RESUMO
Hepatitis C virus (HCV) infection is accelerated following liver transplantation (LT). Single nucleotide polymorphisms (SNPs) near the epidermal growth factor (EGF) (rs4444903), IL28B (rs12979860), and PNPLA3 (rs738409) loci are associated with treatment response, fibrosis, and hepatocellular carcinoma in non-transplant hepatitis C, but allograft population data are limited. We sought to determine the role of these SNPs in 264 patients with HCV who underwent LT between 1990 and 2008. Genotypes were determined from donor wedge/allograft biopsies and recipient explants. Cox proportional hazards model was used to assess time to cirrhosis, liver-related death, and retransplantation, adjusting for donor age and sustained virological response (SVR). Over a median follow-up of 6.3 yr, a trend toward increased progression to graft cirrhosis was observed among recipients of an EGF non-AA vs. AA donor liver (adjusted HR 2.01; 95% CI 0.93-4.34; p = 0.08). No other genotypes predicted cirrhosis development or graft survival. The CC IL28B variant in both recipients and donors was associated with increased rate of SVR (R-CC/D-CC 8/12[67%], R-non-CC/D-CC or R-CC/D-non-CC 23/52[44%], R-non-CC/D-non-CC 12/45[27%], p linear trend = 0.009). Recipient EGF, IL28B, and PNPLA3, and donor IL28B and PNPLA3 genotypes do not predict adverse outcomes in HCV LT recipients. A potential association exists between donor EGF genotype and cirrhosis.
Assuntos
Fator de Crescimento Epidérmico/genética , Hepatite C Crônica/cirurgia , Interleucinas/genética , Lipase/genética , Cirrose Hepática/genética , Transplante de Fígado , Proteínas de Membrana/genética , Polimorfismo de Nucleotídeo Único/genética , Complicações Pós-Operatórias , Adulto , Aloenxertos , Antivirais/uso terapêutico , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/etiologia , Estudos de Coortes , Progressão da Doença , Feminino , Seguimentos , Genótipo , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Hepacivirus/patogenicidade , Hepatite C Crônica/virologia , Humanos , Interferons , Cirrose Hepática/etiologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/etiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Doadores de Tecidos , Transplante Homólogo , Adulto JovemRESUMO
Great progress has been made in understanding the HCV genome and its molecular virology. This understanding has culminated in the development of direct-acting antiviral (DAA) agents targeting HCV viral proteins. Telaprevir (TVR) and boceprevir (BOC) were the first DAAs introduced for treatment of genotype 1 HCV in 2011; when used in combination with pegylated interferon (pegIFN) and ribavirin (RBV), these protease inhibitors improved efficacy in patients with chronic HCV infection compared to the traditional dual therapy. However, this combination was associated with adverse events that often led to early termination of therapy. In late 2013, the FDA approved a second wave of DAAs, sofosbuvir (SOF) and simeprevir (SMV). The use of SOF with SMV opened the door for IFN-free combination regimens. This combination was highly efficacious and well tolerated in patients with HCV genotype 1. Sofosbuvir and ledipasvir (LDV) fixed-dose oral combination (FDC) therapy, and paritaprevir/ritonavir, ombitasvir and dasabuvir ± RBV were recently approved, elevating sustained virologic response (SVR) rates to over 95 %. We are anticipating the approval of additional IFN-free regimens with comparable efficacy and tolerability but with the addition of pangenotypic coverage, fewer drug-drug interactions, and a high barrier to resistance. This review will summarize current management for chronic HCV infection.
