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Berg T, Aehling NF, Bruns T, Welker MW, Weismüller T, Trebicka J, Tacke F, Strnad P, Sterneck M, Settmacher U, Seehofer D, Schott E, Schnitzbauer AA, Schmidt HH, Schlitt HJ, Pratschke J, Pascher A, Neumann U, Manekeller S, Lammert F, Klein I, Kirchner G, Guba M, Glanemann M, Engelmann C, Canbay AE, Braun F, Berg CP, Bechstein WO, Becker T, Trautwein C. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:1397-1573. [PMID: 39250961 DOI: 10.1055/a-2255-7246] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/11/2024]
Affiliation(s)
- Thomas Berg
- Bereich Hepatologie, Medizinischen Klinik II, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Niklas F Aehling
- Bereich Hepatologie, Medizinischen Klinik II, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Tony Bruns
- Medizinische Klinik III, Universitätsklinikum Aachen, Aachen, Deutschland
| | - Martin-Walter Welker
- Medizinische Klinik I Gastroent., Hepat., Pneum., Endokrin. Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - Tobias Weismüller
- Klinik für Innere Medizin - Gastroenterologie und Hepatologie, Vivantes Humboldt-Klinikum, Berlin, Deutschland
| | - Jonel Trebicka
- Medizinische Klinik B für Gastroenterologie und Hepatologie, Universitätsklinikum Münster, Münster, Deutschland
| | - Frank Tacke
- Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Berlin, Deutschland
| | - Pavel Strnad
- Medizinische Klinik III, Universitätsklinikum Aachen, Aachen, Deutschland
| | - Martina Sterneck
- Medizinische Klinik und Poliklinik I, Universitätsklinikum Hamburg, Hamburg, Deutschland
| | - Utz Settmacher
- Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Universitätsklinikum Jena, Jena, Deutschland
| | - Daniel Seehofer
- Klinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Eckart Schott
- Klinik für Innere Medizin II - Gastroenterologie, Hepatologie und Diabetolgie, Helios Klinikum Emil von Behring, Berlin, Deutschland
| | | | - Hartmut H Schmidt
- Klinik für Gastroenterologie und Hepatologie, Universitätsklinikum Essen, Essen, Deutschland
| | - Hans J Schlitt
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg, Regensburg, Deutschland
| | - Johann Pratschke
- Chirurgische Klinik, Charité Campus Virchow-Klinikum - Universitätsmedizin Berlin, Berlin, Deutschland
| | - Andreas Pascher
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Münster, Münster, Deutschland
| | - Ulf Neumann
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Essen, Essen, Deutschland
| | - Steffen Manekeller
- Klinik und Poliklinik für Allgemein-, Viszeral-, Thorax- und Gefäßchirurgie, Universitätsklinikum Bonn, Bonn, Deutschland
| | - Frank Lammert
- Medizinische Hochschule Hannover (MHH), Hannover, Deutschland
| | - Ingo Klein
- Chirurgische Klinik I, Universitätsklinikum Würzburg, Würzburg, Deutschland
| | - Gabriele Kirchner
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg und Innere Medizin I, Caritaskrankenhaus St. Josef Regensburg, Regensburg, Deutschland
| | - Markus Guba
- Klinik für Allgemeine, Viszeral-, Transplantations-, Gefäß- und Thoraxchirurgie, Universitätsklinikum München, München, Deutschland
| | - Matthias Glanemann
- Klinik für Allgemeine, Viszeral-, Gefäß- und Kinderchirurgie, Universitätsklinikum des Saarlandes, Homburg, Deutschland
| | - Cornelius Engelmann
- Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Berlin, Deutschland
| | - Ali E Canbay
- Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Deutschland
| | - Felix Braun
- Klinik für Allgemeine Chirurgie, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Schlewswig-Holstein, Kiel, Deutschland
| | - Christoph P Berg
- Innere Medizin I Gastroenterologie, Hepatologie, Infektiologie, Universitätsklinikum Tübingen, Tübingen, Deutschland
| | - Wolf O Bechstein
- Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - Thomas Becker
- Klinik für Allgemeine Chirurgie, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Schlewswig-Holstein, Kiel, Deutschland
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Wang CI, Chen YY, Yang Y, Gau SY, Huang CY, Tsai TH, Huang KH, Lee CY. Risk of herpes simplex virus infection in solid organ transplant recipients: A population-based cross-sectional study. Ann Epidemiol 2024; 89:21-28. [PMID: 38042439 DOI: 10.1016/j.annepidem.2023.11.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2023] [Revised: 10/24/2023] [Accepted: 11/27/2023] [Indexed: 12/04/2023]
Abstract
BACKGROUND Herpes simplex virus (HSV) is an opportunistic infection antigen in solid organ transplant (SOT) recipients. However, this phenomenon has received limited attention from epidemiologists. Our study aims to determine the HSV infection risk in SOT recipients. METHODS This was a nationwide population-based cross-sectional study based on the National Health Insurance Research Database from 2002 to 2015. We used propensity score matching to avoid selection bias and analyzed the association between HSV infection and SOT recipients with multiple logistic regression analysis. RESULTS At a 3-year follow-up, SOT recipients had a higher risk of developing HSV, with an adjusted odds ratio (aOR) of 3.28 (95% confidence interval (CI), 2.51-4.29). Moreover, at 6-month, 1-year, and 2-year follow-ups, SOT recipients also had an increased risk of HSV than general patients with aORs of 3.85 (95% CI, 2.29-6.49), 4.27 (95% CI, 2.86-6.36), and 3.73 (95% CI, 2.74-5.08), respectively. In the subgroup analysis, lung transplant recipients (aOR = 8.01; 95% CI, 2.39-26.88) exhibited a significantly higher chance of HSV among SOT recipients, followed by kidney transplant recipients (aOR = 3.33; 95% CI, 2.11-5.25) and liver transplant recipients (aOR = 3.15; 95% CI, 2.28-4.34). CONCLUSION HSV can develop at any time after organ transplantation. SOT recipients had a higher risk of HSV infection than the general population at 6 months, 1 year, 2 years, and 3 years after transplantation, with the highest chance at 1 year after. In addition, the patients who underwent lung transplantion were at higher risk for HSV infection than liver or kidney transplant recipients.
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Affiliation(s)
- Ching-I Wang
- School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan; Department of Medical Education, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
| | - Yan-Yu Chen
- School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan; Department of Medical Education, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
| | - Yih Yang
- Department of Obstetrics and Gynecology, E-Da Hospital, I-Shou University, Kaohsiung 824, Taiwan
| | - Shuo-Yan Gau
- School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan
| | - Cheng-Yang Huang
- School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan
| | - Tung-Han Tsai
- Department of Health Services Administration, China Medical University, Taichung 40402, Taiwan
| | - Kuang-Hua Huang
- Department of Health Services Administration, China Medical University, Taichung 40402, Taiwan
| | - Chien-Ying Lee
- Department of Pharmacology, Chung Shan Medical University, Taichung 40201, Taiwan; Department of Pharmacy, Chung Shan Medical University Hospital, Taichung 40201, Taiwan.
