Usefulness of quantitative real-time PCR assay for early detection of cytomegalovirus infection in patients with ulcerative colitis refractory to immunosuppressive therapies

BACKGROUND: Studies suggest that cytomegalovirus (CMV) infection exacerbates ulcerative colitis (UC) refractory to immunosuppressive therapies. Early and accurate diagnosis of CMV infection is important for the treatment of UC. We evaluated the usefulness of quantitative real-time polymerase chain reaction (PCR) for detecting CMV infection in inflamed colonic mucosa of patients with UC refractory to immunosuppressive therapies. METHODS: From 2003 to 2006, 30 patients (mean age: 41 +/- 18 years; 14 men, 16 women) with UC refractory to immunosuppressive therapies were enrolled in the study. We evaluated CMV infection by CMV antigenemia, histologic examination, and quantitative real-time PCR for CMV using colonic mucosa and investigated the clinical outcomes of antiviral therapy. RESULTS: CMV-DNA was detected only in the inflamed colonic mucosa in 17 (56.7%) of 30 patients. Of the 17 CMV-DNA-positive patients, 4 were positive for CMV antigenemia or inclusion bodies on histologic examination; of the 13 CMV-DNA-negative patients none was positive for CMV antigenemia or inclusion bodies. Of the 17 CMV-DNA-positive patients, 12 (70.6%) were treated with ganciclovir for 2 weeks and 10 patients went into remission. Two other patients required colectomy after antiviral therapy. In contrast, of the 13 CMV-DNA-negative patients 12 (92.3%) achieved remission after intensifying their immunosuppressive therapies. CONCLUSIONS: Quantitative real-time PCR assay for detecting CMV-DNA is useful for early, accurate diagnosis of CMV infection in patients with UC refractory to immunosuppressive therapies, enabling prompt and appropriate treatment.     

Clinical significance of cytomegalovirus infection in patients with inflammatory bowel disease

Cytomegalovirus(CMV) infection is common in humans.The virus then enters a "latency phase" and can reactivate to different stimuli such as immunosuppression.The clinical significance of CMV infection in inflammatory bowel disease is different in Crohn’s disease(CD) and ulcerative colitis(UC).CMV does not interfere in the clinical course of CD.However,CMV reactivation is frequent in severe or steroid-resistant UC.It is not known whether the virus exacerbates the disease or simply appears as a bystander of a severe disease.Different methods are used to diagnose CMV colitis.Diagnosis is classically based on histopathological identification of viral-infected cells or CMV antigens in biopsied tissues using haematoxylin-eosin or immunohistochemistry,other tests on blood or tissue samples are currently being investigated.Polymerase chain reaction performed in colonic mucosa has a high sensitivity and a positive result could be associated with a worse prognosis disease;further studies are needed to determine the most appropriate strategy with positive CMV-DNA in colonic mucosa.Specific endoscopic features have not been described in active UC and CMV infection.CMV colitis is usually treated with ganciclovir for several weeks,there are different opinions about whether or not to stop immunosuppressive therapy.Other antiviral drugs may be used.Multicenter controlled studies would needed to determine which subgroup of UC patients would benefit from early antiviral treatment.     

Cytomegalovirus colitis mimics amebic colitis in a man with AIDS

Opportunistic gastrointestinal infections are common in patients with HIV infection; both amebic colitis and cytomegalovirus (CMV) colitis are common causes of chronic diarrhea. It is difficult to distinguish these 2 diseases by nonspecific clinical symptoms such as diarrhea, abdominal pain, and weight loss. Here we report a case of CMV colitis mimicking amebic colitis with elevated indirect hemagglutination assay antibody titer against Entamoeba histolytica and negative IgM antibody titer against CMV. The diagnosis of CMV colitis was confirmed by eosinophilic nucleoli and inclusion bodies in colon biopsies. The patient recovered after ganciclovir and highly active antiretroviral therapy. Exact diagnoses are important for treating opportunistic infections. Other pathogens should be considered in patients with chronic diarrhea who are refractory to initial treatments. Our case highlights the importance of histopathological diagnosis for chronic diarrhea in patients with HIV infection and the possibility of false-positive results for indirect hemagglutination assay antibody against Entamoeba histolytica despite high titers.     

