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      Acute graft-versus-host disease after liver transplantation in a close contact with COVID-19: A case report

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          Abstract

          Acute graft-versus-host disease (aGVHD) is a rare complication after liver transplantation that characterized by high mortality. We presented a case of aGVHD after orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC). The patient suffered from fever, oral ulcer, rashes and diarrhea and had a co-infection with Cytomegalovirus (CMV). Short tandem repeat (STR) analysis for cluster of differentiation (CD3) cells and skin biopsy indicated aGVHD. His regimens included high dose of steroids, ruxolitinib, basiliximab, local liver radiotherapy and antibiotics prophylaxis, with the withdrawal of tacrolimus and MMF. Unfortunately, he developed an acute rejection followed by cytomegalovirus infection and lung infection. Soon afterwards he was sent to “isolation ward” due to high suspicion for clinical coronavirus disease 2019 (COVID-19). Fortunately, He was excluded from COVID-19 after nucleic acid and antibody tests. Though closely contact with other COVID-19 patients for a month, the patient was not affected with COVID-19 through his careful protective measures. Finally, the patient recovered after antiviral and antifungal treatment. To our knowledge, this is the first case report of a patient recovered from aGVHD as a close contact.

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          Graft-versus-host disease.

          James LM Ferrara, John Levine, Pavan Reddy … (2009)
          Haemopoietic-cell transplantation (HCT) is an intensive therapy used to treat high-risk haematological malignant disorders and other life-threatening haematological and genetic diseases. The main complication of HCT is graft-versus-host disease (GVHD), an immunological disorder that affects many organ systems, including the gastrointestinal tract, liver, skin, and lungs. The number of patients with this complication continues to grow, and many return home from transplant centres after HCT requiring continued treatment with immunosuppressive drugs that increases their risks for serious infections and other complications. In this Seminar, we review our understanding of the risk factors and causes of GHVD, the cellular and cytokine networks implicated in its pathophysiology, and current strategies to prevent and treat the disease. We also summarise supportive-care measures that are essential for management of this medically fragile population.
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            Resident human hepatic lymphocytes are phenotypically different from circulating lymphocytes.

            S Norris, C. Collins, D. Doherty … (1998)
            Murine and human studies have documented the existence of subpopulations of lymphocytes in particular tissues that differ phenotypically and functionally from those in peripheral blood and may mature locally. Since little is known about lymphocyte subpopulations in the normal human liver, we have analysed the surface phenotypes of lymphocytes isolated from liver specimens taken from 15 donors at the time of liver transplantation, and compared these with those of peripheral blood lymphocytes. Hepatic lymphocytes were prepared by mechanical dissociation and enzymatic digestion of liver tissue. The cells were stained with a panel of monoclonal antibodies (CD3, CD4, CD8, CD19, CD56, gammadeltaTCR, alphabetaTCR, CD8alpha-chain, CD8alphabeta dimer), and analysed by flow cytometry. In situ characterisation of hepatic lymphocytes was by haematoxylin and eosin staining of fixed liver sections and by immunohistochemical staining for common leukocyte antigen and CD3. Significant numbers of hepatic T lymphocytes were localised to the portal tracts and parenchyma of normal liver specimens. Flow cytometry revealed that the CD4/CD8 ratio (1:3.5) was consistently reversed compared with that in peripheral blood (2:1). Other lymphocyte populations identified include double positive CD3+CD4+CD8+ cells which accounted for a mean of 5.5% (range 3-11.6%) of hepatic CD3+ cells compared with 1.3% in blood (range 0.7-3.6%; p < 0.007), and double negative CD3+ CD4-8- cells (14.5%; range 2.7-29% compared with 5.0%; range 2.1-10.8%, p < 0.02). Over 15% (range 6.8-34%) of all hepatic CD3+ cells expressed a gammadeltaTCR compared to 2.7% (range 0.9-4.7%) of CD3+ peripheral blood lymphocytes (p < 0.004) and almost 50% of these coexpressed CD8. The CD8 alpha-chain was expressed without the beta-chain (CD8alpha+beta-) by 15.4% (range 4-29.1%) of hepatic T cells, but this phenotype was undetectable among peripheral blood lymphocytes (p < 0.009). Cells expressing both the T cell marker CD3 and the natural killer cell marker CD56 constituted 31.6% (range 14-54%) of all hepatic CD3+ lymphocytes but were rarely present amongst peripheral blood lymphocytes (0-6%; p < 0.0001). These data are the first to describe and quantify unconventional T lymphocyte subpopulations in the normal adult human liver which may have specialised functions in regional immune responses and which may differentiate locally. These findings have important implications for our understanding of hepatic immunoregulation and the pathogenic mechanisms involved in viral and immune-mediated liver disease and allograft rejection.
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              Relation of an interleukin-10 promoter polymorphism to graft-versus-host disease and survival after hematopoietic-cell transplantation.

