High-throughput sequencing analysis of post-liver transplantation HCV e2 glycoprotein evolution in the presence and absence of neutralizing monoclonal antibody.
Babcock G J, Iyer S, et al.PLoS ONE [Electronic Resource] 2014 9(6): e100325.
Aims
To evaluate the presence of MAb pre-transplant resistance mutations and to examine the post-transplant evolution of hepatitis c virus (HCV) variants in the presence and absence of MBL-HCV1 antibody, using high-throughput next generation sequencing.
Interventions
Subjects were administered with 11 infusions of MBL-HCV1 (50mg/kg each) or 11 infusions of placebo (0.9% sodium chloride) for 14 days.
Participants
11 participants with HCV genotype 1a infection.
Outcomes
Outcomes included the analysis of HCV E1/E2 variants at the time of viral rebound, pre-transplant prevalence of sequence variation at amino acids 415 and 417, evolution of resistance-associated variants, sequence evolution within the MBL-HCV1 epitope and outside of the MBL-HCV1 epitope.
Follow-up
56 days.
CET Conclusions
This is a very elegant study in which the authors emphasise that HCV infection is the most common cause of end stage liver disease requiring a liver transplant in the USA. In a small phase 2 randomised trial they have used a fully humanised monoclonal antibody (MBL-HCV1) which binds a highly conserved linear epitope of the HCV E2 envelope glycoprotein. They have shown that in patients who received the antibody at around the time of the liver transplant, in comparison with a placebo infusion, that viral rebound was delayed for 7 to 28 days. However rebound did occur and they have shown very nicely indeed using high throughput sequencing technology that mutations in position 415 are very important in the development of resistance to the antibody. However the authors conclude that as there were no safety problems associated with the use of the antibody it might provide a window of opportunity following transplant until liver function is stabilised in which one of the newer protease inhibitors might be given to eliminate the HCV completely. This is a very interesting possible approach to the HCV problem in liver transplantation.
Quality notes
Previously assessed in Chung RT, Gordon FD, Curry MP, Schiano TD, Emre S, et al. (2013) Human monoclonal antibody MBL-HCV1 delays HCV viral rebound following liver transplantation: a randomized controlled study. Am J Transplant 13: 1047–1054.
Trial registration
ClinicalTrials.gov – NCT01121185