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Acute cytomegalovirus infection in liver transplant recipients:An independent risk for venous thromboembolism

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World Journal of Hepatology 2013年第12期5卷 692-695页

作者： Raja GR Edula Kamran Qureshi Hicham Khallafi Department of Medicine Division of Gastroen-terology and HepatologyRutgers New Jersey School of Medi-cineNewark Department of Hepatology Florida Hospital Transplant Center

Acute cytomegalovirus(CMV) infection is a commonly encountered complication in the post liver transplant setting. We present a case of a 71-year-old male with acute CMV infection, initially presenting with a gastro- intestinal bleed due to acute CMV gastritis and later on complicated by acute venous thromboembolism occur- ring as an unprovoked event in the post liver transplant period. Traditional risk factors for venous thromboem- bolism have been well described in the medical litera- ture. Sporadic cases of thromboembolism due to CMV infection in the immune compromised patients have been described, especially in the post kidney transplant patients. Liver transplant recipients are equally prone to CMV infection particularly in the first year after suc- cessful transplantation. Venous thromboembolism in this special population is particularly challenging due to the fact that these patients may have persistent throm- bocytopenia and anticoagulation may be a challenge for the treating physician. Since liver transplantation is severely and universally limited by the availability of donor organs, we feel that this case report will provide valuable knowledge in the day to day management of these patients, whose clinical needs are complex and require a multidisciplinary approach in their care and management. Evidence and pathophysiology link- ing both the conditions is presented along with a brief discussion on the management, common scenarios en- countered and potential impact in this special group of patients.

关键词： cytomegalovirus Venous thromboembo-lism Orthotopic liver transplantation Thrombocytope-nia Hypersplenism

Systemic review and meta-analysis of the association between cytomegalovirus and autoimmune diseases

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Systemic review and meta-analysis of the association between...

Effect of cytomegalovirus infection on cholesterol metabolism

第十一届全国免疫学学术大会

作者： Zheng Qi Lu Meiping Children’s Hospital Zhejiang University School of Medicine

Objective: Infection with cytomegalovirus(CMV) has been considered as one of the major environmental factor that contributes to the pathogenesis of autoimmune diseases, including diabetes(DM), rheumatoid arthritis(RA) and systemic lupus erythematosus(SLE). We sought to determine whether the prevalence of CMV infection occurs more frequently in patients with common autoimmune diseases compared to controls. Methods: We conducted a computerized literature search of the MEDLINE database using the terms "cytomegalovirus" with "diabetes mellitus" or "systemic lupus erythematosus" or "rheumatoid arthritis". Odds ratio(OR) with 95% confidence interval(CI) was used to assess the strength of association between the incidence of HCMV infection and diabetes risk. Funnel plot asymmetry was assessed by the method of Egger’s linear regression test. All of the calculations were performed using STATA version 11.0(STATA Corporation, College Station, TX, USA).Results: Twenty-four studies were included, in which six publications involving 1290 diabetes cases and 1103 controls, eleven publications involving 736 SLE patients and 1060 controls and seven publications involving 283 RA cases and 285 controls met the criteria were analyzed. There was no significant association between CMV infection and DM(odds ratio(OR) of 1.96(95% confidence interval(CI) 0.99-3.90, p=0.000). While positive association was displayed in RA and SLE patients. Patients with RA compared to controls with an OR of 2.49(95% CI 1.75-3.55, p=0.056), SLE with an OR 2.41(95% CI 1.91-3.04, p=0.000). Conclusion: Above all, these findings do not demonstrate an association between CMV infection and DM, therefore do not support the hypothesis that prior CMV infection predisposes to the development of DM, but indicate positive relation with CMV infection toRA and SLE pathogenesis.

关键词： Autoimmune disease cytomegalovirus Meta-analysis

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Effect of cytomegalovirus infection on cholesterol metabolis...

A Case of cytomegalovirus-Induced Arthritis after Lymphocyte-Depleting Therapy for Kidney Allograft Rejection

第十三届江浙沪儿科学术会议暨2016年浙江省医学会儿科...

