Anemia is not predictive of sustained virological response in liver transplant recipients with hepatitis C virus who are treated with pegylated interferon and ribavirin

Abstract

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 ¼ 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) ¼ 0.951, 95% confidence interval (CI) ¼ 0.925-0.978, P ¼ 0.0001], a longer time from LT to therapy (RR ¼ 1.001, 95% CI ¼ 1.000-1.001, P ¼ 0.002), high baseline viremia (RR ¼ 3.2, 95% CI ¼ 1.3-8.1, P ¼ 0.01), cyclosporine A (CSA)-based immunosuppression (RR: 3.472, 95% CI: 1.386-8.695; P ¼ 0.008), and the use of MMF (RR: 5.346, 95% CI: 1.398-20.447; P ¼ 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.

Efficacy of antiviral therapy for hepatitis C after liver transplantation with cyclosporine and tacrolimus: A systematic review and meta-analysis

“…The κ agreement between the 2 reviewers was 0.843 ± 0.020 at this stage, which indicated very good interobserver agreement. After a detailed full‐text review of 225 references, 18 studies, including 14 full‐text articles and 4 abstracts, were included in the systematic review 4, 5, 7, 11, 12, 16‐28. The interobserver agreement at this stage was 1.00.…”

“…The studies were conducted primarily in Europe (n = 13),5, 7, 11, 12, 16, 17, 22‐28 with the remainder originating from North America (n = 4)4, 18‐20 and Japan (n = 1)21; all were published between 2006 and 2012. All but 1 study19 were uncontrolled with prospective (n = 6)5, 7, 16, 20, 23, 24 or retrospective designs (n = 11) 4, 11, 12, 17, 18, 21, 22, 25‐28. The study by Carrión et al17 was a randomized, open‐label, controlled study (AVT versus no treatment); however, we used data only from the treated study arm and, therefore, considered this an uncontrolled, prospective design for our analysis.…”

“…In general, however, the diagnosis of recurrent HCV infections was uniform across all studies and consisted of a combination of detectable HCV RNA in serum (polymerase chain reaction), elevated serum transaminases, and evidence of histological changes in liver biopsy samples compatible with recurrent HCV infections. Nine studies4, 7, 11, 18, 19, 23‐25, 27 provided the pre‐LT AVT history, and they demonstrated that the majority of the patients were IFN‐naive (range = 62%‐100%). The majority of the studies did not explicitly state that the LT procedures were cadaveric in nature, but according to those studies providing this information (n = 5), deceased donor LT was performed for 85% to 100% of the participants 4, 11, 12, 19, 20.…”

“…Eleven studies, including the single RCT, reported on IFN‐based antiviral combination therapy using PEG‐IFN (α2a and/or α2b) and RBV exclusively,5, 7, 11, 16, 17, 19, 20, 22‐24, 27 whereas in 7 studies, standard IFN and PEG‐IFN were each used in a proportion of patients 4, 12, 18, 21, 25, 26, 28. All full‐text publications detailed a treatment schedule including changes in the doses of IFN and RBV (as tolerated by the participants).…”

A US multicenter study of hepatitis C treatment of liver transplant recipients with protease-inhibitor triple therapy

“…As we only assessed anemia during the first 16 weeks of therapy, the impact of anemia with PI-based triple therapy is likely even greater than we report. In addition to the known effects of peginterferon, ribavirin, and telaprevir/boceprevir, contributing factors to anemia in liver transplant recipients include baseline renal insufficiency, cyclosporine based-immunosuppression, low baseline hemoglobin values and mycophenolate mofetil use [22,23]. Given the high prevalence of anemia, lower starting doses of ribavirin should be considered and earlier and/or lower thresholds for ribavirin dose reduction and initiation of erythropoietin should be considered in patients receiving PI-based antiviral therapy.…”