BACKGROUND & AIMS: Recent studies have described a major impact of genetic variations near the IL28B gene on the natural course and outcome of antiviral therapy in chronic hepatitis C. We therefore, aimed to explore the impact of donor and recipient genotypes of these polymorphisms on hepatitis C virus (HCV) liver graft reinfection. METHODS: Donor and recipient genotypes of IL28B rs12979860C>T single nucleotide polymorphism were determined in 91 patients with HCV liver graft reinfection, 47 of whom were treated with pegylated interferon-α (PEG-IFN-α) and ribavirin. IL28B genetic polymorphisms were correlated with the natural course and treatment outcome of recurrent hepatitis C. RESULTS: Patients requiring liver transplantation due to end-stage chronic hepatitis C appeared to be selected toward the adverse genotypes rs12979860 CT/TT compared to non-transplanted HCV-infected patients (p=0.046). Patients with the donor genotype rs12979860 CC had higher peak ALT and HCV RNA serum concentrations than those with CT/TT (p=0.04 and 0.06, respectively). No association was observed between ALT/HCV RNA serum concentrations and recipient genotypes (p>0.3). More important, donor IL28B rs12979860 CC vs. CT/TT genotypes were associated with rapid, complete early, and sustained virologic response (RVR, cEVR, SVR) to treatment with PEG-IFN-α and ribavirin (p=0.003, 0.0012, 0.008, respectively), but weaker associations of recipient genotypes with RVR, cEVR, and SVR were observed as well (p=0.0046, 0.115, 0.118, respectively). CONCLUSIONS: We provide evidence for a dominant, but not exclusive impact of the donor rather than the recipient IL28B genetic background on the natural course and treatment outcome of HCV liver graft reinfection.
BACKGROUND & AIMS: Recent studies have described a major impact of genetic variations near the IL28B gene on the natural course and outcome of antiviral therapy in chronic hepatitis C. We therefore, aimed to explore the impact of donor and recipient genotypes of these polymorphisms on hepatitis C virus (HCV) liver graft reinfection. METHODS:Donor and recipient genotypes of IL28B rs12979860C>T single nucleotide polymorphism were determined in 91 patients with HCV liver graft reinfection, 47 of whom were treated with pegylated interferon-α (PEG-IFN-α) and ribavirin. IL28B genetic polymorphisms were correlated with the natural course and treatment outcome of recurrent hepatitis C. RESULTS:Patients requiring liver transplantation due to end-stage chronic hepatitis C appeared to be selected toward the adverse genotypes rs12979860 CT/TT compared to non-transplanted HCV-infectedpatients (p=0.046). Patients with the donor genotype rs12979860 CC had higher peak ALT and HCV RNA serum concentrations than those with CT/TT (p=0.04 and 0.06, respectively). No association was observed between ALT/HCV RNA serum concentrations and recipient genotypes (p>0.3). More important, donorIL28Brs12979860 CC vs. CT/TT genotypes were associated with rapid, complete early, and sustained virologic response (RVR, cEVR, SVR) to treatment with PEG-IFN-α and ribavirin (p=0.003, 0.0012, 0.008, respectively), but weaker associations of recipient genotypes with RVR, cEVR, and SVR were observed as well (p=0.0046, 0.115, 0.118, respectively). CONCLUSIONS: We provide evidence for a dominant, but not exclusive impact of the donor rather than the recipient IL28B genetic background on the natural course and treatment outcome of HCV liver graft reinfection.
Authors: Kieron B L Lim; Hamid R Sima; M Isabel Fiel; Viktoriya Khaitova; John T Doucette; Maria Chernyiak; Jawad Ahmad; Nancy Bach; Charissa Chang; Priya Grewal; Leona Kim-Schluger; Lawrence Liu; Joseph Odin; Ponni Perumalswami; Sander S Florman; Thomas D Schiano Journal: World J Gastroenterol Date: 2015-05-28 Impact factor: 5.742
Authors: Jennifer E Layden; Scott Cotler; Kimberly A Brown; Michael R Lucey; Helen S Te; Sheila Eswaran; Claus Fimmel; Thomas J Layden; Nina M Clark Journal: Transplantation Date: 2012-07-27 Impact factor: 4.939
Authors: Jennifer E Layden; Bamidele O Tayo; Scott J Cotler; Nina M Clark; Kristine Baraoidan; Scott L Friedman; Richard S Cooper Journal: Transplantation Date: 2014-05-27 Impact factor: 4.939
Authors: Scott W Biggins; James Trotter; Jane Gralla; James R Burton; Kiran M Bambha; Jennifer Dodge; Megan Brocato; Linling Cheng; Matt McQueen; Lisa Forman; Michael Chang; Igal Kam; Gregory Everson; Richard A Spritz; Goran Klintmalm; Hugo R Rosen Journal: J Hepatol Date: 2013-01-15 Impact factor: 25.083