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Szlak J, Magdziak A, Mróz A, Wieszczy-Szczepanik P, Reguła J, Zagórowicz E. Cytomegalovirus infection in patients with active ulcerative colitis: a prospective observational study. Eur J Gastroenterol Hepatol 2025:00042737-990000000-00534. [PMID: 40359279 DOI: 10.1097/meg.0000000000003001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/15/2025]
Abstract
OBJECTIVES The role of cytomegalovirus (CMV) infection in the course of inflammatory bowel disease is still controversial. We aimed to prospectively evaluate the course of ulcerative colitis in patients with exacerbation, in whom CMV status was examined using immunohistochemistry of bowel biopsies. METHODS In a single centre, we followed-up consecutive patients admitted for moderate or severe ulcerative colitis flare between 2016 and 2019. Colectomies, repeated hospitalisations, major treatment modifications, and quality of life (QoL) were recorded. The relationship between categorical variables was examined with the χ2 statistical test or Fisher's exact test. RESULTS Of 84 patients, 16 (19%) were CMV-positive. A Mayo endoscopic score of 3 was more frequent in CMV-positive than CMV-negative patients (81.2 vs. 51.5%; P = 0.048) as was corticosteroid treatment (81.2 vs. 54.4%; P = 0.015). Median follow-up was 2.1 years (range: 0.3-3.6 years). Colectomy was performed in 20 (23.8%) patients, with similar rates in CMV-positive (25%) and CMV-negative patients (23.5%; P = 1.0). Similarly, no differences were found in the frequency of hospitalisation and QoL. The percentage of patients who started biological treatment was higher in the CMV-negative than in the CMV-positive group (58.8 vs. 18.8%; P = 0.005). CONCLUSION CMV infection was present in 19% of consecutive patients hospitalised for ulcerative colitis flare. Corticosteroid treatment and severe endoscopic lesions were observed more often in patients with CMV-positive. In the following 2.1 years, the colectomy rate did not differ between patients with CMV-positive and CMV-negative. Routine screening for CMV in ulcerative colitis exacerbation is not advisable.
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Affiliation(s)
| | | | - Andrzej Mróz
- Department of Pathology and Laboratory Medicine, The Maria Sklodowska-Curie National Research Institute of Oncology
- Department of Pathomorphology, Medical Centre of Postgraduate Education
| | | | - Jaroslaw Reguła
- Department of Microbiology
- Department of Gastroenterology, Hepatology and Clinical Oncology, Medical Centre of Postgraduate Education, Warsaw, Poland
| | - Edyta Zagórowicz
- Department of Microbiology
- Department of Gastroenterology, Hepatology and Clinical Oncology, Medical Centre of Postgraduate Education, Warsaw, Poland
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2
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Singh G, Rentsch C, Beattie W, Christensen B, Macrae F, Segal JP. Long-Term Follow Up of Patients Treated for Inflammatory Bowel Disease and Cytomegalovirus Colitis. Diagnostics (Basel) 2024; 14:2030. [PMID: 39335709 PMCID: PMC11431378 DOI: 10.3390/diagnostics14182030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Revised: 09/04/2024] [Accepted: 09/11/2024] [Indexed: 09/30/2024] Open
Abstract
BACKGROUND Pathological reactivation of latent Cytomegalovirus (CMV) is triggered by inflammation and immunosuppression; both present in the pathogenesis and treatment of Inflammatory Bowel Disease (IBD). Whether CMV reactivation is associated with escalating medical therapy, further hospital admissions, or worse clinical outcomes remains controversial. This study aimed to follow up IBD patients with an index episode of CMV colitis and analyse the clinical outcomes. METHODS A retrospective study of patients with IBD treated for CMV colitis was completed. The outcome results were collected at 6-month and 12-month time points after the first episode of CMV colitis. A total of 13 patients with Ulcerative Colitis and 1 with Crohn's Disease were included. RESULTS CMV colitis recurrence occurred in 29% of patients at 12 months. A total of 43% of patients had changed their biologic dose at 6 months and 29% had escalated their biologic dose at 12 months. At 12 months, 36% of patients had been re-hospitalised, including three colectomies. Disease remission was only achieved by 29% of patients at 12 months. CONCLUSIONS IBD patients with CMV colitis have substantial rates of re-hospitalisation, failed medical therapy, and colectomy. These risks may be greater at <6 months from an index episode of CMV colitis.
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Affiliation(s)
- Gurtej Singh
- Department of Gastroenterology, Royal Melbourne Hospital, Parkville 3052, Australia
| | - Clarissa Rentsch
- Department of Gastroenterology, Royal Melbourne Hospital, Parkville 3052, Australia
| | - William Beattie
- Department of Gastroenterology, Royal Melbourne Hospital, Parkville 3052, Australia
- Department of Gastroenterology, University Hospital Geelong, Geelong 3220, Australia
| | - Britt Christensen
- Department of Gastroenterology, Royal Melbourne Hospital, Parkville 3052, Australia
- Department of Medicine, The University of Melbourne, Parkville 3010, Australia
| | - Finlay Macrae
- Department of Gastroenterology, Royal Melbourne Hospital, Parkville 3052, Australia
- Department of Medicine, The University of Melbourne, Parkville 3010, Australia
| | - Jonathan P. Segal
- Department of Gastroenterology, Royal Melbourne Hospital, Parkville 3052, Australia
- Department of Medicine, The University of Melbourne, Parkville 3010, Australia
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3
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Chen Y, Zheng Q, Wang H, Tang P, Deng L, Li P, Li H, Hou J, Li J, Wang L, Peng J. Integrating transcriptomics and proteomics to analyze the immune microenvironment of cytomegalovirus associated ulcerative colitis and identify relevant biomarkers. BioData Min 2024; 17:26. [PMID: 39192288 DOI: 10.1186/s13040-024-00382-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Accepted: 08/22/2024] [Indexed: 08/29/2024] Open
Abstract
BACKGROUND In recent years, significant morbidity and mortality in patients with severe inflammatory bowel disease (IBD) and cytomegalovirus (CMV) have drawn considerable attention to the status of CMV infection in the intestinal mucosa of IBD patients and its role in disease progression. However, there is currently no high-throughput sequencing data for ulcerative colitis patients with CMV infection (CMV + UC), and the immune microenvironment in CMV + UC patients have yet to be explored. METHOD The xCell algorithm was used for evaluate the immune microenvironment of CMV + UC patients. Then, WGCNA analysis was explored to obtain the co-expression modules between abnormal immune cells and gene level or protein level. Next, three machine learning approach include Random Forest, SVM-rfe, and Lasso were used to filter candidate biomarkers. Finally, Best Subset Selection algorithms was performed to construct the diagnostic model. RESULTS In this study, we performed transcriptomic and proteomic sequencing on CMV + UC patients to establish a comprehensive immune microenvironment profile and found 11 specific abnormal immune cells in CMV + UC group. After using multi-omics integration algorithms, we identified seven co-expression gene modules and five co-expression protein modules. Subsequently, we utilized various machine learning algorithms to identify key biomarkers with diagnostic efficacy and constructed an early diagnostic model. We identified a total of eight biomarkers (PPP1R12B, CIRBP, CSNK2A2, DNAJB11, PIK3R4, RRBP1, STX5, TMEM214) that play crucial roles in the immune microenvironment of CMV + UC and exhibit superior diagnostic performance for CMV + UC. CONCLUSION This 8 biomarkers model offers a new paradigm for the diagnosis and treatment of IBD patients post-CMV infection. Further research into this model will be significant for understanding the changes in the host immune microenvironment following CMV infection.
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Affiliation(s)
- Yang Chen
- Yunnan Provincial Laboratory of Clinical Virology, The First People's Hospital of Yunnan Province, Kunming, Yunnan, 650032, China
- Department of Pathology, The First People's Hospital of Yunnan Province, Kunming, Yunnan, 650032, China
- Department of Pathology, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, 650032, China
| | - Qingqing Zheng
- Department of Pathology, The First People's Hospital of Yunnan Province, Kunming, Yunnan, 650032, China
- Department of Pathology, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, 650032, China
| | - Hui Wang
- Department of Pathology, The First People's Hospital of Yunnan Province, Kunming, Yunnan, 650032, China
- Department of Pathology, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, 650032, China
| | - Peiren Tang
- Department of Pathology, The First People's Hospital of Yunnan Province, Kunming, Yunnan, 650032, China
- Department of Pathology, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, 650032, China
| | - Li Deng
- Department of Pathology, The First People's Hospital of Yunnan Province, Kunming, Yunnan, 650032, China
- Department of Pathology, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, 650032, China
| | - Pu Li
- Department of General Practice, The First People's Hospital of Yunnan Province, Kunming, Yunnan, 650032, China
| | - Huan Li
- Department of Pathology, The First People's Hospital of Yunnan Province, Kunming, Yunnan, 650032, China
- Department of Pathology, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, 650032, China
| | - Jianhong Hou
- Department of Surgery, The First People's Hospital of Yunnan Province, Kunming, Yunnan, 650032, China.
| | - Jie Li
- Academy of Biomedical Engineering, Kunming Medical University, Kunming, Yunnan, 650500, China.
| | - Li Wang
- Department of Pathology, The First People's Hospital of Yunnan Province, Kunming, Yunnan, 650032, China.
