenterology. 1995 Apr;108(4):1088–1096. doi: 10.1016/0016-5085(95)90207-4. [DOI] [PubMed] [Google Scholar]
  11. Féray C., Samuel D., Thiers V., Gigou M., Pichon F., Bismuth A., Reynes M., Maisonneuve P., Bismuth H., Bréchot C. Reinfection of liver graft by hepatitis C virus after liver transplantation. J Clin Invest. 1992 Apr;89(4):1361–1365. doi: 10.1172/JCI115723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gane E. J., Portmann B. C., Naoumov N. V., Smith H. M., Underhill J. A., Donaldson P. T., Maertens G., Williams R. Long-term outcome of hepatitis C infection after liver transplantation. N Engl J Med. 1996 Mar 28;334(13):815–820. doi: 10.1056/NEJM199603283341302. [DOI] [PubMed] [Google Scholar]
  13. Greenson J. K., Svoboda-Newman S. M., Merion R. M., Frank T. S. Histologic progression of recurrent hepatitis C in liver transplant allografts. Am J Surg Pathol. 1996 Jun;20(6):731–738. doi: 10.1097/00000478-199606000-00011. [DOI] [PubMed] [Google Scholar]
  14. Hayashi J., Kishihara Y., Yamaji K., Yoshimura E., Ohmiya M., Tani Y., Ikematsu H., Kashiwagi S. Serum levels of soluble interleukin-2 receptors and effects of interferon-alpha for patients with chronic hepatitis C virus. Dig Dis Sci. 1995 Aug;40(8):1837–1841. doi: 10.1007/BF02212710. [DOI] [PubMed] [Google Scholar]
  15. Imagawa D. K., Millis J. M., Olthoff K. M., Derus L. J., Chia D., Sugich L. R., Ozawa M., Dempsey R. A., Iwaki Y., Levy P. J. The role of tumor necrosis factor in allograft rejection. I. Evidence that elevated levels of tumor necrosis factor-alpha predict rejection following orthotopic liver transplantation. Transplantation. 1990 Aug;50(2):219–225. doi: 10.1097/00007890-199008000-00009. [DOI] [PubMed] [Google Scholar]
  16. Jirillo E., Greco B., Caradonna L., Satalino R., Pugliese V., Cozzolongo R., Cuppone R., Manghisi O. G. Evaluation of cellular immune responses and soluble mediators in patients with chronic hepatitis C virus (cHCV) infection. Immunopharmacol Immunotoxicol. 1995 May;17(2):347–364. doi: 10.3109/08923979509019756. [DOI] [PubMed] [Google Scholar]
  17. 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. 1996 Feb;41(2):315–321. doi: 10.1007/BF02093821. [DOI] [PubMed] [Google Scholar]
  18. Kuzushita N., Hayashi N., Katayama K., Kanto T., Oshita M., Hagiwara H., Kasahara A., Fusamoto H., Kamada T. High levels of serum interleukin-10 are associated with a poor response to interferon treatment in patients with chronic hepatitis C. Scand J Gastroenterol. 1997 Feb;32(2):169–174. doi: 10.3109/00365529709000188. [DOI] [PubMed] [Google Scholar]
  19. König V., Bauditz J., Lobeck H., Lüsebrink R., Neuhaus P., Blumhardt G., Bechstein W. O., Neuhaus R., Steffen R., Hopf U. Hepatitis C virus reinfection in allografts after orthotopic liver transplantation. Hepatology. 1992 Nov;16(5):1137–1143. doi: 10.1002/hep.1840160506. [DOI] [PubMed] [Google Scholar]
  20. Le Moine O., Marchant A., Durand F., Ickx B., Pradier O., Belghiti J., Abramowicz D., Gelin M., Goldman M., Devière J. Systemic release of interleukin-10 during orthotopic liver transplantation. Hepatology. 1994 Oct;20(4 Pt 1):889–892. doi: 10.1002/hep.1840200417. [DOI] [PubMed] [Google Scholar]
  21. McGuinness P. H., Bishop G. A., Painter D. M., Chan R., McCaughan G. W. Intrahepatic hepatitis C RNA levels do not correlate with degree of liver injury in patients with chronic hepatitis C. Hepatology. 1996 Apr;23(4):676–687. doi: 10.1002/hep.510230404. [DOI] [PubMed] [Google Scholar]
  22. Missale G., Ferrari C., Fiaccadori F. Mediatori citochinici nell'infiammazione acuta e nei fenomeni di cronicizzazione delle epatiti virali. Ann Ital Med Int. 1995 Jan-Mar;10(1):14–18. [PubMed] [Google Scholar]
  23. Morishima I., Kumada T., Nakano S., Takeda I., Sugiyama K., Osada T., Kiriyama S., Ohki H., Suga T., Ito O. Serum levels of soluble interleukin-2 receptor in chronic hepatitis C treated with interferon-alpha. Scand J Gastroenterol. 1995 Aug;30(8):807–811. doi: 10.3109/00365529509096332. [DOI] [PubMed] [Google Scholar]
  24. Mosmann T. R., Cherwinski H., Bond M. W., Giedlin M. A., Coffman R. L. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol. 1986 Apr 1;136(7):2348–2357. [PubMed] [Google Scholar]