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Kun-Varga A, Gubán B, Miklós V, Parvaneh S, Guba M, Szűcs D, Monostori T, Varga J, Varga Á, Rázga Z, Bata-Csörgő Z, Kemény L, Megyeri K, Veréb Z. Herpes Simplex Virus Infection Alters the Immunological Properties of Adipose-Tissue-Derived Mesenchymal-Stem Cells. Int J Mol Sci 2023; 24:11989. [PMID: 37569367 PMCID: PMC10418794 DOI: 10.3390/ijms241511989] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2023] [Revised: 06/20/2023] [Accepted: 06/26/2023] [Indexed: 08/13/2023] Open
Abstract
The proper functioning of mesenchymal stem cells (MSCs) is of paramount importance for the homeostasis of the body. Inflammation and infection can alter the function of MSCs, which can also affect the regenerative potential and immunological status of tissues. It is not known whether human herpes simplex viruses 1 and 2 (HSV1 and HSV2), well-known human pathogens that can cause lifelong infections, can induce changes in MSCs. In non-healing ulcers, HSV infection is known to affect deeper tissue layers. In addition, HSV infection can recur after initially successful cell therapies. Our aim was to study the response of adipose-derived MSCs (ADMSCs) to HSV infection in vitro. After confirming the phenotype and differentiation capacity of the isolated cells, we infected the cells in vitro with HSV1-KOS, HSV1-532 and HSV2 virus strains. Twenty-four hours after infection, we examined the gene expression of the cells via RNA-seq and RT-PCR; detected secreted cytokines via protein array; and determined autophagy via Western blot, transmission electron microscopy (TEM) and fluorescence microscopy. Infection with different HSV strains resulted in different gene-expression patterns. In addition to the activation of pathways characteristic of viral infections, distinct non-immunological pathways (autophagy, tissue regeneration and differentiation) were also activated according to analyses with QIAGEN Ingenuity Pathway Analysis, Kyoto Encyclopedia of Genes and Genome and Genome Ontology Enrichment. Viral infections increased autophagy, as confirmed via TEM image analysis, and also increased levels of the microtubule-associated protein light chain 3 (LC3B) II protein. We identified significantly altered accumulation for 16 cytokines involved in tissue regeneration and inflammation. Our studies demonstrated that HSV infection can alter the viability and immunological status of ADMSCs, which may have implications for ADMSC-based cell therapies. Alterations in autophagy can affect numerous processes in MSCs, including the inhibition of tissue regeneration as well as pathological differentiation.
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Affiliation(s)
- Anikó Kun-Varga
- Regenerative Medicine and Cellular Pharmacology Laboratory, Department of Dermatology and Allergology, University of Szeged, H-6720 Szeged, Hungary; (A.K.-V.); (B.G.); (M.G.); (D.S.); (T.M.); (L.K.)
- Doctoral School of Clinical Medicine, University of Szeged, H-6720 Szeged, Hungary
| | - Barbara Gubán
- Regenerative Medicine and Cellular Pharmacology Laboratory, Department of Dermatology and Allergology, University of Szeged, H-6720 Szeged, Hungary; (A.K.-V.); (B.G.); (M.G.); (D.S.); (T.M.); (L.K.)
| | - Vanda Miklós
- Biobank, University of Szeged, H-6720 Szeged, Hungary;
| | - Shahram Parvaneh
- HCEMM-SZTE Skin Research Group, University of Szeged, H-6720 Szeged, Hungary; (S.P.); (Z.B.-C.)
| | - Melinda Guba
- Regenerative Medicine and Cellular Pharmacology Laboratory, Department of Dermatology and Allergology, University of Szeged, H-6720 Szeged, Hungary; (A.K.-V.); (B.G.); (M.G.); (D.S.); (T.M.); (L.K.)
- Interdisciplinary Research Development and Innovation Center of Excellence, University of Szeged, H-6720 Szeged, Hungary
| | - Diána Szűcs
- Regenerative Medicine and Cellular Pharmacology Laboratory, Department of Dermatology and Allergology, University of Szeged, H-6720 Szeged, Hungary; (A.K.-V.); (B.G.); (M.G.); (D.S.); (T.M.); (L.K.)
- Interdisciplinary Research Development and Innovation Center of Excellence, University of Szeged, H-6720 Szeged, Hungary
| | - Tamás Monostori
- Regenerative Medicine and Cellular Pharmacology Laboratory, Department of Dermatology and Allergology, University of Szeged, H-6720 Szeged, Hungary; (A.K.-V.); (B.G.); (M.G.); (D.S.); (T.M.); (L.K.)
- Interdisciplinary Research Development and Innovation Center of Excellence, University of Szeged, H-6720 Szeged, Hungary
| | - János Varga
- Dermatosurgery and Plastic Surgery Unit, Department of Dermatology and Allergology, University of Szeged, H-6720 Szeged, Hungary; (J.V.); (Á.V.)
| | - Ákos Varga
- Dermatosurgery and Plastic Surgery Unit, Department of Dermatology and Allergology, University of Szeged, H-6720 Szeged, Hungary; (J.V.); (Á.V.)
| | - Zsolt Rázga
- Department of Pathology, University of Szeged, H-6720 Szeged, Hungary;
| | - Zsuzsanna Bata-Csörgő
- HCEMM-SZTE Skin Research Group, University of Szeged, H-6720 Szeged, Hungary; (S.P.); (Z.B.-C.)
| | - Lajos Kemény
- Regenerative Medicine and Cellular Pharmacology Laboratory, Department of Dermatology and Allergology, University of Szeged, H-6720 Szeged, Hungary; (A.K.-V.); (B.G.); (M.G.); (D.S.); (T.M.); (L.K.)
- HCEMM-SZTE Skin Research Group, University of Szeged, H-6720 Szeged, Hungary; (S.P.); (Z.B.-C.)
- Interdisciplinary Research Development and Innovation Center of Excellence, University of Szeged, H-6720 Szeged, Hungary
| | - Klára Megyeri
- Department of Medical Microbiology, University of Szeged, H-6720 Szeged, Hungary;
| | - Zoltán Veréb
- Regenerative Medicine and Cellular Pharmacology Laboratory, Department of Dermatology and Allergology, University of Szeged, H-6720 Szeged, Hungary; (A.K.-V.); (B.G.); (M.G.); (D.S.); (T.M.); (L.K.)
- Biobank, University of Szeged, H-6720 Szeged, Hungary;
- Interdisciplinary Research Development and Innovation Center of Excellence, University of Szeged, H-6720 Szeged, Hungary
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Rabbani A, Eghlimi H, Khoshkbarforoushan M, Baziboroun M. The prevalence of latent/chronic infection in liver transplant candidates in Taleghani Hospital of Tehran, Iran, from 2020 until 2021. GASTROENTEROLOGY AND HEPATOLOGY FROM BED TO BENCH 2023; 16:478-485. [PMID: 37070118 PMCID: PMC10105496 DOI: 10.22037/ghfbb.v16i1.2664] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Accepted: 12/01/2022] [Indexed: 04/19/2023]
Abstract
Aim The present study aimed to study the prevalence of various latent infections in pre-transplanted patients. Background Due to chronic immunosuppressive therapy, patients receiving organ transplants are at risk for reactivation of various infections. Due to the complications in the course of diagnosing and treating the post-transplant infection, screening transplant recipients and donors is vital. Methods This retrospective cohort study was performed between March 2020 and 2021. A total of 193 patients receiving a liver transplant in Taleghani Hospital, Tehran, Iran were enrolled. Results One-hundred and three (53.4%) patients were men, with an average age of 48.4 ± 13.3 years. Among viruses, 177 (91.7%) patients had a positive IgG titer for CMV. Anti-EBV IgG was positive in 169 (87.6%) patients. One-hundred and seventy-five (90.7%) patients had a positive IgG titer for the VZV. One-hundred and sixty-six (86.0%) cases had positive IgG anti-HSV antibodies. According to our findings, none of the patients were infected with HIV, but 9 (4.7%) cases and 141 (73.1%) had positive anti-HCV and anti-HAV IgG antibodies, respectively. HBV surface (HBs) antigen was also reported positive in 17 (8.8%) patients, while the HBs antibody was positive in 29 (15.0%) patients. Conclusion In our study, most of the patients had positive serology for latent viral infections such as CMV, EBV, VZV, and HSV, but the prevalence of latent tuberculosis and viral hepatitis was low among transplant candidates.
