Screening Donated Blood for Transfusion-Transmissible Cytomegalovirus Infection among Libyans

Human cytomegalovirus (HCMV) is a ubiquitous DNA-containing herpesvirus causes severe and fatal diseases in immunocompromised patients and a prevalent cause of virus-associated birth defects. Blood transfusion donated for neonates, pregnant women, and immunocom-promised patients should be adequately screened for evidences of CMV infection prior to use in clinical management. The effective national programmes for quality-assured screening of donated blood have not yet been fully established, hence this study was undertaken to assess whether any bloodborne-CMV infections pose a significant threat to the safety of the blood supplies. A total of 200 voluntary blood donor subjects admitted to the Blood Bank of Benghazi/Libya were screened for transfusion-transmissible CMV (TT-CMV) using a highly sensitive CMV total IgG and IgM antibody enzyme immunoassay as well as CMV pp65 anti-genemia assays. We determined that the overall seropositivity for IgG antibodies (80.50%) was higher than that of IgM antibodies (39.00%), but only 2 (1.00%) individuals out of these donors were seropositive for the CMV-antigenic protein pp65. The frequency of CMV infection based on gender was incomparable due to the small population number of blood-donated females. According to age, there was not influence of various age groups on prevalence of anti-CMV IgG antibodies, while a progressive increase in seropositivity of CMV-IgM antibodies with age was detected. The age groups were not significantly associated with CMV prevalence. In contrast, only 2 (1.00%) patients were shown to be positive for all three performed assays indicating a recurrent infection. Our findings prove a risk of primary transfusion-associated transmission of CMV and may provide a policy guidance on ensuring safe blood supplies accessible to all patients who require transfusion.

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.

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.

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.

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.

Management of cytomegalovirus infection and disease in liver transplant recipients

Cytomegalovirus(CMV) is one of the most common viral pathogens causing clinical disease in liver transplant recipients, and contributing to substantial morbidity and occasional mortality. CMV causes febrile illness often accompanied by bone marrow suppression, and in some cases, invades tissues including the transplanted liver allograft. In addition, CMV has been significantly associated with an increased predisposition to acute and chronic allograft rejection, accelerated hepatitis C recurrence, and other opportunistic infections, as well as reduced overall patient and allograft survival. To negate the adverse effects of CMV infection on transplant outcome, its prevention, whether through antiviral prophylaxis or preemptive therapy, is an essential component to the management of liver transplant recipients. Two recently updated guidelines have suggested that antiviral prophylaxis or preemptive therapy are similarly effective in preventing CMV disease in modest-risk CMV-seropositive liver transplant recipients, while antiviral prophylaxis is the preferredstrategy over preemptive therapy for the prevention of CMV disease in high-risk recipients [CMV-seronegative recipients of liver allografts from CMV-seropositive donors(D+/R-)]. However, antiviral prophylaxis has only delayed the onset of CMV disease in many CMV D+/Rliver transplant recipients, and such occurrence of lateonset CMV disease was significantly associated with increased all-cause and infection-related mortality after liver transplantation. Therefore, a search for better strategies for prevention, such as prolonged duration of antiviral prophylaxis, a hybrid approach(antiviral prophylaxis followed by preemptive therapy), or the use of immunologic measures to guide antiviral prophylaxis has been suggested to prevent late-onset CMV disease. The standard treatment of CMV disease consists of intravenous ganciclovir or oral valganciclovir, and if feasible, reduction in pharmacologic immunosuppression. In one clinical trial, oral valganciclovir was as effective as intravenous ganciclovir for the treatment of mild to moderate CMV disease in solid organ(including liver) transplant recipients. The aim of this article is to provide a state-of-the art review of the epidemiology, diagnosis, prevention, and treatment of CMV infection and disease after liver transplantation.

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.

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.

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.

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 positive ulcerative colitis:A single center experience and literature review

AIM:To compare the clinical outcome of cytomegalovirus(CMV)-positive ulcerative colitis(UC) patients with and without antiviral therapy.METHODS:This was a retrospective case-controlled study.The database of UC patients in our institution was scanned for documented presence of CMV on colonic biopsies.Demographics,clinical data,endoscopy findings and pathology reports were extracted from the patients' charts and electronic records.When available,the data from colonoscopies preceding and following the diagnosis of colonic CMV infection were also ex-tracted.The primary outcomes of the study were colectomy/death during hospitalization and the secondary outcomes were colectomy/death through the course of the follow-up.RESULTS:Thirteen patients were included in the study,7(53.5%) of them were treated with gancyclovir and 6(46.5%) were not.Patients treated with antivirals presented with a more severe disease and 57% of them were treated with cyclosporine or infliximab before initiation of gancyclovir,while none of the patients without antivirals required rescue therapy.One patient died and another patient underwent urgent colectomy during hospitalization,both of them from the gancyclovir-treatment group.For the entire follow-up time(13 ± 13 mo),a total of 3 colectomies and one death occurred,all among the antiviral-treated patients(for colectomy:3/7 vs 0/6 patients,P = 0.19;for combined adverse outcome:4/7 vs 0/6 patients,P = 0.07).In 9/13 patients,immunohistochemistry for CMV was performed on biopsies obtained during a subsequent colonoscopy and was positive in one patient only.CONCLUSION:Gancyclovir-treated patients had a more severe disease and outcome,probably unrelated to antiviral therapy.Immunohistochemistry-CMV-positive patients with mild disease may recover without 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.

Current concepts on cytomegalovirus infection after liver transplantation

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 perspectives of prev ention and treatment of CMV disease after liver trans plantation.

