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Xiao L, Ma J, Chen R, Chen J, Wang Q, Tang N, Zhao X, Zhang H, Jiao C. The Impact of Cytomegalovirus Infection on Ulcerative Colitis Relapse: A Multicenter Retrospective Cohort Study. J Inflamm Res 2024; 17:9059-9070. [PMID: 39583855 PMCID: PMC11585274 DOI: 10.2147/jir.s479663] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Accepted: 11/13/2024] [Indexed: 11/26/2024] Open
Abstract
Purpose Cytomegalovirus (CMV) infection exacerbates intestinal inflammation in ulcerative colitis (UC) patients, yet the effect of CMV infection on UC relapse has not been fully elucidated. This study aimed to investigate the impact of CMV infection on UC relapse and identify associated risk factors. Patients and Methods This multicenter retrospective cohort study included UC patients who visited research centers from January 2016 to December 2020. Univariate and multivariate Cox regression analyses were conducted to explore risk factors for UC relapse. Propensity score matching was used to balance the differences in the clinical characteristics between the groups. Results A total of 298 UC patients participated in this study, including 19 with CMV colitis, 37 with CMV viremia, and 242 CMV-negative patients. The 2-year cumulative recurrence rate was higher in patients with CMV colitis than that in CMV-negative patients (84.21% vs 51.65%, p = 0.01). Univariate and multivariate Cox regression analyses confirmed that fecal calprotectin ≥ 250 µg/g, Montreal classification E3, CMV colitis, duration > 48 months, and serum albumin < 30 g/L were independent risk factors for UC relapse at 2 years, whereas the use of biologics for induction of remission was identified as an independent protective factor. Conclusion Our study suggests that the risk of relapse increases among UC patients with CMV colitis over two years. Risk factors for UC relapse at 2 years include fecal calprotectin ≥ 250 μg/g, Montreal classification E3, CMV colitis, UC duration > 48 months, and albumin < 30 g/L, whereas the use of biologics during induction is a protective factor.
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Affiliation(s)
- Linmei Xiao
- Department of Liver Disease, Wuxi No.5 People’s Hospital Affiliated to Jiangnan University, Wuxi, People’s Republic of China
| | - Jingjing Ma
- Department of Gastroenterology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China
| | - Ruidong Chen
- Department of Gastroenterology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China
- Department of Gastroenterology, The Second Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China
| | - Jie Chen
- Northern Jiangsu People’s Hospital/Northern Jiangsu People’s Hospital of Jiangsu Province, Yangzhou, Jiangsu Province, People’s Republic of China
| | - Qiang Wang
- Jiangsu Shengze Hospital, Suzhou, Jiangsu Province, People’s Republic of China
| | - Nana Tang
- Department of Gastroenterology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China
| | - Xiaojing Zhao
- Department of Gastroenterology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China
| | - Hongjie Zhang
- Department of Gastroenterology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China
| | - Chunhua Jiao
- Department of Gastroenterology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China
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2
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Ebrahimi R, Masouri MM, Salehi Amniyeh Khozani AA, Ramadhan Hussein D, Nejadghaderi SA. Safety and efficacy of fecal microbiota transplantation for viral diseases: A systematic review of clinical trials. PLoS One 2024; 19:e0311731. [PMID: 39432486 PMCID: PMC11493255 DOI: 10.1371/journal.pone.0311731] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2024] [Accepted: 09/21/2024] [Indexed: 10/23/2024] Open
Abstract
BACKGROUND Gut microbiota play important roles in several diseases like viral infections. In this systematic review, our objective was to assess the efficacy and safety of fecal microbiota transplantation (FMT) in treating various viral diseases. METHODS We conducted searches on databases including PubMed, Web of Science, Scopus, and Google Scholar until November 2023. Clinical trials reported outcomes related to safety of FMT or its efficacy in patients with viral diseases were included. We excluded other types of studies that enrolled healthy individuals or patients with other disorders and did not use FMT. The assessment of bias risk was conducted using the National Institutes of Health (NIH) study quality evaluation tool. RESULTS Eight studies with total 196 participants were included. Viral diseases were human immunodeficiency virus (HIV), hepatitis B, COVID-19 and Clostridioides difficile coinfection, and cytomegalovirus colitis. In hepatitis B cases, HBeAg clearance was significant in those received FMT (p<0.01), while it was not significant in another one (p = 0.19). A clinical response was noted in 37.5% of patients with cytomegalovirus colitis, with an equal percentage achieving clinical remission post-FMT. There was a significant reduction in Clostridioides difficile relapse rate in FMT group than controls in coinfection of Clostridioides difficile and COVID-19 (2.17% vs. 42.5%, p<0.05). In patients with HIV, partial engraftment of the donor microbiome and increases in alpha diversity were observed after FMT. No severe adverse events were reported. Most studies had fair or good qualities. CONCLUSIONS Our findings revealed FMT as a promising, safe treatment for some viral diseases. It improved viral clearance, clinical outcomes, and inflammation. However, the varying responses and small sample sizes call for more trials on FMT in viral diseases.
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Affiliation(s)
- Rasoul Ebrahimi
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | | | | | - Seyed Aria Nejadghaderi
- HIV/STI Surveillance Research Center, and WHO Collaborating Center for HIV Surveillance, Institute for Futures Studies in Health, Kerman University of Medical Sciences, Kerman, Iran
- Systematic Review and Meta-analysis Expert Group (SRMEG), Universal Scientific Education and Research Network (USERN), Tehran, Iran
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3
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Huang D, Rennie M, Krasovec A, Nagubandi S, Liu S, Ge E, Khehra B, Au M, Sivagnanam S, Kwan V, Rogge C, Mitrev N, Kariyawasam V. Impact of cytomegalovirus on outcomes in acute severe ulcerative colitis: a retrospective observational study. Ther Adv Chronic Dis 2024; 15:20406223241233203. [PMID: 38560721 PMCID: PMC10981253 DOI: 10.1177/20406223241233203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2023] [Accepted: 01/25/2024] [Indexed: 04/04/2024] Open
Abstract
BACKGROUND Concomitant cytomegalovirus (CMV) is highly prevalent in acute severe ulcerative colitis (ASUC) but data for outcomes of CMV positivity in ASUC and the benefit of antiviral therapy remain unclear. OBJECTIVES We aim to determine the impact of CMV positivity, and antiviral therapy, on outcomes such as colectomy-free survival, length of hospital stay and readmission rate, among hospitalized patients with ASUC. DESIGN This is a retrospective, multicentre study of patients admitted with ASUC. METHODS CMV positivity was diagnosed from blood CMV DNA and inpatient colonic biopsies. Background demographics and disease characteristics, clinical characteristics and outcomes during admission and long-term outcomes were obtained from electronic medical records and compared according to the presence of CMV and the use of antiviral therapy. RESULTS CMV was detected in 40 (24%) of 167 ASUC admissions. Previous steroid exposure was the only clinical predictor of CMV positivity on multivariate analysis. Outcomes of greater requirement for rescue therapy (60% versus 33%), longer hospital stay (14.3 versus 9.9 days) and higher readmission rates at 3 and 12 months were associated with CMV positivity. No difference was found in the rate of colectomy or colectomy-free survival. Antiviral therapy was not associated with a lower risk of colectomy but did extend the time to colectomy (126 versus 36 days). CONCLUSION CMV positivity was associated with worse outcomes of need for rescue therapy, hospital stay and readmissions. Antiviral therapy was not found to reduce the risk of colectomy but did extend the time to colectomy. Further prospective studies will be required to more clearly determine its benefit in patients with concomitant CMV and ASUC.
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Affiliation(s)
- Dazhong Huang
- Department of Gastroenterology and Hepatology, Blacktown and Mt Druitt Hospital, Blacktown Road, Blacktown NSW 2148, Australia
- University of Western Sydney, Sydney, Australia
| | - Michael Rennie
- Blacktown and Mt Druitt Hospital, Blacktown, NSW, Australia
- University of Western Sydney, Sydney, Australia
| | | | - Shyam Nagubandi
- Blacktown and Mt Druitt Hospital, Blacktown, NSW, Australia
- University of Western Sydney, Sydney, Australia
| | - Sichang Liu
- Blacktown and Mt Druitt Hospital, Blacktown, NSW, Australia
- University of Western Sydney, Sydney, Australia
| | - Edward Ge
- Blacktown and Mt Druitt Hospital, Blacktown, NSW, Australia
- University of Western Sydney, Sydney, Australia
| | - Barinder Khehra
- Blacktown and Mt Druitt Hospital, Blacktown, NSW, Australia
- University of Western Sydney, Sydney, Australia
| | - Michael Au
- Blacktown and Mt Druitt Hospital, Blacktown, NSW, Australia
- University of Western Sydney, Sydney, Australia
| | - Shobini Sivagnanam
- Blacktown and Mt Druitt Hospital, Blacktown, NSW, Australia
- Australian Clinical Labs, Sydney, Australia
| | - Vu Kwan
- Westmead Hospital, Westmead, NSW, Australia
| | | | - Nikola Mitrev
- Blacktown and Mt Druitt Hospital, Blacktown, NSW, Australia
- University of Western Sydney, Sydney, Australia
| | - Viraj Kariyawasam
- Blacktown and Mt Druitt Hospital, Blacktown, NSW, Australia
- University of Western Sydney, Sydney, Australia
- IBD Sydney, Sydney, Australia
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Hock RA, Yousaf M, Allen JC, Heh E, Raynor M, Padilla O, Peralta DP. A Rare Case of Herpes Simplex Virus and Cytomegalovirus Dual Infection Inducing Unremitting Ulcerative Colitis. Cureus 2023; 15:e45166. [PMID: 37842466 PMCID: PMC10570757 DOI: 10.7759/cureus.45166] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/13/2023] [Indexed: 10/17/2023] Open
Abstract
Ulcerative colitis (UC) is a subtype of inflammatory bowel disease that results in inflammation and ulceration in the lining of the large intestine. Patients with UC are frequently prescribed immunosuppressive medications to treat their symptoms, resulting in an increased risk of reactivation of many latent viruses, including herpes simplex virus (HSV) and cytomegalovirus (CMV). However, it is rare for a patient to present with simultaneous reactivation of both viruses. Here, we document the presentation, hospital course, and clinical findings of a UC patient with HSV and CMV dual infection. We also describe treatment strategies and prophylactic measures for managing a dual infection. This is seen through initiating valganciclovir in the outpatient setting following the diagnosis.
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Affiliation(s)
- Rivers A Hock
- Internal Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, USA
| | - Mohammad Yousaf
- Internal Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, USA
| | - Jesse C Allen
- Internal Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, USA
| | - Ethan Heh
- Internal Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, USA
| | - Mark Raynor
- Internal Medicine, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, USA
| | - Osvaldo Padilla
- Pathology, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, USA
| | - Diego P Peralta
- Infectious Diseases, Texas Tech University Health Sciences Center, El Paso, USA
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5
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Ozdemir B, Atay A, Kayhan MA, Ozin YO, Gokce DT, Altunsoy A, Guner R. Tissue quantitative RT-PCR test for diagnostic significance of cytomegalovirus infection in patients with inflammatory bowel disease and treatment response: Cytomegalovirus infection in patients with inflammatory bowel disease. Medicine (Baltimore) 2023; 102:e34463. [PMID: 37543790 PMCID: PMC10402982 DOI: 10.1097/md.0000000000034463] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Revised: 06/28/2023] [Accepted: 07/03/2023] [Indexed: 08/07/2023] Open
Abstract
Cytomegalovirus (CMV) is an opportunistic pathogen that exacerbates inflammatory bowel disease (IBD). There are no clear diagnostic criteria for CMV infection in IBD patients. The aim of this study was to evaluate the importance of the diagnosis of CMV infection with CMV-DNA polymerase chain reaction (PCR) in the colonic mucosa and the response to antiviral treatment. We retrospectively analyzed the clinical data of 30 patients with IBD (24 men, 6 women; median age: 42 years) who were hospitalized because of IBD exacerbation and whose samples were assessed by tissue CMV-DNA PCR positivity. Most of the IBD patients had ulcerative colitis (90%). The CMV-DNA PCR median value was 8848 copies/mL of tissue (range 90-242,936 copies/mL). Blood CMV-DNA PCR was found to be positive in a small group (33.3%, 10/30) of tissue CMV-DNA PCR-positive cases. immunohistochemistry tests were positive in only 5 of the 23 patients positive for CMV-DNA PCR in the colonic mucosa, and high remission (25/30, 83.3%) was detected with antiviral therapy. Recurrence of CMV colitis infection was observed in 9 of 25 patients who had remission with antiviral therapy. The tissue CMV-DNA PCR test was found to be more useful than blood CMV-DNA PCR and immunohistochemistry tests for diagnosing CMV colitis, and the tissue CMV-DNA PCR test enabled rapid and appropriate treatment.
