Journal
JOURNAL OF HEPATOLOGY
Volume 67, Issue 6, Pages 1334-1339Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jhep.2017.08.011
Keywords
Hepatitis E; HEV; CD30-positive cutaneous T cell lymphoproliferative disorder; Lymphoma; Non-Hodgkin lymphoma; Extra-hepatic manifestation; Endothelial cell; Lymphomatoid papulosis
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Funding
- La Fondation ARC pour la Recherche sur le Cancer (ARC, France)
- Imagine Foundation (France)
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Background & Aim: Several types of unexplained extra-hepatic manifestations, including haematological disorders, have been reported in the context of hepatitis E virus (HEV) infection. However, the underlying mechanism(s) of these manifestations are unknown. We provide evidence that HEV has an extra-hepatic endothelial tropism that can engage cutaneous T cells towards clonality. Methods: A patient with a CD30(+) cutaneous T cell lymphoproliferative disorder (T-LPD) and biopsy-proven chronic HEV infection received three rounds of oral ribavirin treatment, administered either without or with interferon, and eventually achieved a sustained virologic response (SVR). Pathologic, virologic and immunologic investigations were carried out on biopsied skin lesion, and peripheral blood mononuclear cells between the 2nd and 3rd round of antiviral treatment and biopsied liver. Results: Remission of T-LPD was observed upon antiviral treatment, and the patient remained in complete remission after achieving SVR. The T cell analysis showed large CD30(+) lymphocytes surrounding the blood vessels within the CD8(+) T cell infiltrate. HEV was detected within dermal microvascular endothelial cells using immunofluorescence staining, in situ hybridisation and electron microscopy. Infiltrating T cells mostly comprised memory CD8(+) T cells with a tissue-resident memory T cell phenotype. Overall, 98% of extracted T cells were CD8(+) T cells with a Vb signature skewed towards Vb4 and with an oligoclonal profile. T cell clones from T-LPD were more like T cells in the liver than T cells in the blood [odds ratio = 4.55, (3.70-5.60), p < 0.0001]. No somatic mutations were found in the T-LPD exomes. Conclusion: HEV has an extra-hepatic tissue tropism in humans, including dermal endothelium, and can induce CD30(+) T-LPD that is sensitive to antivirals. (C) 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.7
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