              Ping-Hui Tseng, Peter Hansen, Ted Gooley … (2003)
              Polymorphisms in cytokine genes can influence immune responses, inflammation, and tissue injury and may affect the outcome of hematopoietic stem-cell transplantation. We analyzed single-nucleotide polymorphisms in the genes for interleukin-1beta, interleukin-1-receptor antagonist, interleukin-6, interleukin-10 (IL10), and tumor necrosis factor alpha in 570 transplant recipients and their HLA-identical sibling donors. Genotypes were tested for an association with graft-versus-host disease (GVHD) by multivariable analysis. A second cohort of 423 transplant recipients was independently analyzed for the genotype associations identified in the first cohort. The recipient's IL10 promoter region genotype was significantly associated with the risk of acute GVHD in the first cohort. Analysis of all 993 transplant recipients showed that, as compared with the C/C genotype, the IL10 -592A/A genotype was associated with a decreased risk of grade III or IV acute GVHD (hazard ratio, 0.4; 95 percent confidence interval, 0.2 to 0.9; P=0.02) and death in remission (hazard ratio, 0.6; 95 percent confidence interval, 0.3 to 1.0; P=0.05). A haplotype analysis showed that the IL10 -592A allele was a specific marker for a promoter haplotype, T-C-A-T-A, defined by five polymorphisms at positions -3575, -2763, -1082, -819, and -592, respectively. Among recipients of hematopoietic cells from an HLA-identical sibling, the IL10 -592A allele is a marker of a favorable outcome after transplantation. Copyright 2003 Massachusetts Medical Society
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                Author and article information

                Journal
                Journal ID (nlm-ta): Transpl Immunol
                Journal ID (iso-abbrev): Transpl Immunol
                Title: Transplant Immunology
                Publisher: Published by Elsevier B.V.
                ISSN (Print): 0966-3274
                ISSN (Electronic): 1878-5492
                Publication date PMC-release: 1 July 2021
                Publication date (Electronic): 1 July 2021
                Electronic Location Identifier: 101435
                Affiliations
                Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1905 Jiefang Avenue, Wuhan City, Hubei Province, Wuhan 430030, China
                Author notes
                [* ]Corresponding author.
                Article
                Publisher Item ID: S0966-3274(21)00075-7 Publisher ID: 101435
                DOI: 10.1016/j.trim.2021.101435
                PMC ID: 8245304
                PubMed ID: 34216759
                SO-VID: 25b96f2c-dd08-49ee-b393-02be2285daf2
                Copyright © © 2021 Published by Elsevier B.V.
                License:

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                Date received : 28 May 2021
                Date revision received : 29 June 2021
                Date accepted : 29 June 2021
                Categories
                Subject: Article

                ScienceOpen disciplines: Transplantation
                Keywords: orthotopic live transplantation,agvhd,covid-19,close contact
                Data availability:
                ScienceOpen disciplines: Transplantation
                Keywords: orthotopic live transplantation, agvhd, covid-19, close contact

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