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Affiliation(s)
- Burcu Ozdemir
- Department of Infectious Diseases and Clinical Microbiology Clinic, Ankara City Hospital, Ankara, Turkey
| | - Ali Atay
- Department of Gastroenterology, Ankara City Hospital, Ankara, Turkey
| | | | | | | | - Adalet Altunsoy
- Department of Infectious Diseases and Clinical Microbiology, University of Health Sciences Ankara City Hospital, Ankara, Turkey
| | - Rahmet Guner
- Department of Infectious Diseases and Clinical Microbiology Clinic, Ankara Yildirim Beyazit University, Ankara City Hospital, Ankara, Turkey
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6
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Lee J. [Cytomegalovirus Infection in Patients with Inflammatory Bowel Disease]. THE KOREAN JOURNAL OF GASTROENTEROLOGY = TAEHAN SOHWAGI HAKHOE CHI 2022; 80:60-65. [PMID: 36004632 DOI: 10.4166/kjg.2022.094] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Revised: 07/25/2022] [Accepted: 07/25/2022] [Indexed: 06/15/2023]
Abstract
A diagnostic evaluation for cytomegalovirus (CMV) infection is required in patients with inflammatory bowel disease (IBD) who do not respond to steroid or immunomodulatory treatment. However, there is no consensus on an accurate diagnostic method for CMV infection in patients with IBD, and it is difficult to clearly distinguish the exacerbation of ulcerative colitis from CMV colitis. According to several recent studies, the most accurate test method for CMV colitis is quantitative tissue DNA-quantitative PCR, which is recommended as the first-line diagnostic technique along with an immunohistochemistry stain. The benefit of antiviral therapy for CMV infection in patients with IBD is also controversial. Although the definition of viral load is unclear, antiviral therapy can lower the rate of colectomy in CMV infections with a high viral load in patients with IBD. This review presents the latest findings about CMV infections in IBD, based on recently reported studies.
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Affiliation(s)
- Jun Lee
- Department of Internal Medicine, College of Medicine, Chosun University, Gwangju, Korea
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7
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Donor Screening Revisions of Fecal Microbiota Transplantation in Patients with Ulcerative Colitis. J Clin Med 2022; 11:jcm11041055. [PMID: 35207328 PMCID: PMC8879222 DOI: 10.3390/jcm11041055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Revised: 02/14/2022] [Accepted: 02/16/2022] [Indexed: 11/26/2022] Open
Abstract
Fecal microbiota transplantation (FMT) has been recognized as a promising treatment for dysbiosis-related diseases. Since 2014, FMT has been utilized to treat ulcerative colitis (UC) in our clinical studies and has shown efficacy and safety. As donor screening (DS) is the primary step to ensure the safety of FMT, we report our experience with DS and present the screening results to improve the prospective DS criteria and provide references for future studies. The donor candidates were screened according to the DS criteria. The first DS criteria were proposed in June 2014 and revised substantially in May 2018. We further sorted the screening results and costs of laboratory tests. From June 2014 to April 2018, the DS eligibility rate was 50%. The total laboratory testing cost for each candidate was JPY 17,580/USD 160.21. From May 2018 to September 2021, the DS eligibility rate was 25.6%. The total laboratory testing cost for each candidate was JPY 40,740/USD 371.36. The reduction in donor eligibility rates due to more stringent criteria should be considered for cost and safety. Studies must consider the latest updates and make timely modifications in the DS criteria to ensure patient safety.
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8
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Jena A, Mishra S, Singh AK, Sekar A, Sharma V. Cytomegalovirus in ulcerative colitis: an evidence-based approach to diagnosis and treatment. Expert Rev Gastroenterol Hepatol 2022; 16:109-120. [PMID: 35057693 DOI: 10.1080/17474124.2022.2032662] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2021] [Accepted: 01/19/2022] [Indexed: 12/21/2022]
Abstract
INTRODUCTION The detection of cytomegalovirus (CMV) in the setting of inflammatory bowel disease often creates confusion whether CMV is a 'bystander' or 'disease.' AREAS COVERED This review discusses the clinical conundrum of CMV in ulcerative colitis, approach to discriminate infection from disease, and therapeutic considerations (immunosuppressive and anti-CMV treatment). CMV disease should be considered in corticosteroid refractory- dependent and thiopurine refractory disease. Endoscopy may reveal deep punched out ulcers, irregular ulcers, or cobble-stoning. The diagnosis rests on the presence and abundance of viral inclusion bodies on hematoxylin and eosin stain, positive immunohistochemistry, and/or positive tissue polymerase chain reaction. CMV disease is associated with worse outcomes including increased colectomy rates. EXPERT OPINION The timing and duration of antiviral drugs in CMV disease is debatable but depends on the load of CMV in tissue. In high-grade infection, CMV needs to be treated while increasing immunosuppression may work in the setting of low-grade infection. Ganciclovir is the drug of choice for treatment of CMV disease. Tumor necrosis factor inhibitors may be useful for treating underlying disease activity in the setting of CMV. Other emerging therapies include fecal microbiota transplantation. Randomized studies are necessary to define the best timing and duration of anti-CMV therapy.
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Affiliation(s)
- Anuraag Jena
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Shubhra Mishra
- Department of Gastroenterology, AIG Hospitals, Hyderabad, India
| | - Anupam Kumar Singh
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Aravind Sekar
- Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Vishal Sharma
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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9
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Rao A, Gokhale R. Ulcerative Colitis. TEXTBOOK OF PEDIATRIC GASTROENTEROLOGY, HEPATOLOGY AND NUTRITION 2022:401-421. [DOI: 10.1007/978-3-030-80068-0_30] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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10
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Temtem T, Whitworth J, Zhang J, Bagga B. Cytomegalovirus in pediatric inflammatory bowel disease patients with acute severe colitis. Clin Res Hepatol Gastroenterol 2021; 45:101625. [PMID: 33662784 DOI: 10.1016/j.clinre.2021.101625] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2020] [Revised: 12/28/2020] [Accepted: 01/03/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND The prevalence and significance of cytomegalovirus (CMV) colitis in pediatric acute severe colitis is unknown. The aim of this study was to determine the prevalence of CMV in colonic mucosa of children with acute severe refractory colitis and compare the clinical characteristics and outcomes of CMV positive and negative patients. METHODS In a case-control study, colonic biopsy specimens from children with severe refractory colitis were tested for CMV, and matched with non-refractory IBD controls. We characterized CMV positive patients by assessing laboratory values, concurrent medications, and need for surgery as compared with CMV negative refractory colitis patients. RESULTS Colonic biopsies from 96 patients were evaluated for CMV; 48 with severe refractory colitis, and 48 non-refractory controls. There was an increased prevalence of CMV in severe refractory colitis [7/48 (14.6%), P < 0.0001]; all were previously CMV negative. Viral DNA burden on immunohistochemistry was not predictive of response to antiviral therapy or need for surgery at 12 months. Lymphopenia was seen in all CMV positive patients, but this did not demonstrate statistical significance (P = 0.09). We did not see an association between azathioprine or infliximab use and the need for surgery at 12 months. CONCLUSIONS There is an increased prevalence of CMV in colonic biopsies of pediatric patients with severe refractory colitis. Viral burden does not predict clinical outcomes or subsequent need for colectomy.
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Affiliation(s)
- Tsega Temtem
- Le Bonheur Children's Hospital, USA; Department of Pediatrics, Division of Gastroenterology, University of Tennessee Health Sciences Center, USA; University of Louisville, School of Medicine, USA.
| | - John Whitworth
- Le Bonheur Children's Hospital, USA; Department of Pediatrics, Division of Gastroenterology, University of Tennessee Health Sciences Center, USA.
| | - Jie Zhang
- Le Bonheur Children's Hospital, USA; Department of Pathology, University of Tennessee Health Sciences Center. Memphis, TN, USA.
| | - Bindiya Bagga
- Le Bonheur Children's Hospital, USA; Department of Pediatrics, Division of Infectious Diseases, USA.
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11
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Qin Y, Wang G, Kong D, Li G, Wang H, Qin H, Wang H. Risk Factors of Cytomegalovirus Reactivation in Ulcerative Colitis Patients: A Meta-Analysis. Diagnostics (Basel) 2021; 11:diagnostics11111952. [PMID: 34829298 PMCID: PMC8625464 DOI: 10.3390/diagnostics11111952] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2021] [Revised: 10/12/2021] [Accepted: 10/18/2021] [Indexed: 12/30/2022] Open
Abstract
Cytomegalovirus (CMV) infection is associated with exacerbation of disease activity in patients with ulcerative colitis (UC). However, the risk factors for CMV reactivation in this population remain debatable. This meta-analysis was performed to identify the risk factors for CMV reactivation in UC patients. PubMed, Cochrane Library, EMBASE, Web of Science, and China National Knowledge Infrastructure were searched from the inception of these databases to 31 August 2021, with the aim of identifying studies that investigated the risk factors of CMV reactivation in UC patients. A quality assessment of the included studies was performed with the Newcastle-Ottawa Scale. The publication bias was assessed respectively via a funnel plot and Egger’s regression asymmetry test. The robustness and reliability of each outcome were evaluated by sensitivity analysis. Twenty studies were included in the final meta-analysis, comprising a total of 2099 patients with UC. A significantly higher risk of CMV reactivation was observed in patients with severe UC (OR = 1.465, 95% CI: 1.107 to 1.939, p = 0.008), pancolitis (OR = 2.108, 95% CI: 1.586 to 2.800, p = 0.0001), older age of UC onset (MD = 6.212, 95% CI: 2.552 to 9.971, p = 0.001), as well as use of glucocorticoids (OR = 4.175, 95% CI: 3.076 to 5.666, p = 0.001), immunosuppressants (OR = 1.795, 95% CI: 1.289 to 2.501, p = 0.001), and azathioprine (OR = 1.444, 95% CI: 1.012 to 2.061, p = 0.043). However, infliximab treatment was observed not to increase the occurrence of CMV reactivation in patients who suffered from UC. In contrast, 5-aminosalicylic acid (OR = 0.674, 95% CI: 0.492 to 0.924, p = 0.014) was associated with a lower risk of CMV reactivation. Patients with UC should be closely monitored for risk factors of CMV reactivation in order to provide timely diagnosis and antiviral treatment.
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Affiliation(s)
- Yafei Qin
- Department of General Surgery, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin 300052, China; (Y.Q.); (D.K.); (G.L.); (H.W.); (H.Q.)
- Tianjin General Surgery Institute, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin 300052, China
| | - Grace Wang
- Faculty of Medicine, University of Toronto, Toronto, ON M5S2E8, Canada;
| | - Dejun Kong
- Department of General Surgery, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin 300052, China; (Y.Q.); (D.K.); (G.L.); (H.W.); (H.Q.)
- Tianjin General Surgery Institute, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin 300052, China
| | - Guangming Li
- Department of General Surgery, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin 300052, China; (Y.Q.); (D.K.); (G.L.); (H.W.); (H.Q.)
- Tianjin General Surgery Institute, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin 300052, China
| | - Hongda Wang
- Department of General Surgery, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin 300052, China; (Y.Q.); (D.K.); (G.L.); (H.W.); (H.Q.)
- Tianjin General Surgery Institute, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin 300052, China
| | - Hong Qin
- Department of General Surgery, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin 300052, China; (Y.Q.); (D.K.); (G.L.); (H.W.); (H.Q.)
- Tianjin General Surgery Institute, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin 300052, China
| | - Hao Wang
- Department of General Surgery, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin 300052, China; (Y.Q.); (D.K.); (G.L.); (H.W.); (H.Q.)
- Tianjin General Surgery Institute, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin 300052, China
- Correspondence: or ; Tel.: +86-01186-22-60362502
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12
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Kim YS. Does cytomegalovirus load predict the outcome of acute severe ulcerative colitis? Intest Res 2021; 19:357-359. [PMID: 34731562 PMCID: PMC8566827 DOI: 10.5217/ir.2021.00120] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Accepted: 09/10/2021] [Indexed: 12/24/2022] Open
Affiliation(s)
- You Sun Kim
- Correspondence to You Sun Kim, Department of Internal Medicine, Seoul Paik Hospital, Inje University College of Medicine, 9 Mareunnae-ro, Jung-gu, Seoul 04551, Korea. Tel: +82-2-2270-0012, Fax: +82-2-2270-0257, E-mail:
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13
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van Turenhout ST, Berghuis M, Snaebjornsson P, Wilgenhof S, Burgers JA, Haanen JBAG, van Dieren JM. Cytomegalovirus in Steroid-Refractory Immune Checkpoint Inhibition-Related Colitis. J Thorac Oncol 2021; 15:e15-e20. [PMID: 31864555 DOI: 10.1016/j.jtho.2019.07.026] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2019] [Revised: 07/28/2019] [Accepted: 07/28/2019] [Indexed: 02/08/2023]
Affiliation(s)
- Sietze T van Turenhout
- Department of Gastrointestinal Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
| | - Marieke Berghuis
- Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Petur Snaebjornsson
- Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Sofie Wilgenhof
- Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - J A Burgers
- Department of Pulmonology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - John B A G Haanen
- Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Jolanda M van Dieren
- Department of Gastrointestinal Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
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14
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Alacam S, Karabulut N, Bakir A, Onel M, Buyuk M, Gulluoglu M, Agacfidan A. Diagnostic significance of cytomegalovirus DNA quantitation in gastrointestinal biopsies: comparison with histopathological data and blood cytomegalovirus DNA. Eur J Gastroenterol Hepatol 2021; 33:40-45. [PMID: 32658013 DOI: 10.1097/meg.0000000000001840] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVES This study aims to improve the diagnosis of gastrointestinal (GI) cytomegalovirus (CMV) disease. It presents the results of a novel study in which CMV blood viral load (BVL), tissue viral load (TVL) determined by PCR and hematoxylin-eosin (HE)/immunohistochemistry (IHC) results of GI biopsies are examined comparatively. METHODS CMV DNA was investigated by quantitative real-time PCR in blood and GI biopsy specimens of 76 patients suspected of CMV disease. Biopsies were also performed HE/IHC stainings in the pathology laboratory. RESULTS This study included 76 patients whose median age was 34.5 years and 58% (44) were male. Tissue CMV PCR positivity was detected in the highest colon (40/53;75.5%) samples. HE, IHC, blood and tissue CMV PCR positivity rates of all samples were 15.8, 25, 50 and 71.1%, respectively. When IHC was used as the gold standard test for ROC analysis, the optimal cutoff values for the maximum sensitivity and specificity for BVL and TVL were 1.91 log10 copies/ml and 3.82 log10 copies/mg, respectively. Sensitivity and specificity for the cutoff value of tissue CMV DNA were 78.9 and 74.3%, respectively (P < 0.001). CONCLUSION In this study, CMV DNA was detected in 71.1% of the tissue samples of the cases by PCR. Since the sensitivity of the histopathological examinations accepted as the gold standard is low, simultaneous with the histopathological examinations, determination of BVL, TVL and the identification of optimal cutoff values have been shown to support the diagnosis of GI CMV disease.
