Single nucleotide polymorphisms of interleukin-28B (IL28B) rs8099917 are reported to be associated with virologic clearance in interferon-and ribavirin -based treatment for hepatitis C virus (HCV)-infected patients. We examined virologic response in accordance with IL28B polymorphisms in our living donor liver transplantation series under a preemptive interferon and RBV treatment approach. Adequate DNA samples from both the recipient and donor for the study of single nucleotide polymorphisms of IL28B were available from 96 cases and were the subjects of the present study. Various clinical factors related with virologic response including early virologic response (EVR) and sustained virologic response (SVR) were examined. Totally 51% presented with EVR and 44% achieved SVR. Presence of the major allele (TT) in either the recipient or the donor corresponded to SVR of 53% and 48%. Presence of the minor allele (TG or GG) corresponded to SVR of 26% and 32%. Multivariate analysis revealed that genotype of HCV or EVR, but not IL28B polymorphisms in either the recipient or donor, was an independent factor for achieving SVR. When virologic response to treatment was incorporated into analysis, the impact of IL28B polymorphism on virological clearance remained relative to other factors and was not significantly independent.
References
[1]
Lauer GM, Walker BD (2001) Hepatitis C virus infection. N Engl J Med 345: 41–52. doi: 10.1056/nejm200107053450107
[2]
Zeuzem S, Berg T, Moeller B, Hinrichsen H, Mauss S, et al. (2009) Expert opinion on the treatment of patients with chronic hepatitis C. J Viral Hepat 16: 75–90. doi: 10.1111/j.1365-2893.2008.01012.x
[3]
Brown RS (2005) Hepatitis C and liver transplantation. Nature 436: 973–978. doi: 10.1038/nature04083
[4]
Berenguer M, López-Labrador FX, Wright TL (2001) Hepatitis C and liver transplantation. J Hepatol 35: 666–678. doi: 10.1016/s0168-8278(01)00179-9
[5]
Powers KA, Ribeiro RM, Patel K, Pianko S, Nyberg L, et al. (2006) Kinetics of hepatitis C virus reinfection after liver transplantation. Liver Transpl 12: 207–216. doi: 10.1002/lt.20572
[6]
Garcia-Retortillo M, Forns X, Feliu A, Moitinho E, Costa J, et al. (2002) Hepatitis C virus kinetics during and immediately after liver transplantation. Hepatology 35: 680–687. doi: 10.1053/jhep.2002.31773
[7]
Berenguer M, Ferrell L, Watson J, Prieto M, Kim M, et al. (2000) HCV-related fibrosis progression following liver transplantation: increase in recent years. J Hepatol 32: 673–684. doi: 10.1016/s0168-8278(00)80231-7
[8]
Yilmaz N, Shiffman ML, Stravitz RT, Sterling RK, Luketic VA, et al. (2007) A prospective evaluation of fibrosis progression in patients with recurrent hepatitis C virus following liver transplantation. Liver Transpl 13: 975–983. doi: 10.1002/lt.21117
[9]
Forman LM, Lewis JD, Berlin JA, Feldman HI, Lucey MR (2002) The association between hepatitis C infection and survival after orthotopic liver transplantation. Gastroenterology 122: 889–896. doi: 10.1053/gast.2002.32418
[10]
Thuluvath PJ, Krok KL, Segev DL, Yoo HY (2007) Trends in post-liver transplant survival in patients with hepatitis C between 1991 and 2001 in the United States. Liver Transpl 13: 719–724. doi: 10.1002/lt.21123
[11]
Terrault NA, Berenguer M (2006) Treating hepatitis C infection in liver transplant recipients. Liver Transpl 12: 1192–1204. doi: 10.1002/lt.20865
[12]
Berenguer M, Palau A, Fernandez A, Benlloch S, Aguilera V, et al. (2006) Efficacy, predictors of response, and potential risks associated with antiviral therapy in liver transplant recipients with recurrent hepatitis C. Liver Transpl 12: 1067–1076. doi: 10.1002/lt.20737
