Management of cytomegalovirus infection after liver transplantation

Cytomegalovirus(CMV)infection is one of the primary causes of morbidity and mortality following liver transplantation(LT).Based on current worldwide guidelines,the most effective strategies for avoiding post-transplant CMV infection are antiviral prophylaxis and pre-emptive treatment.CMV-IgG serology is the established technique for pretransplant screening of both donors and recipients.The clinical presentation of CMV infection and disease exhibits variability,prompting clinicians to consistently consider this possibility,partic-ularly within the first year post-transplantation or subsequent to heightened immunosuppression.At annual symposia to discuss CMV prevention and how treatment outcomes can be improved,evidence on the incorporation of immune functional tests into clinical practice is presented,and the results of studies with new antiviral treatments are evaluated.Although there are ongoing studies on the use of letermovir and maribavir in solid organ transplantation,a consensus reflected in the guidelines has not been formed.Determining the most appro-priate strategy at the individual level appears to be the key to enhancing out-comes.Although prevention strategies reduce the risk of CMV disease,the disease can still occur in up to 50%of high-risk patients.A balance between the risk of infection and disease development and the use of immunosuppressants must be considered when talking about the proper management of CMV in solid organ transplant recipients.The objective of this study was to establish a compre-hensive framework for the management of CMV in patients who have had LT.

Cytomegalovirus infection in non-immunocompromised critically ill patients:A management perspective

Critically ill patients are a vulnerable group at high risk of developing secondary infections.High disease severity,prolonged intensive care unit(ICU)stay,sepsis,and multiple drugs with immunosuppressive activity make these patients prone to immuneparesis and increase the risk of various opportunistic infections,including cytomegalovirus(CMV).CMV seroconversion has been reported in up to 33%of ICU patients,but its impact on patient outcomes remains a matter of debate.Even though there are guidelines regarding the management of CMV infection in immunosuppressive patients with human immunodeficiency virus/acquired immuno deficiency syndrome,the need for treatment and therapeutic approaches in immunocompetent critically ill patients is still ambiguous.Even the diagnosis of CMV infection may be challenging in such patients due to non-specific symptoms and multiorgan involvement.Hence,a better understanding of the symptomatology,diagnostics,and treatment options may aid intensive care physicians in ensuring accurate diagnoses and instituting therapeutic interventions.

外周血CD4^(+)CD25^(+)Treg细胞、TLR4、hCMV-IgM与动脉粥样硬化型急性脑梗死患者颈动脉粥样硬化的关系

目的探讨外周血CD4^(+)CD25^(+)Treg细胞、TLR4、人巨细胞病毒(hCMV)-IgM与动脉粥样硬化型急性脑梗死(As-ACI)患者颈动脉粥样硬化的关系。方法选取89例As-ACI患者(脑梗死组),另选取健康体检者43例(对照组)。根据颈内动脉超声结果将As-ACI患者分为内膜正常组、内膜增厚组、斑块组、狭窄组。比较各组外周血CD4^(+)CD25^(+)Treg细胞水平、单个核细胞TLR4表达水平、hCMV-IgM抗体阳性率和内膜中膜厚度(IMT)。分析As-ACI患者颈动脉狭窄的危险因素,分析CD4^(+)CD25^(+)Treg细胞、TLR4与IMT的相关性及其对颈动脉狭窄的预测价值。结果脑梗死组CD4^(+)CD25^(+)Treg细胞、HDLC水平低于对照组,TLR4表达、hCMV-IgM抗体阳性率、TC、TG、LDLC、hs-CRP水平、IMT高于对照组(P<0.05)。内膜正常组、内膜增厚组、斑块组、狭窄组CD4^(+)CD25^(+)Treg细胞水平依次降低,TLR4表达、hCMV-IgM抗体阳性率、IMT依次增高(P<0.05)。CD4^(+)CD25^(+)Treg细胞水平与IMT呈负相关,TLR4表达与IMT呈正相关(P<0.05)。高血压、CD4^(+)CD25^(+)Treg表达、TLR4表达、hCMV-IgM抗体阳性是As-ACI患者颈动脉狭窄的危险因素(P<0.05)。CD4^(+)CD25^(+)Treg细胞、TLR4表达水平联合检测的预测价值高于单独检测(P<0.05)。结论外周血CD4^(+)CD25^(+)Treg细胞、TLR4、hCMV-IgM抗体阳性率与As-ACI患者颈动脉粥样硬化进展有关,外周血CD4^(+)CD25^(+)Treg细胞、TLR4联合可以较好预测病变过程。

Pulmonary cytomegalovirus infection:A case report and systematic review

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.

