Association between IL28B gene polymorphisms and plasma HCV-RNA levels in HIV/HCV-co-infected patients.
Labarga P, Soriano V, Caruz A, Poveda E, Di Lello F, Hernandez-Quero J, Moreno S, Bernal E, Miró JM, Leal M, Gutierrez F, Portilla J, Pineda JA; on behalf of CoRIS.
aInfectious Diseases Department, Hospital Carlos III, Madrid, Spain bMolecular Biology Department, Jaen University, Jaen, Spain cInfectious Diseases Unit, Hospital de Valme, Seville, Spain dInfectious Diseases, Hospital San Cecilio, Granada, Spain eInfectious Diseases Service, Hospital Ramón y Cajal, Madrid, Spain fService of Internal Medicine, Hospital Reina Sofía, Murcia, Spain gInfectious Diseases Service, Hospital Clínic, Barcelona, Spain hInfectious Diseases Service, Hospital Virgen del Rocio, Seville, Spain iInfectious Diseases Unit, Hospital de Elche, Elche, Spain jInfectious Diseases Unit, Hospital de Alicante, Alicante, Spain.
Abstract
BACKGROUND: IL28B polymorphisms influence both the rate of spontaneous hepatitis C virus (HCV) clearance and response to interferon α (IFNα)-based therapy. This observation has been reproduced in HIV-co-infected individuals. Controversy exists about the impact of IL28B alleles on HCV load.
METHODS: CoRIS is a nationwide, open cohort of newly diagnosed HIV-1 adults in Spain. In the subset of HCV-co-infected individuals, the relationship between plasma HCV-RNA and IL28B (rs12979860) genotypes was evaluated.
RESULTS: A total of 4670 HIV-1-infected patients had been included in CoRIS up to June 2010. All were naive for IFNα. HCV antibodies were reactive in 895 (19%). Of them, 289 specimens were available and tested positive for plasma HCV-RNA, with median values of 959 900 IU/ml. The rs12979860 genotype distribution in HCV viremic patients was CC 45%, CT 42.2% and TT 12.8%. The median plasma HCV-RNA according to IL28B genotypes was: CC 1 385 000, CT 848 939 and TT 251 189 IU/ml (P = 0.006). The percent
age of patients with HCV-RNA more than 600 000 IU/ml was: CC 67.7%, CT 56.6% and TT 35.1% (P = 0.001). In multivariate analysis, IL28B CC/CT genotypes, infection with HCV genotypes 1/4 and prior intravenous drug users were independent predictors of HCV-RNA more than 600 000 IU/ml.
CONCLUSION: reactive翻译HIV/HCV-co-infected patients with the C allele (CC/CT) at rs12979860 show significantly higher plasma HCV-RNA load than TT carriers. Notably, plasma HCV-RNA levels associated with poorer response to IFNα-based therapy are significantly more frequent in CC/CT than TT carriers. Hypothetically, patients harboring the rs12979860 allele C could display a lower activity of endogenous IFNα, allowing higher HCV replication while keeping an enhanced susceptibility to exogenous IFNα therapy.
PMID: 21378537 [PubMed - as supplied by publisher]
Impact of donor and recipient IL28B rs12979860 genotypes on hepatitis C virus liver graft reinfection.
Lange CM, Moradpour D, Doehring A, Lehr HA, Müllhaupt B, Bibert S, Bochud PY, Antonino AT, Pascual M, Farnik H, Shi Y, Bechstein WO, Moench C, Hansmann ML, Sarrazin C, Lötsch J, Zeuzem S, Hofmann WP.
Medizinische Klinik 1, Germany; Centre Hospitalier Universitaire Vaudois, University of Lausanne, Rue Bugnon 46, CH-1010 Lausanne, Switzerland.
Abstract
BACKGROUND AND AIM: Recent studies 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 which were treated with pegylated interferon-α(PEG-IFN-α) and ribavirin. IL28B genetic polymorp
hisms 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 towards the adverse genotypes rs12979860CT/TT compared to non-transplanted HCV-infected patients (p=0.046). Patients with the donor genotype rs12979860CC had higher peak ALT and HCV RNA serum concentrations than those with CT/TT (p=0.04 and 0.06, respectively). No associations were 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).

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