[13]
Bizollon T, Pradat P, Mabrut JY, Radenne S, Ducerf C, et al. (2007) Histological benefit of retreatment by pegylated interferon alfa-2b and ribavirin in patients with recurrent hepatitis C virus infection post transplantation. Am J Transplant 7: 448–453. doi: 10.1111/j.1600-6143.2006.01619.x
[14]
Wang CS, Ko HH, Yoshida EM, Marra CA, Richardson K (2006) Interferon-based combination anti-viral therapy for hepatitis C virus after liver transplantation: a review and quantitative analysis. Am J Transplant 6: 1586–1599. doi: 10.1111/j.1600-6143.2006.01362.x
[15]
Carrion JA, Navasa M, Garcia-Retortillo M, Garcia-Pagan JC, Crespo G, et al. (2007) Efficacy of antiviral therapy on hepatitis C recurrence after liver transplantation: a randomized controlled study. Gastroenterology 132: 1746–1756. doi: 10.1053/j.gastro.2007.03.041
[16]
Tamura S, Sugawara Y (2008) Treatment strategy for hepatitis C after liver transplantation. J Hepatobiliary Pancreat Surg 15: 111–123. doi: 10.1007/s00534-007-1295-5
[17]
Sugawara Y, Makuuchi M, Matsui Y, Kishi Y, Akamatsu N, et al. (2004) Preemptive therapy for hepatitis C virus after living-donor liver transplantation. Transplantation 78: 1308–1311. doi: 10.1097/01.tp.0000142677.12473.e5
[18]
Tamura S, Sugawara Y, Yamashiki N, Kaneko J, Kokudo N, et al. (2010) Pre-emptive antiviral therapy in living donor liver transplantation for hepatitis C: observation based on a single-center experience. Transpl Int 23: 580–588. doi: 10.1111/j.1432-2277.2009.01023.x
[19]
Ge D, Fellay J, Thompson AJ, Simon JS, Shianna KV, et al. (2009) Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature 461: 399–401. doi: 10.1038/nature08309
[20]
Tanaka Y, Nishida N, Sugiyama M, Kurosaki M, Matsuura K, et al. (2009) Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C. Nat Genet 41: 1105–1109. doi: 10.1038/ng.449
[21]
Suppiah V, Moldovan M, Ahlenstiel G, Berg T, Weltman M, et al. (2009) IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy. Nat Genet 41: 1100–1104. doi: 10.1038/ng.447
[22]
Fukuhara T, Taketomi A, Motomura T, Okano S, Ninomiya A, et al. (2010) Variants in IL28B in liver recipients and donors correlate with response to peg-interferon and ribavirin therapy for recurrent hepatitis C. Gastroenterology 139: 1577–1585. doi: 10.1053/j.gastro.2010.07.058
[23]
Kawaoka T, Takahashi S, Takaki S, Hiramatsu A, Waki K, et al. (2012) Interleukin-28B single nucleotide polymorphism of donors and recipients can predict viral response to pegylated interferon/ribavirin therapy in patients with recurrent hepatitis C after living donor liver transplantation. J Gastroenterol Hepatol 27: 1467–1472. doi: 10.1111/j.1440-1746.2012.07129.x
[24]
Enomoto N, Sakuma I, Asahina Y, Kurosaki M, Murakami T, et al. (1996) Mutations in the nonstructural protein 5A gene and response to interferon in patients with chronic hepatitis C virus 1b infection. N Engl J Med 334: 77–81. doi: 10.1056/nejm199601113340203
[25]
Akuta N, Suzuki F, Sezaki H, Suzuki Y, Hosaka T, et al. (2005) Association of amino acid substitution pattern in core protein of hepatitis C virus genotype 1b high viral load and non-virological response to interferon-ribavirin combination therapy. Intervirology 48: 372–380. doi: 10.1159/000086064
[26]
Honda M, Sakai A, Yamashita T, Nakamoto Y, Mizukoshi E, et al. (2010) Hepatic ISG expression is associated with genetic variation in interleukin 28B and the outcome of IFN therapy for chronic hepatitis C. Gastroenterology 139: 499–509. doi: 10.1053/j.gastro.2010.04.049
[27]