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Affiliation(s)
- Sema Alacam
- Division of Virology and Fundamental Immunology, Department of Medical Microbiology, Istanbul Faculty of Medicine, Istanbul University
| | - Nuran Karabulut
- Division of Virology and Fundamental Immunology, Department of Medical Microbiology, Istanbul Faculty of Medicine, Istanbul University
| | - Ayfer Bakir
- Division of Virology and Fundamental Immunology, Department of Medical Microbiology, Istanbul Faculty of Medicine, Istanbul University
| | - Mustafa Onel
- Division of Virology and Fundamental Immunology, Department of Medical Microbiology, Istanbul Faculty of Medicine, Istanbul University
| | - Melek Buyuk
- Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Mine Gulluoglu
- Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Ali Agacfidan
- Division of Virology and Fundamental Immunology, Department of Medical Microbiology, Istanbul Faculty of Medicine, Istanbul University
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15
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Abstract
Despite multiple studies, the role of cytomegalovirus [CMV] infection in exacerbating the severity of inflammation in ulcerative colitis [UC], and its response to treatment, remain debatable. Additionally, the optimal diagnostic tests for CMV infection in the setting of UC relapse, and timing of antiviral treatment initiation, remain unclear. The challenge faced by gastroenterologists is to differentiate between an acute UC flare and true CMV colitis. It seems that the presence of CMV colitis, as defined by the presence of intranuclear or intracellular inclusion bodies on haematoxylin and eosin [H&E] staining and/or positive immunohistochemistry [IHC] assay on histology, is associated with more severe colitis. Patients with CMV infection and acute severe colitis are more resistant to treatment with corticosteroids than non-infected patients. This refractoriness to steroids is related to colonic tissue CMV viral load and number of inclusion bodies [high-grade CMV infection] which may have a pronounced effect on clinical outcomes and colectomy rates. Whereas many studies showed no effect for antiviral treatment on colectomy rates in CMV-infected UC patients, there was a significant difference in colectomy rates of patients with high-grade infection who received anti-viral therapy compared with those who did not receive treatment. It was therefore proposed that high-grade CMV disease indicates that the virus is acting as a pathogen, whereas in those with low-grade CMV disease, the severity of IBD itself is more likely to influence outcome. The different algorithms that have been put forward for the management of patients with UC and concomitant CMV infection are discussed.
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Affiliation(s)
- Fadi H Mourad
- Department of Internal Medicine, American University of Beirut Medical Centre, Beirut, Lebanon
- Gastroenterology and Liver Services, Concord Hospital, Sydney, NSW, Australia
| | - Jana G Hashash
- Department of Internal Medicine, American University of Beirut Medical Centre, Beirut, Lebanon
| | - Viraj C Kariyawasam
- Gastroenterology and Liver Services, Concord Hospital, Sydney, NSW, Australia
| | - Rupert W Leong
- Gastroenterology and Liver Services, Concord Hospital, Sydney, NSW, Australia
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16
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Jentzer A, Veyrard P, Roblin X, Saint-Sardos P, Rochereau N, Paul S, Bourlet T, Pozzetto B, Pillet S. Cytomegalovirus and Inflammatory Bowel Diseases (IBD) with a Special Focus on the Link with Ulcerative Colitis (UC). Microorganisms 2020; 8:1078. [PMID: 32698383 PMCID: PMC7409252 DOI: 10.3390/microorganisms8071078] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Revised: 07/10/2020] [Accepted: 07/12/2020] [Indexed: 12/16/2022] Open
Abstract
Cytomegalovirus (CMV) infects approximately 40% of adults in France and persists lifelong as a latent agent in different organs, including gut. A close relationship is observed between inflammation that favors viral expression and viral replication that exacerbates inflammation. In this context, CMV colitis may impact the prognosis of patients suffering from inflammatory bowel diseases (IBDs), and notably those with ulcerative colitis (UC). In UC, the mucosal inflammation and T helper cell (TH) 2 cytokines, together with immunomodulatory drugs used for controlling flare-ups, favor viral reactivation within the gut, which, in turn, increases mucosal inflammation, impairs corticoid and immunosuppressor efficacy (the probability of steroid resistance is multiplied by more than 20 in the case of CMV colitis), and enhances the risk for colectomy. This review emphasizes the virological tools that are recommended for exploring CMV colitis during inflammatory bowel diseases (IBD) and underlines the interest of using ganciclovir for treating flare-ups associated to CMV colitis in UC patients.
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Affiliation(s)
- Alexandre Jentzer
- GIMAP EA 3064, Medicine Faculty of Saint-Etienne, University of Lyon, 69007 Lyon, France; (A.J.); (P.V.); (X.R.); (N.R.); (S.P.); (T.B.); (B.P.)
- Laboratory of infectious agents and hygiene, University Hospital Saint-Etienne, 42055 Saint-Etienne, France
- Laboratory of Immunology, University Hospital Saint-Etienne, 42055 Saint-Etienne, 42055 Saint-Etienne, France
| | - Pauline Veyrard
- GIMAP EA 3064, Medicine Faculty of Saint-Etienne, University of Lyon, 69007 Lyon, France; (A.J.); (P.V.); (X.R.); (N.R.); (S.P.); (T.B.); (B.P.)
- Department of Gastroenterology, University Hospital Saint-Etienne, 42055 Saint-Etienne, France
| | - Xavier Roblin
- GIMAP EA 3064, Medicine Faculty of Saint-Etienne, University of Lyon, 69007 Lyon, France; (A.J.); (P.V.); (X.R.); (N.R.); (S.P.); (T.B.); (B.P.)
- Department of Gastroenterology, University Hospital Saint-Etienne, 42055 Saint-Etienne, France
| | - Pierre Saint-Sardos
- Laboratory of Bacteriology, University Hospital of Clermont-Ferrand, 63100 Clermont-Ferrand, France;
| | - Nicolas Rochereau
- GIMAP EA 3064, Medicine Faculty of Saint-Etienne, University of Lyon, 69007 Lyon, France; (A.J.); (P.V.); (X.R.); (N.R.); (S.P.); (T.B.); (B.P.)
| | - Stéphane Paul
- GIMAP EA 3064, Medicine Faculty of Saint-Etienne, University of Lyon, 69007 Lyon, France; (A.J.); (P.V.); (X.R.); (N.R.); (S.P.); (T.B.); (B.P.)
- Laboratory of Immunology, University Hospital Saint-Etienne, 42055 Saint-Etienne, 42055 Saint-Etienne, France
| | - Thomas Bourlet
- GIMAP EA 3064, Medicine Faculty of Saint-Etienne, University of Lyon, 69007 Lyon, France; (A.J.); (P.V.); (X.R.); (N.R.); (S.P.); (T.B.); (B.P.)
- Laboratory of infectious agents and hygiene, University Hospital Saint-Etienne, 42055 Saint-Etienne, France
| | - Bruno Pozzetto
- GIMAP EA 3064, Medicine Faculty of Saint-Etienne, University of Lyon, 69007 Lyon, France; (A.J.); (P.V.); (X.R.); (N.R.); (S.P.); (T.B.); (B.P.)
- Laboratory of infectious agents and hygiene, University Hospital Saint-Etienne, 42055 Saint-Etienne, France
| | - Sylvie Pillet
- GIMAP EA 3064, Medicine Faculty of Saint-Etienne, University of Lyon, 69007 Lyon, France; (A.J.); (P.V.); (X.R.); (N.R.); (S.P.); (T.B.); (B.P.)
- Laboratory of infectious agents and hygiene, University Hospital Saint-Etienne, 42055 Saint-Etienne, France
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17
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Arslan F, Vahaboğlu H. Cytomegalovirus and inflammatory bowel disease; reconsidering a 'result or reason dilemma' in terms of viral pathogenesis and medical ethics. Expert Rev Gastroenterol Hepatol 2020; 14:307-309. [PMID: 32228242 DOI: 10.1080/17474124.2020.1745631] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Affiliation(s)
- Ferhat Arslan
- Department of Infectious Diseases and Clinical Microbiology, Istanbul Medeniyet University , Istanbul, Turkey
| | - Haluk Vahaboğlu
- Department of Infectious Diseases and Clinical Microbiology, Istanbul Medeniyet University , Istanbul, Turkey
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18
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Yokoyama Y, Yamakawa T, Hirano T, Kazama T, Hirayama D, Wagatsuma K, Nakase H. Current Diagnostic and Therapeutic Approaches to Cytomegalovirus Infections in Ulcerative Colitis Patients Based on Clinical and Basic Research Data. Int J Mol Sci 2020; 21:ijms21072438. [PMID: 32244555 PMCID: PMC7177554 DOI: 10.3390/ijms21072438] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Revised: 03/28/2020] [Accepted: 03/30/2020] [Indexed: 12/12/2022] Open
Abstract
Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus (the human herpesvirus 5) and an opportunistic pathogen that primarily infects HIV-positive and other immuno-compromised patients. Retrospective studies in the field of inflammatory bowel disease (IBD) have suggested a relationship between a concomitant colonic HCMV infection and poor outcomes in patients with an ulcerative colitis (UC) due to the presence of HCMV in surgical specimens of patients with a toxic megacolon or a steroid-resistant UC. Therefore, gastroenterologists have focused on the contribution of HCMV infections in the exacerbation of UC. Numerous studies have addressed the benefits of treating colonic HCMV reactivation in UC using an antiviral treatment. However, its clinical relevance remains uncertain as only a few prospective studies have assessed the direct relationship between clinical outcomes and the viral load of HCMV in colonic tissues. HCMV reactivation can be triggered by inflammation according to fundamental research studies. Thus, optimal control of intestinal inflammation is essential for preventing an HCMV reactivation in the intestinal mucosa. Indeed, several reports have indicated the effectiveness of an anti-tumor necrosis factor-alpha (TNFα) treatment in patients with an active UC and concomitant HCMV infections. In this review, we describe the mechanism of HCMV reactivation in UC cases and discuss the current issues regarding diagnosis and treatment of HCMV infections in UC patients.
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19
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Lamb CA, Kennedy NA, Raine T, Hendy PA, Smith PJ, Limdi JK, Hayee B, Lomer MCE, Parkes GC, Selinger C, Barrett KJ, Davies RJ, Bennett C, Gittens S, Dunlop MG, Faiz O, Fraser A, Garrick V, Johnston PD, Parkes M, Sanderson J, Terry H, Gaya DR, Iqbal TH, Taylor SA, Smith M, Brookes M, Hansen R, Hawthorne AB. British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults. Gut 2019; 68:s1-s106. [PMID: 31562236 PMCID: PMC6872448 DOI: 10.1136/gutjnl-2019-318484] [Citation(s) in RCA: 1490] [Impact Index Per Article: 248.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2019] [Revised: 06/10/2019] [Accepted: 06/10/2019] [Indexed: 02/06/2023]
Abstract
Ulcerative colitis and Crohn's disease are the principal forms of inflammatory bowel disease. Both represent chronic inflammation of the gastrointestinal tract, which displays heterogeneity in inflammatory and symptomatic burden between patients and within individuals over time. Optimal management relies on understanding and tailoring evidence-based interventions by clinicians in partnership with patients. This guideline for management of inflammatory bowel disease in adults over 16 years of age was developed by Stakeholders representing UK physicians (British Society of Gastroenterology), surgeons (Association of Coloproctology of Great Britain and Ireland), specialist nurses (Royal College of Nursing), paediatricians (British Society of Paediatric Gastroenterology, Hepatology and Nutrition), dietitians (British Dietetic Association), radiologists (British Society of Gastrointestinal and Abdominal Radiology), general practitioners (Primary Care Society for Gastroenterology) and patients (Crohn's and Colitis UK). A systematic review of 88 247 publications and a Delphi consensus process involving 81 multidisciplinary clinicians and patients was undertaken to develop 168 evidence- and expert opinion-based recommendations for pharmacological, non-pharmacological and surgical interventions, as well as optimal service delivery in the management of both ulcerative colitis and Crohn's disease. Comprehensive up-to-date guidance is provided regarding indications for, initiation and monitoring of immunosuppressive therapies, nutrition interventions, pre-, peri- and postoperative management, as well as structure and function of the multidisciplinary team and integration between primary and secondary care. Twenty research priorities to inform future clinical management are presented, alongside objective measurement of priority importance, determined by 2379 electronic survey responses from individuals living with ulcerative colitis and Crohn's disease, including patients, their families and friends.