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Affiliation(s)
- Amirhassan Rabbani
- Department of General Surgery, Ayatollah Taleghani Hospital, Shahid Beheshti University of Medical Science, Tehran, Iran
| | - Hesameddin Eghlimi
- Department of General Surgery, Ayatollah Taleghani Hospital, Shahid Beheshti University of Medical Science, Tehran, Iran
| | - Mina Khoshkbarforoushan
- Department of General Surgery, Ayatollah Taleghani Hospital, Shahid Beheshti University of Medical Science, Tehran, Iran
| | - Mana Baziboroun
- Clinical Research of Development Unit of Rohani Hospital, Babol University of Medical Sciences, Babol, Iran
- Infectious Disease and Tropical Medicine Research Center, Shahid Beheshti University of Medical Science, Tehran, Iran
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Jothimani D, Venugopal R, Vij M, Rela M. Post liver transplant recurrent and de novo viral infections. Best Pract Res Clin Gastroenterol 2020; 46-47:101689. [PMID: 33158469 PMCID: PMC7519014 DOI: 10.1016/j.bpg.2020.101689] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Accepted: 09/22/2020] [Indexed: 01/31/2023]
Abstract
Survival following liver transplantation has changed dramatically owing to improvement in surgical techniques, peri-operative care and optimal immunosuppressive therapy. Post-Liver transplant (LT) de novo or recurrent viral infection continues to cause major allograft dysfunction, leading to poor graft and patient survival in untreated patients. Availability of highly effective antiviral drugs has significantly improved post-LT survival. Patients transplanted for chronic hepatitis B infection should receive life-long nucleos(t)ide analogues, with or without HBIg for effective viral control. Patients with chronic hepatitis C should be commenced on directly acting antiviral (DAA) drugs prior to transplantation. DAA therapy for post-LT recurrent hepatitis C infection is associated with close to 100% sustained virological response (SVR), irrespective of genotype. De novo chronic Hepatitis E infection is an increasingly recognised cause of allograft dysfunction in LT recipients. Untreated chronic HEV infection of the graft may lead to liver fibrosis and allograft failure. CMV and EBV can reactivate leading to systemic illness following liver transplantation. With COVID-19 pandemic, post-transplant patients are at risk of SARS-Co-V2 infection. Majority of the LT recipients require hospitalization, and the mortality in this population is around 20%. Early recognition of allograft dysfunction and identification of viral aetiology is essential in the management of post-LT de novo or recurrent infections. Optimising immunosuppression is an important step in reducing the severity of allograft damage in the treatment of post-transplant viral infections. Viral clearance or control can be achieved by early initiation of high potency antiviral therapy.
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Affiliation(s)
- Dinesh Jothimani
- Institute of Liver Disease and Transplantation, Dr Rela Institute and Medical Centre, Bharath Institute of Higher Education and Research, Chennai, India.
| | - Radhika Venugopal
- Institute of Liver Disease and Transplantation, Dr Rela Institute and Medical Centre, Bharath Institute of Higher Education and Research, Chennai, India
| | - Mukul Vij
- Institute of Liver Disease and Transplantation, Dr Rela Institute and Medical Centre, Bharath Institute of Higher Education and Research, Chennai, India
| | - Mohamed Rela
- Institute of Liver Disease and Transplantation, Dr Rela Institute and Medical Centre, Bharath Institute of Higher Education and Research, Chennai, India
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Abati E, Gagliardi D, Velardo D, Meneri M, Conte G, Cinnante C, Bresolin N, Comi G, Corti S. Herpes Simplex virus type 2 myeloradiculitis with a pure motor presentation in a liver transplant recipient. Transpl Infect Dis 2019; 22:e13236. [PMID: 31868290 DOI: 10.1111/tid.13236] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2019] [Revised: 10/31/2019] [Accepted: 12/09/2019] [Indexed: 12/25/2022]
Abstract
In this case report, we describe the first PCR-confirmed case of HSV2 myeloradiculitis with a purely motor presentation, occurring in a 68-year-old liver transplant recipient. The patient reported ascending weakness with no sensory nor sphincteric symptoms, thereby resembling acute demyelinating inflammatory neuropathy, or Guillain-Barré syndrome. HSV2 was detected in cerebrospinal fluid by PCR, and the patient was successfully treated with intravenous Acyclovir.
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Affiliation(s)
- Elena Abati
- Department of Pathophysiology and Transplantation (DEPT), Dino Ferrari Centre, Neuroscience Section, University of Milan, Milan, Italy
| | - Delia Gagliardi
- Department of Pathophysiology and Transplantation (DEPT), Dino Ferrari Centre, Neuroscience Section, University of Milan, Milan, Italy
| | - Daniele Velardo
- Neurology Unit, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Megi Meneri
- Neurology Unit, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Giorgio Conte
- Neuroradiology Unit, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Claudia Cinnante
- Neuroradiology Unit, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Nereo Bresolin
- Department of Pathophysiology and Transplantation (DEPT), Dino Ferrari Centre, Neuroscience Section, University of Milan, Milan, Italy.,Neurology Unit, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Giacomo Comi
- Department of Pathophysiology and Transplantation (DEPT), Dino Ferrari Centre, Neuroscience Section, University of Milan, Milan, Italy.,Neurology Unit, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Stefania Corti
- Department of Pathophysiology and Transplantation (DEPT), Dino Ferrari Centre, Neuroscience Section, University of Milan, Milan, Italy.,Neurology Unit, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
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Lee DH, Zuckerman RA. Herpes simplex virus infections in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant 2019; 33:e13526. [PMID: 30859647 DOI: 10.1111/ctr.13526] [Citation(s) in RCA: 54] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2019] [Accepted: 02/27/2019] [Indexed: 12/19/2022]
Abstract
These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of HSV in the pre- and post-transplant period. A majority of transplant recipients are seropositive for HSV-1 or 2. Compared with immunocompetent persons, SOT recipients shed HSV more frequently, have more severe clinical manifestations, and are slower to respond to therapy. Most HSV infection is diagnosed on clinical grounds, but patients may present with atypical lesions and/or other clinical manifestations. Acquisition from the donor is rare. Polymerase chain reaction is the preferred diagnostic test unless culture is needed for resistance testing. For limited mucocutaneous lesions, oral therapy can be used; however, in severe, disseminated, visceral or CNS involvement, acyclovir doses of up to 10 mg/kg every 8 hours intravenously should be initiated. Acyclovir-resistant HSV is less common in SOT patients than in HSCT and can be treated with foscarnet, though other novel therapies are currently under investigation. HSV-specific prophylaxis should be considered for all HSV-1 and HSV-2-seropositive organ recipients who are not receiving antiviral medication for CMV prevention that has activity against HSV.
