Characterization of the Cross-Neutralizing Antibody Response Against Hepatitis C Virus in the Liver Transplantation Setting

Abstract

Neutralizing antibody (nAb) activity during the course of natural infection is believed to be crucial to combating virus propagation. The aim of this study was to measure the impact of nAb response on HCV early kinetics and genetic evolution in the liver transplantation (LT) setting. A cohort of 28 patients undergoing LT for HCV-related cirrhosis was included in the study. Viral load, nAb titers and hypervariable region 1 (HVR1) sequences were determined in serum samples obtained before and at different time points after LT. Serum nAb titers were assessed using HCV pseudoparticles (HCVpp). HVR1 sequences were obtained by direct sequencing. Patients were classified according to viral kinetic patterns (plateau or increasing), during the first week after LT. All patients demonstrated high titers of nAbs before LT, although this was not associated with early kinetic patterns or HVR1 evolution during the first week after LT. We found that in patients with plateau HCV early kinetics, the virus required adaptive mutations, while in those with increasing viral loads, the HVR1 region remained largely conserved (p = 0.015). These data suggest that HCV adaptation via selection of the best-fitted variants may account for early viral kinetics following LT.