- Department of Pathology, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, 650032, China.
| | - Jun Peng
- Department of Surgery, The First People's Hospital of Yunnan Province, Kunming, Yunnan, 650032, China.
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4
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Maresca R, Varca S, Di Vincenzo F, Ainora ME, Mignini I, Papa A, Scaldaferri F, Gasbarrini A, Giustiniani MC, Zocco MA, Laterza L. Cytomegalovirus Infection: An Underrated Target in Inflammatory Bowel Disease Treatment. J Clin Med 2023; 13:130. [PMID: 38202138 PMCID: PMC10779749 DOI: 10.3390/jcm13010130] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Revised: 12/20/2023] [Accepted: 12/22/2023] [Indexed: 01/12/2024] Open
Abstract
CMV infection is still a matter of concern in IBD patients, especially regarding the disease's relapse management. Why IBD patients, particularly those affected by ulcerative colitis, are more susceptible to CMV reactivation is not totally explained, although a weakened immune system could be the reason. Various techniques, ranging from serology to histology, can be employed to detect intestinal CMV infection; however, there is currently disagreement in the literature regarding the most effective diagnostic test. Furthermore, CMV involvement in steroid resistance has been broadly discussed, but whether CMV infection is a cause or consequence of the disease severity and, consequently, steroid refractoriness is still debated. Its potential contribution to the lack of response to advanced therapy and small molecules must be more valued and wholly explored. In this review, we look at the actual literature on CMV in IBD patients, and we suggest a pragmatic algorithm for clinical practice management of CMV infection.
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Affiliation(s)
- Rossella Maresca
- CEMAD Digestive Diseases Center, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Rome, Italy; (R.M.); (S.V.); (F.D.V.); (M.E.A.); (I.M.); (A.P.); (F.S.); (A.G.); (L.L.)
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Simone Varca
- CEMAD Digestive Diseases Center, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Rome, Italy; (R.M.); (S.V.); (F.D.V.); (M.E.A.); (I.M.); (A.P.); (F.S.); (A.G.); (L.L.)
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Federica Di Vincenzo
- CEMAD Digestive Diseases Center, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Rome, Italy; (R.M.); (S.V.); (F.D.V.); (M.E.A.); (I.M.); (A.P.); (F.S.); (A.G.); (L.L.)
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Maria Elena Ainora
- CEMAD Digestive Diseases Center, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Rome, Italy; (R.M.); (S.V.); (F.D.V.); (M.E.A.); (I.M.); (A.P.); (F.S.); (A.G.); (L.L.)
| | - Irene Mignini
- CEMAD Digestive Diseases Center, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Rome, Italy; (R.M.); (S.V.); (F.D.V.); (M.E.A.); (I.M.); (A.P.); (F.S.); (A.G.); (L.L.)
| | - Alfredo Papa
- CEMAD Digestive Diseases Center, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Rome, Italy; (R.M.); (S.V.); (F.D.V.); (M.E.A.); (I.M.); (A.P.); (F.S.); (A.G.); (L.L.)
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Franco Scaldaferri
- CEMAD Digestive Diseases Center, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Rome, Italy; (R.M.); (S.V.); (F.D.V.); (M.E.A.); (I.M.); (A.P.); (F.S.); (A.G.); (L.L.)
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Antonio Gasbarrini
- CEMAD Digestive Diseases Center, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Rome, Italy; (R.M.); (S.V.); (F.D.V.); (M.E.A.); (I.M.); (A.P.); (F.S.); (A.G.); (L.L.)
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Maria Cristina Giustiniani
- Department of Pathology, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy;
| | - Maria Assunta Zocco
- CEMAD Digestive Diseases Center, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Rome, Italy; (R.M.); (S.V.); (F.D.V.); (M.E.A.); (I.M.); (A.P.); (F.S.); (A.G.); (L.L.)
- Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Lucrezia Laterza
- CEMAD Digestive Diseases Center, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Rome, Italy; (R.M.); (S.V.); (F.D.V.); (M.E.A.); (I.M.); (A.P.); (F.S.); (A.G.); (L.L.)
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5
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Dunleavy KA, Cross RK, Raffals LE. Causes, Diagnostic Testing, and Treatment of Residual Symptoms in Patients With IBD With Quiescent Disease. Am J Gastroenterol 2023; 118:1909-1914. [PMID: 36988311 DOI: 10.14309/ajg.0000000000002267] [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] [Received: 02/12/2023] [Accepted: 03/23/2023] [Indexed: 03/30/2023]
Affiliation(s)
- Katie A Dunleavy
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
- Division of Gastroenterology and Hepatology, University of Maryland, Baltimore, Maryland, USA
| | - Raymond K Cross
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
- Division of Gastroenterology and Hepatology, University of Maryland, Baltimore, Maryland, USA
| | - Laura E Raffals
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
- Division of Gastroenterology and Hepatology, University of Maryland, Baltimore, Maryland, USA
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6
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Shelygin YA, Ivashkin VT, Achkasov SI, Reshetov IV, Maev IV, Belousova EA, Vardanyan AV, Nanaeva BA, Adamyan LV, Drapkina OM, Namazova-Baranova LS, Razumovsky AY, Revishvili AS, Khatkov IE, Shabunin AV, Livzan MA, Sazhin AV, Timerbulatov VM, Khlynova OV, Abdulganieva DI, Abdulkhakov RA, Aleksandrov TL, Alekseeva OP, Alekseenko SA, Anosov IS, Bakulin IG, Barysheva OY, Bolikhov KV, Veselov VV, Golovenko OV, Gubonina IV, Dolgushina AI, Zhigalova TN, Kagramanova AV, Kashnikov VN, Knyazev OV, Kostenko NV, Likutov AA, Lomakina EY, Loranskaya ID, Mingazov AF, Moskalev AI, Nazarov IV, Nikitina NV, Odintsova AH, Omelyanovsky VV, Osipenko MF, Оshchepkov АV, Pavlenko VV, Poluektova EA, Rodoman GV, Segal AM, Sitkin SI, Skalinskaya MI, Surkov AN, Sushkov OI, Tarasova LV, Uspenskaya YB, Frolov SA, Chashkova EY, Shifrin OS, Shcherbakova OV, Shchukina OB, Shkurko TV, Makarchuk PA. Clinical guidelines. Crohn’s disease (К50), adults. KOLOPROKTOLOGIA 2023; 22:10-49. [DOI: 10.33878/2073-7556-2023-22-3-10-49] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/17/2024]
Affiliation(s)
- Yury A. Shelygin
- Ryzhikh National Medical Research Center of Coloproctology; Russian Medical Academy of Continuous Professional Education
| | | | - Sergey I. Achkasov
- Ryzhikh National Medical Research Center of Coloproctology; Russian Medical Academy of Continuous Professional Education
| | - Igor V. Reshetov
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - Igor V. Maev
- Moscow State University of Medicine and Dentistry named after A.I. Evdokimov
| | | | | | | | - Leila V. Adamyan
- Moscow State University of Medicine and Dentistry named after A.I. Evdokimov; Mational Medical Research Center of Obstetrics and Gynecology named after V.I. Kulakov
| | - Oksana M. Drapkina
- Moscow State University of Medicine and Dentistry named after A.I. Evdokimov; National Medical Research Center for Therapy and Preventive Medicine
| | - Leila S. Namazova-Baranova
- Reseach Instinute of Pediatrics and Child Health Protection of the Central Clinical Hospital of the Russian Academy of Sciences
| | | | - Amiran Sh. Revishvili
- A.V. Vishnevsky National Medical Research Center of Surgery; Russian Medical Academy of Continuous Professional Education
| | - Igor E. Khatkov
- Moscow Clinical/research Center named after A.S. Loginov" of the Moscow Department of Health
| | | | | | | | | | - Olga V. Khlynova
- Perm State Medical University named after Academician E.A. Wagner" of the Ministry of Health of Russia
| | | | | | | | - Olga P. Alekseeva
- Nizhny Novgorod Regional Clinical Hospital named after N.A. Semashko
| | | | - Ivan S. Anosov
- Ryzhikh National Medical Research Center of Coloproctology
| | - Igor G. Bakulin
- I.I. Mechnikov Northwestern State Medical University of the Ministry of Health of Russia
| | - Olga Yu. Barysheva
- Petrozavodsk State University of the Ministry of Education and Science of Russia
| | | | - Viktor V. Veselov
- Ryzhikh National Medical Research Center of Coloproctology; Russian Medical Academy of Continuous Professional Education
| | | | | | | | | | - Anna V. Kagramanova
- Moscow Clinical/research Center named after A.S. Loginov" of the Moscow Department of Health
| | | | - Oleg V. Knyazev
- Moscow Clinical/research Center named after A.S. Loginov" of the Moscow Department of Health
| | | | | | | | | | | | | | | | | | - Alfia H. Odintsova
- Clinical Hospital of the Ministry of Health of the Republic of Tatarstan
| | | | | | | | | | | | | | | | - Stanislav I. Sitkin
- I.I. Mechnikov Northwestern State Medical University of the Ministry of Health of Russia
| | - Maria I. Skalinskaya
- I.I. Mechnikov Northwestern State Medical University of the Ministry of Health of Russia
| | - Andrey N. Surkov
- Reseach Instinute of Pediatrics and Child Health Protection of the Central Clinical Hospital of the Russian Academy of Sciences
| | | | | | | | | | | | - Oleg S. Shifrin
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | | | - Oksana B. Shchukina
- First St. Petersburg State Medical University named after Academician I.P. Pavlov
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7
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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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8
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Boulagnon-Rombi C, Marchal A, Lirsac M, Svrcek M. [Inflammatory bowel diseases: Scoring and pathological reports optimization]. Ann Pathol 2023:S0242-6498(23)00083-4. [PMID: 37059601 DOI: 10.1016/j.annpat.2023.03.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Revised: 03/13/2023] [Accepted: 03/26/2023] [Indexed: 04/16/2023]
Abstract
The two main forms of inflammatory bowel disease (IBD) are ulcerative colitis (UC) and Crohn's disease (CD). Both diseases have inflammatory flare-ups that alternate with periods of remission. The pathologist may examine biopsies of the digestive tract from IBD patients in different contexts: at the time of the initial diagnosis, in the event of a disease flare-up in order to differentiate a flare of the disease from another cause, particularly an infectious one, and during the long term follow-up of the disease in order to detect the occurrence of dysplastic lesions. Pathologists are increasingly involved in the evaluation of inflammatory activity during the follow-up of IBD patients. The therapeutic management of IBD has evolved significantly and the emergence of new treatments allows a global approach targeting endoscopic mucosal healing. However, mucosal healing is not always correlated with histological healing. Numerous studies have shown the value of histological evaluation during follow-up. A higher score for histological activity in ulcerative colitis predicts a higher likelihood of neoplasia. Histological activity is a better predictor than endoscopic inflammation of the risk. In UC, histological remission may be a long-term therapeutic goal but its role in CD remains unclear. Different scores have been developed to quantify the inflammatory activity of IBD patients and the response to treatment. The aim of this review is to present the main activity scores used in the follow-up of IBD, their interest, their evaluation and their limitations.