  25. Müller H., Otto G., Goeser T., Arnold J., Pfaff E., Theilmann L. Recurrence of hepatitis C virus infection after orthotopic liver transplantation. Transplantation. 1992 Oct;54(4):743–745. [PubMed] [Google Scholar]
  26. Napoli J., Bishop G. A., McGuinness P. H., Painter D. M., McCaughan G. W. Progressive liver injury in chronic hepatitis C infection correlates with increased intrahepatic expression of Th1-associated cytokines. Hepatology. 1996 Oct;24(4):759–765. doi: 10.1002/hep.510240402. [DOI] [PubMed] [Google Scholar]
  27. Quiroga J. A., Martin J., Pardo M., Carreño V. Serum levels of soluble immune factors and pathogenesis of chronic hepatitis C, and their relation to therapeutic response to interferon-alpha. Dig Dis Sci. 1994 Nov;39(11):2485–2496. doi: 10.1007/BF02087671. [DOI] [PubMed] [Google Scholar]
  28. Reiser M., Marousis C. G., Nelson D. R., Lauer G., González-Peralta R. P., Davis G. L., Lau J. Y. Serum interleukin 4 and interleukin 10 levels in patients with chronic hepatitis C virus infection. J Hepatol. 1997 Mar;26(3):471–478. doi: 10.1016/s0168-8278(97)80409-6. [DOI] [PubMed] [Google Scholar]
  29. Romagnani S. Biology of human TH1 and TH2 cells. J Clin Immunol. 1995 May;15(3):121–129. doi: 10.1007/BF01543103. [DOI] [PubMed] [Google Scholar]
  30. Rosen H. R., Shackleton C. R., Higa L., Gralnek I. M., Farmer D. A., McDiarmid S. V., Holt C., Lewin K. J., Busuttil R. W., Martin P. Use of OKT3 is associated with early and severe recurrence of hepatitis C after liver transplantation. Am J Gastroenterol. 1997 Sep;92(9):1453–1457. [PubMed] [Google Scholar]
  31. Simsek H., Kadayifci A. Serum interleukin 2 and soluble interleukin 2 receptor in chronic active hepatitis C: effect of interferon therapy. J Int Med Res. 1996 May-Jun;24(3):239–245. doi: 10.1177/030006059602400302. [DOI] [PubMed] [Google Scholar]
  32. Singh N., Gayowski T., Ndimbie O. K., Nedjar S., Wagener M. M., Yu V. L. Recurrent hepatitis C virus hepatitis in liver transplant recipients receiving tacrolimus: association with rejection and increased immunosuppression after transplantation. Surgery. 1996 Apr;119(4):452–456. doi: 10.1016/s0039-6060(96)80147-4. [DOI] [PubMed] [Google Scholar]
  33. Stratta R. J., Shaefer M. S., Cushing K. A., Markin R. S., Reed E. C., Langnas A. N., Pillen T. J., Shaw B. W., Jr A randomized prospective trial of acyclovir and immune globulin prophylaxis in liver transplant recipients receiving OKT3 therapy. Arch Surg. 1992 Jan;127(1):55–64. doi: 10.1001/archsurg.1992.01420010065009. [DOI] [PubMed] [Google Scholar]
  34. Tilg H., Wilmer A., Vogel W., Herold M., Nölchen B., Judmaier G., Huber C. Serum levels of cytokines in chronic liver diseases. Gastroenterology. 1992 Jul;103(1):264–274. doi: 10.1016/0016-5085(92)91122-k. [DOI] [PubMed] [Google Scholar]
  35. Torre D., Zeroli C., Giola M., Ferrario G., Fiori G. P., Bonetta G., Tambini R. Serum levels of interleukin-1 alpha, interleukin-1 beta, interleukin-6, and tumor necrosis factor in patients with acute viral hepatitis. Clin Infect Dis. 1994 Feb;18(2):194–198. doi: 10.1093/clinids/18.2.194. [DOI] [PubMed] [Google Scholar]
  36. Tsai S. L., Liaw Y. F., Chen M. H., Huang C. Y., Kuo G. C. Detection of type 2-like T-helper cells in hepatitis C virus infection: implications for hepatitis C virus chronicity. Hepatology. 1997 Feb;25(2):449–458. doi: 10.1002/hep.510250233. [DOI] [PubMed] [Google Scholar]
  37. Wright T. L., Donegan E., Hsu H. H., Ferrell L., Lake J. R., Kim M., Combs C., Fennessy S., Roberts J. P., Ascher N. L. Recurrent and acquired hepatitis C viral infection in liver transplant recipients. Gastroenterology. 1992 Jul;103(1):317–322. doi: 10.1016/0016-5085(92)91129-r. [DOI] [PubMed] [Google Scholar]
  38. Zhang D. F., Ren H., Jia X. P., Zhou Y. S. Serum tumor necrosis factor (TNF) in the pathogenesis of clinical hepatic failure of HCV and/or HBV infection. Chin Med J (Engl) 1993 May;106(5):335–338. [PubMed] [Google Scholar]
  39. Zhou S., Terrault N. A., Ferrell L., Hahn J. A., Lau J. Y., Simmonds P., Roberts J. P., Lake J. R., Ascher N. L., Wright T. L. Severity of liver disease in liver transplantation recipients with hepatitis C virus infection: relationship to genotype and level of viremia. Hepatology. 1996 Nov;24(5):1041–1046. doi: 10.1002/hep.510240510. [DOI] [PubMed] [Google Scholar]

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