Dill MT, Duong FH, Vogt JE, Bibert S, Bochud PY, et al. (2011) Interferon-induced gene expression is a stronger predictor of treatment response than IL28B genotype in patients with hepatitis C. Gastroenterology 140: 1021–1031. doi: 10.1053/j.gastro.2010.11.039
[28]
Bochud PY, Bibert S, Negro F, Haagmans B, Soulier A, et al. (2011) IL28B polymorphisms predict reduction of HCV RNA from the first day of therapy in chronic hepatitis C. J Hepatol 55: 980–988. doi: 10.1016/j.jhep.2011.01.050
[29]
Charlton MR, Thompson A, Veldt BJ, Watt K, Tillmann H, et al. (2011) Interleukin-28B polymorphisms are associated with histological recurrence and treatment response following liver transplantation in patients with hepatitis C virus infection. Hepatology 53: 317–324. doi: 10.1002/hep.24074
[30]
Duarte-Rojo A, Veldt BJ, Goldstein DD, Tillman HL, Watt KD, et al. (2012) The course of posttransplant hepatitis C infection: comparative impact of donor and recipient source of the favorable IL28B genotype and other variables. Transplantation 94: 197–203. doi: 10.1097/tp.0b013e3182547551
[31]
Lange CM, Moradpour D, Doehring A, Lehr HA, Müllhaupt B, et al. (2011) Impact of donor and recipient IL28B rs12979860 genotypes on hepatitis C virus liver graft reinfection. J Hepatol 55: 322–327. doi: 10.1016/j.jhep.2010.10.037
[32]
Eurich D, Boas-Knoop S, Ruehl M, Schulz M, Carrillo ED, et al. (2011) Relationship between the interleukin-28b gene polymorphism and the histological severity of hepatitis C virus-induced graft inflammation and the response to antiviral therapy after liver transplantation. Liver Transpl 17: 289–298. doi: 10.1002/lt.22235
[33]
Crespo G, Carrión JA, Coto-Llerena M, Mari？o Z, Lens S, et al. (2013) Combinations of simple baseline variables accurately predict sustained virological response in patients with recurrent hepatitis C after liver transplantation. J Gastroenterol 48: 762–769. doi: 10.1007/s00535-012-0680-2
[34]
Coto-Llerena M, Pérez-Del-Pulgar S, Crespo G, Carrión JA, Martínez SM, et al. (2011) Donor and recipient IL28B polymorphisms in HCV-infected patients undergoing antiviral therapy before and after liver transplantation. Am J Transplant 11: 1051–1057. doi: 10.1111/j.1600-6143.2011.03491.x
[35]
Thompson AJ, Muir AJ, Sulkowski MS, Ge D, Fellay J, et al. (2010) Interleukin-28B polymorphism improves viral kinetics and is the strongest pretreatment predictor of sustained virologic response in genotype 1 hepatitis C virus. Gastroenterology 139: 120–129. doi: 10.1053/j.gastro.2010.04.013
[36]
Toyoda H, Kumada T, Tada T, Hayashi K, Honda T, et al. (2012) Predictive value of early viral dynamics during peginterferon and ribavirin combination therapy based on genetic polymorphisms near the IL28B gene in patients infected with HCV genotype 1b. J Med Virol 84: 61–70. doi: 10.1002/jmv.22272
[37]
Poordad F, McCone J Jr, Bacon BR, Bruno S, Manns MP, et al. (2011) Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med 364: 1195–1206. doi: 10.1056/nejmoa1010494
[38]
Sherman KE, Flamm SL, Afdhal NH, Nelson DR, Sulkowski MS, et al. (2012) Response-guided telaprevir combination treatment for hepatitis C virus infection. N Engl J Med 365: 1014–1024. doi: 10.1056/nejmoa1014463
[39]
Jacobson IM, McHutchison JG, Dusheiko G, Di Bisceglie AM, Reddy KR, et al. (2011) Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med 364: 2405–2416. doi: 10.1056/nejmoa1012912
[40]
McCaughan GW (2012) New therapies against HCV: expected risks and challenges associated with their use in the liver transplant setting. J Hepatol 57: 1361–1367. doi: 10.1016/j.jhep.2012.07.035