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Affiliation(s)
- Camille Boulagnon-Rombi
- Service de pathologie, CHU de Reims, 51092 Reims, France; CNRS, MEDyC UMR 7369, université de Reims Champagne Ardenne, 51097 Reims, France.
| | - Aude Marchal
- Émile-Gallé groupe, centre de pathologie, Nancy, France
| | | | - Magali Svrcek
- Université de la Sorbonne, Paris, France; Service d'anatomie et cytologie pathologiques, Sorbonne université, hôpital Saint-Antoine, AP-HP, Paris, France
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9
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Shelygin YA, Ivashkin VT, Belousova EA, Reshetov IV, Maev IV, Achkasov SI, Abdulganieva DI, Alekseeva OA, Bakulin IG, Barysheva OY, Bolikhov KV, Vardanyan AV, Veselov AV, Veselov VV, Golovenko OV, Gubonina IV, Denisenko VL, Dolgushina AI, Kashnikov VN, Knyazev OV, Kostenko NV, Lakhin AV, Makarchuk PA, Moskalev AI, Nanaeva BA, Nikitin IG, Nikitina NV, Odintsova AK, Omelyanovskiy VV, Оshchepkov AV, Pavlenko VV, Poluektova EA, Sitkin SI, Sushkov OI, Tarasova LV, Tkachev AV, Тimerbulatov VM, Uspenskaya YB, Frolov SA, Khlynova OV, Chashkova EY, Chesnokova OV, Shapina MV, Sheptulin AA, Shifrin OS, Shkurko TV, Shchukina OB. Ulcerative colitis (K51), adults. KOLOPROKTOLOGIA 2023; 22:10-44. [DOI: 10.33878/2073-7556-2023-22-1-10-44] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/26/2023]
Affiliation(s)
- Yu. A. Shelygin
- Ryzhikh National Medical Research Center of Coloproctology; Russian Medical Academy of Continous Professional Education
| | - V. T. Ivashkin
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | | | - I. V. Reshetov
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - I. V. Maev
- Moscow State University of Medicine and Dentistry named after A.I. Evdokimov
| | - S. I. Achkasov
- Ryzhikh National Medical Research Center of Coloproctology; Russian Medical Academy of Continous Professional Education
| | | | | | - I. G. Bakulin
- North-Western State Medical University named after I.I. Mechnikov
| | | | | | | | | | - V. V. Veselov
- Ryzhikh National Medical Research Center of Coloproctology; Russian Medical Academy of Continous Professional Education
| | - O. V. Golovenko
- Ryzhikh National Medical Research Center of Coloproctology; Russian Medical Academy of Continous Professional Education
| | | | - V. L. Denisenko
- Educational Establishment Vitebsk State Order of Peoples’ Friendship Medical University
| | - A. I. Dolgushina
- Federal State Budgetary Educational Institution of Higher Education «South-Ural State Medical University» of the Ministry of Healthcare of the Russian Federation
| | | | - O. V. Knyazev
- GBUZ Moscow Clinical Scientific Center named after Loginov MHD
| | - N. V. Kostenko
- Federal State Budgetary Educational Institution of Higher Education «Astrakhan State Medical University» of the Ministry of Health of the Russian Federation
| | | | | | - A. I. Moskalev
- Ryzhikh National Medical Research Center of Coloproctology
| | - B. A. Nanaeva
- Ryzhikh National Medical Research Center of Coloproctology
| | - I. G. Nikitin
- Pirogov Russian National Research Medical University
| | | | - A. Kh. Odintsova
- GAUZ «RCH» of the Ministry of Health of the Republic of Tatarstan
| | | | - A. V. Оshchepkov
- GBUZ SO «SOKB No. 1» of the Ministry of Health of the Sverdlovsk Region
| | | | - E. A. Poluektova
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - S. I. Sitkin
- North-Western State Medical University named after I.I. Mechnikov
| | - O. I. Sushkov
- Ryzhikh National Medical Research Center of Coloproctology
| | - L. V. Tarasova
- Federal State Budgetary Educational Institution of Higher Education «Chuvash State University named after I.N. Ulyanov»
| | - A. V. Tkachev
- Federal State Budgetary Educational Institution of Higher Education «Rostov State Medical University» of the Ministry of Health of the Russian Federation
| | | | | | - S. A. Frolov
- Ryzhikh National Medical Research Center of Coloproctology
| | - O. V. Khlynova
- Perm State Medical University named after E.A. Wagner (PSMU) of the Ministry of Healthcare of the Russian Feaderation
| | - E. Yu. Chashkova
- Federal State Budgetary Scientific Institution «Irkutsk Scientific Center for Surgery and Traumatology»
| | | | - M. V. Shapina
- Ryzhikh National Medical Research Center of Coloproctology; Russian Medical Academy of Continous Professional Education
| | - A. A. Sheptulin
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - O. S. Shifrin
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - T. V. Shkurko
- Ryzhikh National Medical Research Center of Coloproctology
| | - O. B. Shchukina
- First St. Petersburg State Medical University named after Academician I.P. Pavlov of the Ministry of Health of Russia
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Wang W, Chen X, Pan J, Zhang X, Zhang L. Epstein-Barr Virus and Human Cytomegalovirus Infection in Intestinal Mucosa of Chinese Patients With Inflammatory Bowel Disease. Front Microbiol 2022; 13:915453. [PMID: 35711779 PMCID: PMC9195000 DOI: 10.3389/fmicb.2022.915453] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Accepted: 05/09/2022] [Indexed: 12/30/2022] Open
Abstract
Objective This study aimed to determine the frequency of Epstein–Barr virus (EBV), cytomegalovirus (CMV) in mucosa and blood of inflammatory bowel disease (IBD) patients in China and evaluate their correlation with the clinical disease activities. Methods Peripheral blood and endoscopic fresh colonic mucosal samples were collected from a cohort of 287 IBD patients and 50 controls. Viral DNA load was analyzed through quantitative real-time PCR. The clinical disease activity of ulcerative colitis (UC) and Crohn’s disease (CD) was assessed by the Mayo Clinic Score and Crohn’s disease activity index, respectively. Results Among 287 IBD patients, 228 (79.4%) were positive for EBV and 99 (34.5%) were positive for CMV. EBV and CMV infection rates are significantly higher than those in the control group (28.0%, p < 0.05; 4.0%, p < 0.05). In addition, EBV/CMV prevalence increases as clinical activities progress [For EBV infection, the prevalence was 53.93% (48/89) in the mild group, 87.00% (87/100) in the moderate group, and 94.90% (93/98) in the severe group; and for CMV infection, the prevalence was 3.37% (3/89) in the mild group, 27.00% (27/100) in the moderate group, and 70.41% (69/98) in the severe group]. EBV and CMV loads are related to clinical disease activities (p < 0.05). In addition, viral load in the intestinal mucosa of patients with acute exacerbation of IBD is higher than that of patients in remission. Conclusion High prevalence of EBV and CMV is found in patients with IBD, and their prevalence is related to clinical disease activities. In addition, the viral load in the intestinal mucosa is associated with the status of mucosa in the same patients (active phase versus remission phase). Detection of viral load on mucosal specimens with quantitative real-time PCR is a feasible method to monitor EBV and CMV infection in IBD patients.