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Affiliation(s)
- Christopher Andrew Lamb
- Newcastle University, Newcastle upon Tyne, UK
- Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK
| | - Nicholas A Kennedy
- Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
- University of Exeter, Exeter, UK
| | - Tim Raine
- Cambridge University Hospitals NHS FoundationTrust, Cambridge, UK
| | - Philip Anthony Hendy
- Chelsea and Westminster Hospital NHS Foundation Trust, London, UK
- Imperial College London, London, UK
| | - Philip J Smith
- Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK
| | - Jimmy K Limdi
- The Pennine Acute Hospitals NHS Trust, Manchester, UK
- University of Manchester, Manchester, UK
| | - Bu'Hussain Hayee
- King's College Hospital NHS Foundation Trust, London, UK
- King's College London, London, UK
| | - Miranda C E Lomer
- King's College London, London, UK
- Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - Gareth C Parkes
- Barts Health NHS Trust, London, UK
- Barts and the London School of Medicine and Dentistry, London, UK
| | - Christian Selinger
- Leeds Teaching Hospitals NHS Trust, Leeds, UK
- University of Leeds, Leeds, UK
| | | | - R Justin Davies
- Cambridge University Hospitals NHS FoundationTrust, Cambridge, UK
- University of Cambridge, Cambridge, UK
| | - Cathy Bennett
- Systematic Research Ltd, Quorn, UK
- Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland
| | | | - Malcolm G Dunlop
- University of Edinburgh, Edinburgh, UK
- Western General Hospital, Edinburgh, UK
| | - Omar Faiz
- Imperial College London, London, UK
- St Mark's Hospital, Harrow, UK
| | - Aileen Fraser
- University Hospitals Bristol NHS Foundation Trust, Bristol, UK
| | | | | | - Miles Parkes
- Cambridge University Hospitals NHS FoundationTrust, Cambridge, UK
| | - Jeremy Sanderson
- King's College London, London, UK
- Guy's and St Thomas' NHS Foundation Trust, London, UK
| | | | - Daniel R Gaya
- Glasgow Royal Infirmary, Glasgow, UK
- University of Glasgow, Glasgow, UK
| | - Tariq H Iqbal
- Queen Elizabeth Hospital Birmingham NHSFoundation Trust, Birmingham, UK
- University of Birmingham, Birmingham, UK
| | - Stuart A Taylor
- University College London, London, UK
- University College London Hospitals NHS Foundation Trust, London, UK
| | - Melissa Smith
- Brighton and Sussex University Hospitals NHS Trust, Brighton, UK
- Brighton and Sussex Medical School, Brighton, UK
| | - Matthew Brookes
- Royal Wolverhampton NHS Trust, Wolverhampton, UK
- University of Wolverhampton, Wolverhampton, UK
| | - Richard Hansen
- Royal Hospital for Children Glasgow, Glasgow, UK
- University of Glasgow, Glasgow, UK
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20
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Abstract
Ulcerative colitis and Crohn's disease are the principal forms of inflammatory bowel disease. Both represent chronic inflammation of the gastrointestinal tract, which displays heterogeneity in inflammatory and symptomatic burden between patients and within individuals over time. Optimal management relies on understanding and tailoring evidence-based interventions by clinicians in partnership with patients. This guideline for management of inflammatory bowel disease in adults over 16 years of age was developed by Stakeholders representing UK physicians (British Society of Gastroenterology), surgeons (Association of Coloproctology of Great Britain and Ireland), specialist nurses (Royal College of Nursing), paediatricians (British Society of Paediatric Gastroenterology, Hepatology and Nutrition), dietitians (British Dietetic Association), radiologists (British Society of Gastrointestinal and Abdominal Radiology), general practitioners (Primary Care Society for Gastroenterology) and patients (Crohn's and Colitis UK). A systematic review of 88 247 publications and a Delphi consensus process involving 81 multidisciplinary clinicians and patients was undertaken to develop 168 evidence- and expert opinion-based recommendations for pharmacological, non-pharmacological and surgical interventions, as well as optimal service delivery in the management of both ulcerative colitis and Crohn's disease. Comprehensive up-to-date guidance is provided regarding indications for, initiation and monitoring of immunosuppressive therapies, nutrition interventions, pre-, peri- and postoperative management, as well as structure and function of the multidisciplinary team and integration between primary and secondary care. Twenty research priorities to inform future clinical management are presented, alongside objective measurement of priority importance, determined by 2379 electronic survey responses from individuals living with ulcerative colitis and Crohn's disease, including patients, their families and friends.
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21
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Xuan L, Ren L, Han F, Gong L, Wan Z, Yang S, Liu H, Lv Y, Liu L. Cytomegalovirus Infection Exacerbates Experimental Colitis by Promoting IL-23 Production. Inflammation 2019; 43:326-335. [PMID: 31701354 DOI: 10.1007/s10753-019-01122-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Many studies have demonstrated an association between cytomegalovirus (CMV) infection and inflammatory bowel disease (IBD). Moreover, CMV infection is more common in patients with severe or steroid-refractory IBD. However, it is not clarified whether CMV worsens IBD or if it is merely a surrogate marker for IBD. Here, we used the dextran sodium sulfate (DSS)-induced colitis model to investigate if CMV infection exacerbates colitis. The mice were injected intraperitoneally with 10 MOI of murine CMV (MCMV) and thereafter, chronic colitis was induced by one cycle of DSS exposure. Anti-IL-23R mAb at 20 μg/mice and pyrrolidine dithiocarbamate (PDTC), an effective NF-κB inhibitor, at 50 mg/kg were administrated to the mice. The MCMV-infected mice had a shorter colon length and a higher histopathology score than the mock inoculum-treated mice, while anti-IL-23R mAb administration ameliorated the pathological changes. Expression of IL-23, phospho-NF-κB p65, and phospho-IκBα was upregulated in colon tissues of the MCMV-infected mice compared to mock inoculum-treated mice, while treatment with PDTC attenuated colonic IL-23 production. These data demonstrated that CMV infection could accelerate IBD development. This effect may be due to its activation on NF-κB signaling pathway and subsequently IL-23 production.
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Affiliation(s)
- Lingling Xuan
- Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Beijing, 100020, China
| | - Lulu Ren
- Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Beijing, 100020, China
| | - Feifei Han
- Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Beijing, 100020, China
| | - Lili Gong
- Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Beijing, 100020, China
| | - Zirui Wan
- Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Beijing, 100020, China
| | - Song Yang
- Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Beijing, 100020, China
| | - He Liu
- Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Beijing, 100020, China
| | - Yali Lv
- Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Beijing, 100020, China.
| | - Lihong Liu
- Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Beijing, 100020, China.
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Yilmaz Karadag F, Arslan F, Caskurlu H, Cag Y, Vahaboglu H. Efficacy of antiviral treatment in cytomegalovirus detected ulcerative colitis: meta-analysis of available data. Scand J Gastroenterol 2019; 54:1346-1352. [PMID: 31718340 DOI: 10.1080/00365521.2019.1688860] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Aim: This meta-analysis aimed to pool available data regarding the efficacy of ganciclovir treatment among cytomegalovirus-detected ulcerative colitis patients.Methods: We screened PubMed, Ovid, Web of Science and Cochrane databases for relevant studies, and four investigators independently evaluated the studies for eligibility. The primary outcome was surgical resection or death from ulcerative colitis. The data were then pooled via DerSimonian-Laird estimator and Mantel-Haenszel (MH) method, two points added for continuity correction and random-effects model fitted in the Bayesian framework. We first constructed a Bugs model with Student t-distribution as prior for between-study heterogeneity. The model was fitted by Gibbs sampler (JAGS) to produce a marginal posterior distribution.Results: Our screening identified 15 eligible studies for final data synthesis and combined data from 191 ganciclovir-treated and 166 non-treated patients. Effect estimates from the fixed-effects meta-analysis model did not encourage ganciclovir treatment (OR, 1.43; 95% CIs [0-95, 2.16]), with a negligible unaccounted heterogeneity (I2 = 0%). The Bayesian random-effects model generated high-density credible intervals, suggesting a high probability, that future studies will also not encourage ganciclovir treatment (mu, 1.028; 95% credible intervals [0.054, 2.238]; 80% credible intervals [0.401, 1.703]) which indicates that future studies will favor non-treatment of ulcerative colitis with ganciclovir.Conclusions: Data produced in this study do not encourage ganciclovir treatment for UC patients. However, studies included in this analysis were observational, and thus, inherited severe selection bias. We suggest randomized controlled studies be conducted to make firm recommendations in this context.
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Affiliation(s)
- Fatma Yilmaz Karadag
- Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji, Istanbul Medeniyet Universitesi, Istanbul, Turkey
| | - Ferhat Arslan
- Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji, Istanbul Medeniyet Universitesi, Istanbul, Turkey
| | - Hulya Caskurlu
- Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji, Istanbul Medeniyet Universitesi, Istanbul, Turkey
| | - Yasemin Cag
- Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji, Istanbul Medeniyet Universitesi, Istanbul, Turkey
| | - Haluk Vahaboglu
- Enfeksiyon Hastalıkları ve Klinik Mikrobiyoloji, Istanbul Medeniyet Universitesi, Istanbul, Turkey
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Oh SJ, Lee CK, Kim YW, Jeong SJ, Park YM, Oh CH, Kim JW, Kim HJ. True cytomegalovirus colitis is a poor prognostic indicator in patients with ulcerative colitis flares: the 10-year experience of an academic referral inflammatory bowel disease center. Scand J Gastroenterol 2019; 54:976-983. [PMID: 31356759 DOI: 10.1080/00365521.2019.1646798] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Background and aims: The impact of cytomegalovirus (CMV) colitis on long-term outcomes of ulcerative colitis (UC) flares remains controversial. Methods: A total of 257 UC patients with moderate-to-severe flares were observed for a mean follow-up of 41.2 months. CMV colitis was defined as histopathologic confirmation of CMV inclusions obtained from macroscopic endoscopic lesions in patients with UC flares. An independent gastrointestinal pathologist prospectively reviewed all specimens. A poor outcome was defined as any of hospitalization, colectomy or death during the follow-up period. Results: The prevalence of CMV colitis was 14% (36/257) over the 10-year study period (2007-2016). When compared to the controls, patients with CMV colitis were characterized by older age, higher disease activity, endoscopic deep ulcerations and more frequent use of immunosuppressive drugs (all p < .05). In total, 57 outcome events (50 hospitalizations, seven colectomies) were observed among the study population (44.7% in patients with CMV colitis vs. 18.9% in controls). The cumulative probability of a poor outcome was significantly greater in the patients with CMV colitis than in the controls (log-rank test p < .001). In a multivariable analysis, CMV colitis remained as an independent predictor of a poor outcome (hazard ratio; 2.27; 95% confidence interval: 1.12-4.60). Despite a generally favorable response to antiviral therapy (79%), the risk of recurrent CMV colitis remained quite high (57%). Most of the recurrences developed within 8 months (75%). Conclusions: True CMV colitis is a poor prognostic indicator among patients with UC flares. An effective strategy for managing recurrent CMV colitis is urgently needed (KCT0003296).
