Liver Transplantation and Hepatology Unit, Research Center, La Fe Hospital, Valencia, Spain.
Liver Transpl. 2011 Nov;17(11):1318-27. doi: 10.1002/lt.22387.
In the immunocompetent setting, antiviral therapy-related anemia has recently been shown to be associated with a sustained virological response (SVR). Our goal was to assess whether this is also true for liver transplantation (LT). We included 160 LT patients with recurrent hepatitis C virus (HCV) who were treated with pegylated interferon and ribavirin (RBV) between 2002 and 2010; 76% of the patients were men, the median age of the patients was 56 years (range = 33-75 years), 63% had advanced fibrosis, and 86% were infected with HCV genotype 1a or 1b. The baseline immunosuppression was tacrolimus in 56% of the patients. Mycophenolate mofetil (MMF) was used in 15%. Anemia was defined as a hemoglobin (Hb) level < 10 g/dL. Significant anemia was present when the Hb decline was >5 g/dL. Anemia and significant anemia developed in 67% and 41% of the patients, respectively. Erythropoietin was used in 60%. Factors independently associated with significant anemia included low estimated creatinine clearance [relative risk (RR) = 0.951, 95% confidence interval (CI) = 0.925-0.978, P = 0.0001], a longer time from LT to therapy (RR = 1.001, 95% CI = 1.000-1.001, P = 0.002), high baseline viremia (RR = 3.2, 95% CI = 1.3-8.1, P = 0.01), cyclosporine A (CSA)-based immunosuppression (RR: 3.472, 95% CI: 1.386-8.695; P = 0.008), and the use of MMF (RR: 5.346, 95% CI: 1.398-20.447; P = 0.014). An SVR occurred in 43% of the patients; the factors associated with an SVR included baseline variables (younger recipient age, younger donor age, infections with non-1 HCV genotypes, body mass index, and mild fibrosis) and on-treatment factors related to adherence or viral kinetics. Anemia resulted in RBV dose reductions but was not associated with the virological response at any time. In conclusion, anemia is a very frequent complication in LT patients during antiviral therapy and is associated with increased RBV dose reduction but not with an SVR. Predictors of anemia include MMF or CSA immunosuppression, high viremia, and renal insufficiency.
在免疫功能正常的情况下,抗病毒治疗相关的贫血最近被证明与持续病毒学应答(SVR)有关。我们的目标是评估这是否也适用于肝移植(LT)。我们纳入了 160 例因丙型肝炎病毒(HCV)复发而接受聚乙二醇干扰素和利巴韦林(RBV)治疗的 LT 患者;76%的患者为男性,患者的中位年龄为 56 岁(范围=33-75 岁),63%的患者有晚期纤维化,86%的患者感染 HCV 基因型 1a 或 1b。基线时 56%的患者接受他克莫司免疫抑制治疗,15%的患者接受霉酚酸酯(MMF)治疗。贫血定义为血红蛋白(Hb)水平<10 g/dL。当 Hb 下降>5 g/dL 时,存在显著贫血。分别有 67%和 41%的患者出现贫血和显著贫血。60%的患者使用了促红细胞生成素。与显著贫血相关的独立因素包括估算的肌酐清除率低[相对风险(RR)=0.951,95%置信区间(CI)=0.925-0.978,P=0.0001]、LT 后治疗时间较长(RR=1.001,95%CI=1.000-1.001,P=0.002)、基线病毒载量高(RR=3.2,95%CI=1.3-8.1,P=0.01)、环孢素 A(CSA)为基础的免疫抑制(RR:3.472,95%CI:1.386-8.695;P=0.008)和使用 MMF(RR:5.346,95%CI:1.398-20.447;P=0.014)。43%的患者获得了 SVR;与 SVR 相关的因素包括基线变量(年轻的受者年龄、年轻的供者年龄、非 1 型 HCV 基因型感染、体重指数和轻度纤维化)和与依从性或病毒动力学相关的治疗期间变量。贫血导致 RBV 剂量减少,但在任何时间均与病毒学应答无关。总之,贫血是 LT 患者抗病毒治疗期间非常常见的并发症,与 RBV 剂量减少增加有关,但与 SVR 无关。贫血的预测因素包括 MMF 或 CSA 免疫抑制、高病毒血症和肾功能不全。