A M Duca1, S de la Fuente2, M J Citores2, A B Cuenca2, E Cisneros3, N Escamilla4, I Baños4, C Vilches3, V Cuervas-Mons4. 1. Unidad de Trasplante Hepático, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain. Electronic address: ani_duca@yahoo.com. 2. Departamento de Medicina Interna, Hospital Universitario Puerta de Hierro Majadahonda (IDIPHIM), Madrid, Spain. 3. Laboratorio de Inmunogenética e Histocompatibilidad, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain. 4. Unidad de Trasplante Hepático, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain.
Abstract
INTRODUCTION: New-onset diabetes mellitus after transplantation (NODAT) in patients undergoing liver transplantation (LT) for hepatitis C virus (HCV)-related cirrhosis is associated with more aggressive HCV recurrence on the graft, rapid progression of fibrosis, and lower rate of sustained viral response to antiviral therapy. The CC genotype at rs12979860 of the IL28B is associated with greater rates of spontaneous clearance of HCV and response to antiviral therapy. IL28B acts on the interferon-stimulated genes through the JAK-STAT pathway, which is related to the development of insulin resistance. The aim of this study was to investigate whether IL28B rs12979860 polymorphism is associated with the development of NODAT after LT for cirrhosis owing to HCV infection. METHODS: We analyzed 99 patients (age, 52.7 ± 9.4 years; 70% male) who underwent LT for HCV-related cirrhosis, with ≥1 year of follow-up and with available DNA sample. NODAT was defined starting from the sixth month after LT, according to the international consensus guidelines. Genotyping was carried out by real-time polymerase chain reaction and analysis of the melting temperature with the LightCycler 480 system. RESULTS: Twenty-eight patients (28.3%) developed NODAT. CC genotype at rs12979860 of IL28B was associated with a lesser incidence of NODAT versus non-CC genotypes (P = .05; odds ratio, 0.31; 95% CI, 0.11-0.92). We did not find any association between NODAT and age at transplantation, gender, pretransplant body mass index, presence of hepatocellular carcinoma, type of initial immunosuppression (cyclosporine, tacrolimus or corticosteroids) or acute rejection treated with steroids. CONCLUSION: The CC genotype at rs12979860 of IL28B is a protective factor for NODAT in patients with LT for HCV-related cirrhosis.
INTRODUCTION: New-onset diabetes mellitus after transplantation (NODAT) in patients undergoing liver transplantation (LT) for hepatitis C virus (HCV)-related cirrhosis is associated with more aggressive HCV recurrence on the graft, rapid progression of fibrosis, and lower rate of sustained viral response to antiviral therapy. The CC genotype at rs12979860 of the IL28B is associated with greater rates of spontaneous clearance of HCV and response to antiviral therapy. IL28B acts on the interferon-stimulated genes through the JAK-STAT pathway, which is related to the development of insulin resistance. The aim of this study was to investigate whether IL28Brs12979860 polymorphism is associated with the development of NODAT after LT for cirrhosis owing to HCV infection. METHODS: We analyzed 99 patients (age, 52.7 ± 9.4 years; 70% male) who underwent LT for HCV-related cirrhosis, with ≥1 year of follow-up and with available DNA sample. NODAT was defined starting from the sixth month after LT, according to the international consensus guidelines. Genotyping was carried out by real-time polymerase chain reaction and analysis of the melting temperature with the LightCycler 480 system. RESULTS: Twenty-eight patients (28.3%) developed NODAT. CC genotype at rs12979860 of IL28B was associated with a lesser incidence of NODAT versus non-CC genotypes (P = .05; odds ratio, 0.31; 95% CI, 0.11-0.92). We did not find any association between NODAT and age at transplantation, gender, pretransplant body mass index, presence of hepatocellular carcinoma, type of initial immunosuppression (cyclosporine, tacrolimus or corticosteroids) or acute rejection treated with steroids. CONCLUSION: The CC genotype at rs12979860 of IL28B is a protective factor for NODAT in patients with LT for HCV-related cirrhosis.