Outcome of cytomegalovirus infections in patients with inflammatory bowel disease

OBJECTIVE: The aim of this study was to determine the outcome of cytomegalovirus (CMV) infections complicating the course of inflammatory bowel disease (IBD). METHODS: The records and clinical courses were reviewed for all IBD patients who were evaluated at the IBD Center of the Cedars-Sinai Medical Center and who developed CMV infection. RESULTS: Ten patients with severe, medically refractory IBD (five ulcerative colitis, three Crohn's colitis, and two indeterminate colitis) developed CMV infection. All but two were hospitalized with exacerbation of their underlying disease and were receiving immunosuppressive treatment with steroids, thiopurines, and/or cyclosporine at the time CMV infection was recognized. Eight patients had documented colonic CMV (one had concurrent upper GI tract involvement), one developed interstitial CMV and Pneumocystis carinii pneumonia, and one developed primary CMV mononucleosis. Prompt treatment with ganciclovir and withdrawal of immunosuppressive treatment resulted in gradual improvement and induction of remission of the underlying IBD in five patients. The patient with concomitant CMV and P. carinii pneumonitis died. In two patients, treatment with ganciclovir did not alter the clinical course of their IBD, and one of them underwent colectomy. In one patient CMV was found on the resected colonic specimen. One patient with primary CMV infection responded also to ganciclovir treatment. CONCLUSIONS: CMV infection may aggravate the course of seemingly refractory IBD in patients who either fail to respond or experience worsening of symptoms despite immunosuppressive therapy. Expedient evaluation, prompt treatment intervention with ganciclovir, and withdrawal of immunosuppressive treatment may avoid complications and mortality. This regimen leads to improvement of the underlying IBD in most patients.     

Primary cytomegalovirus infectious colitis complicating Crohn's disease successfully treated with oral valganciclovir

Most cases of cytomegalovirus (CMV) colitis that develop in patients with inflammatory bowel disease (IBD) are caused by reactivation of a latent virus. Primary CMV infections are rare in adult patients. Treatment with immunosuppressive agents increases the infection risk in patients with IBD. We present a 26 year old lady with primary CMV colitis, superimposed on underlying Crohn's colitis. The diagnosis was confirmed by a viral-like prodrome, a positive CMV IgM titer, presence of low avidity IgG antibodies to CMV, high CMV DNA titers in the plasma, and immunohistological detection of CMV positive cells in her colonic mucosa. The patient responded to initial treatment with intravenous ganciclovir with a fall in plasma levels of CMV DNA, treatment was completed with oral valganciclovir until plasma CMV DNA levels became undetectable.     

Long-Term Outcomes of Cytomegalovirus Reactivation in Patients with Moderate to Severe Ulcerative Colitis: A Multicenter Study

Background/Aims

Cytomegalovirus (CMV) reactivations are frequently observed in patients with active ulcerative colitis (UC), and ganciclovir therapy is effective in patients with steroid-refractory UC. This study aimed to determine the long-term outcomes of CMV reactivation and the long-term therapeutic efficacy of ganciclovir treatment.

Methods

This retrospective multicenter study included a cohort of 72 patients with moderate-to-severe UC who were evaluated for CMV reactivation at the time of their initial UC flare. Colectomy, disease relapse, and the recurrence rate of CMV reactivation were investigated.

Results

The mean duration of follow-up for the 72 patients was 43.16±19.78 months (range, 1 to 67 months). The cumulative colectomy (log-rank, p=0.025) and disease flare-up rates (log-rank, p=0.048) were significantly higher in the CMV-positive group. Of the 11 patients who were successfully treated with ganciclovir in the initial treatment, three patients (27.3%) experienced CMV reactivation, and six patients (54.5%) experienced poor outcomes, such as the need for colectomy or a steroid-dependent state.

Conclusions

The patients who had CMV-reactivated UC showed poor outcomes at the long-term follow-up, and the long-term efficacy of ganciclovir therapy was marginal. Careful assessment is necessary for patients who exhibit evidence of CMV reactivation.     

Cytomegalovirus and ulcerative colitis: Place of antiviral therapy

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.     

Cytolytic IgM antibody to cytomegalovirus in primary cytomegalovirus infection in humans

Suspensions of cytomegalovirus (CMV)-infected human foreskin fibroblasts were used to measure cytolytic antibody (CyA) to CMV in serum by a 51Cr release assay. CyA was associated with IgM but not with IgG antibody to CMV, required rabbit or human complement, and was directed at a surface antigen. CyA was detectable for one to three months in the sera of 16 patients with community-acquired CMV infection and in the sera of 20 of 22 renal transplant recipients with primary CMV infection. CyA was found less frequently in the sera of renal transplant recipients with reactivated CMV infection and occurred almost exclusively when the donor was seropositive for CMV. One individual, unlike many patients with CyA, was free of symptoms. Sera from patients with either rheumatoid factor-positive arthritis or heterophil-positive infectious mononucleosis and from 70 of 71 control patients with other types of antibody to CMV yielded no 51Cr release.     