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Affiliation(s)
- Dong H Lee
- Division of Infectious Diseases and HIV Medicine, College of Medicine, Drexel University, Philadelphia, Pennsylvania
| | - Richard A Zuckerman
- Infectious Disease Service for Transplant and Immunocompromised Hosts, Section of Infectious Disease and International Health, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire
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Dermatological Disorders following Liver Transplantation: An Update. Can J Gastroenterol Hepatol 2019; 2019:9780952. [PMID: 31058114 PMCID: PMC6463607 DOI: 10.1155/2019/9780952] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2018] [Revised: 02/24/2019] [Accepted: 03/11/2019] [Indexed: 02/08/2023] Open
Abstract
Patients undergoing liver transplantation (LT) are at a high risk of dermatological complications compared to the general population as a result of long-term use of immunosuppressant. However, the risk is not as high as other solid organ transplantations (SOT), particularly for skin cancer. The liver is considered as an immune privileged organ since it has a low prevalence of humoral rejection in contrast to other SOT, and thus, LT requires a minimal amount of immunosuppressants compared to other SOT recipients. However, because of the large volume of the liver, patients with LT have higher donor lymphocytes that sometimes may trigger graft-versus-host-disease, yet it is rare. On the other hand, the vast majority of the nonspecific dermatological lesions linked with cirrhosis improve after removal of diseased liver or due to the immunosuppressant used after LT. Nevertheless, dermatological infections related to bacteria, viruses, and fungus after LT are not uncommon. Additionally, the incidence of IgE-mediated food allergies develops in 12.2% of LT patients and may present as life-threatening conditions such as urticaria and/or angioedema and hypersensitivity. Moreover, skin malignancies after LT are a matter of concern. Thus, posttransplant dermatological care should be provided to all LT patients for any suspicious dermatological lesions. Our goal is to give an outline of the dermatological manifestation associated with LT for the clinicians by collecting the published data from all archived case reports.
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Abstract
Liver transplantation has become an important treatment modality for patients with end-stage liver disease/cirrhosis, acute liver failure, and hepatocellular carcinoma. Although surgical techniques and immunosuppressive regimens for liver transplantation have improved significantly over the past 20 years, infectious complications continue to contribute to the morbidity and mortality in this patient population. The use of standardized screening protocols for both donors and recipients, coupled with targeted prophylaxis against specific pathogens, has helped to mitigate the risk of infection in liver transplant recipients. Patients with chronic liver disease and cirrhosis have immunological deficits that place them at increased risk for infection while awaiting liver transplantation. The patient undergoing liver transplantation is prone to develop healthcare-acquired infections due to multidrug-resistant organisms that could potentially affect patient outcomes after transplantation. The complex nature of liver transplant surgery that involves multiple vascular and hepatobiliary anastomoses further increases the risk of infection after liver transplantation. During the early post-transplantation period, healthcare-acquired bacterial and fungal infections are the most common types of infection encountered in liver transplant recipients. The period of maximal immunosuppression that occurs at 1–6 months after transplantation can be complicated by opportunistic infections due to both primary infection and reactivation of latent infection. Severe community-acquired infections can complicate the course of liver transplantation beyond 12 months after transplant surgery. This chapter provides an overview of liver transplantation including indications, donor-recipient selection criteria, surgical procedures, and immunosuppressive therapies. A focus on infections in patients with chronic liver disease/cirrhosis and an overview of the specific infectious complications in liver transplant recipients are presented.
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Viral Hepatitis Recommendations for Solid-Organ Transplant Recipients and Donors. Transplantation 2018; 102:S66-S71. [PMID: 29381580 DOI: 10.1097/tp.0000000000002013] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
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11
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Abstract
The α herpes viruses HSV-1, HSV-2, and VZV often reactivate in the setting of immune suppression after solid organ transplantation. Oral or genital mucocutaneous disease is the most common clinical manifestation of HSV disease while VZV manifests as varicella (or chickenpox) or reactivation herpes zoster, characterized by a diffuse rash, or a painful unilateral vesicular eruption in a dermatomal distribution, respectively. The diagnosis of HSV and VZV is primarily based on history and clinical presentation, although diagnostic tests may be necessary for atypical presentations of disease. Treatment usually involves oral or intravenous antiviral therapy, depending on severity of illness.
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Affiliation(s)
- Cybele Lara Abad
- Division of Infectious Diseases, Department of Medicine, Mayo Clinic, Rochester, MN
| | - Raymund R Razonable
- Division of Infectious Diseases, Department of Medicine, Mayo Clinic, Rochester, MN; The William J. Von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN.
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12
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Abad CL, Razonable RR. Treatment of alpha and beta herpesvirus infections in solid organ transplant recipients. Expert Rev Anti Infect Ther 2016; 15:93-110. [PMID: 27911112 DOI: 10.1080/14787210.2017.1266253] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
INTRODUCTION Human herpesviruses frequently cause infections in solid organ transplant (SOT) recipients. Areas covered: We provide an overview of the clinical impact of alpha and beta herpesviruses and highlight the mechanisms of action, pharmacokinetics, clinical indications, and adverse effects of antiviral drugs for the management of herpes simplex virus, varicella zoster virus and cytomegalovirus. We comprehensively evaluated key clinical trials that led to drug approval, and served as the foundation for management guidelines. We further provide an update on investigational antiviral agents for alpha and beta herpesvirus infections after SOT. Expert commentary: The therapeutic armamentarium for herpes infections is limited by the emergence of drug resistance. There have been major efforts for discovery of new drugs against these viruses, but the results of early-phase clinical trials have been less than encouraging. We believe, however, that more antiviral drug options are needed given the adverse side effects associated with current antiviral agents, and the emergence of drug-resistant virus populations in SOT recipients. Likewise, optimized use and strategies are needed for existing and novel antiviral drugs against alpha and beta-herpesviruses in SOT recipients.
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Affiliation(s)
- C L Abad
- a Division of Infectious Diseases, Department of Medicine , Mayo Clinic , Rochester , MN , USA.,b Department of Medicine, Section of Infectious Diseases , University of the Philippines - Philippine General Hospital , Manila , Philippines
| | - R R Razonable
- a Division of Infectious Diseases, Department of Medicine , Mayo Clinic , Rochester , MN , USA.,c The William J. Von Liebig Center for Transplantation and Clinical Regeneration , Mayo Clinic , Rochester , MN , USA
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13
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Hepatobiliary Quiz Answers-17 (2016). J Clin Exp Hepatol 2016; 6:73-6. [PMID: 27194902 PMCID: PMC4862109 DOI: 10.1016/j.jceh.2016.03.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
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14
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Bhat V, Joshi A, Sarode R, Chavan P. Cytomegalovirus infection in the bone marrow transplant patient. World J Transplant 2015; 5:287-291. [PMID: 26722656 PMCID: PMC4689939 DOI: 10.5500/wjt.v5.i4.287] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2015] [Revised: 09/09/2015] [Accepted: 11/17/2015] [Indexed: 02/05/2023] Open
Abstract
Cytomegalovirus (CMV) infection is an important contributor to the morbidity and mortality associated with bone marrow transplantation (BMT). Infection may lead to CMV disease involving multiple organs such as pneumonia, gastroenteritis, retinitis, central nervus system involvement and others. CMV seropositivity is an important risk factor and approximately half of BMT recipients will develop clinically significant infection most commonly in the first 100 d post-transplant. The commonly used tests to diagnose CMV infection in these patients include the pp65 antigenemia test and the CMV DNA polymerase chain reaction (PCR) assay. Because of its greater sensitivity and lesser turnaround time, the CMV PCR is nowadays the preferred test and serves as a main guide for pre-emptive therapy. Methods of CMV prevention include use of blood products from seronegative donors or leukodepleted products. Prophylaxis or pre-emptive therapy strategies for CMV prevention may be used post-transplant with the latter becoming more common. The commonly used antivirals for pre-emptive therapy and CMV disease management include intravenous gancyclovir and foscarnet. The role of intravenous immunoglobulin, although used commonly in CMV pneumonia is not clear.