The Prevalence of Human Cytomegalovirus Viremia among HIV-1 Infected Individuals Undergoing Antiretroviral Therapy

HIV infection is an emerging health issue in Libya, particularly among young adults. Human cytomegalovirus (HCMV) is a prevalent infectious agent that presents with subclinical and fatal diseases in immunosuppressed individuals including HIV-infected individuals. Although the impact of HCMV infection in HIV-positive patients is well documented in several regions, epidemiologic estimates concerning HCMV co-infection among HIV-infected individuals remain limited in Libya. Hence, this cross-sectional study was undertaken to derive data regarding the prevalence of active HCMV viremia among HIV-infected individuals undergoing antiretroviral therapy (ART) from Libya. A total of 90 consented HIV-infected subjects followed by the National Center for Disease Control (NCDC) of Benghazi/Libya were recruited in this study and investigated for HCMV-IgG, HCMV-IgM specific antibodies, detection of HCMV lower matrix phosphoprotein (pp65) antigen, and detection of HCMV-DNA using qPCR to assess the prevalence of HCMV viremia. We determined that 77 (85.56%) of subjects were seropositive for HCMV-IgG antibodies, whereas the seropositivity for HCMV-IgM was 3.33% (3/90 subjects). Our results also revealed that 4.44% (4/90) of participants had viral antigenemia based on the laboratory diagnosis of HCMV-pp65. Regarding the PCR, we were able to detect the DNA of HCMV only in 3/90 subjects (3.33%) suggesting an active viremic condition. The detection of HCMV DNA along with the HCMV-pp65 in HIV-positive individuals highlights the necessity of early diagnosis to manage the progression of the disease. Furthermore, we highly recommend the use of anti-HCMV therapy in viremic individuals in combination with ART to reduce the burden of HCMV complications.

Destructive effects on endothelial cells of grafts in cytomegalovirus DNA-positive patients after keratoplasty

AIM:To investigate corneal graft survival rate and endothelial cell density(ECD)loss after keratoplasty in cytomegalovirus(CMV)positive patients.METHODS:This was a retrospective cohort study.We analyzed the clinical data of patients who underwent viral DNA detection in aqueous humor/corneal tissue collected during keratoplasty from March 2015 to December 2018 at the Peking University Third Hospital,Beijing,China.To further evaluate the effect of CMV on graft survival rate and ECD loss,patients were divided into three groups:1)CMV DNA positive(CMV+)group;2)viral DNA negative(virus-)group,comprising virus-group eyes pairwise matched to eyes in the CMV+group according to ocular comorbidities;3)control group,comprising virus-group eyes without ocular comorbidities.The follow-up indicators including graft survival rate,ECD,ECD loss,and central corneal thickness(CCT),were analyzed by Tukey honestly significant difference(HSD)test.RESULTS:Each group included 29 cases.The graft survival rate in CMV+group were lowest among the three groups(P=0.000).No significant difference in donor graft ECD was found among three groups(P=0.54).ECD in the CMV+group was lower than the virus-group at 12(P=0.009),and 24mo(P=0.002)after keratoplasties.Furthermore,ECD loss was higher in the CMV+group than in the virus-group in the middle stage(6-12mo)postkeratoplasty(P=0.017),and significantly higher in the early stage(0-6mo)in the virus-group than in the control group(P=0.000).CONCLUSION:CMV reduces the graft survival rate and exerts persistent detrimental effects on the ECD after keratoplasty.The graft ECD loss associate with CMV infection mainly occurrs in the middle stage(6-12mo postoperatively),while ocular comorbidities mainly affects ECD in the early stage(0-6mo postoperatively).