作者：沈一燚刘志峰金玉郑必霞王春莉郭红梅朱梦姝南京医科大学附属南京儿童医院消化科

Objective:Combination with the effect of cytomegalovirus infection on lipid metabolism,we explore whether the cytomegalovirus infection can affect the expression of key enzymes in bile acid synthesis and related proteins of bile acid metabolism,such as CYP7 A1、CYP27 A1、 BSEP and NTCP apart from directly harm liver cells and bile duct,to study the mechanism of cholestasis Method:Newborn mice was infected with MCMV and observe the influence of the MCMV infection on the expression of CYP7 A1、 CYP27 A1、BSEP and NTCP,to further explore the mechanism of cholestasis caused by MCMV infection Result:The growth of mice in experimental group was worse than that of control group.The weight of the MCMV infected group was significantly lower than that of the control group at 3、 7 and 14 days(t=2.339,p<0.05).Besides,inflammatory cell infiltration、 the larger volume of liver cells and the necrosis cells could be observed in part of liver pathological sections of CMV infected mice.The Serological levers of ALT(t=3.217,p<0.01) and LDL(t=2.575,p<0.05) in the experimental group was significantly higher than that of the control group.The HDL levers were significantly lower in the experimental group(t=2.235,p<0.05).The expression of CYP7 A1(t=2.038,p<0.05),CYP27 A1(t=2.223,p<0.05),NTCP(t=2.883,p<0.05) and BSEP(t=2.322,p<0.05) were significantly decreased in MCMV infected mice.Conclusion:The MCMV infection mice shows liver damage,liver function and abnormal lipid metabolism.The CYP7 A1 and CYP27 A1 expression is reduced in MCMV infected mice,which inhibit serum cholesterol metabolism and result in abnormal lipid metabolism.Also the expression of BSEP and NTCP decreased in the experimental group,leading to bile acid metabolism abnormalities.

关键词： cytomegalovirus CYP7A1 CYP27A1 BSEP NTCP

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Open Journal of Nephrology 2012年第1期2卷 1-4页

作者： Richard Fuquay James Eric Cooper Health Science Center Division of Renal Diseases and Hypertension Transplant Center University of Colorado Denver Aurora USA Health Science Center Division of Renal Diseases and Hypertension University of Colorado Denver Aurora USA

cytomegalovirus viremia and tissue-invasive disease are common after kidney transplantation. Chemoprophylaxis has made substantial improvement in this clinical problem. Here we report a 29-year-old woman who had kidney allograft rejection and received lymphocyte-depleting therapy. She presented with a new oligo-arthritis that led to 2 successive arthrocenteses. The etiology of the inflammation could not be determined initially. On the second arthrocentesis, a synovial fluid cytomegalovirus polymerase chain reaction test was positive. The patient responded to treatment with valganciclovir, had negative follow-up serum cytomegalovirus polymerase chain reaction tests, and experienced resolution of her joint inflammation. We review briefly the data for cytomegalovirus chemoprophylaxis, preemptive screening, and treatment recommendations.

关键词： cytomegalovirus (Mesh) Arthritis (Mesh) Kidney Transplantation (Mesh) Immunosuppression (Mesh) Chemoprevention (Mesh) Valganciclovir (Mesh)

Current concepts on cytomegalovirus infection after liver transplantation

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World Journal of Hepatology 2010年第9期2卷 325-336页

