Hepatitis C virus long‐term persistence in peripheral blood mononuclear cells in patients with haemophilia. Detection of occult genotype 1

Abstract

Peripheral blood mononuclear cells (PBMC) from chronic hepatitis C virus-infected persons can harbour viral variants that are not detected in plasma samples. We explored the presence and persistence of HCV genotypes in plasma and PBMC cultures from 25 HCV-monoinfected and 25 HIV/HCV-coinfected patients with haemophilia. Cell cultures were performed at different time points between 1993 and 2010-2011, and the HCV genome was examined in culture supernatants. Sequential plasma samples were studied during the same time period. Analysing sequential plasma samples, 21% of patients had mixed-genotype infections, while 50% had mixed infections determined from PBMC culture supernatants. HIV coinfection was significantly associated with the presence of mixed infections (OR = 4.57, P = 0.02; 95% CI = 1.38-15.1). In our previous study, genotype 1 was found in 72% of 288 patients of this cohort. Similar results were obtained with the sequential plasma samples included in this study, 69% had genotype 1. However, when taking into account plasma samples and the results from PBMC supernatants, genotype 1 was identified in 94% of the population. The PBMC-associated variants persisted for 10 years in some subjects, emphasizing their role as long-term reservoirs. The presence of genotype 1 in PBMC may be associated with therapeutic failure and should not be disregarded when treating haemophilic patients who have been infected by contaminated factor concentrates. The clinical implications of persistent lymphotropic HCV variants deserve further examination among multiple exposed groups of HCV-infected patients.

Alterations in the iron homeostasis network: A driving force for macrophage-mediated hepatitis C virus persistency

“…Despite the fact that the very existence of long-term occult extra-hepatic HCV reservoirs is strongly debated, 44 they would explain several clinical manifestations of the disease, like HCV persistence and recurrence following treatment or liver transplantation. 40,45,[46][47][48][49] Due to their role in iron homeostasis, reticuloendothelial macrophages, including Kupffer cells, may be full of iron at any given time. 18 Iron loading of co-cultured macrophages resulted in enhanced HCV replication in both cell populations.…”