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Affiliation(s)
- Shin Ju Oh
- Center for Crohn's and Colitis, Department of Gastroenterology, Kyung Hee University College of Medicine , Seoul , South Korea
| | - Chang Kyun Lee
- Center for Crohn's and Colitis, Department of Gastroenterology, Kyung Hee University College of Medicine , Seoul , South Korea
| | - Youn-Wha Kim
- Department of Pathology, Kyung Hee University College of Medicine , Seoul , South Korea
| | - Su Jin Jeong
- Department of Statistics Support, Medical Science Research Institute, Kyung Hee University Medical Center , Seoul , South Korea
| | - Yoo Min Park
- Center for Crohn's and Colitis, Department of Gastroenterology, Kyung Hee University College of Medicine , Seoul , South Korea
| | - Chi Hyuk Oh
- Center for Crohn's and Colitis, Department of Gastroenterology, Kyung Hee University College of Medicine , Seoul , South Korea
| | - Jung-Wook Kim
- Center for Crohn's and Colitis, Department of Gastroenterology, Kyung Hee University College of Medicine , Seoul , South Korea
| | - Hyo Jong Kim
- Center for Crohn's and Colitis, Department of Gastroenterology, Kyung Hee University College of Medicine , Seoul , South Korea
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Hissong E, Chen Z, Yantiss RK. Cytomegalovirus reactivation in inflammatory bowel disease: an uncommon occurrence related to corticosteroid dependence. Mod Pathol 2019; 32:1210-1216. [PMID: 30952971 DOI: 10.1038/s41379-019-0258-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2018] [Revised: 01/30/2019] [Accepted: 01/31/2019] [Indexed: 02/07/2023]
Abstract
Cytomegalovirus promotes mucosal injury in patients with inflammatory bowel disease, historically affecting 10-25% of ulcerative colitis patients with refractory disease. Viral reactivation is likely related to long-term corticosteroid therapy, which is no longer central to maintenance of patients with inflammatory bowel disease. We hypothesize that viral detection rates have decreased in the modern era, reflecting widespread use of immunomodulatory agents to control inflammation. We performed this study to evaluate the relationships between medical regimens and cytomegalovirus detection rates among patients with inflammatory bowel disease. We searched our database for all patients with established inflammatory bowel disease and severe flares diagnosed from 2002 to 2017. Patients maintained with corticosteroid therapy were considered to be corticosteroid-dependent and those treated with other agents were classified as corticosteroid-independent, provided they had not received corticosteroids within 6 months of colonoscopy. Biopsy samples were reviewed for viral inclusions and subjected to cytomegalovirus immunohistochemistry, and rates of viral detection were compared between groups. There were 135 corticosteroid-dependent patients; most had ulcerative colitis flares occurring during the 2002-2009 period. Patients with ulcerative colitis and Crohn disease were equally represented in the corticosteroid-independent group (n = 133) and most were evaluated for disease flares during the 2010-2017 interval. Cytomegalovirus was detected in 13 (8%) cases; 9 (69%) were diagnosed from 2002 to 2009 and all were obtained from corticosteroid-dependent patients (p = < 0.001). We conclude that rates of cytomegalovirus-related enterocolitis are declining among inflammatory bowel disease patients, reflecting a shift away from corticosteroid-based maintenance therapy in favor of more effective agents that do not promote viral reactivation.
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Affiliation(s)
- Erika Hissong
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.
| | - Zhengming Chen
- Division of Biostatistics and Epidemiology, Department of Healthcare Policy and Research, Weill Cornell Medicine, New York, NY, USA
| | - Rhonda K Yantiss
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA
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Ahmed I, Kassem W, Salam Y, Furnari M, Mehta T. Outcome of Cytomegalovirus Colitis in Inflammatory Bowel Disease with Different Regimes of Ganciclovir. Middle East J Dig Dis 2018; 10:220-229. [PMID: 31049169 PMCID: PMC6488501 DOI: 10.15171/mejdd.2018.114] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2018] [Accepted: 09/02/2018] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Cytomegalovirus (CMV) infection is common in individuals with inflammatory bowel disease (IBD) and is responsible for relapse, increased severity, and poor outcome if left untreated. Ganciclovir is the mainstay of treatment but data regarding its use, mode of administration, and duration of treatment is poorly described. We reviewed the practice of treating CMV colitis with different regimes of ganciclovir at a district NHS hospital to compare the clinical outcome. METHODS 35 patients with IBD and concurrent diagnosis of CMV infection were evaluated. The parameters studied were clinical outcome in term of clinical response, length of hospital stay, readmission, or colectomy with three different regimes of ganciclovir, in addition to treatment for IBD. RESULTS 35 patients with IBD (ulcerative colitis = 23, Crohn's disease = 5, Indeterminate colitis = 7) and positive diagnosis of CMV infection were studied. Clinical outcome with two weeks of intravenous (IV) ganciclovir regime was superior than one week of IV ganciclovir and two weeks of oral Valganciclovir in term of clinical response on day 15 (95.8% vs 74%, 24.3%, respectively p = 0.45) and colectomy rate within 3 months (6.25% vs 27.3%, vs 25%, respectively). CONCLUSION CMV colitis is associated with poor outcome in patient with IBD if left untreated. 2 weeks IV ganciclovir was associated with a better outcome than 1 week of IV treatment or oral treatment.
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Affiliation(s)
- Iftikhar Ahmed
- School of Medicine, University of Southampton, UK
- Department of Medicine, Aldara Hospital and Medical Centre, Riyadh, KSA
| | - Wael Kassem
- Department of Medicine, Aldara Hospital and Medical Centre, Riyadh, KSA
| | - Yazen Salam
- School of Medicine, Alfaisal University, Riyadh, KSA
| | | | - Tina Mehta
- Department of Gastroenterology, Royal United Hospital Bath, UK
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Siegmund B. Cytomegalovirus infection associated with inflammatory bowel disease. Lancet Gastroenterol Hepatol 2018; 2:369-376. [PMID: 28397701 DOI: 10.1016/s2468-1253(16)30159-5] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2016] [Revised: 10/11/2016] [Accepted: 10/13/2016] [Indexed: 12/18/2022]
Abstract
Refractory colitis in patients with inflammatory bowel disease is a complicated clinical disorder that might, in some patients, even necessitate surgery. Hence the diagnosis of additional complications is of utmost importance. Colitis mediated by cytomegalovirus is one such complication. The high seroprevalence and latent nature of cytomegalovirus, with the possibility of viral replication without mediating disease, poses a real challenge for the diagnosis of cytomegalovirus-mediated colitis. The challenge in daily clinical practice is to distinguish cytomegalovirus replication from cytomegalovirus-mediated colitis in patients with inflammatory bowel disease who have refractory colitis. This Review discusses the scientific literature and provides a diagnostic and therapeutic algorithm for clinical practice.
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Affiliation(s)
- Britta Siegmund
- Medizinische Klinik für Gastroenterologie, Infektiologie, Rheumatologie, Charité-Universitätsmedizin Berlin, Berlin, Germany.
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Le PH, Kuo CJ, Wu RC, Hsu JT, Su MY, Lin CJ, Chiu CT. Pancolitis associated with higher mortality risk of cytomegalovirus colitis in patients without inflammatory bowel disease. Ther Clin Risk Manag 2018; 14:1445-1451. [PMID: 30154661 PMCID: PMC6108329 DOI: 10.2147/tcrm.s172071] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Cytomegalovirus (CMV) colitis typically presents in immunocompromised and inflammatory bowel disease (IBD) patients. Several studies have been conducted on the endoscopic characteristics of CMV colitis in IBD patients. OBJECTIVES The endoscopic findings of CMV colitis in non-IBD patients and their relationship with inhospital mortality are unclear. We aimed to describe the endoscopic presentation in these patients and to determine the endoscopic predictors of inhospital mortality. PATIENTS AND METHODS Patients with CMV colitis diagnosed using histology between April 2002 and December 2016 at the Linkou Chang Gung Memorial Hospital, Taiwan, were retrospectively enrolled. Patients diagnosed with IBD during follow-up were excluded. Patient data, including underlying diseases, endoscopic presentation, laboratory data, clinical course, complications, and clinical outcomes, were collected. The independent risk factors for inhospital mortality were analyzed with logistic regression. The difference of overall survival was compared using Kaplan-Meier survival curve and log rank test. All statistical calculations were performed using SPSS software, version 21. RESULTS Sixty-nine patients were enrolled, and 8 IBD patients were excluded. Within the 61 non-IBD patients, 31 were diagnosed by colonoscopy and others by sigmoidoscopy. Ulceration (77%) was the most common endoscopic finding, followed by a cobblestone appearance (19.7%), colitis with/without erosions (9.8%), pseudomembrane (9.8%), and tumor/polyp-like lesions (8.2%). Among the patients who underwent full-length colonoscopy, 35.3% presented with right-sided colitis, 23.5% with left-sided colitis, and 32.4% with pancolitis. Pancolitis was identified as a negative predictor of inhospital mortality (odds ratio, 6.8; 95% confidence interval, 1.233-37.497; p=0.028) and overall survival (log rank p=0.018). CONCLUSION Colonoscopy is recommended for precise CMV colitis diagnosis and outcome prediction in non-IBD patients.
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Affiliation(s)
- Puo-Hsien Le
- Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan,
- Taiwan Association for the Study of Small Intestinal Diseases, Taoyuan, Taiwan,
| | - Chia-Jung Kuo
- Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan,
- Taiwan Association for the Study of Small Intestinal Diseases, Taoyuan, Taiwan,
- College of Medicine, Chang Gung University, Taoyuan, Taiwan,
| | - Ren-Chin Wu
- College of Medicine, Chang Gung University, Taoyuan, Taiwan,
- Department of Pathology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Jun-Te Hsu
- College of Medicine, Chang Gung University, Taoyuan, Taiwan,
- Department of General Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Ming-Yao Su
- Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan,
- Taiwan Association for the Study of Small Intestinal Diseases, Taoyuan, Taiwan,
- College of Medicine, Chang Gung University, Taoyuan, Taiwan,
| | - Chun-Jung Lin
- Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan,
- College of Medicine, Chang Gung University, Taoyuan, Taiwan,
| | - Cheng-Tang Chiu
- Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan,
- Taiwan Association for the Study of Small Intestinal Diseases, Taoyuan, Taiwan,
- College of Medicine, Chang Gung University, Taoyuan, Taiwan,
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Johnson J, Affolter K, Boynton K, Chen X, Valentine J, Peterson K. CMV Disease in IBD: Comparison of Diagnostic Tests and Correlation with Disease Outcome. Inflamm Bowel Dis 2018; 24:1539-1546. [PMID: 29718356 DOI: 10.1093/ibd/izy045] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2017] [Indexed: 12/20/2022]
Abstract
BACKGROUND Significance of cytomegalovirus (CMV) in inflammatory bowel disease (IBD) is unclear due to pathobiology, numerous CMV tests, and disparate treatment outcomes. METHODS Retrospective chart review was done on patients with positive qualitative CMV tissue polymerase chain reaction (PCR) from 2005-2013 at a tertiary referral hospital. Frequency of PCR+, hematoxylin and eosin staining(HE)+, histopathology and immunohistochemistry (IHC)+ was assessed. IHC was assessed on a sample of PCR- tissues. Surgery rates were correlated with CMV testing and treatment. RESULTS PCR was done on 310 samples from 180 patients. Thirty-seven samples were PCR+ (51.4% PCR+ only, 35.1% IHC/PCR+, 13.5% HE/IHC/PCR+). The H&E frequently failed to detect CMV identified on extensive IHC. Of 13 PCR- samples tested with IHC, 100% were negative. Twenty-five patients were CMV+ (40% PCR+, 40% IHC/PCR+, 20% HE/IHC/PCR+). Surgery rates increased with number of positive tests: 60% in IHC/PCR+ and 80% in HE/IHC/PCR+, compared to 26.8% in PCR- or PCR+ (P = 0.03, P = 0.02, respectively). There were 20/25 PCR+ patients who received CMV treatment. Surgery occurred in 80% of HE+ patients despite treatment and 100% of IHC+ patients without treatment. CONCLUSIONS Rates of CMV+ testing and surgical risk varied by test modality. PCR+ results were most frequent but alone did not detect clinically significant CMV. HE+ testing was least frequent and associated with highest surgical rate, despite treatment. CMV treatment may benefit IHC+ patients most, supporting immunostaining as optimal diagnostic test for clinically significant CMV in IBD. In PCR+ samples, HE frequently did not detect CMV identified on extensive IHC. In PCR- samples, data suggest IHC is likely negative. Consider using qualitative PCR to guide extensive immunostaining.
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Affiliation(s)
- Jessica Johnson
- Division of Gastroenterology and Hepatology, University of Utah, Salt Lake City, UT, USA
| | | | | | | | - John Valentine
- Division of Gastroenterology and Hepatology, University of Utah
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Evidence-based consensus on opportunistic infections in inflammatory bowel disease (republication). Intest Res 2018; 16:178-193. [PMID: 29743831 PMCID: PMC5934591 DOI: 10.5217/ir.2018.16.2.178] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2018] [Revised: 04/08/2018] [Accepted: 04/16/2018] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel disease (IBD) patients are a high-risk population for opportunistic infections. The IBD group of the Chinese Society of Gastroenterology of the Chinese Medical Association organized an expert group to discuss and develop this consensus opinion. This consensus opinion referenced clinical study results from China and other countries to provide guidance for clinical practices. Eight major topics, including cytomegalovirus infection, Epstein-Barr virus infection, viral hepatitis, bacterial infection, Mycobacterium tuberculosis infection, fungal infection, parasitic infection, and vaccines were introduced in this article.
