Distinct Immune Imprints of Post-Liver Transplantation Hepatitis C Persist Despite Viral Clearance.
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Authors
Aregay, AmareEngel, Bastian
Port, Kerstin
Vondran, Florian W R
Bremer, Birgit
Niehaus, Christian
Khera, Tanvi
Richter, Nicolas
Jaeckel, Elmar
Cornberg, Markus
Taubert, Richard
Wedemeyer, Heiner
Issue Date
2021-02-28
Metadata
Show full item recordAbstract
Recurrence or de novo infection of hepatitis C virus (HCV) after liver transplantation (LT) has been associated with progressive graft hepatitis that can be improved by treatment with novel direct-acting antivirals. Cases of rejection episodes have been described during and after HCV treatment. The evolution of innate and adaptive immune response during and after cure of HCV LT is unknown. We studied 74 protein biomarkers in the plasma of LT patients receiving antiviral therapy. In addition, deep immune phenotyping of both the myeloid and lymphoid immune cell subsets in peripheral blood mononuclear cells was performed. We found that LT patients with active HCV infection displayed distinct alterations of inflammatory protein biomarkers, such as C-X-Cmotif chemokine 10 (CXCL10), caspase 8, C-C motif chemokine 20 (CCL20), CCL19, interferon γ, CUB domain-containing protein 1 (CDCP1), interleukin (IL)-18R1, CXCL11, CCL3, IL8, IL12B, tumor necrosis factor-beta, CXCL6, osteoprotegerin, IL10, fms-related tyrosine kinase 3 ligand, hepatocyte growth factor, urokinase-type plasminogen activator, neurotrophin-3, CCL4, IL6, tumornecrosis factor receptor superfamily member 9, programmed death ligand 1, IL18, and monocyte chemotactic protein 1, and enrichment of peripheral immune cell subsets unlike patients without HCV infection who received transplants. Interestingly, patients who cleared HCV after LT did not normalize the altered inflammatory milieu nor did the peripheral immune cell subsets normalize to what would be seen in the absence of HCV recurrence. Overall, these data indicate that HCV-specific imprints on inflammatory analytes and immune cell subsets after LT are not completely normalized by therapy-induced HCV elimination. This is in line with the clinical observation that cure of HCV after LT did not trigger rejection episodes in many patients.Citation
Liver Transpl. 2021 Jun;27(6):887-899. doi: 10.1002/lt.26031.Affiliation
CiiM, Zentrum für individualisierte Infektionsmedizin, Feodor-Lynen-Str.7, 30625 Hannover.Publisher
WileyDOI
10.1002/lt.26031PubMed ID
33641215Type
ArticleLanguage
enEISSN
1527-6473ae974a485f413a2113503eed53cd6c53
10.1002/lt.26031
Scopus Count
The following license files are associated with this item:
- Creative Commons
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