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15
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16
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Mezochow AK, Henry R, Blumberg EA, Kotton CN. Transfusion transmitted infections in solid organ transplantation. Am J Transplant 2015; 15:547-54. [PMID: 25612502 DOI: 10.1111/ajt.13006] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2014] [Revised: 08/13/2014] [Accepted: 08/28/2014] [Indexed: 01/25/2023]
Abstract
While the risk of infectious disease transmission through blood transfusion has been greatly reduced as a result of improved screening methods, transfusion-transmissible infections remain a concern for transplant recipients, especially those receiving multiple transfusions. Although transfusion and transplant recipients are at risk for similar infections, the current reporting requirements for infections transmitted by transfusions and organ transplantation vary greatly and remain distinctly separate with no communication between reporting systems. This article reviews 23 past reports of transfusion-transmitted infections in organ recipients acquired through transfusions. While cytomegalovirus was a major focus of such reports in the 1980s, more recent reports have focused on West Nile virus transmission. Additionally, this article highlights challenges in determining transfusion-transmitted infection risk in transplant recipients related to the current reporting systems.
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Affiliation(s)
- A K Mezochow
- U.S. Department of Health and Human Services, Office of the Assistant Secretary for Health, Division of Blood and Tissue Safety and Availability, Washington, DC
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17
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Hanson K, Alexander B. Strategies for the prevention of infection after solid organ transplantation. Expert Rev Anti Infect Ther 2014; 4:837-52. [PMID: 17140359 DOI: 10.1586/14787210.4.5.837] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
Infection is a frequent complication of organ transplantation and is associated with significant morbidity and mortality. Preventative antimicrobial strategies are a key component of the care received by transplant patients. This review summarizes the evidence supporting anti-infective prophylaxis in this setting. Specific recommendations for the prevention of bacterial, fungal, viral and parasitic infection after transplant are made, with a focus on recent developments in the field of transplant infectious diseases.
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Affiliation(s)
- Kimberly Hanson
- Duke University Medical Center, Division of Infectious Diseases and International Health, Duke Clinical Microbiology Laboratory, NC 27710, USA.
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18
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Côté-Daigneault J, Carrier F, Toledano K, Wartelle-Bladu C, Willems B. Herpes simplex hepatitis after liver transplantation: case report and literature review. Transpl Infect Dis 2014; 16:130-4. [DOI: 10.1111/tid.12178] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2013] [Revised: 05/08/2013] [Accepted: 09/22/2013] [Indexed: 12/20/2022]
Affiliation(s)
- J. Côté-Daigneault
- Hepatology Service; Department of Medicine; Saint-Luc Hospital; CHUM; University of Montreal; Montreal Quebec Canada
| | - F.M. Carrier
- Intensive Care Service; Department of Medicine; Saint-Luc Hospital; CHUM; University of Montreal; Montreal Quebec Canada
- Department of Anaesthesiology; Saint-Luc Hospital; CHUM; University of Montreal; Montreal Quebec Canada
| | - K. Toledano
- Intensive Care Service; Department of Medicine; Saint-Luc Hospital; CHUM; University of Montreal; Montreal Quebec Canada
| | - C. Wartelle-Bladu
- Hepatology Service; Department of Medicine; Saint-Luc Hospital; CHUM; University of Montreal; Montreal Quebec Canada
| | - B. Willems
- Hepatology Service; Department of Medicine; Saint-Luc Hospital; CHUM; University of Montreal; Montreal Quebec Canada
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19
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Shah U. Infections of the Liver. DISEASES OF THE LIVER IN CHILDREN 2014. [PMCID: PMC7121352 DOI: 10.1007/978-1-4614-9005-0_15] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/04/2022]
Abstract
The portal vein carries blood from the gastrointestinal tract to the liver and in so doing carries microbes as well. The liver may therefore be involved in infections with a myriad number of microbial organisms. While some of these infections most commonly occur in the immunocompromised host, others affect the immune competence. Hepatic infections may be primary in nature or secondary, as part of systemic or contagious disease. The purpose of this chapter is to provide a brief overview of the various infections of the liver in the pediatric patient.
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20
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Pietrucha-Dilanchian P, Tanawuttiwat T, Abbo L, Regatieri A, Chaparro S, Ruiz P, Morris M. Fatal herpes simplex virus type 2 hepatitis in a heart transplant recipient: a case report and review of the literature. Transpl Infect Dis 2013; 15:E87-96. [DOI: 10.1111/tid.12077] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2012] [Revised: 12/13/2012] [Accepted: 12/23/2012] [Indexed: 11/30/2022]
Affiliation(s)
| | - T. Tanawuttiwat
- Division of Cardiology; Jackson Memorial Hospital; University of Miami; Miami; Florida; USA
| | - L. Abbo
- Division of Infectious Diseases; Jackson Memorial Hospital/University of Miami Miller School of Medicine; Miami; Florida; USA
| | - A. Regatieri
- Division of Infectious Diseases; Jackson Memorial Hospital/University of Miami Miller School of Medicine; Miami; Florida; USA
| | - S. Chaparro
- Division of Cardiology; Jackson Memorial Hospital; University of Miami; Miami; Florida; USA
| | - P. Ruiz
- Division of Transplantation; Department of Surgery; University of Miami; Miami; Florida; USA
| | - M.I. Morris
- Division of Infectious Diseases; Jackson Memorial Hospital/University of Miami Miller School of Medicine; Miami; Florida; USA
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21
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Wilck MB, Zuckerman RA. Herpes simplex virus in solid organ transplantation. Am J Transplant 2013; 13 Suppl 4:121-7. [PMID: 23465005 DOI: 10.1111/ajt.12105] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Affiliation(s)
- M B Wilck
- Division of Infectious Diseases, Hospital of University of Pennsylvania, Philadelphia, PA, USA
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22
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Zuckerman RA, Limaye AP. Varicella zoster virus (VZV) and herpes simplex virus (HSV) in solid organ transplant patients. Am J Transplant 2013; 13 Suppl 3:55-66; quiz 66. [PMID: 23347214 DOI: 10.1111/ajt.12003] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2012] [Revised: 09/06/2012] [Accepted: 09/07/2012] [Indexed: 01/25/2023]
Abstract
Varicella zoster virus (VZV) and the two herpes simplex viruses (HSV) are human α-herpesviruses that establish life-long latency in neural ganglia after initial primary infection. In the solid organ transplant (SOT) population, manifestations of VZV or HSV may be seen in up to 70% of recipients if no prophylaxis is used, some of them life and organ threatening. While there are effective vaccines to prevent VZV primary infection and reactivation in immunocompetent adults, these vaccines are contraindicated after SOT because they are live-virus vaccines. For HSV, prevention has focused primarily on antiviral strategies because the immunologic correlates of protection and control are different from VZV, making vaccine development more challenging. Current antiviral therapy remains effective for the majority of clinical VZV and HSV infections.
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Affiliation(s)
- R A Zuckerman
- Department of Medicine, Section of Infectious Disease and International Health, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA
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23
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Carratalà J, Montejo M, Pérez-Romero P. Infections caused by herpes viruses other than cytomegalovirus in solid organ transplant recipients. Enferm Infecc Microbiol Clin 2012; 30 Suppl 2:63-9. [PMID: 22542037 DOI: 10.1016/s0213-005x(12)70084-8] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Despite great advances in solid organ transplantation (SOT) in recent decades, infection remains a major cause of morbidity and mortality among SOT recipients. Members of the herpesvirus family are the most common viral pathogens causing disease in this patient population. Herpes viruses are large enveloped DNA viruses that commonly reactivate during periods of severe immunosuppression. Currently, infections caused by herpes viruses continue to complicate clinical management of transplant patients. Although cytomegalovirus (CMV) is the most important virus of this family and is the subject of active research, herpes simplex virus (HSV) and varicella-zoster virus (VZV) can also lead to severe disease. Epstein-Barr virus (EBV) associated with post-transplant lymphoproliferative disease is increasingly recognized as a major complication of SOT. There is less information available on the role and impact of other viruses of the herpesvirus family, such as the human herpes virus 6 (HHV-6), human herpes virus 7 (HHV-7) and human herpes virus 8 (HHV-8). This review summarizes current knowledge regarding epidemiology, clinical manifestations, diagnosis, treatment and prevention of infections caused by herpes viruses other than CMV in SOT recipients.