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Cytomegalovirus infection and steroid-refractory inflammatory bowel disease: possible relationship from an updated meta-analysis. Ir J Med Sci 2018; 187:935-942. [DOI: 10.1007/s11845-018-1752-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2017] [Accepted: 01/17/2018] [Indexed: 12/19/2022]
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Evidence-based consensus on opportunistic infections in inflammatory bowel disease. J Dig Dis 2018; 19:54-65. [PMID: 29330905 DOI: 10.1111/1751-2980.12578] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/12/2018] [Indexed: 01/30/2023]
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Paul M, Gupta E, Jain P, Rastogi A, Bhatia V. Diagnostic utility of quantitative cytomegalovirus DNA polymerase chain reaction in intestinal biopsies from patients with inflammatory bowel disease. J Lab Physicians 2018; 10:38-43. [PMID: 29403203 PMCID: PMC5784291 DOI: 10.4103/jlp.jlp_94_17] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
OBJECTIVES Diagnostic utility of cytomegalovirus (CMV) DNA quantitative polymerase chain reaction (qPCR) in inflammatory bowel disease (IBD) has not been established. We aimed to compare diagnostic utility of qPCR for CMV in biopsy specimens with blood, serology, and histopathology. MATERIALS AND METHODS A total of 132 patients were included (92 ulcerative colitis [UC], 9 Crohn's disease, and 31 unclassified IBD). Comparison between CMV IgM, CMV DNA qPCR in biopsy, in blood and histopathology was done. Positive result in any of the test was considered as CMV infection. Various risk factors for CMV association with IBD were analyzed. RESULTS Confirmed CMV infection was seen in 41 (31.1%) patients. Diagnostic sensitivity of different assays was: DNA in biopsy seen in 37 (90.2%), DNA in blood in 19 (46.3%), CMV IgM in 15 (36.5%), and histopathology in 8 (19.5%). Thirty-two UC cases were further followed up for a median time of 14.0 (R: 3-31) months. They were grouped as group I - biopsy and blood DNA both positive (14, 43.7%), Group II - biopsy positive and blood negative (17, 53.1%), and Group III - biopsy negative but blood positive (1, 3.1%). CMV DNA viral load in Group I was significantly higher (mean: 4.2 ± 1.0 log10 copies/mg) than Group II (mean: 3.2 ± 0.6 copies/mg) and Group III (viral load: 2.69 log10 copies/ml), P < 0.001. Steroid refractoriness was seen more in Group I cases (n = 9) P < 0.001. A cutoff of ≥2.5 log10 copies/mg of DNA in tissue was predictive for steroid refractoriness (AUROC = 0.84). CONCLUSIONS Quantitation of CMV DNA in intestinal biopsy is a useful diagnostic tool and can predict response to steroid treatment in patients with UC.
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Affiliation(s)
- Mousumi Paul
- Department of Clinical Virology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Ekta Gupta
- Department of Clinical Virology, Institute of Liver and Biliary Sciences, New Delhi, India
- Address for correspondence: Dr. Ekta Gupta, Department of Clinical Virology, Institute of Liver and Biliary Sciences, Vasant Kunj, New Delhi - 110 070, India. E-mail:
| | - Priyanka Jain
- Department of Clinical Research, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Archana Rastogi
- Department of Pathology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Vikram Bhatia
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
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Le PH, Lin WR, Kuo CJ, Wu RC, Hsu JT, Su MY, Lin CJ, Chiu CT. Clinical characteristics of cytomegalovirus colitis: a 15-year experience from a tertiary reference center. Ther Clin Risk Manag 2017; 13:1585-1593. [PMID: 29290686 PMCID: PMC5735984 DOI: 10.2147/tcrm.s151180] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Cytomegalovirus (CMV) colitis is considered rare in immunocompetent patients. OBJECTIVE The predictors of mortality and the differences between immunocompetent and immunocompromised patients with this disease remain unknown. Thus, the aim of this retrospective cohort study was to clarify these issues. PATIENTS AND METHODS We enrolled all patients who were histologically diagnosed with CMV colitis between April 2002 and December 2016 in the Linkou Chang Gung Memorial Hospital. Patients were divided into two groups: immunocompetent and immunocompromised, and the differences between them were analyzed to develop in-hospital mortality predictors. RESULTS A total of 69 patients (42, immunocompetent; 27, immunocompromised) were enrolled. The most common symptoms were melena in the immunocompetent group and diarrhea in the immunocompromised group. The in-hospital mortality rate showed no statistically significant difference between the two groups (26.2% vs 25.9%, P=0.981). Early diagnosis was the only significant independent predictor of in-hospital mortality (odds ratio [OR] 1.075, 95% CI 1.005-1.149, P=0.035). The cutoff of diagnostic timing was 9 days from admission, derived from the receiver operating characteristic curve using the Youden index. CONCLUSION CMV colitis in immunocompetent patients is markedly more common and fatal than has generally been acknowledged. Being alert to different ways in which this disease can present itself will enable early diagnosis and significantly reduce mortality.
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Affiliation(s)
- Puo-Hsien Le
- Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital
- Taiwan Association for the Study of Small Intestinal Diseases
| | - Wey-Ran Lin
- Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital
- College of Medicine, Chang Gung University
| | - Chia-Jung Kuo
- Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital
- Taiwan Association for the Study of Small Intestinal Diseases
- College of Medicine, Chang Gung University
| | - Ren-Chin Wu
- College of Medicine, Chang Gung University
- Department of Pathology
| | - Jun-Te Hsu
- College of Medicine, Chang Gung University
- Department of General Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Ming-Yao Su
- Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital
- Taiwan Association for the Study of Small Intestinal Diseases
- College of Medicine, Chang Gung University
| | - Chun-Jung Lin
- Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital
| | - Cheng-Tang Chiu
- Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital
- Taiwan Association for the Study of Small Intestinal Diseases
- College of Medicine, Chang Gung University
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Lv YL, Han FF, Jia YJ, Wan ZR, Gong LL, Liu H, Liu LH. Is cytomegalovirus infection related to inflammatory bowel disease, especially steroid-resistant inflammatory bowel disease? A meta-analysis. Infect Drug Resist 2017; 10:511-519. [PMID: 29276397 PMCID: PMC5733908 DOI: 10.2147/idr.s149784] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Human cytomegalovirus (HCMV) infection has been associated with inflammatory bowel disease (IBD). Numerous studies have been conducted to analyze the association between HCMV infection and risk of IBD and steroid-resistant IBD, but no clear consensus had been reached. OBJECTIVES The aim of this study was to confirm this relationship precisely by doing a systematic review and meta-analysis. STUDY DESIGN We identified relevant studies through a search of PubMed and Embase. Studies were eligible for inclusion if they 1) evaluated the association between HCMV infection and IBD disease; 2) evaluated the association between HCMV infection and steroid-resistant IBD disease; 3) were case-control studies or nested case-control studies; 4) provided the numbers (or percentage) of positivity for HCMV infection in cases and controls, respectively. Data were extracted and analyzed independently by two investigators. RESULTS AND CONCLUSION A total of 18 studies including 1,168 patients and 951 health groups was identified, and HCMV infection was distinctly confirmed as a risk factor for the occurrence and development of IBD. When involving 17 studies including 1,306 IBD patients, a total of 52.9% of patients in the cytomegalovirus (CMV)-positive groups were observed to have steroid resistance, compared with 30.2% of patients in the CMV-negative groups. There was a significant difference in the risk of steroid resistance between people exposed to HCMV infection and those not exposed HCMV infection in IBD patients. This meta-analysis suggested that HCMV infection is associated with an increased risk for IBD and steroid-resistant IBD.
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Affiliation(s)
- Ya-li Lv
- Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China
| | - Fei-fei Han
- Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China
| | - Yang-jie Jia
- Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China
| | - Zi-rui Wan
- Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China
| | - Li-li Gong
- Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China
| | - He Liu
- Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China
| | - Li-hong Liu
- Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China
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Abstract
The incidence of pediatric-onset ulcerative colitis (UC) is rising. Children often present with a more severe disease phenotype as compared to adults with over a third requiring hospitalization for the management of acute severe ulcerative colitis (ASUC). Further, in pediatric patients presenting with inflammatory bowel disease (IBD) limited to the colon, a definitive diagnosis of UC vs. Crohn's disease is often unclear. Here, we review the unique aspects of pediatric ASUC including the epidemiology, diagnosis, medical, and surgical management of this disease.
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Affiliation(s)
- Vei Shaun Siow
- Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Riha Bhatt
- Division of Gastroenterology, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania
| | - Kevin P Mollen
- Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Division of Pediatric Surgery, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania.
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Seo H, Chang K, Lee SH, Song EM, Kim GU, Seo M, Lee HS, Hwang SW, Yang DH, Kim KJ, Ye BD, Byeon JS, Myung SJ, Yang SK, Park SH. Long-term outcomes of infliximab treatment and predictors of response in 195 patients with ulcerative colitis: a hospital-based cohort study from Korea. Scand J Gastroenterol 2017; 52:857-863. [PMID: 28502189 DOI: 10.1080/00365521.2017.1323229] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Large-scale studies regarding the long-term efficacy of infliximab (IFX) treatment in non-Caucasian patients with ulcerative colitis (UC) are lacking. STUDY We analyzed the long-term outcomes of IFX in 195 Korean UC patients who received scheduled IFX treatments at Asan Medical Center. IFX failure was defined as IFX discontinuation due to colectomy or non-response to IFX, and additionally UC-related hospitalization or a need for rescue corticosteroids during the course of IFX. RESULTS Between December 2006 and October 2016, a total of 3101 infusions of IFX were administered to 195 patients over a median period of 21 months. At the end of the follow-up, 86 patients (44.1%) were still receiving IFX without failure. IFX was stopped in 73 (37.4%) patients due to colectomy (23 patients, 11.8%), non-response to IFX (35 patients, 17.9%) or other reasons such as adverse events or patients' preferences (15 patients, 7.7%). An additional 36 (18.5%) patients experienced IFX failure during follow-up due to a need for rescue corticosteroids (13 patients, 6.7%), UC-related hospitalization (8 patients, 4.1%), or both (15 patients, 7.7%). The survival free of IFX failure was 58.1% at 1 year, 50.7% at 3 years and 44.8% at 5 years. In a multivariate regression analysis, cytomegalovirus colitis within 3 months before IFX initiation was a predictor of IFX failure (hazard ratio 1.57; 95% confidence interval 1.04-2.37; p = .032). CONCLUSIONS The long-term efficacy of IFX in a large, real-life cohort of Korean UC patients appears to be comparable to that in previously published Western studies.
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Affiliation(s)
- Hyungil Seo
- a Department of Gastroenterology , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea
| | - Kiju Chang
- a Department of Gastroenterology , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea
| | - Sun-Ho Lee
- a Department of Gastroenterology , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea
| | - Eun-Mi Song
- a Department of Gastroenterology , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea
| | - Gwang-Un Kim
- a Department of Gastroenterology , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea
| | - Myeongsook Seo
- a Department of Gastroenterology , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea
| | - Ho-Su Lee
- b Health Screening and Promotion Center , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea
| | - Sung-Wook Hwang
- a Department of Gastroenterology , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea
- c Inflammatory Bowel Disease Center , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea
| | - Dong-Hoon Yang
- a Department of Gastroenterology , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea
| | - Kyung-Jo Kim
- a Department of Gastroenterology , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea
- c Inflammatory Bowel Disease Center , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea
| | - Byong Duk Ye
- a Department of Gastroenterology , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea
- c Inflammatory Bowel Disease Center , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea
| | - Jeong-Sik Byeon
- a Department of Gastroenterology , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea
| | - Seung-Jae Myung
- a Department of Gastroenterology , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea
| | - Suk-Kyun Yang
- a Department of Gastroenterology , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea
- c Inflammatory Bowel Disease Center , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea
| | - Sang Hyoung Park
- a Department of Gastroenterology , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea
- c Inflammatory Bowel Disease Center , University of Ulsan College of Medicine, Asan Medical Center , Seoul , Korea
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Park SC, Jeen YM, Jeen YT. Approach to cytomegalovirus infections in patients with ulcerative colitis. Korean J Intern Med 2017; 32:383-392. [PMID: 28490715 PMCID: PMC5432807 DOI: 10.3904/kjim.2017.087] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2017] [Accepted: 03/06/2017] [Indexed: 12/16/2022] Open
Abstract
Cytomegalovirus (CMV) reactivation is common in patients with severe ulcerative colitis (UC), and may ref lect exacerbation of mucosal inf lammation and/or administration of immunosuppressants. The question of whether CMV is an active pathogen or 'an innocent bystander' in the exacerbation of UC remains controversial. Patients with UC exacerbated by reactivated CMV experience worse prognoses than those without CMV reactivation and antiviral therapy significantly reduces the need for colectomy in patients with severe UC and high-grade CMV infection, indicating that CMV plays a role in UC prognosis. Therefore, the CMV status of patients on immunosuppressants, particularly those with steroid-refractory or -dependent UC, should be tested. When CMV is detected, be performed based on should adequate treatment the extent of the viral load and the presence of certain clinical features including a large ulcer. Anti-tumor necrosis factor agents may be useful for treating CMV colitis complicating UC.