Coexisting cytomegalovirus colitis in an immunocompetent patient with Clostridioides difficile colitis:A case report

BACKGROUND Clostridioides difficile(C.difficile)colitis is one of the most common infections in hospitalized patients,characterized by fever and diarrhea.It usually improves after appropriate antibiotic treatment;if not,comorbidities should be considered.Cytomegalovirus(CMV)colitis is a possible co-existing diagnosis in patients with C.difficile infection with poor treatment response.However,compared with immunocompromised patients,CMV colitis in immunocompetent patients is not well studied.CASE SUMMARY We present an unusual case of co-existing CMV colitis in an immunocompetent patient with C.difficile infection.An 80-year-old female patient was referred to the infectious disease department due to diarrhea,abdominal discomfort,and fever for 1 wk during her hospitalization for surgery.C.difficile toxin B polymerase chain reaction on stool samples was positive.After C.difficile infection was diagnosed,oral vancomycin treatment was administered.Her symptoms including diarrhea,fever and abdominal discomfort improved for ten days.Unfortunately,the symptoms worsened again with bloody diarrhea and fever.Therefore,a sigmoidoscopy was performed for evaluation,showing a longitudinal ulcer on the sigmoid colon.Endoscopic biopsy confirmed CMV colitis,and the clinical symptoms improved after using ganciclovir.CONCLUSION Co-existing CMV colitis should be considered in patients with aggravated C.difficile infection on appropriate treatment,even in immunocompetent hosts.

Human Herpes Virus Type 2 ( HSV2 ), Human Cytomegalovirus (HCMV) in the Male Genital Tract and Fertilization

The possibility of infection of the human male genital tract by human herpes virus type 2 (HSV2) or human cytomegalovirus (HCMV) is well established and their sexual transmission has been the object of many studies. Moreover, medically assisted procreation, which helps in numerous fertility problems, raises the question of new viral risks linked to the application of these new technologies. In this review, we shall consider current knowledge in terms of the presence of HSV 2 and HCMV in the different parts of the genital tract of immunocompetent or immunodepressed men. We shall also consider the possibility of viral transmission by the sexual act or by the various techniques used in medically assisted procreation. We shall describe studies in human beings and in animals.

巨细胞病毒活动性感染患儿NK细胞及GGT水平与HCMV DNA的相关性

目的探讨巨细胞病毒(HCMV)活动性感染患儿自然杀伤(NK)细胞及γ-谷氨酰转肽酶(GGT)水平与HCMV DNA的相关性。方法选取2021年6月—2022年6月濉溪县医院收治的150例HCMV活动性感染患儿纳入研究对象,根据HCMV DNA水平将患儿分为低载量组(n=52)、中载量组(n=64)、高载量组(n=34),另外选取我院同期50名健康婴儿作为对照组。比较4组的肝功能指标[天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、碱性磷酸酶(ALP)、总胆汁酸(TBA)、GGT]及NK细胞水平,分析肝功能指标及NK细胞与HCMV DNA的相关性。结果4组AST、ALT、ALP、TBA比较无明显差异(P>0.05),4组GGT分别为(10.28±2.69)U/L、(15.64±3.13)U/L、(18.56±3.22)U/L、(23.77±4.17)U/L,4组NK细胞分别为(4.87±1.04)%、(6.14±1.15)%、(13.55±2.33)%、(19.84±3.27)%,GGT、NK随HCMV DNA载量升高而上升(P<0.05);经相关性分析,AST、ALT、ALP、TBA与HCMV DNA无明显相关性(P>0.05),NK细胞、GGT与HCMV DNA呈现正相关(P<0.05)。结论NK细胞及GGT水平与HCMV DNA具有相关性,检测HCMV DNA有助于HCMV活动性感染的诊断,但无法评估病情严重程度。