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Affiliation(s)
- Wei Wang
- Department of Laboratory Medicine, Shanxi Provincial People's Hospital, Taiyuan, China
| | - Xin Chen
- Department of Laboratory Medicine, The 908th Hospital of Chinese PLA Joint Logistics Support Force, Nanchang, China
| | - Jie Pan
- Department of Pathology, Stanford University School of Medicine, Palo Alto, CA, United States
| | - Xianhui Zhang
- Department of Rheumatology, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Tongji Medical College, Huazhong University of Science and Technology, Taiyuan, China
| | - Liyun Zhang
- Department of Rheumatology, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Tongji Medical College, Huazhong University of Science and Technology, Taiyuan, China
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11
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Yang H, Qian J. Current Status of Cytomegalovirus Colitis Among Patients With Inflammatory Bowel Disease in China: A Questionnaire-Based Multicenter Study. Inflamm Bowel Dis 2022; 28:S45-S51. [PMID: 34984462 DOI: 10.1093/ibd/izab358] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Indexed: 01/25/2023]
Abstract
BACKGROUND Cytomegalovirus (CMV) causes infection in patients with inflammatory bowel disease (IBD). This study investigated the prevalence of CMV colitis, the current status of laboratory testing equipment, and physicians' opinions regarding CMV and IBD in China. METHODS This retrospective multicenter study was conducted by Chinese members of the Asian Organization for Crohn's and Colitis and included 36 hospitals/institutes divided according to municipality, provincial capital city, and prefectural-level city. A survey questionnaire was administered, and chi-square and Fisher's exact tests were performed. RESULTS A total of 4823 inpatients with ulcerative colitis (UC) and 4622 inpatients with Crohn's disease (CD) were included. The percentages of patients with moderate UC in the provincial capital city and municipality were significantly higher than that in the prefectural-level city (38.3% vs 29.1% and 40.1% vs 29.1%, respectively). The percentage of patients with mild CD was significantly lower in the provincial capital city than in the prefectural-level city and municipality (30.4% vs 40.3%; 30.4% vs 39.3%, respectively). There were 3.1% patients with UC and 0.8% patients with CD who had CMV colitis. The prevalence of CMV colitis was lower in patients with CD than in patients with UC (0.8% vs 3.1%). Of the 150 patients with UC and concurrent CMV colitis, 17.3% patients underwent surgery, 2.0% died, and 23.3% experienced complications. Punched-out ulcerations were the major characteristic features for detecting CMV colitis. Approximately 77.8% of hospitals possessed testing facilities capable of conducting CMV immunohistochemistry. CONCLUSIONS CMV colitis is an important issue during the disease progression of IBD. However, improvement in knowledge and facilities is required to enhance the prognosis of patients.
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Affiliation(s)
- Hong Yang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China
| | - Jiaming Qian
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China
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12
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Chen Y, Shen J. Core indicators of an evaluation and guidance system for quality of care in inflammatory bowel disease centers: A critical review. EClinicalMedicine 2022; 46:101382. [PMID: 35434585 PMCID: PMC9011022 DOI: 10.1016/j.eclinm.2022.101382] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Revised: 02/18/2022] [Accepted: 03/22/2022] [Indexed: 02/07/2023] Open
Abstract
The mission of the IBD Quality Care Evaluation Center (IBDQCC) is to establish indicators of quality of care (QoC), certify IBD units to generate a network of IBD quality care, and eventually improve the national level of IBD healthcare. The final list of 28 core and 13 secondary IBD QoC indicators suitable for the healthcare system in China were selected using a Delphi consensus methodology. Units that met all core indicators were qualified as "regional"; units that met all core indicators together with more than 50% of the secondary indicators received a rating of "excellence." Using the selected QoC core indicators for certifying IBD units, a network of IBD quality care units covering the majority of IBD patients in China was established. Funding This work was financially supported by Cultivation Funding for Clinical Scientific Research Innovation, Renji Hospital, School of Medicine, Shanghai Jiaotong University (RJPY-LX-004), National Natural Science Foundation of China (No. 81,770,545), Shanghai Science and Technology Innovation Initiative (21SQBS02302), and Cultivated Funding for Clinical Research Innovation, Renji Hospital, School of Medicine, Shanghai Jiaotong University (RJPY-LX-004).
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Affiliation(s)
- Yueying Chen
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Inflammatory Bowel Disease Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, 160# Pu Jian Ave, Shanghai 200127, China
| | - Jun Shen
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Inflammatory Bowel Disease Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, 160# Pu Jian Ave, Shanghai 200127, China
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13
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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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Kochan K, Keskin EB, Seven G, Bas S, Kiremitci S, Gecer M, Senturk H. Effects of tissue cytomegalovirus quantitative polymerase chain reaction in the management of ulcerative colitis flare-ups: Should we wave aside? Arab J Gastroenterol 2021; 22:297-304. [PMID: 34872846 DOI: 10.1016/j.ajg.2021.11.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2021] [Revised: 11/13/2021] [Accepted: 11/16/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND STUDY AIMS The role of cytomegalovirus (CMV) infection for disease reactivation in ulcerative colitis (UC) patients remains controversial and diagnostic tests are yet to be standardized. We aimed to define the clinical relevance of CMV detection by mucosal polymerase chain reaction (PCR) in UC patients by comparing the clinical course of UC in CMV-treated and CMV-untreated groups in tissue CMV-PCR positive cases. PATIENTS AND METHODS In this retrospective study, 141 patients diagnosed with moderate-to-severe UC admitted to our clinic with disease flare, colonic tissue CMV PCR was assessed. RESULTS The median age of the study population was 39 years, and 99 (70.2%) patients were male. Eighty-eight (62.4%) patients were CMV-PCR (+) and 53 (37.6%) were CMV PCR (-). The CMV-PCR (+) and CMV PCR (-) groups showed no significant difference concerning age, sex, disease duration, site of involvement and disease activity and administered treatments. The median tissue CMV-PCR was 41,098 IU/mL (IQR:2,344.25-136,192). Thirty-four of 88 CMV-PCR (+) patients received antiviral therapy. The tissue CMV-PCR level of patients who received antiviral therapy was 124,381 IU/mL (IQR: 19,309-412,335), and it was 6,292 IU/mL (IQR: 997-71,154) in patients who did not receive antiviral therapy; (p < 0.001). Sixteen (47.1%) of 34 patients who received antiviral therapy achieved remission. Two of the non-responders underwent colectomy (one because of dysplasia and one who did not respond subsequent biologic agent either). Remaing 16 achieved remission by escalating the immunsuppresive/biologic agent therapy. CONCLUSION CMV infection is responsible for only a minority of cases of UC flares and all are steroid-resistant cases. Most of the patients non-responsive to antiviral treatment respond to increased anti-inflammatory treatment. Hesitancy in the decision of escalating immunsuppresive treatment rather than CMV disease may be responsible for worsening disease course and increased colectomy rate in a significant number of the patients who are tissue CMV-PCR (+).
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Affiliation(s)
- Koray Kochan
- Division of Gastroenterology, Bezmialem University School of Medicine, Istanbul, Turkey
| | - Elmas Biberci Keskin
- Division of Gastroenterology, Bezmialem University School of Medicine, Istanbul, Turkey
| | - Gulseren Seven
- Division of Gastroenterology, Bezmialem University School of Medicine, Istanbul, Turkey
| | - Suleyman Bas
- Division of Internal Medicine, Sancaktepe Sehit Prof. Dr. Ilhan Varank Training and Research Hospital, Istanbul, Turkey
| | - Sercan Kiremitci
- Division of Gastroenterology, Bezmialem University School of Medicine, Istanbul, Turkey
| | - Melin Gecer
- Division of Pathology, Bezmialem University School of Medicine, Istanbul, Turkey
| | - Hakan Senturk
- Division of Gastroenterology, Bezmialem University School of Medicine, Istanbul, Turkey.
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Abstract
BACKGROUND Data about cytomegalovirus (CMV) colitis in children are scarce. We aimed to describe the characteristics of childhood CMV colitis in terms of risk factors, clinical symptoms, diagnosis, therapeutic approaches, and outcomes. METHODS Inflammatory bowel disease (IBD) and non-IBD patients with CMV colitis diagnosed by histology and tissue CMV PCR at 2 tertiary centers between January 2017 and November 2019 were studied. Clinical and laboratory data were retrieved from medical records. Underlying conditions, immune status, response to therapy and outcomes were described and followed up to 6 months after diagnosis. RESULTS A total of 16 children (8 non-IBD, 7 ulcerative colitis and 1 Crohn's disease) with CMV colitis were included. All patients had persistent diarrhea (bloody in 13 cases). There was a significant age difference between IBD and non-IBD children (P < 0.05). The final diagnosis in 1 patient was immunodeficiency with a mutation in JAK1 gene. Three children were categorized as apparently immunocompromised and 4 children as apparently immunocompetent. Ulcer was not visible in 2 children from the non-IBD group. The mean fecal calprotectin level of IBD children was significantly higher than that of non-IBD children (376.12 ± 231.21 µg/g vs. 160.96 ± 69.94 µg/g, P < 0.05). After follow-up, 1 patient died because of another reason. Ganciclovir was used in 14 of 16 children for 3 weeks and the treatment was continued with valganciclovir in selected 6 children. CONCLUSIONS CMV colitis is a rare but overlooked cause of prolonged diarrhea in immunocompetent and immunocompromised children. CMV colitis might present without any ulcer formation at colonoscopy in infants.