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Affiliation(s)
- Sung Chul Park
- Department of Internal Medicine, Kangwon National University Hospital, Chuncheon, Korea
| | - Yoon Mi Jeen
- Department of Pathology, Soon Chun Hyang University Seoul Hospital, Seoul, Korea
- Correspondence to Yoon Mi Jeen, M.D. Department of Pathology, Soon Chun Hyang University Seoul Hospital, 59 Daesagwan-ro, Yongsan-gu, Seoul 04401, Korea Tel: +82-2-709-9435 Fax: +82-2-709-9441 E-mail:
| | - Yoon Tae Jeen
- Department of Internal Medicine, Korea University Anam Hospital, Seoul, Korea
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Weng MT, Tung CC, Lee YS, Leong YL, Shieh MJ, Shun CT, Wang CY, Wong JM, Wei SC. Cytomegalovirus colitis in hospitalized inflammatory bowel disease patients in Taiwan: a referral center study. BMC Gastroenterol 2017; 17:28. [PMID: 28193173 PMCID: PMC5307794 DOI: 10.1186/s12876-017-0586-9] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2016] [Accepted: 02/09/2017] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Colitis is exacerbated in patients with concurrent cytomegalovirus (CMV) infection and inflammatory bowel disease (IBD). We assessed the prevalence and clinical features of CMV colitis in hospitalized IBD patients. METHODS A retrospective study reviewed the data from January 1, 1998 through December 31, 2013 compiled at the National Taiwan University Hospital. The CMV colitis patients' demographic data, clinical information, treatment regimens, pathologic findings, and outcome were analyzed. RESULTS A total of 673 IBD patients were hospitalized during the study period. There were 312 patients diagnosed with Crohn's disease (CD) and 361 with ulcerative colitis (UC). CMV colitis was diagnosed as having positive inclusion bodies in colonic tissue. Six of the 312 CD patients (1.9%) and five of the 361 UC patients (1.4%) were diagnosed with CMV colitis. Compared to CD patients without CMV colitis, patients with CMV colitis were more often older (p < 0.005). Higher steroid usage was noted in the CMV positive group compared to age and gender matched CMV negative IBD patients (81.8% vs. 51.5%). Eight patients received ganciclovir treatment. Three patients who did not receive antiviral treatment had colitis flare-ups after the index admission. CONCLUSIONS The prevalence of CMV colitis in hospitalized IBD inpatients was 1.6% in Taiwan. Two associated factors for CMV colitis in hospitalized IBD patients were that they were elderly in CD and were on higher doses of steroids. Routine histopathology studies and/or PCR for refractory colitis patients are suggested to diagnose CMV colitis. Once the diagnosis is made, antiviral treatment is recommended to decrease the colitis relapse rate.
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Affiliation(s)
- Meng-Tzu Weng
- Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, No. 7 Chung-Shan South Road, Taipei City, Taiwan
- Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan
- Department of Chemical Engineering & Materials Science, Yuan-Ze University, Taoyuan, Taiwan
| | - Chien-Chih Tung
- Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, No. 7 Chung-Shan South Road, Taipei City, Taiwan
| | - Yi-Shuan Lee
- Department of Pathology and Forensic Medicine, National Taiwan University Hospital and College of Medicine, Taipei City, Taiwan
| | - Yew-Loong Leong
- Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, No. 7 Chung-Shan South Road, Taipei City, Taiwan
- Department of Internal Medicine, West Garden Hospital, Taipei City, Taiwan
| | - Ming-Jium Shieh
- Department of Oncology, National Taiwan University Hospital and College of Medicine, Taipei City, Taiwan
| | - Chia-Tung Shun
- Department of Pathology and Forensic Medicine, National Taiwan University Hospital and College of Medicine, Taipei City, Taiwan
| | - Cheng-Yi Wang
- Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, No. 7 Chung-Shan South Road, Taipei City, Taiwan
| | - Jau-Min Wong
- Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, No. 7 Chung-Shan South Road, Taipei City, Taiwan
| | - Shu-Chen Wei
- Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, No. 7 Chung-Shan South Road, Taipei City, Taiwan.
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Choi CH, Moon W, Kim YS, Kim ES, Lee BI, Jung Y, Yoon YS, Lee H, Park DI, Han DS. [Second Korean Guideline for the Management of Ulcerative Colitis]. THE KOREAN JOURNAL OF GASTROENTEROLOGY = TAEHAN SOHWAGI HAKHOE CHI 2017; 69:1-28. [PMID: 28135789 DOI: 10.4166/kjg.2017.69.1.1] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/17/2025]
Abstract
Ulcerative colitis (UC) is a chronic inflammatory bowel disorder characterized by a relapsing and remitting course. The direct and indirect costs of the treatment of UC are high, and the quality of life of patients is reduced, especially during exacerbation of the disease. The incidence and prevalence of UC in Korea are still lower than those of Western countries, but have been rapidly increasing during the past decades. Various medical and surgical therapies, including biologics, are currently used for the management of UC. However, many challenging issues exist, which sometimes lead to differences in practice between clinicians. Therefore, the Inflammatory Bowel Disease Study Group of the Korean Association for the Study of Intestinal Diseases established the first Korean guideline for the management of UC in 2012. This is an update of the first guideline. It was generally made by the adaptation of several foreign guidelines as was the first edition, and encompasses treatment of active colitis, maintenance of remission, and indication of surgery for UC. The specific recommendations are presented with the quality of evidence and classification of recommendations.
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Affiliation(s)
- Chang Hwan Choi
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Won Moon
- Department of Internal Medicine, Kosin University College of Medicine, Busan, Korea
| | - You Sun Kim
- Department of Internal Medicine, Seoul Paik Hospital, Inje University College of Medicine, Seoul, Korea
| | - Eun Soo Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea
| | - Bo In Lee
- Division of Gastroenterology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Yunho Jung
- Division of Gastroenterology, Department of Medicine, Soonchunhyang University College of Medicine, Cheonan, Korea
| | - Yong Sik Yoon
- Division of Colon and Rectal Surgery, Department of Surgery, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea
| | - Heeyoung Lee
- Center for Preventive Medicine and Public Health, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Dong Il Park
- Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Dong Soo Han
- Department of Internal Medicine, Hanyang University College of Medicine, Guri, Korea
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Yang SK. How Does the Epidemiology of Inflammatory Bowel Disease Differ between East and West? A Korean Perspective. Inflamm Intest Dis 2017; 2:95-101. [PMID: 30018960 DOI: 10.1159/000454712] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Background Though low compared with those in Western countries, the incidence and prevalence of inflammatory bowel disease (IBD) are rapidly increasing in Asia. If we could understand the differences in IBD epidemiology between Asian and Western countries, we might gain insights into the etiopathogenesis of IBD as well as guidance for personalized therapy. Summary In Asia, unlike in the West, Crohn's disease (CD) predominantly occurs in men and involves a high prevalence of perianal fistulas. Moreover, in Korean CD patients, ileocolonic involvement is predominant, whereas isolated colonic involvement is very uncommon. In both ulcerative colitis (UC) and CD, extraintestinal manifestations, such as primary sclerosing cholangitis, as well as a positive family history of IBD are less frequent in Asian patients. However, as the prevalence of IBD rises in Korea, so does the frequency of a positive family history. While the colectomy rate among Korean UC patients is lower, the intestinal resection rate in CD patients is similar in Korea and in the West. Infectious problems that can adversely influence IBD management are usually more common in Asia. Key Messages IBD in Asians differs from that in Westerners in many aspects, including demographic and clinical characteristics, prognosis, and associated problems.
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Affiliation(s)
- Suk-Kyun Yang
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea
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Shukla T, Singh S, Tandon P, McCurdy JD. Corticosteroids and Thiopurines, But Not Tumor Necrosis Factor Antagonists, are Associated With Cytomegalovirus Reactivation in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis. J Clin Gastroenterol 2017; 51:394-401. [PMID: 27875356 DOI: 10.1097/mcg.0000000000000758] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND The association between cytomegalovirus (CMV) reactivation and individual immunosuppressive agents in inflammatory bowel disease (IBD) has not been clearly defined. Therefore, we performed a systematic review and meta-analysis to assess this association. METHODS Multiple electronic databases were searched systematically through July 2015 for observational studies reporting CMV reactivation (based on serum-based or tissue-based tests) in IBD patients stratified by medication exposure. We estimated summary odds ratios (ORs) and 95% confidence intervals (CI) using random-effects model. Study quality was assessed using the Newcastle-Ottawa scale. RESULTS Sixteen observational studies were identified. As compared with nonexposed patients, exposure to corticosteroids (CS) (12 studies, 1180 patients, 52.3% exposed; OR, 2.05; 95% CI, 1.40-2.99) and thiopurines (14 studies, 1273 patients, 24.1% exposed; OR, 1.56; 95% CI, 1.01-2.39) was associated with increased risk of CMV reactivation. In contrast, as compared with patients not exposed to tumor necrosis factor (TNF) antagonists, exposure to TNF antagonists was not associated with an increased risk of CMV reactivation (7 studies, 818 patients, 18.5% exposed; OR, 1.44; 95% CI, 0.93-2.24). The results remained stable for CS and thiopurines when the analysis was limited to hospitalized patients, and by a tissue-based diagnosis. Studies were limited in the ability to assess the impact of concomitant immunosuppressive therapy, duration of medication exposure, and disease severity. CONCLUSIONS On the basis of 16 observational studies, exposure to CS or thiopurines, but not TNF antagonists, was associated with an increased risk of CMV reactivation in IBD patients.
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Affiliation(s)
- Tushar Shukla
- *Division of Gastroenterology and Hepatology, The Ottawa Hospital, Ottawa, ON, Canada †Division of Gastroenterology, University of California San Diego, La Jolla, CA
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Choi CH, Moon W, Kim YS, Kim ES, Lee BI, Jung Y, Yoon YS, Lee H, Park DI, Han DS. Second Korean guidelines for the management of ulcerative colitis. Intest Res 2017; 15:7-37. [PMID: 28239313 PMCID: PMC5323310 DOI: 10.5217/ir.2017.15.1.7] [Citation(s) in RCA: 53] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2017] [Revised: 01/10/2017] [Accepted: 01/11/2017] [Indexed: 12/12/2022] Open
Abstract
Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by a relapsing and remitting course. The direct and indirect costs of the treatment of UC are high, and the quality of life of patients is reduced, especially during exacerbation of the disease. The incidence and prevalence of UC in Korea are still lower than those of Western countries, but have been rapidly increasing during the past decades. Various medical and surgical therapies, including biologics, are currently used for the management of UC. However, many challenging issues exist, which sometimes lead to differences in practice between clinicians. Therefore, the IBD study group of the Korean Association for the Study of Intestinal Diseases established the first Korean guidelines for the management of UC in 2012. This is an update of the first guidelines. It was generally made by the adaptation of several foreign guidelines as was the first edition, and encompasses treatment of active colitis, maintenance of remission, and indication of surgery for UC. The specific recommendations are presented with the quality of evidence and classification of recommendations.
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Affiliation(s)
- Chang Hwan Choi
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Won Moon
- Department of Internal Medicine, Kosin University College of Medicine, Busan, Korea
| | - You Sun Kim
- Department of Internal Medicine, Seoul Paik Hospital, Inje University College of Medicine, Seoul, Korea
| | - Eun Soo Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea
| | - Bo-In Lee
- Division of Gastroenterology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Yunho Jung
- Division of Gastroenterology, Department of Medicine, Soonchunhyang University College of Medicine, Cheonan, Korea
| | - Yong Sik Yoon
- Division of Colon and Rectal Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Heeyoung Lee
- Center for Preventive Medicine and Public Health, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Dong Il Park
- Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Dong Soo Han
- Department of Internal Medicine, Hanyang University Guri Hospital, Guri, Korea
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Shen L, Youssef D, Abu-Abed S, Malhotra SK, Atkinson K, Vikis E, Melich G, MacKenzie S. Cytomegalovirus duodenitis associated with life-threatening duodenal hemorrhage in an immunocompetent patient: A case report. Int J Surg Case Rep 2017; 33:102-106. [PMID: 28292662 PMCID: PMC5348597 DOI: 10.1016/j.ijscr.2017.02.029] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2017] [Accepted: 02/18/2017] [Indexed: 02/07/2023] Open
Abstract
INTRODUCTION Cytomegalovirus (CMV) is known to be opportunistic in immunocompromised patients. However, there have been emerging cases of severe CMV infections found in immunocompetent patients. Gastrointestinal (GI) CMV disease is the most common manifestation affecting immunocompetent patients, with duodenal involvement being exceedingly rare. Presented is a case of an immunocompetent patient with life-threatening bleeding caused by CMV duodenitis, requiring surgical intervention. PRESENTATION OF CASE A 60-year-old male with history of disseminated Methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia and aortic valve infective endocarditis, presented with life-threatening upper GI hemorrhage. Endoscopy revealed ulcerations, with associated generalized mucosal bleeding in the duodenum. After repeated endoscopic therapies and failed interventional-radiology arterial embolization, the patient required a duodenectomy and associated total pancreatectomy, to control the duodenal hemorrhage. Pathologic review of the surgical specimen demonstrated CMV duodenitis. Systemic ganciclovir was utilized postoperatively. DISCUSSION GI CMV infections should be on the differential diagnosis of immunocompetent patients presenting with uncontrollable GI bleeding, especially in critically ill patients due to transiently suppressed immunity. Endoscopic and histopathological examinations are often required for diagnosis. Ganciclovir is first-line treatment. Surgical intervention may be considered if there is recurrent bleeding and CMV duodenitis is suspected because of high potential for bleeding-associated mortality. CONCLUSION Presented is a rare case of life-threatening GI hemorrhage caused by CMV duodenitis in an immunocompetent patient. The patient failed endoscopic and interventional-radiology treatment options, and ultimately stabilized after surgical intervention.