HIV/AIDS患者并发EBV和HCMV感染临床免疫学特征及影响因素分析

目的调查人类免疫缺陷病毒/获得性免疫缺陷综合征(human immunodeficiency virus/acquired immune deficiency syndrome,HIV/AIDS)患者感染EB病毒(Epstein-Barr virus,EBV)和人类巨细胞病毒(human Cytomegalovirus,HCMV)的情况,检测相关临床免疫学指标,分析其影响因素。方法选取2022年1~12月在长沙市第一医院住院并接受EBV和HCMV筛查的1093例HIV/AIDS患者。流式细胞术检测CD4^(+)T淋巴细胞数量;荧光定量PCR检测HIVRNA载量、EBV-DNA载量和HCMV-DNA载量。采用SPSS 27.0统计学软件进行统计分析,并通过Logistic回归分析HIV/AIDS患者并发病毒感染的危险因素。结果1093例HIV/AIDS患者中,EBV-DNA阳性率为48.22%(527/1093),HCMV-DNA阳性率为19.03%(208/1093)。随着CD4^(+)T淋巴细胞数量增加,EBV-DNA和HCMV-DNA的阳性率下降(χ^(2)=39.50,143.0,均P<0.001);随着HIV-RNA载量增加,EBV-DNA和HCMV-DNA的阳性率增加,差异具有统计学意义(χ^(2)=46.18,124.3,均P<0.001)。另外,患者接受抗逆转录病毒治疗(antiretroviral therapy,ART)也可明显降低EBV-DNA和HCMV-DNA的阳性率,差异具有统计学意义(χ^(2)=30.60,96.59,均P<0.001)。CD4^(+)T淋巴细胞数量和HIV-RNA载量有显著的负相关关系(r=-0.49,P<0.001)。Logistic回归分析显示CD4^(+)T淋巴细胞数量<200个/μl(OR=1.46,95%CI:1.02~2.08,P=0.037),HIV-RNA载量>200 copies/ml(OR=1.70,95%CI:1.18~2.44,P=0.004),年龄>30岁(OR=2.15,95%CI:1.44~3.19,P<0.001)是HIV/AIDS患者并发EB病毒感染的危险因素;未持续接受ART(OR=1.83,95%CI:1.10~3.02,P=0.019),HIV-RNA载量>200 copies/ml(OR=2.56,95%CI:1.50~4.35,P<0.001),CD4^(+)T淋巴细胞数量<200个/μl(OR=4.61,95%CI:2.57~8.28,P<0.001)是HIV/AIDS患者并发HCMV感染的危险因素。结论在艾滋病的治疗与管理中,当CD4^(+)T淋巴细胞数量下降(<200个/μl),HIV-RNA载量升高(>200 copies/ml)或者年龄>30岁时,应加强对病毒的监测和ART,减少HIV/AIDS患者机会性感染的可能。

Human Cytomegalovirus Infection Inhibits the Differentiation of Human Hippocampus Neural Precursor Cells into Astrocytes

HCMV is a major cause of congenital brain disease in humans, and its neuropathogenesis is not yet fully understood. The objective of the present study is to investigate the effect of human cytomegalovirus (HCMV) infection on human hippocampus neural precursor cell (NPCs) differentiation in vitro. Fetal hippocampus tissue was dissociated mechanically and then cultured in proliferation medium with EGF and bFGF. The identification and purity of the NPCs were confirmed by using immunofluorescence to detect the expression of the NPCs marker-Nestin. To drive NPCs differentiation, bFGF and EGF were withdrawn from the medium and replaced with FBS (10%). HCMV AD169 (MOI=5) was added into the differentiation medium at the onset of the differentiation. After 7 days of differentiation, in order to confirm whether NPCs are permissive for HCMV infection, immunofluorescence was used to stain for the presence of immediate early (IE) and late (pp65) HCMV proteins in the infected cells. The effects of HCMV infection on NPCs’ differentiation was observed by detecting the ratio of nestin and GFAP positive cells with confocal microscopy and immunofluorescence. The data showed that 95%±8% of the cells (passage 4-8) cultured were Nestin positive which suggested that majority of the cells were NPCs. On day 7 postinfection, most of the infected cells were IE and PP65 positive. The percentage of Nestin-positive cells were 93%±10% and 50%±19% (t=6.03, p<0.01) and those of GFAP-positive cells were 55±17% and 81%±11% (t=3.77, p<0.01) in HCMV treated and control groups respectively. These findings indicate that NPCs are HCMV permissive cells and HCMV (AD 169) infection suppresses the differentiation of Hippocampus-genetic human NPCs into astrocytes. These effects may provide part of the explanation for the abnormalities in brain development associated with congenital HCMV infection.

