Tratamento da Hepatite C com medicamentos de ação direta (DAAS) em pacientes com doença renal crônica e estado pós transplante renal

• Ano de defesa: 2019
• Autor(a) principal: Michels, Fernanda Bellini Lunardi [UNIFESP]
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
• Palavras-chave em Português: Chronic Hepatitis C; Hemodialysis; Kidney Transplant; Treatment; Sofosbuvir; Hepatite C; Insuficiência Renal Crônica; Hemodiálise; Transplante Renal
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=7748243; https://repositorio.unifesp.br/handle/11600/59143

Background: Hepatitis C treatment has undergone several changes in the last few years and currently direct-acting antivirals (DAAs) have made this infection curable, also in patients with chronic kidney disease (CKD). Although, there are few data about the sofosbuvir (SOF) use and its renal impact on this population and caution is recommended when glomerular filtration rate (GFR) <30 ml/min. The aim of this study was to evaluate the efficacy and safety of hepatitis C treatment with DAAs including SOF in patients with CKD in conservative treatment, hemodialysis and post-kidney transplant; to evaluate the renal impact in non-dialytic patients. Methods: Cross-sectional study with inclusion of patients with hepatitis C and CKD who underwent treatment with DAAs from January 2016 to August 2017 in a referral center in São Paulo. The efficacy was evaluated through viral load (HCV-RNA), considering a sustained virological response (SVR) after 12 and/or 24 weeks post treatment (SVR12 and SVR24) as cure. The safety was determined by adverse events (AEs) and ribavirin (RBV), when associated, was introduced gradually in all GFR <60 ml/min patients, targeting: 500 mg/day for GFR 30-59 ml/min; 250 mg/day for GFR 15-29 ml/min; 250 mg three times a week for GFR <15 ml/min or hemodialysis. To determine the impact of SOF on renal function, creatinine (Cr) values were observed at baseline, during and after treatment with its increment established by AKIN classification (acute kidney injury network): AKIN I – 0,3 mg/dL elevation or 1,5 to 1,9 fold at baseline Cr; AKIN II: 2 to 3 fold elevation; AKIN III: above 3 fold elevation or Cr ≥ 4,0 mg/dl with an acute increase of at least 0,5 mg/dl. Results: 242 patients were included, 52,5% female, with mean age of 60 years. The association of SOF + daclatasvir (DCV) was predominant in 75,3% of the cases and anemia was present in 28% of the patients who used RBV (p = 0,040). The SVR12 and SVR24 rates were 99,3% and 98,1%. The treatment was well tolerated with few AEs, being the most prevalent: asthenia (57,8%), pruritus (41,2%), headache (40,8%) and irritability (40,4%). Among the CKD in conservative treatment and renal transplant patients, Cr values had AKIN I oscillations in 12,5% of the cases during treatment, persisting in only 7,9% of the sample after ends treatment, of which 2,0% had GFR <30 ml/min, initially, dropping to 1,1% after the use of SOF. Only 0,5% and 1,6% progressed with AKIN II and AKIN III elevation. Conclusions: DAAs are safe and effective in CKD patients, presenting high SVR rates, good tolerability and few severe AEs in this population. The association with RBV increases the risk of anemia, so its gradually introduction seems to be favorable in GFR <60 ml/min patients. SOF in GFR <30 ml/min patients does not present a significant renal impact, with serum Cr returning to baseline values after treatment.