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.     

IL-23／IL-17炎症轴在溃疡性结肠炎中的作用

目的探讨IL-23／IL-17炎症轴在溃疡性结肠炎（UC）中的变化及意义。方法按照2007年济南标准选择UC组患者20例,对照组16例。利用细胞内细胞因子染色和四色荧光抗体流式细胞术对肠黏膜固有层单个核细胞作表型分析,比较Th1、Th2、Th17比例的改变。Westernblot检测肠黏膜IL-17、IL-23表达。数据以中位数和四分位间距即M（QR）形式表示,行相关统计。结果（1）肠黏膜中Th17的比例在UC组中较对照组明显增加（P〈0．05）,为3．75％比1．25％,且重度活动较轻度活动患者增加明显（P〈0．05）,为8．30％比1．20％。肠黏膜中Th1的比例在UC组和对照组中分别为13．60％和9．10％,Th2的比例在UC和对照组中分别为1．10％和1．15％,差异均无统计学意义（P〉0．05）,不同活动度患者间差异亦无统计学意义（P〉0．05）。（2）UC组患者肠黏膜中IL-17表达较对照组明显升高（P〈0．05）,为0．20％比0．10％,且IL-17表达与UC患者疾病评分呈正相关（r=0．50,P=0．02）。（3）IL-23表达在UC组和对照组分别是0．13％和0．07％,差异有统计学意义（P〈0．05）。结论IL-23／IL-17炎症轴在溃疡性结肠炎的发病中具有重要作用,它可能成为UC治疗的有效靶点。     

Cytomegalovirus in colorectal cancer and idiopathic ulcerative colitis

Cytomegalovirus (CMV) is a genus in the family Herpesviridae that has been associated with gastrointestinal syndromes. In this work we looked for a possible association of CMV infection with colorectal cancer and ulcerative colitis (UC). Blood and enteric tissue samples of 14 patients with colorectal cancer and of 21 with UC were subjected to a nested-PCR that amplifies part of the gB gene of CMV and also to immunohistochemistry using a specific monoclonal antibody to IE 76 kDa protein of CMV. CMV was detected by nested-PCR in the blood and/or the enteric tissue of nine (64.3%) colorectal cancer and 16 (76.2%) ulcerative colitis patients. In the immunohistochemistry it was observed that 12 (12/21, 57.1%) positive enteric tissue samples of patients with UC and none from patients with colorectal cancer (0/14) were positive to CMV. The positivity of CMV infections in the UC patient group (12/21, 57.1%) showed by both techniques, was significantly higher (p = 0.015) than that observed for colorectal cancer patients (2/14, 14.3%). These results suggest an association of ulcerative colitis with CMV infection of the enteric tissue.     

Acute cytomegalovirus infection superimposed on corticosteroid-naïve ulcerative colitis

Most cases of cytomegalovirus (CMV) colitis that develop in patients with inflammatory bowel disease (IBD) are caused by a reactivation of a latent virus; acute CMV infections are rare. Treatment with immunosuppressive agents further increases the infection risk. Here, we present a 32-year-old man with acute CMV-mononucleosis and colitis, superimposed on corticosteroid-na?ve ulcerative colitis (UC). The diagnosis was confirmed by a viral-like prodrome, positive CMV antigenemia (C7-HRP), a positive CMV IgM titer, the presence of atypical lymphocytes, mild transaminase elevation, and immunohistological detection of CMV positive cells in his colonic mucosa. Gancyclovir was intravenously administered, and all symptoms were improved.     

Effect of intensive granulocyte and monocyte adsorptive apheresis in patients with ulcerative colitis positive for cytomegalovirus