Specific endoscopic features of ulcerative colitis complicated by cytomegalovirus infection

AIM:To identify specific colonoscopic findings in patients with ulcerative colitis (UC) complicated by cyto-megalovirus (CMV) infection.METHODS: Among UC patients who were hospitalized due to exacerbation of symptoms, colonoscopic findings were compared between 15 CMV-positive patients and 58 CMV-negative patients. CMV infection was determined by blood test for CMV antigenemia. Five aspects of mucosal changes were analyzed (loss of vascular pattern, erythema, mucosal edema, easy bleeding, and mucinous exudates) as well as five aspects of ulcerative change (wide mucosal defect, punched-out ulceration, longitudinal ulceration, irregular ulceration, and cobble-stone-like appearance). Sensitivity, specificity, positive predictive value, and negative predictive value of each finding for CMV positivity were determined.RESULTS: The sensitivity of irregular ulceration for positive CMV was 100%. The specificity of wide mucosal defect was 95%. Punched-out ulceration and lon-gitudinal ulceration exhibited relatively high sensitivity and specificity (more than 70% for each).CONCLUSION:Specific colonoscopic findings in patients with UC complicated by CMV infection were identified. These findings may facilitate the early diagnosis of CMV infection in UC patients.

Natural history of cytomegalovirus infection in a series of patients diagnosed with moderate-severe ulcerative colitis

AIM： To evaluate the natural history of human cytomegalovirus （HCMV） infection in a series of 28 ulcerative colitis patients in whom the search for HCMV was positive. METHODS： A series of 85 patients with moderate-se- vere ulcerative colitis flare-up were evaluated for a HCMV search by performing a haematoxylin and eosin stain, immunohistochemical assay and nested polymerase chain reaction on rectal biopsies. Among 85 screened patients （19 of whom were steroid resistant/dependant）, 28 were positive for HCMV; after remission the patients were followed up clinically and histologically. RESULTS： Among the 22 patients with complete follow- up, in 8 （36%） patients HCMV-DNA persisted in the in- testinal specimens. Among the HCMV positive patients, 4 （50%） experienced at least one moderate-severeflare-up of colitis without evidence of peripheral HCMV. Among the 14 HCHV negative patients, 3 with pouches developed pouchiUs and 5 out of 11 （45%） experienced a colitis flare-up. CONCLUSION： Our preliminary results suggest that HCHV may remain in the colon afber an acute coltis flare- up despite remission; it seems that the virus is not responsible for the disease relapse.

Long-term follow-up of ulcerative colitis patients treated on the basis of their cytomegalovirus antigen status

AIM:To clarify the impact of cytomegalovirus(CMV)activation and antiviral therapy based on CMV antigen status on the long-term clinical course of ulcerative colitis(UC)patients.METHODS:UC patients with flare-up were divided into CMV-positive and-negative groups according to the CMV antigenemia assay.The main treatment strategy provided for the patients in the CMV-positive group comprised a dose reduction of corticosteroids and administration of ganciclovir.RESULTS:The median number of days to initial remission was significantly greater for the patients in the CMV-positive group(21 d vs 16 d,P=0.009).However,the relapse rate after remission and colectomy rate during more than 30 mo of observation did not differ between the two groups.Multivariate analysis revealed that administration of ganciclovir was the only independent factor for avoiding colectomy in patients of the CMV-positive group.CONCLUSION:CMV antigen status did not significantly affect the long-term prognosis in UC patients under treatment with appropriate antiviral therapy.

Cytomegalovirus infection in liver transplant recipients: Updates on clinical management

Cytomegalovirus(CMV) infection is a common complication after liver transplantation, and it is associated with multiple direct and indirect effects. Management of CMV infection and disease has evolved over the years,and clinical guidelines have been recently updated.Universal antiviral prophylaxis and a pre-emptive treatment strategy are options for prevention. A currentlyrecruiting randomized clinical trial is comparing the efficacy and safety of the two prevention strategies in the highest risk D+R- liver recipients. Drug-resistant CMV infection remains uncommon but is now increasing in incidence. This highlights the currently limited therapeutic options, and the need for novel drug discoveries.Immunotherapy and antiviral drugs with novel mechanisms of action are being investigated, including letermovir(AIC246) and brincidofovir(CMX001). This article reviews the current state of CMV management after liver transplantation, including the updated practice guidelines, and summarizes the data on investigational drugs and vaccines in clinical development.

