Impact of Anti-HCV Therapy and HCV-RNA Titer on Graft Survival after Liver Transplant in Patients with HCV

Abstract

Background: HCV related end stage liver disease is becoming the leading indication for liver transplant (OLTx), however it's prognosis is still dismal. Even though the relapse of the HCV infection is almost universal, certainly some of the liver recipients with HCV relapse can maintain good graft function as long as the liver recipients without HCV infection. The rate of sustained viral response (SVR) in the treatment of recurrent HCV after OLTx using interferon or pegylated interferon (peg IFN) have been reported as ranging from 5 to 50%, and once SVR was established, the degree of graft inflammation and fibrosis were downgraded. However the long-term outcome after the anti-viral therapy for recurrent HCV have not been addressed yet. The aim of this study is to identify the factor that can affect graft survival after the OLTx for the HCV related patients, and evaluate the impact of the anti-HCV therapy on the long-term graft survivals. Methods: Four handred fifty six patients, who underwent OLTx in University of Miami/Jackson Memorial Hospital since 2002 to 2006, were reviewed retrospectively. Patients with hepatocellular carcinoma were excluded. One handred sixty one recipients had HCV-related liver disease (HepC), and 295 uninfected contolols were identified (control). Graft loss was defined as at time of recipient's death or time of retransplant. Anti-HCV therapy using peg IFN with ribavirin (pegIFN/Rib) was initiated when the patients showed abnormal allo-graft function and HCV re-infection confirmed by histologically. Median follow-up time was 45 month (range 0-79 months). Statistical analysis was performed using R version 2.7.2. Results: One handred five grafts were lost in total of 456 recipients. Graft survival in HCV was shorter than control, without reaching significance (p=0.56). The cumulative incidence of early graft loss (graft loss within 2 years after OLTx) was higher in HCV than controls (26% in HCV and 16% in controls). High postoperative HCV-RNA titer (more than 500,000 IU/ml), administration of muromonab-CD3 and MELD score greater than 20 appeared to be significant predictive factors for early graft loss from logistic regression analysis among HepC (p=0.04, 0.002 and 0.03, respectively). One handred patients underwent peg IFN/Rib therapy in total of 161 HepC patients, and the SVR in our series was 21%. 5 year graft survival from the patients with or without pegIFN/Rib were 77% and 57%, respectively. The cumulative graft survival of the patients with pegIFN/Rib was significantly longer than the patients without pegIFN/Rib (p< 0.001). Also, lower postoperative HCV-RNA titer appeared to be significant predictors for long-term graft survival from log rank test (p=0.003). Conclusion: High HCV-RNA titer was implicated in early graft loss after OLTx, whereas lower HCV-RNA titer had positive impact for long-term graft survival in patients with HCV. PegIFN with ribavirin therapy after OLTx also had a positive impact for long-term graft survival in patients with HCV.