Background and aimCytomegalovirus (CMV) exacerbates ulcerative colitis (UC) refractory to immunosuppressive therapies. The conditions under which CMV reactivation occurs in patients with UC, however, is unclear. In addition, the diagnostic and treatment strategies for UC positive for CMV have not been established. Granulocyte and monocyte adsorptive apheresis (GMAA) is natural biological therapy for UC in which the granulocytes/macrophages producing inflammatory cytokines are removed. We investigated the rate of colonic CMV reactivation and the efficacy of GMAA in active UC patients positive for CMV without concomitant corticosteroid (CS) therapy.MethodsFifty-one active UC patients without concomitant CS therapy were enrolled. Colonic CMV reactivation was examined by real-time polymerase chain reaction (PCR) using biopsy specimen and/or histological examination. All patients were treated with intensive GMAA (twice per week). Rates of clinical remission and mucosal healing were compared between UC patients positive and negative for CMV.ResultsOf 51 patients, 15 (29.4%) were diagnosed as CMV positive. The clinical remission rates following intensive GMAA did not differ between UC patients positive and negative for CMV (73.3% vs 69.4%, p = 0.781). Proportion of patients achieving mucosal healing was also similar between these two groups. CMV-DNA became negative in all UC patients positive for CMV who achieved clinical remission 1 week after completion of intensive GMAA.ConclusionsIntestinal inflammation might trigger CMV reactivation in a subpopulation of active UC patients without CS treatment. GMAA could be a promising option for active UC positive for CMV.     

Acute CMV-Colitis in a Patient with a History of Ulcerative Colitis

A symptomatic cytomegalovirus (CMV) infection usually occurs in patients with debilitating diseases, immunosuppression, transplantations and acquired immunodeficiency syndrome (AIDS). Gastrointestinal infections with CMV, especially colitis, are usually found in immunocompromised patients and rarely affect immunocompetent subjects. Here we report the case of a young female patient with a history of ulcerative colitis (UC) who presented with an acute attack of colitis caused by CMV infection. This was documented by the presence of CMV early antigen, antibodies and evidence of CMV in the colonic mucosa. After combined anti-inflammatory and antiviral treatment the patient recovered completely. As most attention is given to CMV-pathogeneity in immunocompromised patients, here we discuss the relationship to inflammatory bowel diseases.     

Acute CMV-colitis in a patient with a history of ulcerative colitis

A symptomatic cytomegalovirus (CMV) infection usually occurs in patients with debilitating diseases, immunosuppression, transplantations and acquired immunodeficiency syndrome (AIDS). Gastrointestinal infections with CMV, especially colitis, are usually found in immunocompromised patients and rarely affect immunocompetent subjects. Here we report the case of a young female patient with a history of ulcerative colitis (UC) who presented with an acute attack of colitis caused by CMV infection. This was documented by the presence of CMV early antigen, antibodies and evidence of CMV in the colonic mucosa. After combined anti-inflammatory and antiviral treatment the patient recovered completely. As most attention is given to CMV-pathogeneity in immunocompromised patients, here we discuss the relationship to inflammatory bowel diseases.     

Acute Cytomegalovirus Infection Is a Risk Factor in Refractory and Complicated Inflammatory Bowel Disease

The role of cytomegalovirus (CMV) infection in patients with inflammatory bowel disease (IBD) is controversial. Although CMV has been specifically associated with refractory disease, the strength and nature of this association have been a subject of debate. The aim of this study was to evaluate the prevalence and outcome of acute cytomegalovirus infection in patients with severe refractory and complicated inflammatory bowel disease. Seventy-two patients with active IBD (both ulcerative colitis [UC] and Crohn’s diseases [CD]) were included in this study. Thorough history taking and physical examination of all patients was made with special emphasis on symptoms and signs of CMV disease. Colonoscopic assessment was made for the extent and activity of IBD and collection of specimen. Prevalence of CMV infection was estimated by serology; anti-CMV IgM and IgG antibodies, and pathologic studies of colonic biopsies used conventional haematoxylin and eosin (H & E) and immunohistochemistry (IHC) with monoclonal antibodies. Complete blood count and liver function tests were done for all patients. Among 72 patients with active inflammatory bowel disease, 23 (31.9%) were resistant to intravenous steroids. CMV was detected in eight (six with UC and two with CD) of the 23 (34.8%) steroid-resistant patients and in only one (3.2%) patient in the remaining 31 patients under steroid treatment and was not detected in 18 IBD patients not using steroids. Among nine CMV-positive IBD patients, six (66.6%) were female and six had fever; cervical lymphadenopathy was found in five patients and splenomegaly in two, compared to no patients in the CMV-negative group (P = 0.01 and 0.03, respectively). Leucopenia and thrombocytopenia were predominantly seen in the CMV-positive versus CMV-negative patients (2.1±0.3 vs. 5.9±3.4 and 98±34 vs. 165±101, respectively). Pancolitis was found in five of nine CMV-positive IBD patients whereas in only two patients out of 63 in the CMV-negative group (P = 0.005). Acute CMV infection in patients with IBD is not rare and is often underestimated. CMV infection in patients with refractory or complicated IBD should be ruled out before aggressive immunosuppressive therapy. High clinical index of suspicion for the association of CMV infection with IBD should be directed towards female IBD patients presenting with fever, lymphadenopathy, splenomegaly, leucopenia, and mild hepatitis. CMV IHC is significantly more sensitive than routine H & E stain and should be considered as part of the routine evaluation of IBD patients with severe exacerbation or steroid-refractory disease before proceeding with other medical or surgical therapy that may not be necessary once the CMV is treated.     