Comparison of intravitreal ganciclovir monotherapy and combination with foscarnet as initial therapy for cytomegalovirus retinitis

AIM：To compare the effectiveness between multiple intravitreal injections of ganciclovir alone and combined with foscarnet as initial treatment for patients with newlyonset cytomegalovirus retinitis （CMVR）.METHODS：The retrospective study observed 37 patients（58 eyes） who suffered from CMVR onset between 2013 and 2015. Among them, 35 eyes underwent 4 weekly intravitreal injections of 3.0 mg ganciclovir, and 23 eyes underwent 4 weekly injections of 3.0 mg ganciclovir combined with 2.4 mg foscarnet. Visual acuity, intraocular pressure and viral load of cytomegalovirus （CMV） in aqueous humor measured by real-time polymerase chain reaction were compared before and after each injection.RESULTS：CMV-DNA copies in aqueous humor decreased remarkably in both groups. The average of CMV-DNA copies in patients’ aqueous decreased from 38.3×10~4 copies/mL at baseline to 2.2×10~4 copies/mL after the 4^（th） injection in patients who were treated with ganciclovir monotherapy,and decreased from 76.9×10~4 copies/mL to 11.3×10~4 copies/mL after 4 continuous injections of ganciclovir combined with foscarnet. No significant difference was found in reduction of viral load, change of visual acuities or intraocular pressures between monotherapy or combined therapy.CONCLUSION：Results of this study show that the initial effectiveness of treating CMVR after 4 weekly intravitreal injections is not significantly different from ganciclovir alone or combined with foscarnet. Continuous injection of ganciclovir alone is sufficient in treating immunosuppressive patients with newly-onset CMVR.

Two strategies for prevention of cytomegalovirus infections after liver transplantation

AIM: To analyze differences in patients' clinical course, we compared two regimes of either preemptive therapy or prophylaxis after liver transplantation.METHODS: This retrospective study was reviewed and approved by the institutional review board of the University of Leipzig. Cytomegalovirus(CMV) prophylaxis with valganciclovir hydrochloride for liver transplant recipients was replaced by a preemptive strategy in October 2009. We retrospectively compared liver transplant recipients 2 years before and after October 2009. During the first period, all patients received valganciclovir daily. During the second period all patients included in the analysis were treated following a preemptive strategy. Outcomes included one year survival and therapeutic intervention due to CMV viremia or infection.RESULTS: Between 2007 and 2010 n = 226 patients underwent liver transplantation in our center. n = 55 patients were D^+/R^- high risk recipients and were excluded from further analysis. A further 43 patients had to be excluded since CMV prophylaxis/preemptive strategy was not followed although there was no clinical reason for the deviation. Of the remaining 128 patients whose data were analyzed, 60 receivedprophylaxis and 68 were treated following a preemptive strategy. The difference in overall mortality was not significant, nor was it significant for one-year mortality where it was 10%(95%CI: 8%-28%, P = 0.31) higher for the preemptive group. No significant differences in blood count abnormalities or the incidence of sepsis and infections were observed other than CMV. In total, 19 patients(14.7%) received ganciclovir due to CMV viremia and/or infections. Patients who were treated according to the preemptive algorithm had a significantly higher rate risk of therapeutic intervention with ganciclovir [n = 16(23.5%) vs n = 3(4.9%), P = 0.003)].CONCLUSION: These data suggest that CMV prophylaxis is superior to a preemptive strategy in patients undergoing liver transplantation.

Cytomegalovirus and ulcerative colitis:Place of antiviraltherapy

The link between cytomegalovirus(CMV) infection and inflammatory bowel diseases remains an important subject of debate. CMV infection is frequent in ulcerative colitis(UC) and has been shown to be potentially harmful. CMV reactivation needs to be diagnosed using methods that include in situ detection of viral markers by immunohistochemistry or by nucleic acid amplification techniques. Determination of the density of infection using quantitative tools(numbers of infected cells or copies of the genome) is particularly important. Although CMV reactivation can be considered as an innocent bystander in active flareups of refractory UC, an increasing number of studies suggest a deleterious role of CMV in this situation. The presence of colonic CMV infection is possibly linked to a decreased response to steroids and other immunosuppressive agents. Some treatments, notably steroids and cyclosporine A, have been shown to favor CMV reactivation, which seems not to be the case for therapies using anti-tumor necrosis factor drugs. According to these findings, in flare-ups of refractory UC, it is now recommended to look for the presence of CMV reactivation by using quantitative tools in colonic biopsies and to treat them with ganciclovir in cases of high viral load or severe disease.