Cholestasis, ascites and pancytopenia in an immunocompetent adult with severe cytomegalovirus hepatitis

Human cytomegalovirus(CMV) is a herpesvirus,which establishes lifelong latency after primary infection and leads to severe disease in immunocompromised patients. However,CMV infection in immunocompetent patients is usually asymptomatic and severe organ damage is rarely reported. We report a case of severe CMV hepatitis in an immunocompetent patient presenting with cholestasis,portal hypertensionrelated ascites and pancytopenia. The patient was asymptomatic with normal liver function and negative CMV DNA after two weeks of antiviral therapy. This case is an example of a common infection with an uncommon presentation,and suggests that testing for CMV should be carried out,even in patients with normal immune status,presenting with severe liver damage or cholestasis.

Antiviral therapy in cytomegalovirus-positive ulcerative colitis:A systematic review and meta-analysis

AIM:To evaluate the impact of antiviral treatment on cytomegalovirus(CMV)-positive ulcerative colitis patients.METHODS:We performed a systematic review and meta-analysis(MA)of comparative cohort and casecontrol studies published between January 1966 and March 2013.Studies focusing on colectomy series and studies including only less than 3 patients in the treated or non-treated arm were excluded.The primary outcome was colectomy within 30 d of diagnosis.Secondary outcomes included colectomy during the follow-up period Subgroup analyses by method of detection of CMV,study design,risk of bias and country of origin were performed.Quality of studies was evalu-ated according to modified New-Castle Ottawa Scale.RESULTS:After full-text review,nine studies with a total of 176 patients were included in our MA.All the included studies were of low to moderate quality.Patients who have received antiviral treatment had a higher risk of 30-d colectomy(OR=2.40;95%CI:1.05-5.50;I2=37.2%).A subgroup analysis including only patients in whom CMV diagnosis was based did not demonstrate a significant difference between the groups(OR=3.41;95%CI:0.39-29.83;I2=56.9%).Analysis of long-term colectomy rates was possible for 6 studies including110 patients.No statistically significant difference was found between the treated and untreated groups(OR=1.71;95%CI:0.71-4.13;6 studies,I2=0%).Analysis of mortality rate was not possible due to a very limited number of cases.Stratification of the outcomes by disease severity was not possible.CONCLUSION:No positive association between antiviral treatment and a favorable outcome was demonstrated.These findings should be interpreted cautiously due to primary studies’quality and potential biases.

Colon perforation due to antigenemia-negative cytomegalovirus gastroenteritis after liver transplantation: A case report and review of literature

BACKGROUND Cytomegalovirus(CMV) remains a critical complication after solid-organ transplantation. The CMV antigenemia(AG) test is useful for monitoring CMV infection. Although the AG-positivity rate in CMV gastroenteritis is known to be low at onset, almost all cases become positive during the disease course. We treated a patient with transverse colon perforation due to AG-negative CMV gastroenteritis, following a living donor liver transplantation(LDLT).CASE SUMMARY The patient was a 52-year-old woman with decompensated liver cirrhosis as a result of autoimmune hepatitis who underwent a blood-type compatible LDLT with her second son as the donor. On day 20 after surgery, upper and lower gastrointestinal endoscopy(GE) revealed multiple gastric ulcers and transverse colon ulcers. The biopsy tissue immunostaining confirmed a diagnosis of CMV gastroenteritis. On day 28 after surgery, an abdominal computed tomography revealed transverse colon perforation, and simple lavage and drainage were performed along with an urgent ileostomy. Although the repeated remission and aggravation of CMV gastroenteritis and acute cellular rejection made the control of immunosuppression difficult, the upper GE eventually revealed an improvement in the gastric ulcers, and the biopsy samples were negative for CMV. The CMV-AG test remained negative, therefore, we had to evaluate the status of the CMV infection on the basis of the clinical symptoms and GE.CONCLUSION This case report suggests a monitoring method that could be useful for AGnegative CMV gastroenteritis after a solid-organ transplantation.

Comparative analysis of cytomegalovirus retinitis and microvascular retinopathy in patients with acquired immunodeficiency syndrome

AIM：To compare the clinical manifestation of cytomegalovirus（CMV）retinitis and microvascular retinopathy（MVR）in patients with acquired immunodeficiency syndrome（AIDS）in China.METHODS：A total of 93 consecutive patients with AIDS,including 41 cases of CMV retinitis and 52 cases of MVR were retrospectively reviewed.Highly active antiretroviral therapy（HAART）status was recorded.HIV and CMV immunoassay were also tested.CD4＋T-lymphocyte count and blood CMV-DNA test were performed in all patients.Aqueous humor CMV-DNA test was completed in 39patients.Ophthalmological examinations including best corrected visual acuity（BCVA,by International Standard Vision Chart）,intraocular pressure（IOP）,slit-lamp biomicroscopy,indirect ophthalmoscopy were performed.RESULTS：In MVR group,the anterior segment examination was normal in all patients with a mean BCVA of 0.93±0.13.Blood CMV-DNA was 0（0,269 000）and 42 patients（80.77%）did not receive HAART.In CMV retinitis group,13 patients（31.71%）had anterior segment abnormality.The mean BCVA was 0.64±0.35 and blood CMV-DNA was 3470（0,1 450 000）.Nineteen patients（46.34%）had not received HAART.MVR group and CMV retinitis group the positive rates of aqueous CMV-DNA were 0 and 50%,respectively.Two patients with MVR progressed to CMV retinitis during the follow-up period.CONCLUSION：In comparison of CMV,patients with MVR have relatively mild visual function impairment.Careful ophthalmological examination and close follow-up are mandatory,especially for patients who have systemic complications,positive CMV-DNA test and without received HAART.