Cytomegalovirus colitis followed by ischemic colitis in a non-immunocompromised adult:A case report

We report a rare case of cytomegalovirus(CMV) colitis followed by severe ischemic colitis in a nonimmunocompromised patient. An 86-year-old woman was admitted after experiencing episodes of vomiting and diarrhea. The next day, hematochezia was detected without abdominal pain. The initial diagnosis of ischemic colitis was based on colonoscopy and histological findings. The follow-up colonoscopy revealed a prolonged colitis. Immunohistochemical staining detected CMVpositive cells following conservative therapy. Intravenous ganciclovir therapy led to successful healing of ulcers and disappearance of CMV-positive cells. The prevalence of CMV infection is common in adults. CMV colitis is relatively common in immunocompromised patients; however, it is rare in immunocompetent patients. In our case, CMV infection was allowed to be established due to the disruption of the colonic mucosa by the prior severe ischemic colitis. Our experience suggests that biopsies may be necessary to detect CMV and the prompt management of CMV colitis should be instituted when intractable ischemic colitis is observed.     

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.     

Hemorrhagic colitis caused by dasatinib following cytomegalovirus enterocolitis in a patient with chronic myelogenous leukemia in the second chronic phase

A 26-year-old female progressed to blastic crisis (BC) after three months administration of imatinib for chronic myelogenous leukemia (CML) chronic phase (CP) and was treated with a dasatinib containing chemotherapy regimen. After remission to second CP, she was hospitalized because of fever and hemorrhagic diarrhea during dasatinib maintenance therapy. She was diagnosed as having cytomegalovirus (CMV) colitis because CMV antigen in blood leukocytes was positive and CMV-positive cells were also detected on staining of an ileocecal mucosal biopsy specimen with an anti-CMV antibody. Although blood leukocyte CMV antigen and CMV staining in colonic mucosa became negative after ganciclovir treatment, hemorrhagic diarrhea did not improve. However, after discontinuance of dasatinib, hemorrhagic colitis drastically improved and did not recur after administration of nilotinib. It is possible that hemorrhagic diarrhea occurred due to dasatinib-related hemorrhagic colitis. Previous case reports have indicated that CD8-positive T-lymphocytes infiltrate the colonic mucosa in dasatinib-related hemorrhagic colitis, and the same pathological findings were seen in our case. Dasatinib may cause hemorrhagic colitis via immunological mechanisms in CML. Dasatinib-related gastrointestinal bleeding is less frequent in Japan compared to that in western countries, and Japanese cases diagnosed as having hemorrhagic colitis are extremely rare.     

Detection of cytomegalovirus by immunohistochemistry of colonic biopsies and quantitative blood polymerase chain reaction: evaluation of agreement in ulcerative colitis

Objectives: Cytomegalovirus (CMV) often reactivates in ulcerative colitis (UC). In diagnostics, along with immunohistochemistry (IHC) of colonic biopsies, blood CMV polymerase chain reaction (PCR) is gaining increasing application. We aimed to assess agreement between the density of infected colonic cells by IHC and the viral load in the blood by PCR.

Material and methods: We retrospectively identified patients with active UC or indeterminate colitis in whom blood CMV PCR had been performed while biopsies had been taken simultaneously. The latter were re-evaluated and the numbers of IHC–positive cells per square millimetre counted.

Results: The analyses extended to 234 sample pairs, among which there were 184 cases (78.6% of the total) in which IHC was equal to 0. The median among the remaining 50 non-zero values for IHC was 1.7 cells/mm². PCR was equal to 0 in 192 cases (82.1%), while the median among the remaining 42 non-zero values was 4995.3?IU/ml. The Spearman correlation coefficient was 0.43 (p?5.6 cells/mm²), where PCR?>?0 had a sensitivity of 0.615 and a specificity of 0.846.

Conclusions: In active CMV colitis, the specificity and negative predictive value of blood PCR are high, while the sensitivity grows with the intensity of colon infection. A highly positive result could justify the administration of antiviral treatment being brought forward in selected patients.