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Affiliation(s)
- Jordi Carratalà
- Department of Infectious Diseases, Institut d'Investigació Biomèdica de Bellvitge, Hospital Universitari de Bellvitge, Universitat de Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain.
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2-[4,5-Difluoro-2-(2-fluorobenzoylamino)-benzoylamino]benzoic acid, an antiviral compound with activity against acyclovir-resistant isolates of herpes simplex virus types 1 and 2. Antimicrob Agents Chemother 2012; 56:5735-43. [PMID: 22908173 DOI: 10.1128/aac.01072-12] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Herpes simplex viruses 1 and 2 (HSV-1 and HSV-2) are responsible for lifelong latent infections in humans, with periods of viral reactivation associated with recurring ulcerations in the orofacial and genital tracts. In immunosuppressed patients and neonates, HSV infections are associated with severe morbidity and, in some cases, even mortality. Today, acyclovir is the standard therapy for the management of HSV infections. However, the need for novel antiviral agents is apparent, since HSV isolates resistant to acyclovir therapy are frequently isolated in immunosuppressed patients. In this study, we assessed the anti-HSV activity of the antiadenoviral compounds 2-[2-(2-benzoylamino)-benzoylamino]benzoic acid (benzavir-1) and 2-[4,5-difluoro-2-(2-fluorobenzoylamino)-benzoylamino]benzoic acid (benzavir-2) on HSV-1 and HSV-2. Both compounds were active against both viruses. Importantly, benzavir-2 had potency similar to that of acyclovir against both HSV types, and it was active against clinical acyclovir-resistant HSV isolates.
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25
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Ischemia-Reperfusion Injury and Ischemic-Type Biliary Lesions following Liver Transplantation. J Transplant 2012; 2012:164329. [PMID: 22530107 PMCID: PMC3316988 DOI: 10.1155/2012/164329] [Citation(s) in RCA: 71] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2011] [Revised: 12/19/2011] [Accepted: 12/23/2011] [Indexed: 12/14/2022] Open
Abstract
Ischemia-reperfusion (I-R) injury after liver transplantation (LT) induces intra- and/or extrahepatic nonanastomotic ischemic-type biliary lesions (ITBLs). Subsequent bile duct stricture is a significant cause of morbidity and even mortality in patients who underwent LT. Although the pathogenesis of ITBLs is multifactorial, there are three main interconnected mechanisms responsible for their formation: cold and warm I-R injury, injury induced by cytotoxic bile salts, and immunological-mediated injury. Cold and warm ischemic insult can induce direct injury to the cholangiocytes and/or damage to the arterioles of the peribiliary vascular plexus, which in turn leads to apoptosis and necrosis of the cholangiocytes. Liver grafts from suboptimal or extended-criteria donors are more susceptible to cold and warm I-R injury and develop more easily ITBLs than normal livers. This paper, focusing on liver I-R injury, reviews the risk factors and mechanisms leading to ITBLs following LT.
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26
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Geramizadeh B. Early Post-liver Transplantation Fever in a Child. Int J Organ Transplant Med 2012; 3:101-2. [PMID: 25013630 PMCID: PMC4089280] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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27
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Abstract
Chronic rejection of liver graft is an insidious process. Major immunosuppression medications such as tacrolimus, cyclosporin, and sirolimus have dose-related toxicity and narrow therapeutic windows. Certain drugs can affect metabolism of calcineurin inhibitors. Primary care physicians should be vigilant for any unusual opportunistic infection in liver transplant recipients. The quality of life of liver transplant recipients is an important aspect of care by primary care physicians. Alcohol relapse and possibility of depression in liver transplant recipients should be a continuous concern for primary care physicians. This article provides a guideline for the care of liver transplant recipients.
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Affiliation(s)
- Augustine J Sohn
- Department of Family Medicine, College of Medicine, University of Illinois at Chicago, 1919 West Taylor Street, Chicago, IL 60612, USA.
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28
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Abstract
Hepatitis E, usually an acute hepatitis in the immunocompetent, has a chronic form described in immunocompromised hosts. We report the clinical course and outcome of an adult liver transplant recipient whose posttransplant period was complicated by chronic hepatitis E, Epstein-Barr virus infection, and cellular rejection of the graft.
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Herpes viruses in transplant recipients: HSV, VZV, human herpes viruses, and EBV. Hematol Oncol Clin North Am 2011; 25:171-91. [PMID: 21236397 DOI: 10.1016/j.hoc.2010.11.012] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
The herpes viruses are responsible for a wide range of diseases in patients following transplant, resulting from direct viral effects and indirect effects, including tumor promotion. Effective treatments and prophylaxis exist for the neurotropic herpes viruses HSV-1, HSV-2, varicella zoster virus, and possibly HHV-6. Antivirals seem to be less effective at prevention of the tumor-promoting effects of Epstein-Barr virus and HHV-8. Reduction in immunosuppression is the cornerstone to treatment of many diseases associated with herpes virus infections.
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30
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Weigand K, Schnitzler P, Schmidt J, Chahoud F, Gotthardt D, Schemmer P, Stremmel W, Sauer P. Cytomegalovirus infection after liver transplantation incidence, risks, and benefits of prophylaxis. Transplant Proc 2010; 42:2634-2641. [PMID: 20832559 DOI: 10.1016/j.transproceed.2010.04.025] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2009] [Revised: 10/16/2009] [Accepted: 04/21/2010] [Indexed: 01/08/2023]
Abstract
BACKGROUND Cytomegalovirus (CMV) infection and related disease is a feared complication after liver transplantation. Antiviral prophylaxis is recommended in clinical practice guidelines depending on the CMV status of both donor and recipient as well as the individual risk profile. METHODS We retrospectively analyzed 211 liver transplant recipients with respect to the incidence of CMV infection after transplantation, the influence of donor and recipient CMV status, and the effect of antiviral prophylaxis. In addition, the underlying liver disease and immunosuppressive regimen were compared with the incidence of CMV infection. Patients were divided into 4 groups according to CMV donor/recipient (D/R) profile: group A (D-/R-) 28 patients (13.3%), group B (D-/R+) 64 patients (30.3%), group C (D+/R+) 79 patients (37.4%), and group D (D+/R-) 40 patients (19.0%). RESULTS CMV infection was observed in 17.9%, 29.7%, 24.1%, and 22.5% of the patients, respectively, with no significant difference in infection rates between the groups. CMV infection occurred in 5 patients (17.9%) in the presumed low-risk profile (group A), despite an antiviral prophylaxis in 4 out of these 5 patients. In contrast, CMV infection occurred in only 9/40 patients (22.5%) in the presumed high-risk profile (group D). The most frequent infection rates were found in groups B and C (R+ groups). After successful treatment of CMV infection, no recurrence was detected. Underlying liver disease or immunosuppressive protocol had no influence on CMV infection. CONCLUSION Approximately one fourth of patients will acquire CMV infection after liver transplantation independent of donor/recipient status. Surprisingly, antiviral prophylaxis does not seem to be sufficient to reduce this proportion of patients, either in presumed high-risk or in presumed low-risk situations.
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Affiliation(s)
- K Weigand
- Department of Gastroenterology and Hepatology, University Hospital Heidelberg, Germany.