IL28B polymorphism and cytomegalovirus predict response to treatment in Egyptian HCV type 4 patients

AIM:To test whether the status of positive cytomegalovirus(CMV) DNA detection adds to the predictive value of IL28B and to further categorize C/T allele carriers.METHODS:This study included 166 chronic hepatitis C(CHC) patients who received combined interferon and ribavirin therapy for 48 wk,84 spontaneous hepatitis C virus(HCV) resolvers who were positive for IgG anti-HCV antibody and negative for HCV RNA,and 100 healthy subjects who were negative for both HCV antibodies and RNA as controls.Genomic DNA from peripheral blood was used for IL28B rs.12979860 single nucleotide polymorphism(SNP) and CMV DNA detection.A 139 bp fragment containing IL28B SNP was amplified in all subjects by polymerase chain reaction using a specifically designed primer.Then the IL28B rs.12979860 SNP was detected by restriction fragment length polymorphism(RFLP) genotyping.The presence of CMV DNA was tested by amplification of the gB1 gene using nested polymerase chain reaction.The role of CMV and IL28B rs.12979860 SNP genotypes in determining the response rate to combined interferon therapy and clinical status of patients were statistically analyzed.RESULTS:Current data showed that 67% of patients carrying the IL28B 12979860 C/C allele had a sustained viral response(SVR) while the genotypes C/T and TT were associated with lower SVR rates,50% and 48%,respectively.SVR rates for the C/C allele were lower than other HCV genotypes and/or other populations.Genotype CC was associated with the response to interferon(P = 0.025).Genotype C/C was reduced from 48% in controls to 14% in CHC patients suggesting its protective role against progression to chronicity.The majority of spontaneously cleared subjects(86%) were C/C,confirming its protective role.The C/T allele was present in 71% of CHC patients compared with 38% of controls,so the use of IL28B SNP genotyping only in these patients may be of little value as a predictor of response.CMV reactivation occurred in 40% of CHC patients.Co-infection with CMV seriously diminished the response to interferon(IFN) therapy,with SVR rates in C/C genotypes 87.5% in CMV-negative patients and 12.5% in CMV-positive patients(P < 0.0001).SVR rates among C/T carriers were reduced to < 50% in patients with positive CMV DNA while the non-response rate doubled.These data indicate that a supplemental assay for CMV viremia adds to the prognostic value of IL28B genotyping.CONCLUSION:The results suggest that both genetic(i.e.,spontaneous) and therapeutic(IFN-based therapy) arms are complementary in the battle against HCV.CMV DNA testing may be of value to better predict the response to IFN,particularly in IL28B C/T carriers.

Characteristic endoscopic findings and risk factors for cytomegalovirus-associated colitis in patients with active ulcerative colitis

AIM: To identify characteristic endoscopic findings and risk factors for cytomegalovirus(CMV)-associated colitis in patients with active ulcerative colitis(UC).METHODS: A total of 149 UC patients admitted to the Department of Gastroenterology, Nagoya University Hospital, from January 2004 to December 2013 with exacerbation of UC symptoms were enrolled in this retrospective study. All medical records, including colonoscopy results, were reviewed. CMV infection was determined by the presence of CMV antigen, CMV inclusion bodies in biopsy specimens, or positive specific immunohistochemical staining for CMV. Multivariate analysis was used to identify independent risk factors for CMV colitis.RESULTS: Multivariate analysis indicated independent associations with the extent of disease(pancolitis) anduse of > 400 mg corticosteroids for the previous 4 wk. In contrast, no association was seen with sex, age at UC diagnosis, immunomodulator use, or infliximab use. Punched-out ulceration was also significantly associated with CMV infection in patients with active UC(odds ratio = 12.672, 95%CI: 4.210-38.143).CONCLUSION: Identification of a total corticosteroid dose > 400 mg for 4 wk, extensive colitis and a specific endoscopic finding of punched-out ulcer might facilitate the more rapid diagnosis and timely initiation of antiviral therapy for CMV-associated colitis in patients with active UC.