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16
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Song J, Bhuta R, Baig K, Parkman HP, Malik Z. COVID-19 infection manifesting as a severe gastroparesis flare: A case report. Medicine (Baltimore) 2021; 100:e25467. [PMID: 33832159 PMCID: PMC8036087 DOI: 10.1097/md.0000000000025467] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2020] [Revised: 03/12/2021] [Accepted: 03/18/2021] [Indexed: 12/23/2022] Open
Abstract
RATIONALE Coronavirus disease 2019 (COVID-19) is a disease caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which commonly presents with symptoms including fever, cough, and dyspnea. More recently, however, some patients have tested positive for COVID-19 after developing gastrointestinal (GI) symptoms either solely or in conjunction with respiratory symptoms. This may be due to SARS-CoV-2 infection of the GI tract. In patients with chronic GI illnesses, COVID-19 may initially present as a flare of their underlying GI conditions as viruses have historically been implicated in exacerbations of GI disorders, including gastroparesis. PATIENT CONCERNS We report a case of a 37-year-old female with a history of diabetic gastroparesis who presented to the Emergency Department (ED) with nausea and vomiting similar to her gastroparesis flares. DIAGNOSES Her symptoms in the ED failed to improve with fluids and anti-emetic medications. After developing a fever, she was tested and found to be positive for COVID-19. INTERVENTIONS She was started on antibiotic, steroid, and antiviral medications. OUTCOMES Her symptoms improved, her fever defervesced on day 4 of hospitalization, and she was discharged on day 5 of hospitalization. The patient reported symptom improvement at a follow-up outpatient gastroenterology visit 2 months after hospitalization. LESSONS To the best of our knowledge, at the present time, this is the first report of a patient with COVID-19 presenting with signs and symptoms of a gastroparesis flare. This case illustrates that COVID-19 may present in an exacerbation of symptoms of an underlying disorder, such as a severe gastroparesis flare, in a patient with underlying gastroparesis. Initial presentation of these patients manifesting as a flare of their chronic GI disease, more severe than usual, should prompt an index of suspicion for COVID-19.
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Affiliation(s)
- Jun Song
- Temple University Hospital, Department of Medicine
| | - Rajiv Bhuta
- Section of Gastroenterology and Hepatology, Department of Medicine, Temple University School of Medicine, Philadelphia, PA, USA
| | - Kamal Baig
- Section of Gastroenterology and Hepatology, Department of Medicine, Temple University School of Medicine, Philadelphia, PA, USA
| | - Henry P. Parkman
- Section of Gastroenterology and Hepatology, Department of Medicine, Temple University School of Medicine, Philadelphia, PA, USA
| | - Zubair Malik
- Section of Gastroenterology and Hepatology, Department of Medicine, Temple University School of Medicine, Philadelphia, PA, USA
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17
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Gugliesi F, Pasquero S, Griffante G, Scutera S, Albano C, Pacheco SFC, Riva G, Dell’Oste V, Biolatti M. Human Cytomegalovirus and Autoimmune Diseases: Where Are We? Viruses 2021; 13:260. [PMID: 33567734 PMCID: PMC7914970 DOI: 10.3390/v13020260] [Citation(s) in RCA: 48] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Revised: 02/03/2021] [Accepted: 02/05/2021] [Indexed: 12/14/2022] Open
Abstract
Human cytomegalovirus (HCMV) is a ubiquitous double-stranded DNA virus belonging to the β-subgroup of the herpesvirus family. After the initial infection, the virus establishes latency in poorly differentiated myeloid precursors from where it can reactivate at later times to cause recurrences. In immunocompetent subjects, primary HCMV infection is usually asymptomatic, while in immunocompromised patients, HCMV infection can lead to severe, life-threatening diseases, whose clinical severity parallels the degree of immunosuppression. The existence of a strict interplay between HCMV and the immune system has led many to hypothesize that HCMV could also be involved in autoimmune diseases (ADs). Indeed, signs of active viral infection were later found in a variety of different ADs, such as rheumatological, neurological, enteric disorders, and metabolic diseases. In addition, HCMV infection has been frequently linked to increased production of autoantibodies, which play a driving role in AD progression, as observed in systemic lupus erythematosus (SLE) patients. Documented mechanisms of HCMV-associated autoimmunity include molecular mimicry, inflammation, and nonspecific B-cell activation. In this review, we summarize the available literature on the various ADs arising from or exacerbating upon HCMV infection, focusing on the potential role of HCMV-mediated immune activation at disease onset.
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Affiliation(s)
- Francesca Gugliesi
- Department of Public Health and Pediatric Sciences, University of Turin, 10126 Turin, Italy; (F.G.); (S.P.); (S.S.); (C.A.); (S.F.C.P.); (V.D.)
| | - Selina Pasquero
- Department of Public Health and Pediatric Sciences, University of Turin, 10126 Turin, Italy; (F.G.); (S.P.); (S.S.); (C.A.); (S.F.C.P.); (V.D.)
| | - Gloria Griffante
- Department of Translational Medicine, Molecular Virology Unit, University of Piemonte Orientale Medical School, 28100 Novara, Italy;
| | - Sara Scutera
- Department of Public Health and Pediatric Sciences, University of Turin, 10126 Turin, Italy; (F.G.); (S.P.); (S.S.); (C.A.); (S.F.C.P.); (V.D.)
| | - Camilla Albano
- Department of Public Health and Pediatric Sciences, University of Turin, 10126 Turin, Italy; (F.G.); (S.P.); (S.S.); (C.A.); (S.F.C.P.); (V.D.)
| | - Sergio Fernando Castillo Pacheco
- Department of Public Health and Pediatric Sciences, University of Turin, 10126 Turin, Italy; (F.G.); (S.P.); (S.S.); (C.A.); (S.F.C.P.); (V.D.)
| | - Giuseppe Riva
- Otorhinolaryngology Division, Department of Surgical Sciences, University of Turin, 10126 Turin, Italy;
| | - Valentina Dell’Oste
- Department of Public Health and Pediatric Sciences, University of Turin, 10126 Turin, Italy; (F.G.); (S.P.); (S.S.); (C.A.); (S.F.C.P.); (V.D.)
| | - Matteo Biolatti
- Department of Public Health and Pediatric Sciences, University of Turin, 10126 Turin, Italy; (F.G.); (S.P.); (S.S.); (C.A.); (S.F.C.P.); (V.D.)
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Gilmore RB, Taylor KM, Morrissey CO, Gardiner BJ. Cytomegalovirus in inflammatory bowel disease: a clinical approach. Intern Med J 2020; 52:365-368. [PMID: 33009857 DOI: 10.1111/imj.15085] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Revised: 09/25/2020] [Accepted: 09/27/2020] [Indexed: 11/29/2022]
Abstract
Cytomegalovirus (CMV) infection can be a challenging clinical problem in patients with inflammatory bowel disease (IBD), particularly ulcerative colitis. Clinical presentation is difficult to distinguish from an underlying disease flare. A number of diagnostic modalities are now available and when combined can aid clinicians in the identification of patients who are most likely to benefit from antiviral therapy. The aim of this article is to review the available literature and outline a practical approach to the diagnosis and management of CMV in patients with IBD. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Robert B Gilmore
- Department of Gastroenterology, Alfred Health, Melbourne, Victoria, Australia.,Department of Gastroenterology, Austin Health, Melbourne, Victoria, Australia
| | - Kirstin M Taylor
- Department of Gastroenterology, Alfred Health, Melbourne, Victoria, Australia.,Central Clinical School, Monash University, Melbourne, Victoria, Australia
| | - C Orla Morrissey
- Central Clinical School, Monash University, Melbourne, Victoria, Australia.,Department of Infectious Disease, Alfred Health, Melbourne, Victoria, Australia
| | - Bradley J Gardiner
- Central Clinical School, Monash University, Melbourne, Victoria, Australia.,Department of Infectious Disease, Alfred Health, Melbourne, Victoria, Australia
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Yang H, Wu K, Zhang H, Owyang Q, Miao Y, Gu F, Hu N, Zou K, Sheng J, Li J, Zheng P, Liu Y, Li J, Wang X, Wu Y, Yuan Y, Chen C, Pang Y, Cui M, Qian J. IgA, albumin, and eosinopenia as early indicators of cytomegalovirus infection in patients with acute ulcerative colitis. BMC Gastroenterol 2020; 20:294. [PMID: 32891125 PMCID: PMC7487863 DOI: 10.1186/s12876-020-01434-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2020] [Accepted: 08/21/2020] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Cytomegalovirus (CMV) infection can significantly complicate and worsen the condition of acute severe ulcerative colitis (UC) patients. We aimed to explore the predictive risk factors to prevent and identify CMV infection at an early stage in acute UC patients. METHODS A total of 115 moderate-to-severe active UC patients from 17 hospitals throughout China were enrolled. Active CMV infection was diagnosed by one of the following: CMV pp65 antigens, CMV IgM antibodies or CMV DNA. We identified the independent risk factors by multivariate analyses. RESULTS A total of 64 of 115 active UC patients had active CMV infection. Compared to the non-CMV-infected patients, the CMV-infected patients had a tendency to be male and to exhibit abdominal pain; fever; oral ulcers; eosinopenia; low albumin, immunoglobulin (Ig) A, IgM, and IgG levels; increased high-sensitivity C-reactive protein (hsCRP) levels; hyponatremia; pancolonic lesions; initial onset type; severe activity; and glucocorticoid (high-dose) and immunosuppressive agent use (P < 0.05). In further multivariate analyses, the use of high-dose glucocorticoids (OR 13.55, 95% CI 2.49-73.61, P < 0.01) and immunosuppressive agents (OR 11.23, 95% CI 1.05-119.99, P = 0.04) were independent risk factors for CMV infection. A decrease eosinophil and albumin levels were risk factors for CMV infection. With every 0.1*10^9/L decrease in the peripheral blood eosinophil level or 1 g/L decrease in the serum albumin level, the risk for CMV infection in UC patients increased by 5.21-fold (1/0.192) or 1.19-fold (1/0.839), respectively. CONCLUSIONS High-dose glucocorticoid and immunosuppressive agent treatment significantly increase the risk of CMV infection, and correcting eosinopenia and low albumin levels may help prevent CMV infection in UC patients.