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31
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Shiley K, Blumberg E. Herpes Viruses in Transplant Recipients: HSV, VZV, Human Herpes Viruses, and EBV. Infect Dis Clin North Am 2010; 24:373-93. [DOI: 10.1016/j.idc.2010.01.003] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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32
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Zuckerman R, Wald A. Herpes simplex virus infections in solid organ transplant recipients. Am J Transplant 2009; 9 Suppl 4:S104-7. [PMID: 20070669 DOI: 10.1111/j.1600-6143.2009.02900.x] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Affiliation(s)
- R Zuckerman
- Department of Medicine, Section of Infectious Disease and International Health, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA
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33
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Nagro F, Pacchiionl D, Meadardini A, Bussolati G, Bonine F. In situ hybridizaiton in Viral hepatitis. ACTA ACUST UNITED AC 2008. [DOI: 10.1111/j.1600-0676.1992.tb01052.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
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Stollenwerk N, Harper RW, Sandrock CE. Bench-to-bedside review: rare and common viral infections in the intensive care unit--linking pathophysiology to clinical presentation. CRITICAL CARE : THE OFFICIAL JOURNAL OF THE CRITICAL CARE FORUM 2008; 12:219. [PMID: 18671826 PMCID: PMC2575602 DOI: 10.1186/cc6917] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Viral infections are common causes of respiratory tract disease in the outpatient setting but much less common in the intensive care unit. However, a finite number of viral agents cause respiratory tract disease in the intensive care unit. Some viruses, such as influenza, respiratory syncytial virus (RSV), cytomegalovirus (CMV), and varicella-zoster virus (VZV), are relatively common. Others, such as adenovirus, severe acute respiratory syndrome (SARS)-coronavirus, Hantavirus, and the viral hemorrhagic fevers (VHFs), are rare but have an immense public health impact. Recognizing these viral etiologies becomes paramount in treatment, infection control, and public health measures. Therefore, a basic understanding of the pathogenesis of viral entry, replication, and host response is important for clinical diagnosis and initiating therapeutic options. This review discusses the basic pathophysiology leading to clinical presentations in a few common and rare, but important, viruses found in the intensive care unit: influenza, RSV, SARS, VZV, adenovirus, CMV, VHF, and Hantavirus.
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Affiliation(s)
- Nicholas Stollenwerk
- Division of Pulmonary and Critical Care Medicine, University of California-Davis School of Medicine, Davis, CA, USA
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36
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Lima R, Santos P, Malafronte P, Muller H, Caiaffa-Filho H, Sens Y. Oral Manifestation of Cytomegalovirus Associated With Herpes Simplex Virus in Renal Transplant Recipient. Transplant Proc 2008; 40:1378-81. [DOI: 10.1016/j.transproceed.2008.03.138] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2007] [Accepted: 03/06/2008] [Indexed: 10/21/2022]
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Wilson SR, Wilson JH, Buonocore L, Palin A, Rose JK, Reuter JD. Intranasal immunization with recombinant vesicular stomatitis virus expressing murine cytomegalovirus glycoprotein B induces humoral and cellular immunity. Comp Med 2008; 58:129-139. [PMID: 18524170 PMCID: PMC2703170] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2007] [Revised: 11/10/2007] [Accepted: 11/29/2007] [Indexed: 05/26/2023]
Abstract
Cytomegalovirus is a leading cause of morbidity and mortality among neonatal and immunocompromised patients. The use of vaccine prophylaxis continues to be an effective approach to reducing viral infections and their associated diseases. Murine cytomegalovirus (mCMV) has proven to be a valuable animal model in determining the efficacy of newly developed vaccine strategies in vivo. Live recombinant vesicular stomatitis viruses (rVSV) have successfully been used as vaccine vectors for several viruses to induce strong humoral and cellular immunity. We tested the ability of intranasal immunization with an rVSV expressing the major envelope protein of mCMV, glycoprotein B (gB), to protect against challenge with mCMV in a mouse model. rVSV-gB-infected cells showed strong cytoplasmic and cell surface expression of gB, and neutralizing antibodies to gB were present in mice after a single intranasal vaccination of VSV-gB. After challenge with mCMV, recovery of live virus and viral DNA was significantly reduced in immunized mice. In addition, primed splenocytes produced a CD8+ IFNgamma response to gB. The ability to induce an immune response to a gene product through mucosal vaccination with rVSV-gB represents a potentially effective approach to limiting CMV-induced disease.
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Affiliation(s)
- Steven R Wilson
- Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA.
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38
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Egli A, Bergamin O, Müllhaupt B, Seebach J, Mueller N, Hirsch H. Cytomegalovirus-associated chorioretinitis after liver transplantation: case report and review of the literature. Transpl Infect Dis 2008; 10:27-43. [DOI: 10.1111/j.1399-3062.2007.00285.x] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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Castón JJ, Cisneros JM, Torre-Cisneros J. [Effects of viral infection on transplant recipients]. Enferm Infecc Microbiol Clin 2008; 25:535-48. [PMID: 17915112 PMCID: PMC7130329 DOI: 10.1157/13109990] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
Viral infection remains an important cause of morbidity and mortality in transplant recipients. The risk of viral infection in these patients depends on several factors, such as the type of organ transplanted, the intensity of immunosuppression, and the recipient's susceptibility. In additional to direct effects, viral infection cause indirect effects, including greater risk of replication of other viruses, graft rejection, opportunistic infections and other specific entities for each type of transplant. These indirect effects result from the immunomodulatory activity of some viruses, such as cytomegalovirus and human herpes virus-6. For the most part, quantitative molecular tests have replaced serologic testing and in vitro culture for diagnosing infection. This approach is particularly prominent for cytomegalovirus, Epstein-Barr virus, hepatitis B virus, and hepatitis C virus. Despite these diagnostic advances, the development of specific antiviral agents and effective antiviral vaccines is limited. Thus, prophylactic strategies are still essential in transplant recipients.
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Affiliation(s)
- Juan José Castón
- Unidad Clínica de Enfermedades Infecciosas. Hospital Universitario Reina Sofía. Córdoba. España
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40
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Sneller MC, Lane HC. Infections in the immunocompromised host. Clin Immunol 2008. [DOI: 10.1016/b978-0-323-04404-2.10031-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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41
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Norvell JP, Blei AT, Jovanovic BD, Levitsky J. Herpes simplex virus hepatitis: an analysis of the published literature and institutional cases. Liver Transpl 2007; 13:1428-34. [PMID: 17902129 DOI: 10.1002/lt.21250] [Citation(s) in RCA: 168] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Hepatitis is a rare complication of herpes simplex virus (HSV), often leading to acute liver failure (ALF), liver transplantation (LT), and/or death. Our aim was to identify variables associated with either survival or progression (death/LT), based on an analysis of cases in the literature and our institution. A total of 137 cases (132 literature, 5 institutional) of HSV hepatitis were identified. The main features at clinical presentation were fever (98%), coagulopathy (84%), and encephalopathy (80%). Rash was seen in less than half of patients. Most cases (58%) were first diagnosed at autopsy and the diagnosis was suspected clinically prior to tissue confirmation in only 23%. Overall, 74% of cases progressed to death or LT, with 51% in acyclovir-treated patients as compared to 88% in the untreated subjects (P=0.03). Variables on presentation associated with death or need for LT compared to spontaneous survival: male gender, age>40 yr, immunocompromised state, ALT>5,000 U/L, platelet count<75x10(3)/L, coagulopathy, encephalopathy, and absence of antiviral therapy. In conclusion, HSV hepatitis has a high mortality and is often clinically unsuspected. Patients who are male, older, immunocompromised, and/or presenting with significant liver dysfunction are more likely to progress to death and should thus be evaluated for LT early. Based on the frequent delay in HSV diagnosis, low risk-benefit ratio, and significantly improved outcomes, empiric acyclovir therapy for patients presenting with ALF of unknown etiology is recommended until HSV hepatitis is excluded.
