1区 · 医学
Article
作者: Chung, R. T. ; Gondon, F. D. ; Curry, M. P. ; Schiano, T. D. ; Emre, S. ; Corey, K. ; Markmann, J. F. ; Hertl, M. ; Pomposelli, J. J. ; Pomfret, E. A. ; Floman, S. ; Schilsky, M. ; Broering, T. J. ; Finberg, R. W. ; Szabo, G. ; Zamore, P. D. ; Khettry, U. ; Babcock, G. J. ; Ambrosino, D. M. ; Leav, B. ; Leney, M. ; Smith, H. L. ; Molrine, D. C.
Rapid allograft infection complicates liver transplantation (LT) in patients with hepatitis C virus (HCV). Pegylated interferon-α and ribavirin therapy after LT has significant toxicity and limited efficacy. The effect of a human monoclonal antibody targeting the HCV E2 glycoprotein (MBL-HCV1) on viral clearance was examined in a randomized, double-blind, placebo-controlled pilot study in patients infected with HCV genotype 1a undergoing LT. Subjects received 11 infusions of 50 mg/kg MBL-HCV1 (n=6) or placebo (n=5) intravenously with three infusions on day of transplant, a single infusion on days 1 through 7 and one infusion on day 14 after LT. MBL-HCV1 was well-tolerated and reduced viral load for a period ranging from 7 to 28 days. Median change in viral load (log10 IU/mL) from baseline was significantly greater (p=0.02) for the antibody-treated group (range -3.07 to -3.34) compared to placebo group (range -0.331 to -1.01) on days 3 through 6 posttransplant. MBL-HCV1 treatment significantly delayed median time to viral rebound compared to placebo treatment (18.7 days vs. 2.4 days, p<0.001). As with other HCV monotherapies, antibody-treated subjects had resistance-associated variants at the time of viral rebound. A combination study of MBL-HCV1 with a direct-acting antiviral is underway.