作者： Sang-Oh Lee Raymund R Razonable Division of Infectious Diseases College of Me dicineMayo ClinicRochester Department of Infectious Diseases Asan Medical CenterUniv ersity of Ulsan College of Medicine Division of Infectious Diseases and the William J von Liebig Transplant Center College of MedicineMayo ClinicRochester

cytomegalovirus (CMV) is the most common viral pa- thogen that negatively impacts on the outcome of liver transplantation. CMV cause febrile illness often ac com panied by bone marrow suppression, and in some cases, invades tissues including the transplanted allog raft. In addition, CMV has been signif icantly asso- ciated with an increased predisposition to allograft re- jection, accelerated hepatitis C recurrence, and other opportunistic infections, as well as reduced overall pa tient and allograft survival. To negate the adverse effects of CMV on outcome, its prevention, whether through antiviral prophylaxis or preemptive therapy, is regarded as an essential component to the medical management of liver transplant patients. Two recent guidelines have suggested that antiviral prophylaxis or preemptive therapy are similarly effective in preventing CMV disease in modest-risk CMV-seropositive liver trans plant recipients, while antiviral prophylaxis is the preferred strategy over preemptive therapy for the preven tion of CMV disease in high-risk recipients [CMV-ser o-negative recipients of liver allografts from CMV-seropositive donors (D+/R-)]. However, antiviral prophylax is has only delayed the onset of CMV disease in many CMV D+/R- liver transplant recipients, and at least in one study, such occurrence of late-onset primary CMV disease was significantly associated with increased mortality after liver transplantation. Therefore, optimized strategies for prevention are needed, and aggressive treatment of CMV infection and disease should be pursued. The standard treatment of CMV disease consists of intravenous ganciclovir or oral valganciclovir, and if fea sible, one should also reduce the degree of immuno-suppression. In one recent controlled clinical trial, val ganc iclovir was found to be as effective and safe as intravenous ganciclovir for the treatment of mild to mo d erate CMV disease in solid organ (including liver) tran splant recipients. In this article, the authors review the current state and the future

关键词： cytomegalovirus Outcome Hepatitis Transplantation Valganciclovir Prophylaxis Treatment

Cecal vanishing tumor associated with cytomegalovirus infection in an immunocompetent elderly adult

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World Journal of Gastrointestinal Oncology 2010年第11期2卷 417-420页

作者： Shinsuke Kawasaki Satoshi Osawa Ken Sugimoto Takahiro Uotani Masafumi Nishino Takanori Yamada Mitsushige Sugimoto Takahisa Furuta Mutsuhiro Ikuma First Department of Medicine Hamamatsu University School of Medicine 1-20-1 Handayama Higashi-ku Hamamatsu 431-3192 Japan Center for Clinical Research Hamamatsu University School of Medicine 1-20-1 Handayama Higashi-ku Hamamatsu 431-3192 Japan

Gastrointestinal involvement in cytomegalovirus (CMV) infection is well documented among immunocompromised patients and is also observed in immunocompetent individuals. The presentation of this infection can sometimes mimic those of other diseases, thus making accurate diagnosis difficult. We herein report a rare case of an immunocompetent elderly adult with gastrointestinal CMV infection that presented as a vanishing tumor at the cecum. A 76-year old man initially presented with lower abdominal pain. Colonoscopy revealed a tumorous lesion with irregular ulceration observed at the ileocecal valve. Histological findings of a biopsy specimen revealed intranuclear inclusions which were positive for CMV on immunohistochemical staining. However, this tumorous lesion disappeared within 7 wk from the initialhospital visit without any further treatment. Inflammatory pseudotumors associated with CMV infection should be considered as a differential diagnosis of tumorous lesions in the colon, even in immunocompetent adults.

关键词： cytomegalovirus colitis Vanishing tumor Elderly adult Inflammatory pseudotumor Immunocompetent host

DETECTION OF cytomegalovirus(CMV) IMMEDIATE EARLY ANTIGEN IN KIDNEY BIOPSIES AND TRANSPLANT NEPHRECTOMIES

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Journal of Pharmaceutical Analysis 2004年第1期16卷 88-91页