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Affiliation(s)
- John P Norvell
- Department of Internal Medicine, Division of Hepatology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
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42
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Adams PL. The Kidney Transplant Recipient: Identification and Preparation. Semin Dial 2007. [DOI: 10.1111/j.1525-139x.1992.tb00484.x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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43
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Transmission of viral disease to the recipient through the donor liver. Curr Opin Organ Transplant 2007; 12:231-241. [DOI: 10.1097/mot.0b013e32814e6b67] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
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Abstract
Herpesvirus infections are common complications of organ transplantation. The most frequent herpesvirus infections are caused by cytomegalovirus (CMV), herpes simplex (HSV) and varicella zoster (VZV). Despite expansion of the therapeutic armamentarium, HSV and VZV continue to cause morbidity and occasional mortality in transplant recipients. Here we review the incidence and risk factors for HSV and VZV disease, their clinical presentation, effects of newer immunosuppressive regimens and prophylaxis for HSV and VZV in solid organ transplant recipients.
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Affiliation(s)
- G G Miller
- Department of Medicine, Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
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Nebbia G, Mattes FM, Ramaswamy M, Quaglia A, Verghese G, Griffiths PD, Burroughs A, Geretti AM. Primary herpes simplex virus type-2 infection as a cause of liver failure after liver transplantation. Transpl Infect Dis 2006; 8:229-32. [PMID: 17116138 DOI: 10.1111/j.1399-3062.2006.00144.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
We report a case of fatal primary herpes simplex virus type-2 (HSV-2) infection following liver transplantation, which manifested with fever and liver failure in the absence of muco-cutaneous disease. The infection was characterized by high levels of HSV DNA in blood and the patient's inability to mount HSV-specific T-cell responses while showing preserved T-cell responses against cytomegalovirus. The donor was HSV-1 immunoglobulin G (IgG) seronegative and HSV-2 IgG seropositive, whereas the recipient was HSV-1 and HSV-2 IgG seronegative, suggesting that the graft may have been the source of the infection. In HSV-seronegative recipients of grafts from HSV-seropositive donors, HSV infection should be included in the differential diagnosis of a febrile illness, regardless of the absence of muco-cutaneous disease. In this setting, real-time polymerase chain reaction applied to blood samples provides a sensitive, rapid, and quantitative diagnostic tool.
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Affiliation(s)
- G Nebbia
- Department of Virology, Royal Free and University College Hospital, London, UK
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46
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Duckro AN, Sha BE, Jakate S, Hayden MK, Simon DM, Saltzberg SN, Arai S, Kessler HA. Herpes simplex virus hepatitis: expanding the spectrum of disease. Transpl Infect Dis 2006; 8:171-6. [PMID: 16913977 DOI: 10.1111/j.1399-3062.2006.00133.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
We describe 2 transplant patients with herpes simplex virus (HSV) hepatitis who were minimally symptomatic throughout their illness. The spectrum of disease caused by HSV hepatitis is more variable than previously reported in this population. HSV hepatitis should be considered in immunocompromised hosts with elevated transaminases without evidence of fulminant hepatic necrosis.
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Affiliation(s)
- A N Duckro
- Department of Medicine, Section of Infectious Diseases, Rush University Medical Center, 600 S. Paulina, Chicago, IL 60612, USA
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47
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Díaz-Pedroche C, Lumbreras C, San Juan R, Folgueira D, Andrés A, Delgado J, Meneu JC, Morales JM, Moreno-Elola A, Hernando S, Moreno-González E, Aguado JM. Valganciclovir preemptive therapy for the prevention of cytomegalovirus disease in high-risk seropositive solid-organ transplant recipients. Transplantation 2006; 82:30-5. [PMID: 16861938 DOI: 10.1097/01.tp.0000225830.76907.d0] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
BACKGROUND The role of valganciclovir in the prevention of cytomegalovirus (CMV) disease in high-risk seropositive transplant patients is not known. METHODS We prospectively followed 301 seropositive solid organ transplant recipients to assess the efficacy and safety of valganciclovir (VGCV) in the prevention of CMV disease in high-risk patients. Asymptomatic patients with an antigenemia test >or=25 positive cells/2x10(5) polymorphonuclear cells received valganciclovir 900 mg twice a day as preemptive therapy until resolution of antigenemia (minimum 14 days). Additionally, patients treated with antilymphocytic drugs for more than 6 days received prophylaxis with VGCV 900 mg once a day during 90 days. Mean follow-up was 14 months (range 6-20 months). RESULTS Thirty-eight patients received VGCV; 24 as preemptive therapy and 14 due to the use of antilymphocytic drugs. No patient developed CMV disease during the follow-up. Viral load (antigenemia) decreased a mean of 78% from baseline after 7 days of VGCV therapy (P=0.024) and 98% at day 14 (P=0.029). Two patients showed a relapse of the antigenemia test >or=25 positive cells and were successfully treated with a repeated course of VGCV. Leukopenia (<2500/mm3) developed in 3/24 (12.5%) recipients in the preemptive therapy group and required to discontinuing the drug in one of them. CONCLUSIONS VGCV is safe and highly efficacious in the prevention of CMV disease in high-risk seropositive organ transplant recipients.
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Affiliation(s)
- Carmen Díaz-Pedroche
- Infectious Diseases Unit, Hospital Universitario Doce de Octubre, Universidad Complutense, Madrid, Spain
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Abstract
Despite the progress made in graft and patient survival in recent years, infectious complications remain a major source of morbidity and mortality in pediatric solid organ transplant recipients. The risk of infection after transplant is determined by the interaction of several factors, including age, type of organ transplanted, type and intensity of immunosuppression, environmental exposures, and the consequences of invasive procedures. Compared with adult transplant recipients, children are at higher risk of developing primary infection with various organisms after transplantation, as they often lack previous immunity from natural exposure to many microbes and often have not completed their primary immunization series at the time of transplantation. This article provides an overview of the risk factors, timing, and types of infectious complications associated with organ transplantation in children.
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Affiliation(s)
- Monica Fonseca-Aten
- Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Marian G. Michaels
- Division of Allergy, Immunology and Infectious Diseases, Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania
- Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
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49
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Campsen J, Hendrickson R, Bak T, Wachs M, Kam I, Nash R, Russ P, Levi M. Herpes simplex in a liver transplant recipient. Liver Transpl 2006; 12:1171-3. [PMID: 16799938 DOI: 10.1002/lt.20823] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Jeffrey Campsen
- Department of Surgery, University of Colorado Health Sciences Center, Denver, CO 80262, USA
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50
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Humar A, Michaels M. American Society of Transplantation recommendations for screening, monitoring and reporting of infectious complications in immunosuppression trials in recipients of organ transplantation. Am J Transplant 2006; 6:262-74. [PMID: 16426310 DOI: 10.1111/j.1600-6143.2005.01207.x] [Citation(s) in RCA: 375] [Impact Index Per Article: 19.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
In recent years, major progress has been made in the development, investigation and clinical application of novel immunosuppressive drug therapies to prevent acute rejection. Critical to the ultimate clinical application of new drug therapies is the ongoing performance of large multi-center clinical trials. However, there has been a paucity of infectious disease monitoring built into these protocols. Given that infectious complications are a major source of morbidity and mortality in transplant recipients, the assessment of the magnitude of risk of infection associated with a given immunosuppressive strategy may be as important as the assessment of rejection. For the above reasons, screening, monitoring and reporting recommendations for common transplant-associated infections were developed for use in clinical trials evaluating immunosuppressive strategies. These recommendations have two major goals: (i) to provide clinically relevant definitions for tracking infectious complications occurring in participants in immunosuppressive trials and (ii) where appropriate, to recommend specific laboratory monitoring and surveillance methods.
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