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Affiliation(s)
- Hong Yang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, 100730, P.R. China
| | - Kaichun Wu
- Department of Gastroenterology, Xijin Hospital, The Fourth Military Medical University, Xi'an, China
| | - Hongjie Zhang
- Department of Gastroenterology, Jiangsu Province Hospital, Nanjing, China
| | - Qin Owyang
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, China
| | - Yinglei Miao
- Department of Gastroenterology, First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Fang Gu
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Naizhong Hu
- Department of Gastroenterology, First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Kaifang Zou
- Department of Gastroenterology, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
| | - Jianqiu Sheng
- Department of Gastroenterology, General Hospital of Beijing Military Region, Beijing, China
| | - Jin Li
- Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Ping Zheng
- Department of Gastroenterology, Shanghai General Hospital, Shanghai, China
| | - Yulan Liu
- Department of Gastroenterology, Peking University People's Hospital, Beijing, China
| | - Junxia Li
- Department of Gastroenterology, Peking University First Hospital, Beijing, China
| | - Xiaodi Wang
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing, China
| | - Yongdong Wu
- Department of Gastroenterology, Beijing Friendship Hospital of Capital Medical University, Beijing, China
| | - Yaozong Yuan
- Department of Gastroenterology, Ruijin Hospital of Shanghai Jiaotong University School of Medicine, Shanghai, China
| | - Chunxiao Chen
- Department of Gastroenterology, First Affiliated Hospital of Zhejiang University, Beijing, China
| | - Yanhua Pang
- Department of Gastroenterology, Beijing Chao-Yang Hospital, Beijing, China
| | - Meihua Cui
- Department of Gastroenterology, Aerospace Central Hospital, Beijing, China
| | - Jiaming Qian
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, 100730, P.R. China.
- Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, P.R. China.
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20
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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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21
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Magdziak A, Szlak J, Mróz A, Wieszczy P, Zagórowicz E. A stool test in patients with active ulcerative colitis helps exclude cytomegalovirus disease. Scand J Gastroenterol 2020; 55:664-670. [PMID: 32552149 DOI: 10.1080/00365521.2020.1771760] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Objectives: In severe ulcerative colitis (UC) bowel biopsy is recommended to detect the cytomegalovirus (CMV) infection capable of complicating the course of the disease. Histopathology with immunohistochemistry (IHC) is time-consuming, and a blood polymerase chain reaction (PCR) for CMV DNA is used as an alternative, notwithstanding nothing more than a moderate correlation between the two. We aimed to detect CMV DNA in the stools of patients with active UC, and to compare the results with CMV IHC in bowel biopsies.Materials and methods: Measurement of CMV DNA in stools (copies/ml) entailed PCR, while biopsies assessed inflammation activity (Geboes scale), as well as counts of numbers of CMV IHC-positive cells/biopsy. The severity of UC was assessed using the Mayo score, stool calprotectin and concentrations of C-reactive protein in the blood.Results: 89 of the above pairs of tests for CMV were performed among 75 patients. CMV was detected in 36/89 stool specimens and 19/89 bowel biopsies. The sensitivity of the stool-CMV PCR was thus 84.7%, while specificity was of 71.4%. The negative predictive value was 94.3% and the positive predictive value 44.4%. No difference in the severity of UC was noted between the stool CMV DNA positive and negative groups. Similarly, there was no difference in the severity of UC between the CMV IHC positive and negative groups, except for the Geboes score, more often found to be higher in CMV IHC-positive patients (p = .002).Conclusions: CMV DNA was detected in the stools of 40.4% of patients with active UC. A negative test result may help to exclude bowel CMV disease.
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Affiliation(s)
- Agnieszka Magdziak
- The Maria Sklodowska-Curie National Research Institute of Oncology, Department of Microbiology, Warsaw, Poland
| | - Jakub Szlak
- The Maria Sklodowska-Curie National Research Institute of Oncology, Department of Gastroenterology, Warsaw, Poland
| | - Andrzej Mróz
- The Center of Postgraduate Medical Education, Department of Pathomorphology, Warsaw, Poland.,The Maria Sklodowska-Curie National Research Institute of Oncology, Department of Pathology and Laboratory Medicine, Warsaw, Poland
| | - Paulina Wieszczy
- The Maria Sklodowska-Curie National Research Institute of Oncology, Department of Cancer Prevention, Warsaw, Poland.,Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
| | - Edyta Zagórowicz
- The Maria Sklodowska-Curie National Research Institute of Oncology, Department of Gastroenterology, Warsaw, Poland.,The Center of Postgraduate Medical Education, Department of Gastroenterology and Hepatology and Clinical Oncology, Warsaw, Poland
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22
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Bohossian HB, Lopes EW, Roller LA, Ananthakrishnan AN, Zukerberg LR. Case 8-2020: An 89-Year-Old Man with Recurrent Abdominal Pain and Bloody Stools. N Engl J Med 2020; 382:1042-1052. [PMID: 32160667 DOI: 10.1056/nejmcpc1913476] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Affiliation(s)
- Hacho B Bohossian
- From the Department of Medicine, Newton-Wellesley Hospital, Newton (H.B.B.), and the Department of Medicine, Tufts University School of Medicine (H.B.B.), the Departments of Medicine (E.W.L., A.N.A.), Radiology (L.A.R.), and Pathology (L.R.Z.), Massachusetts General Hospital, and the Departments of Medicine (E.W.L., A.N.A.), Radiology (L.A.R.), and Pathology (L.R.Z.), Harvard Medical School, Boston - all in Massachusetts
| | - Emily W Lopes
- From the Department of Medicine, Newton-Wellesley Hospital, Newton (H.B.B.), and the Department of Medicine, Tufts University School of Medicine (H.B.B.), the Departments of Medicine (E.W.L., A.N.A.), Radiology (L.A.R.), and Pathology (L.R.Z.), Massachusetts General Hospital, and the Departments of Medicine (E.W.L., A.N.A.), Radiology (L.A.R.), and Pathology (L.R.Z.), Harvard Medical School, Boston - all in Massachusetts
| | - Lauren A Roller
- From the Department of Medicine, Newton-Wellesley Hospital, Newton (H.B.B.), and the Department of Medicine, Tufts University School of Medicine (H.B.B.), the Departments of Medicine (E.W.L., A.N.A.), Radiology (L.A.R.), and Pathology (L.R.Z.), Massachusetts General Hospital, and the Departments of Medicine (E.W.L., A.N.A.), Radiology (L.A.R.), and Pathology (L.R.Z.), Harvard Medical School, Boston - all in Massachusetts
| | - Ashwin N Ananthakrishnan
- From the Department of Medicine, Newton-Wellesley Hospital, Newton (H.B.B.), and the Department of Medicine, Tufts University School of Medicine (H.B.B.), the Departments of Medicine (E.W.L., A.N.A.), Radiology (L.A.R.), and Pathology (L.R.Z.), Massachusetts General Hospital, and the Departments of Medicine (E.W.L., A.N.A.), Radiology (L.A.R.), and Pathology (L.R.Z.), Harvard Medical School, Boston - all in Massachusetts
| | - Lawrence R Zukerberg
- From the Department of Medicine, Newton-Wellesley Hospital, Newton (H.B.B.), and the Department of Medicine, Tufts University School of Medicine (H.B.B.), the Departments of Medicine (E.W.L., A.N.A.), Radiology (L.A.R.), and Pathology (L.R.Z.), Massachusetts General Hospital, and the Departments of Medicine (E.W.L., A.N.A.), Radiology (L.A.R.), and Pathology (L.R.Z.), Harvard Medical School, Boston - all in Massachusetts
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23
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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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24
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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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25
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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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26
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A Practical Review of Cytomegalovirus in Gastroenterology and Hepatology. Gastroenterol Res Pract 2019; 2019:6156581. [PMID: 30984257 PMCID: PMC6431500 DOI: 10.1155/2019/6156581] [Citation(s) in RCA: 53] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2018] [Accepted: 02/05/2019] [Indexed: 02/06/2023] Open
Abstract
Human cytomegalovirus (CMV) is a ubiquitous Herpesviridae virus with a wide spectrum of pathology in humans. Host immunity is a major determinant of the clinical manifestation of CMV and can vary widely in the gastroenterology and hepatology practice setting. Immunocompetent patients generally develop a benign, self-limited mononucleosis-like syndrome whereas gastrointestinal tissue-invasive disease is more frequently seen in immunocompromised and inflammatory bowel disease patients. Additionally, liver allograft dysfunction is a significant consequence of CMV infection in liver transplant patients. While polymerase chain reaction and immunohistochemistry techniques allow for the reliable and accurate detection of CMV in the human host, the diagnostic value of different serologic, endoscopic, and histologic tests depends on a variety of factors. Similarly, latent CMV, CMV infection, and CMV disease carry different significance depending on the patient population, and the decision to initiate antiviral therapy can be complex and patient-specific. This review will focus on the pathophysiology, diagnosis, and management of CMV in patient populations relevant to the practice of gastroenterology and hepatology-liver transplant recipients, inflammatory bowel disease patients, and otherwise immunocompetent patients.