作者：燕航薛武军田普训郭奇何晓丽 Department of Renal Transplantation

Objective To investigate the relationship between CMV infection and renal allograft rejection. Methods 39 kidney biopsies and transplant nephrectomies were collected and investigated for CMV immediate early antigen by immunohistochemistry. Results In 14 out of 39 tissue specimens CMV immediate early antigen were found. 8 biopsies from normal donor kidneys were negative; only 1 (10%) in 10 tissue specimens with early stage acute rejection was positive; 5(55.6%) in 9 biopsies with late stage acute rejection and 8 (66.7%) in 12 tissue blocks with chronic rejection were positive. Compared with normal kidney tissues, the infections in tissues with early stage acute rejection didn't increase obviously, but increased obviously in kidney tissue specimens with late stage rejection and with chronic rejection (P< 0.05). Conclusion CMV infection appears to contribute to late stage acute rejection and chronic rejection after renal transplantation.

关键词： renal transplantation cytomegalovirus immunohistochemistry immediate early antigen allograft rejection

A ModelSystem of Prim ary Murine Hepatocytes Infected byMurine Cytom egalovirus

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Journal of Huazhong University of Science and Technology(Medical Sciences) 1999年第3期19卷 185-189页

作者： FANG Feng , NIE Xingcao , LI Ge Department of Pediatrics, Tongji Hospital, Tongji Medical University, Wuhan 430030 Department of Pediatrics Tongji Hospital Tongji Medical University Wuhan 430030

In order to establish a model system of the murine hepatocyte infection by murine cytomegalovirus (MCMV), the primary cultured murine hepatocytes were obtained in a modified low serum medium system by a non perfusion method, and then infected by Smith strain MCMV. Infected hepatocytes showed characteristic cytopathic effect (CPE) at 30 h after infection, in which a large number of viral particles was found and ultrastructures were destroyed (as revealed by disappearance of bile canalicula and organelles) under the electron microscope and MCMV immediate early genes were detected by in situ hybridization. Meanwhile, infected cells produced albumin significantly less than corresponding uninfected controls. On the contrary, uninfected controls simultaneously cultured under the same conditions showed normal function and ultratructure (glycogen rosettes, bile canalicula, wheel like mitochondria and well developed rough and smooth endoplasmic reticula). These results demonstrated that a model system of primary cultured murine hepatocytes infected by MCMV was successfully set up.

关键词： primary culture murine hepatocyte cytomegalovirus model

Pulmonary cytomegalovirus infection:A case report and systematic review

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World Journal of Meta-Analysis 2023年第5期11卷 151-166页

作者： Awotar Kanika Jonathan Soldera Department of Acute Medicine University of South WalesCardiff CF371DLUnited Kingdom

BACKGROUND cytomegalovirus(CMV)is a common virus that can cause the first infection in childhood or adolescence and reactivate later in life due to immunosuppression.CMV pneumonia is a rare illness in immunocompetent patients but is one of the most significant opportunistic infections in immunocompromised patients.AIM To report a case and review published cases of pulmonary CMV infection in both immunocompromised and immunocompetent patients.METHODS We conducted a systematic search on the MEDLINE(PubMed)database,without date or language restrictions,to identify relevant studies using Medical Subject Headings and Health Science Descriptors.We manually searched the reference lists of the included studies.Simple descriptive analysis was used to summarize the results.RESULTS Our search identified 445 references,and after screening,43 studies reporting 45 cases were included in the final analysis,with 29(64%)patients being immunocompromised and 16(36%)being immunocompetent.Fever(82%)and dyspnea(75%)were the most common clinical findings.Thoracic computed tomography showed bilateral ground-glass opacities,a relevant differential diagnosis for severe acute respiratory syndrome coronavirus 2 infection.The majority of patients(85%)received antiviral therapy,and 89%of patients recovered,while 9%of patients died.CONCLUSION CMV pneumonia should be considered as a differential diagnosis for coronavirus disease 2019 pneumonia,especially in immunocompromised patients.Clinicians should be aware of the clinical presentation,management,and outcomes of CMV pneumonia to guide appropriate treatment decisions.

关键词： cytomegalovirus Immunocompromised Immunocompetent Severe acute respiratory syndrome coronavirus 2 Coronavirus disease 2019 Ganciclovir