RESUMEN
BACKGROUND & AIMS: Treating chronic hepatitis C (CHC) in patients with end-stage renal disease (ESRD) has suboptimal tolerability and cure rates. Safety and efficacy of sofosbuvir plus simeprevir regimen in CHC-infected patients with ESRD on haemodialysis (HD) or glomerular filtration rate (GFR) <30 ml/min is unknown. We evaluated the safety and efficacy of sofosbuvir and simeprevir in this special patient population. METHODS: All (n = 17) patients in the analysis had ESRD on HD or GFR <30 ml/min. All received sofosbuvir 400 mg daily and simeprevir 150 mg daily, without ribavirin for 12 weeks. Safety and efficacy data were collected; including SVR4 and SVR12 data for all patients after completing therapy. RESULTS: In this 17 patient cohort, eight (47%) were cirrhotic, four (24%) had stage three liver fibrosis and 13 (76%) were genotype 1A. All 17 have completed 12 weeks of therapy. Treatment was overall well tolerated with no treatment discontinuations reported. Four (24%) patients reported mild adverse events (AE). These AEs were insomnia (n = 2), headache (n = 1), nausea (n = 1) and worsening anaemia requiring blood transfusion (n = 1). All 17 patients reached post-treatment week-12 follow-up, and achieved SVR12 or virological cure (100% SVR12). CONCLUSIONS: Daily, full dose of sofosbuvir plus simeprevir for 12 weeks of therapy appears to be well tolerated in patients with ESRD on HD or GFR <30 ml/min. Most common AEs resembled those of healthier CHC patients without significant renal impairment. The cure rates obtained in this cohort treated with sofosbuvir and simeprevir are dramatically superior to any previous treatment regimen studied & published in this special patient population.
Asunto(s)
Antivirales/administración & dosificación , Hepatitis C Crónica/tratamiento farmacológico , Fallo Renal Crónico/complicaciones , Simeprevir/administración & dosificación , Sofosbuvir/administración & dosificación , Anciano , Antivirales/efectos adversos , Quimioterapia Combinada , Femenino , Tasa de Filtración Glomerular , Hepacivirus/genética , Hepatitis C Crónica/complicaciones , Humanos , Fallo Renal Crónico/terapia , Cirrosis Hepática/complicaciones , Masculino , Persona de Mediana Edad , Diálisis Renal , Simeprevir/efectos adversos , Sofosbuvir/efectos adversos , Respuesta Virológica Sostenida , TexasRESUMEN
BACKGROUND: Elevated serum cholesterol levels may stimulate proliferation in adenomatous polyps (AP). Our aim was to determine how a reduction of low-density lipoprotein (LDL) cholesterol levels in patients taking statins influences the incidence of APs. METHODS: We performed a retrospective study of patients taking statins who were found to have > or =1 APs on an index colonoscopy, and who also had a follow-up colonoscopy within 3 to 5 years. Patients were divided into 2 groups: (1) those with > or =30% reduction in LDL levels and (2) those with < 30% reduction in LDL levels during the interval between colonoscopies. Univariate and multivariate analysis were evaluated for their association with advanced APs. RESULTS: We identified 231 patients. Univariate analysis showed that patients with > or =30% LDL reduction had fewer mean total numbers of APs (2.6 versus 3.3, P = 0.02), fewer advanced APs (14% versus 26%, P = 0.04), and smaller APs (5 mm versus 6.1 mm, P = 0.01) than those with <30% reduction in LDL. Multiple logistic regression analysis confirmed that > or =30% LDL reduction was associated with smaller APs (P < 0.01). Subjects with > or =30% LDL reduction also had a 53% reduced incidence of advanced APs (OR, 0.47; CI, 0.22-0.96; P < 0.05). These findings remained significant even when adjusted for nonsteroidal antiinflammatory drug use, age, family history of APs, and body mass index. CONCLUSIONS: A reduction in LDL levels of > or=30% during a 3- to 5-year period of statin therapy was associated with a 53% reduction in the incidence of advanced APs, even after adjustment for other known polyp risk factors.
Asunto(s)
LDL-Colesterol/sangre , Pólipos del Colon/sangre , Inhibidores de Hidroximetilglutaril-CoA Reductasas/sangre , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Pólipos del Colon/diagnóstico , Pólipos del Colon/epidemiología , Pólipos del Colon/etiología , Pólipos del Colon/prevención & control , Colonoscopía , Estudios de Seguimiento , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Incidencia , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
Obesity has been associated with an increased risk for colonic adenomatous polyps (APs) and colorectal cancers, but the influence of obesity on the development of advanced APs is not clear. The purpose of this study is to determine the influence of obesity on the prevalence of advanced APs in a male veteran population. We performed a retrospective study of patients (n = 2,903) with histologically confirmed APs on an index colonoscopy. APs were evaluated for advanced features (size > or = 1 cm in diameter and/or a villous component and/or high grade dysplasia). Patients were categorized as: normal weight (BMI > 18.5 and < 25), overweight (BMI > or = 25 and < 30), and obese (BMI > or = 30). An association between clinical factors and advanced APs was sought by Kruskal-Wallis test and Pearson Chi-square. Multiple logistic regression analysis was used to determine independent predictors for advanced APs. We identified 2,903 male patients with APs (mean age 64 + 1.1(SE) years; 770 (27%) normal weight, 1,029 (35%) overweight, 1,104 (38%) obese. By univariate analysis, obese patients had a greater prevalence of advanced APs than the overweight and normal weight patients (28 vs. 23 vs. 24%, p = 0.025). Multiple logistic regression analysis confirmed the association of obesity and advanced APs (OR = 1.01, CI = 1-1.02, p = 0.04). For every one-unit increase in BMI above 30, there was a corresponding 1% increase in the frequency of finding advanced APs. Obesity in male veteran patients is associated with the finding of advanced APs on colonoscopy. We speculate that obesity may increase the risk for CRC by promoting the development of advanced APs.