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27
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Whaley KG, Rosen MJ. Contemporary Medical Management of Acute Severe Ulcerative Colitis. Inflamm Bowel Dis 2019; 25:56-66. [PMID: 29889235 PMCID: PMC6290785 DOI: 10.1093/ibd/izy208] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2017] [Indexed: 02/07/2023]
Abstract
Acute severe ulcerative colitis is a medical emergency that requires prompt recognition, evaluation, and intervention. Patients require hospital admission with laboratory, radiographic, and endoscopic evaluation with initiation of corticosteroid treatment. Despite early intervention, many patients require salvage medical therapy, with some progressing to colectomy. Here we review important concepts and recent advances in the evaluation and medical management of adult and pediatric patients with acute severe ulcerative colitis.
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Affiliation(s)
- Kaitlin G Whaley
- Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Michael J Rosen
- Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio
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28
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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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29
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Levin A, Yaari S, Stoff R, Caplan O, Wolf DG, Israeli E. Diagnosis of Cytomegalovirus Infection during Exacerbation of Ulcerative Colitis. Digestion 2018; 96:142-148. [PMID: 28848127 DOI: 10.1159/000479865] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2017] [Accepted: 07/27/2017] [Indexed: 02/04/2023]
Abstract
BACKGROUND/AIMS The role of cytomegalovirus (CMV) reactivation during exacerbations of ulcerative colitis (UC) is yet a matter of debate, and assessment of CMV infection in UC patients remains an ongoing challenge. We aimed to identify associated parameters and compare detection methods for CMV infection during UC exacerbation. METHODS Clinical, pathological and virological parameters were retrospectively analyzed in all patients hospitalized in our institution for UC exacerbation between January 2009 and April 2015, who underwent full evaluation for CMV infection in colonic tissue by histopathology, immunohistochemistry (IHC) and CMV-PCR. RESULTS Of 28 patients who underwent full examination for tissue CMV-infection, 13 (46.4%) were found to be positive for CMV. Tissue CMV-PCR was more sensitive for the detection of CMV infection than histopathology and IHC. CMV-positive patients had a statistically higher frequency of recent steroid treatment and fever, with higher mean partial Mayo scores and lower mean albumin levels. There were no significant differences between CMV-positive and CMV-negative patients in terms of age, severity of colitis and disease duration. In a multivariable model, only recent steroid treatment and fever were independently associated with colonic CMV infection. CONCLUSIONS This study provides a clinical model to detect the presence of CMV infection in patients hospitalized with UC exacerbation, which could direct proper investigation and facilitate timely empirical therapy.
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Affiliation(s)
- Avi Levin
- Strang Laboratory of Apoptosis and Cancer Biology, Howard Hughes Medical Institute, The Rockefeller University, New York, NY, USA
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ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Soluble immune effector molecules [I]: anti-tumor necrosis factor-α agents). Clin Microbiol Infect 2018; 24 Suppl 2:S10-S20. [DOI: 10.1016/j.cmi.2017.12.025] [Citation(s) in RCA: 111] [Impact Index Per Article: 15.9] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2017] [Revised: 12/25/2017] [Accepted: 12/30/2017] [Indexed: 12/14/2022]
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Antiviral Treatment for Colonic Cytomegalovirus Infection in Ulcerative Colitis Patients Significantly Improved Their Surgery Free Survival. J Clin Gastroenterol 2018; 52:e27-e31. [PMID: 27875354 DOI: 10.1097/mcg.0000000000000759] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
BACKGROUND The frequency of cytomegalovirus (CMV) colitis in steroid-refractory inflammatory bowel disease has been reported to range from 15.8% to 34.0%. Infected patients are more likely to become hospitalized, have longer lengths of stay, and higher mortality rates. Current data are limited to small scale studies and showed conflicting result regarding the role of antiviral therapy. AIMS (1) To investigate the role of antiviral treatment in ulcerative colitis (UC) patients with CMV infection. (2) To investigate the role of viremia in the outcomes of these patients. MATERIALS AND METHODS The Cleveland Clinic pathology database identified 1478 patients who had colon biopsy and were tested for CMV during 1990 to 2013. After inclusion and exclusion, 41 UC patients were selected. Among them, 24 (58.5%) received treatment, 17 (41.5%) did not. A total of 14 demographic data and 4 clinical outcomes (surgery free survival, hospitalization, rehospitalization, and mortality) were compared between treated and nontreated patients. The same outcomes were also compared in patients who received treatment based on their viremia status. RESULTS All demographic variables are similar between those treated and nontreated groups. Antiviral therapy significantly improved the surgery free survival within 30 days, and lasted 70 months (P<0.01). In contrast, hospitalization, rehospitalization, and mortality were comparable (P>0.05). No significant difference was observed in any of the clinical outcomes based on viremia status. CONCLUSIONS Our small scale study demonstrates that antiviral treatment for colonic CMV infection significantly improves the surgery free survival short-term and long-term in patients with UC.
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Wethkamp N, Nordlohne EM, Meister V, Helwig U, Respondek M. Identification of clinically relevant cytomegalovirus infections in patients with inflammatory bowel disease. Mod Pathol 2018; 31:527-538. [PMID: 29192648 DOI: 10.1038/modpathol.2017.149] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2016] [Revised: 09/13/2017] [Accepted: 09/14/2017] [Indexed: 12/20/2022]
Abstract
Several lines of evidence indicate that cytomegalovirus infection can be substantially associated with onset of inflammatory bowel disease, especially in patients refractory to immunosuppressive treatment. As cytomegalovirus is widely spread in the population, here we present a quantitative detection system suitable to differentiate clinically relevant cytomegalovirus infection from common latent cytomegalovirus. Using a quantitative real-time PCR approach, cytomegalovirus viral load was evaluated in 917 formalin-fixed and paraffin-embedded colon biopsy samples of 136 patients diagnosed with inflammatory bowel disease. Besides initial cytomegalovirus testing, the PCR system was also used to monitor therapy response after antiviral treatment. Cytomegalovirus DNA was detected in 37 patients (27%) with varying viral loads ranging from 5 to 8.7 × 105 copies/105 cells. Thereof, 13 patients (35%) received an antiviral treatment with 12 of them going into remission (92%). Later, five patients displayed a relapse and three patients who agreed to restart antiviral treatment again showed positive therapy response. A retrospective comparison of viral loads with antiviral therapy response revealed a threshold of 600 cytomegalovirus copies/105 cells as indicative for clinically relevant infection. Of note, sensitivity of cytomegalovirus detection by immunohistochemistry was found to be insufficient to reliably identify antiviral therapy responders. In conclusion, quantitative real-time PCR using formalin-fixed biopsy samples is suitable for detection of cytomegalovirus infection in tissue samples of patients with inflammatory bowel disease. Moreover, it allows the definition of a viral load threshold, predictive for clinical relevance concerning antiviral therapy response.
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Affiliation(s)
- Nils Wethkamp
- Molecular Diagnostics, Practice of Pathology, Vechta, Germany
| | | | - Volker Meister
- Gastroenterology, Medical Department, St Marien-Hospital, Vechta, Germany
| | - Ulf Helwig
- Shared Practice for Internal Medicine, Oldenburg, Germany
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Kopylov U, Papamichael K, Katsanos K, Waterman M, Bar-Gil Shitrit A, Boysen T, Portela F, Peixoto A, Szilagyi A, Silva M, Maconi G, Har-Noy O, Bossuyt P, Mantzaris G, Barreiro de Acosta M, Chaparro M, Christodoulou DK, Eliakim R, Rahier JF, Magro F, Drobne D, Ferrante M, Sonnenberg E, Siegmund B, Muls V, Thurm T, Yanai H, Dotan I, Raine T, Levin A, Israeli E, Ghalim F, Carbonnel F, Vermeire S, Ben-Horin S, Roblin X. Impact of Infliximab and Cyclosporine on the Risk of Colectomy in Hospitalized Patients with Ulcerative Colitis Complicated by Cytomegalovirus-A Multicenter Retrospective Study. Inflamm Bowel Dis 2017; 23:1605-1613. [PMID: 28590343 DOI: 10.1097/mib.0000000000001160] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
BACKGROUND Cytomegalovirus (CMV) is frequently detected in patients with ulcerative colitis (UC). The impact of CMV infection on the outcome of UC exacerbation remains unclear. The benefit of combining antiviral with anti-inflammatory treatment has not been evaluated yet. The aim of this study was to compare the outcome of CMV-positive hospitalized patients with UC treated with antiviral therapy either alone or combined with salvage anti-inflammatory therapy (infliximab [IFX] or cyclosporine A [CsA]). METHODS This was a multicenter retrospective study of hospitalized CMV-positive patients with UC. The patients were classified into 2 groups: antiviral-if treated with antivirals alone; combined-if treated with both antiviral and anti-inflammatory therapy. The outcomes included the rate of colectomy in both arms during the course of hospitalization and after 3/12 months. RESULTS A total of 110 patients were included; 47 (42.7%) patients did not receive IFX nor CsA; 36 (32.7%) received IFX during hospitalization or within 1 month before hospitalization; 20 (18.1%) patients received CsA during hospitalization; 7 (6.4%) were exposed to both IFX and CsA. The rate of colectomy was 14.5% at 30 days, 20.0% at 3 months, and 34.8% at 12 months. Colectomy rates were similar across treatment groups. No clinical and demographic variables were independently associated with the risk of colectomy. CONCLUSIONS IFX or cyclosporine therapy is not associated with additional risk for colectomy over antiviral therapy alone in hospitalized CMV-positive patients with UC.