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Affiliation(s)
- Lucy Shen
- Department of General Surgery, Royal Columbian Hospital, University of British Columbia, New Westminster, BC, Canada.
| | - David Youssef
- Department of General Surgery, Royal Columbian Hospital, University of British Columbia, New Westminster, BC, Canada
| | - Suzan Abu-Abed
- Department of Pathology, Royal Columbian Hospital, University of British Columbia, New Westminster, BC, Canada
| | - Sangita K Malhotra
- Department of Infectious Diseases, Royal Columbian Hospital, University of British Columbia, New Westminster, BC, Canada
| | - Kenneth Atkinson
- Department of Gastroenterology, Royal Columbian Hospital, University of British Columbia, New Westminster, BC, Canada
| | - Elena Vikis
- Department of General Surgery, Royal Columbian Hospital, University of British Columbia, New Westminster, BC, Canada
| | - George Melich
- Department of General Surgery, Royal Columbian Hospital, University of British Columbia, New Westminster, BC, Canada
| | - Shawn MacKenzie
- Department of General Surgery, Royal Columbian Hospital, University of British Columbia, New Westminster, BC, Canada
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Beswick L, Ye B, van Langenberg DR. Toward an Algorithm for the Diagnosis and Management of CMV in Patients with Colitis. Inflamm Bowel Dis 2016; 22:2966-2976. [PMID: 27763950 DOI: 10.1097/mib.0000000000000958] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
INTRODUCTION Concurrent cytomegalovirus (CMV) in inflammatory bowel disease-related colitis is an important yet complex clinical scenario associated with high rates of colectomy and other morbidity. This review aimed to examine the literature to produce a comprehensive diagnostic and treatment algorithm for the management of CMV in patients with colitis. METHODS A systematic literature review was conducted via PubMed/Medline databases until August 31, 2015, using multiple keywords in English language and where original data only presented. RESULTS This review discusses the concept of CMV reactivation which frequently occurs in inflammatory bowel disease-related colitis, most commonly in those presenting with steroid-refractory colitis. In this context, although signifying a poorer prognosis, in most cases, the virus is nonpathogenic and thus antiviral treatment is unhelpful. However, when reactivation gives rise to true CMV disease (colitis) as best discriminated by histology with immunohistochemistry (and the density of such) in colonic biopsy tissue, the patient does benefit from antivirals. CONCLUSION Diagnostic-based patient selection and treatment is integral to optimal outcomes in CMV, and therefore we propose an algorithm based on these concepts that now requires prospective evaluation.
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Affiliation(s)
- Lauren Beswick
- *Department of Gastroenterology, Eastern Health, Melbourne, Victoria, Australia; and †Eastern Health Clinical School, Monash University, Melbourne, Victoria, Australia
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Chen JH, Andrews JM, Kariyawasam V, Moran N, Gounder P, Collins G, Walsh AJ, Connor S, Lee TWT, Koh CE, Chang J, Paramsothy S, Tattersall S, Lemberg DA, Radford-Smith G, Lawrance IC, McLachlan A, Moore GT, Corte C, Katelaris P, Leong RW. Review article: acute severe ulcerative colitis - evidence-based consensus statements. Aliment Pharmacol Ther 2016; 44:127-144. [PMID: 27226344 DOI: 10.1111/apt.13670] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2015] [Revised: 12/18/2015] [Accepted: 04/27/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND Acute severe ulcerative colitis (ASUC) is a potentially life-threatening complication of ulcerative colitis. AIM To develop consensus statements based on a systematic review of the literature of the management of ASUC to improve patient outcome. METHODS Following a literature review, the Delphi method was used to develop the consensus statements. A steering committee, based in Australia, generated the statements of interest. Three rounds of anonymous voting were carried out to achieve the final results. Acceptance of statements was pre-determined by ≥80% votes in 'complete agreement' or 'agreement with minor reservation'. RESULTS Key recommendations include that patients with ASUC should be: hospitalised, undergo unprepared flexible sigmoidoscopy to assess severity and to exclude cytomegalovirus colitis, and be provided with venous thromboembolism prophylaxis and intravenous hydrocortisone 100 mg three or four times daily with close monitoring by a multidisciplinary team. Rescue therapy such as infliximab or ciclosporin should be started if insufficient response by day 3, and colectomy considered if no response to 7 days of rescue therapy or earlier if deterioration. With such an approach, it is expected that colectomy rate during admission will be below 30% and mortality less than 1% in specialist centres. CONCLUSION These evidenced-based consensus statements on acute severe ulcerative colitis, developed by a multidisciplinary group, provide up-to-date best practice recommendations that improve and harmonise management as well as provide auditable quality assessments.
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Affiliation(s)
- J-H Chen
- Concord Hospital, Sydney, NSW, Australia
| | - J M Andrews
- Royal Adelaide Hospital, Adelaide, SA, Australia
| | | | - N Moran
- Concord Hospital, Sydney, NSW, Australia
| | - P Gounder
- Concord Hospital, Sydney, NSW, Australia
| | - G Collins
- Concord Hospital, Sydney, NSW, Australia
| | - A J Walsh
- St. Vincent Hospital, Sydney, NSW, Australia
| | - S Connor
- Liverpool Hospital, Sydney, NSW, Australia
| | - T W T Lee
- Wollongong Hospital, Wollongong, NSW, Australia
| | - C E Koh
- Royal Prince Alfred Hospital, Sydney, NSW, Australia
| | - J Chang
- Concord Hospital, Sydney, NSW, Australia
| | | | - S Tattersall
- Royal North Shore Hospital, Sydney, NSW, Australia
| | - D A Lemberg
- Sydney Children's Hospital, Sydney, NSW, Australia
| | - G Radford-Smith
- Royal Brisbane and Women's Hospital, Brisbane, Qld, Australia
| | - I C Lawrance
- Saint John of God Hospital, Perth, WA, Australia
| | | | - G T Moore
- Monash Medical Centre, Melbourne, Vic., Australia
| | - C Corte
- Concord Hospital, Sydney, NSW, Australia
| | | | - R W Leong
- Concord Hospital, Sydney, NSW, Australia
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Lee HS, Park SH, Kim SH, Kim J, Choi J, Lee HJ, Kim WS, Lee JM, Kwak MS, Hwang SW, Yang DH, Kim KJ, Ye BD, Byeon JS, Myung SJ, Yoon YS, Yu CS, Kim JH, Yang SK. Risk Factors and Clinical Outcomes Associated with Cytomegalovirus Colitis in Patients with Acute Severe Ulcerative Colitis. Inflamm Bowel Dis 2016; 22:912-918. [PMID: 26829410 DOI: 10.1097/mib.0000000000000675] [Citation(s) in RCA: 62] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Cytomegalovirus (CMV) colitis can contribute to an unfavorable outcome of acute severe ulcerative colitis (ASUC). The purpose of this study was to evaluate the clinical outcomes of ASUC according to the CMV status and identify risk factors for CMV colitis in patients with ASUC. METHODS We retrospectively analyzed patients with ASUC from 2011 to 2014 according to the criteria of Truelove and Witts. CMV colitis was diagnosed by histopathological and/or immunohistochemical analysis of tissue samples. The risk factors for CMV colitis were investigated and clinical outcomes were assessed using the rate of rescue therapy and colectomy. RESULTS Of 149 patients with ASUC, 50 (33.6%) were diagnosed with CMV colitis. During admission, 16 of 149 patients (10.7%) underwent colectomy: 7 of 50 (14.0%) in the ASUC-CMV group versus 9 of 99 (9.1%) in the ASUC-only group (P = 0.364). The need for rescue therapy was 2.28-fold higher in the ASUC-CMV group than in the ASUC-only group in multivariate analysis (95% confidence interval, 1.10-4.72). Multivariate analysis also revealed that recent use of high-dose steroids (odds ratio, 3.30; 95% confidence interval, 1.33-8.19) and a higher Mayo score (odds ratio, 1.58; 95% confidence interval, 1.05-2.38) were risk factors for CMV colitis. CONCLUSIONS CMV colitis often occurs in ASUC, particularly in patients who have recently been treated with high-dose steroids and have a higher Mayo score on admission. Patients with ASUC and CMV colitis seem to have a poorer prognosis, as indicated by the greater need for rescue therapy.
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Affiliation(s)
- Ho-Su Lee
- *Health Screening and Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; and Departments of †Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea, ‡Infectious Diseases, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea, §Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea, and ‖Colon and Rectal Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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Pillet S, Pozzetto B, Roblin X. Cytomegalovirus and ulcerative colitis: Place of antiviral therapy. World J Gastroenterol 2016; 22:2030-2045. [PMID: 26877608 PMCID: PMC4726676 DOI: 10.3748/wjg.v22.i6.2030] [Citation(s) in RCA: 65] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2015] [Revised: 11/19/2015] [Accepted: 12/19/2015] [Indexed: 02/06/2023] Open
Abstract
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 flare-ups 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.
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Römkens TEH, Bulte GJ, Nissen LHC, Drenth JPH. Cytomegalovirus in inflammatory bowel disease: A systematic review. World J Gastroenterol 2016; 22:1321-30. [PMID: 26811669 PMCID: PMC4716042 DOI: 10.3748/wjg.v22.i3.1321] [Citation(s) in RCA: 59] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2015] [Revised: 10/12/2015] [Accepted: 11/30/2015] [Indexed: 02/06/2023] Open
Abstract
AIM To identify definitions of cytomegalovirus (CMV) infection and intestinal disease, in inflammatory bowel disease (IBD), to determine the prevalence associated with these definitions. METHODS We conducted a systematic review and interrogated PubMed, EMBASE and Cochrane for literature on prevalence and diagnostics of CMV infection and intestinal disease in IBD patients. As medical headings we used "cytomegalovirus" OR "CMV" OR "cytomegalo virus" AND "inflammatory bowel disease" OR "IBD" OR "ulcerative colitis" OR "colitis ulcerosa" OR "Crohn's disease". Both MeSH-terms and free searches were performed. We included all types of English-language (clinical) trials concerning diagnostics and prevalence of CMV in IBD. RESULTS The search strategy identified 924 citations, and 52 articles were eligible for inclusion. We identified 21 different definitions for CMV infection, 8 definitions for CMV intestinal disease and 3 definitions for CMV reactivation. Prevalence numbers depend on used definition, studied population and region. The highest prevalence for CMV infection was found when using positive serum PCR as a definition, whereas for CMV intestinal disease this applies to the use of tissue PCR > 10 copies/mg tissue. Most patients with CMV infection and intestinal disease had steroid refractory disease and came from East Asia. CONCLUSION We detected multiple different definitions used for CMV infection and intestinal disease in IBD patients, which has an effect on prevalence numbers and eventually on outcome in different trials.
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Antiviral Therapy in Steroid-refractory Ulcerative Colitis with Cytomegalovirus: Systematic Review and Meta-analysis. Inflamm Bowel Dis 2015. [PMID: 26197450 DOI: 10.1097/mib.0000000000000489] [Citation(s) in RCA: 68] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND The role of antiviral therapy in patients with ulcerative colitis (UC) with cytomegalovirus (CMV) remains unclear. We therefore performed a systematic review and meta-analysis to assess the association between antiviral therapy and the risk of colectomy. METHODS Multiple electronic databases were searched systematically through July 2014 for studies reporting the risk of colectomy in patients with UC with CMV stratified by treatment with antiviral agents. Colectomy rates were assessed for the overall cohort and stratified by corticosteroid (CS) refractoriness. We estimated summary odds ratios and 95% confidence intervals, using random-effects model, and used Grading of Recommendations Assessment, Development, and Evaluation criteria to appraise the quality of evidence. RESULTS Fifteen observational studies (333 patients with UC with CMV, 43.2% treated with antiviral agents) were identified, of which 8 stratified patients according to CS-refractory disease (55.4% treated with antiviral agents). Antiviral therapy resulted in a significantly lower risk of colectomy in patients with CS-refractory disease (odds ratio, 0.20; 95% confidence interval, 0.08-0.49; I = 0%) but not in the overall population of patients with UC (odds ratio, 0.92; 95% confidence interval, 0.31-2.76; I = 65). The quality evidence was low. The results were stable when restricting the analysis to patients with a tissue diagnosis of CMV and studies that defined CS-refractory disease as a failure to respond to intravenous CS. CONCLUSIONS Antiviral therapy may benefit a subgroup of patients with UC who are refractory to CS. Further prospective trials are required to confirm these findings.
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Abstract
In the more recent years since the introduction of anti-TNF therapy, the treatment strategy in chronic inflammatory bowel disease has developed more towards an early intensive, often double immunosuppression. While this leads to an improved therapeutic success, this intensified therapy also increases the risk for side effects and especially for infectious complications. The early detection of this complication in the immunocompromised patient is often more difficult due to the potential broad spectrum of infectious agents, the often atypical presentation in conjunction with the immunosuppression as well as often similar symptoms regarding intestinal infectious complications common for a flare of the underlying disease. In the first part, this overview will discuss the broad spectrum of potential infectious complications, using pulmonary infections as an example and presenting an algorithm for detection and therapy. In the second part, common intestinal infectious complications will be discussed from diagnosis to therapy.
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Affiliation(s)
- Torsten Kucharzik
- Department of General Internal Medicine and Gastroenterology, University Teaching Hospital Lüneburg, Lüneburg, Germany
| | - Christian Maaser
- Department of Geriatric Medicine, University Teaching Hospital Lüneburg, Lüneburg, Germany
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