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Affiliation(s)
- Uri Kopylov
- 1Department of Gastroenterology, Sheba Medical Center, Tel Hashomer, and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; 2Department of Gastroenterology, Evaggelismos Hospital, Athens, Greece; 3Department of Clinical and Experimental Medicine, KU Leuven, Translational Research Center for Gastrointestinal Disorders (TARGID), Leuven, Belgium; 4Department of Gastroenterology, University Hospital of Ioannina, Ioannina, Greece; 5Department of Gastroenterology, Rambam Health Care Campus, B. Rappaport Faculty of Medicine, the Technion, Haifa, Israel; 6Shaare Zedek Medical Center, Digestive Diseases Institute, Jerusalem, Israel; 7Department of Gastroenterology, Herlev University Hospital, Herlev, Denmark; 8Department of Gastroenterology, Hospital Universidade Coimbra, Coimbra, Portugal; 9Department of Gastroenterology, Centro Hospitalar São João, Porto, Portugal; 10Department of Gastroenterology, Jewish General Hospital, Montreal, Québec, Canada; 11Department of Gastroenterology, Luigi Sacco' University Hospital, Milan, Italy; 12Department of Gastroenterology, Imelda GI Clinical Research Center, Bonheiden, Belgium; 13IBD Unit, Gastroenterology Department, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain; 14Department of Gastroenterology, Hospital Universitario de La Princesa, Madrid, Spain; 15Department of Gastroenterology, CHU Dinant Godinne, UCL Namur, Yvoir, Belgium; 16Department of Gastroenterology, University Medical Centre Ljubljana, Slovenia; 17Department of Medicine (Gastroenterology, Infectious Diseases, Rheumatology), Charité-Universitätsmedizin Berlin, Berlin, Germany; 18Department of Gastroenterology and Hepatology, CHU Saint-Pierre, Université Libre de Bruxelles, Brussels, Belgium; 19Department of Gastroenterology and Liver Diseases, IBD Center, Tel Aviv Sourasky Medical Center, Affiliated to the Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel; 20Department of Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom; 21Department of Gastroenterology, Hadassah Medical Center, Jerusalem, Israel; 22Service de Gastroentérologie, Hôpital Universitaire de Bicêtre, Université Paris Sud, Assistance Publique-Hôpitaux de Paris, le Kremlin Bicêtre, Paris, France; and 23Department of Gastroenterology, CHU de Saint-Etienne, Saint Etiennne, France
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Abstract
Cytomegalovirus (CMV), the largest of the herpesviruses, causes a wide range of clinical syndromes, from asymptomatic infection to severe disease in immunocompromised hosts. Laboratory methods for diagnosis include molecular testing, antigenemia, culture, serology, and histopathology. Treatment of CMV infection and disease is indicated in selected immunocompromised hosts, and preventive approaches are indicated in high-risk groups. This chapter reviews the epidemiology, clinical aspects, and the laboratory diagnosis and management of CMV in immunocompromised hosts.
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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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Knyazev OV, Parfenov AI, Kagramanova AV, Ruchkina IN, Shcherbakov PL, Shakhpazyan NK, Noskova KK, Ivkina TI, Khomeriki SG. [Long-term infliximab therapy for ulcerative colitis in real clinical practice]. TERAPEVT ARKH 2017; 88:46-52. [PMID: 27636927 DOI: 10.17116/terarkh201688846-52] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
AIM to retrospectively evaluate the efficiency of long-term infliximab (INF) therapy in patients with refractory ulcerative colitis (UC). SUBJECTS AND METHODS The investigation enrolled 48 patients with refractory UC who had taken IFL in 2008 to 2014. Steroid-dependent or steroid-refractory UC was established in 40 (83.3%) patients; 8 (16.7%) were noted to be refractory to therapy with azathioprine or 6-mercaptopurine. Cytomegalovirus DNA was identified in the biopsy specimens of the large intestinal mucosa (LIM) from 7 patients. One patient received antiviral therapy. Induction therapy with IFL was in its administration in a dose of 5 mg/kg at 0, 2, and 6 weeks, then maintenance therapy was continued every 8 weeks. RESULTS After an IFL induction cycle, 3 (6.3%) patients were unresponsive to therapy and were excluded from the investigation. At present, 25 (55.5%) of the 45 patients who have responded to the therapy continue to take IFL 5 mg/kg every 8 weeks and are in clinical remission; 4 (8.8%) patients receive intensified IFL therapy. Initially 23 patients received combined therapy with IFL + an immunosuppressive drug; 22 had IFL monotherapy. Escape from the effect of the performed therapy was observed in 5 (11.1%) patients, which required its intensification. The intensified therapy resulted in sustained remission in 4 (8.8%) patients; colectomy was carried out in one (2.2%) case. Secondary loss of response to IFL, its intolerance, development of severe infectious complications, which did not allow for further maintenance therapy with IFL, were seen in 11 (24.4%) patients; 5 (11.1%) stopped the therapy because they had been excluded from the additional drug subsidy list. Maintenance therapy with IFL proved successful during 64 months in 29 (64.4%) of the 45 patients and during 64 months if its intensity, when the occasion required, was enhanced. CONCLUSION The long-term use of IFL in UC confirmed its high efficacy in achieving clinical response, in inducing a clinical remission and its capacity to heal LIM, and in sustaining remission.
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Affiliation(s)
- O V Knyazev
- Moscow Clinical Research and Practical Center, Moscow Healthcare Department, Moscow, Russia
| | - A I Parfenov
- Moscow Clinical Research and Practical Center, Moscow Healthcare Department, Moscow, Russia
| | - A V Kagramanova
- Moscow Clinical Research and Practical Center, Moscow Healthcare Department, Moscow, Russia
| | - I N Ruchkina
- Moscow Clinical Research and Practical Center, Moscow Healthcare Department, Moscow, Russia
| | - P L Shcherbakov
- Moscow Clinical Research and Practical Center, Moscow Healthcare Department, Moscow, Russia
| | | | - K K Noskova
- Moscow Clinical Research and Practical Center, Moscow Healthcare Department, Moscow, Russia
| | - T I Ivkina
- Moscow Clinical Research and Practical Center, Moscow Healthcare Department, Moscow, Russia
| | - S G Khomeriki
- Moscow Clinical Research and Practical Center, Moscow Healthcare Department, Moscow, Russia
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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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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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Zhang WX, Ma CY, Zhang JG, He F, Liu QM, Cheng A, Liu T, Zhang J, Wang J, Bu X, Xie Y, Diao Z, Bai J. Effects of cytomegalovirus infection on the prognosis of inflammatory bowel disease patients. Exp Ther Med 2016; 12:3287-3293. [PMID: 27882151 PMCID: PMC5103780 DOI: 10.3892/etm.2016.3763] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2015] [Accepted: 09/06/2016] [Indexed: 12/29/2022] Open
Abstract
The aim of the present study was to investigate the effects of cytomegalovirus (CMV) infection on the prognosis of inflammatory bowel disease (IBD). Various databases were searched using a combination of keywords associated with CMV infection and IBD. Subsequent to the selection of relevant studies in line with strict inclusion and exclusion criteria, a meta-analysis was conducted using the Stata 12.0 software. A total of 195 studies were initially retrieved, including 28 studies in Chinese and 167 in English. Following the exclusion of unsuitable studies, 7 cohort studies with 374 IBD patients were included in the meta-analysis. The results of the present study identified significant differences between patients with and without CMV infection regarding the disease duration of IBD [standardized mean difference, -0.81; 95% confidence interval (CI), -1.19 to -0.43; P<0.001], the efficacy of corticosteroid therapy [relative risk (RR), 1.24; 95% CI, 1.02-1.49; P=0.029], the colectomy rate (RR, 2.13; 95% CI, 1.03-4.40; P=0.042) and the incidence of severe IBD (RR, 1.32; 95% CI, 1.04-1.67; P=0.022). Considering the IBD onset area, patients with CMV infection may have higher susceptibility to pancolitis (RR, 1.31; 95% CI; 1.01-1.72; P=0.045); however, no difference in susceptibility to left-sided IBD was observed between patients with or without CMV infection (RR, 0.97; 95% CI, 0.72-1.30; P=0.828). In conclusion, CMV infection may be associated with the disease duration, efficacy of corticosteroid therapy, colectomy rate, severe IBD incidence and disease location of IBD; thus, the presence of CMV infection may be considered as an important biomarker for determining the prognosis of IBD.
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Affiliation(s)
- Wei-Xia Zhang
- Department of Critical Care Medicine, Linyi People's Hospital, Linyi, Shandong 276003, P.R. China
| | - Cheng-Yan Ma
- Department of Critical Care Medicine, Linyi People's Hospital, Linyi, Shandong 276003, P.R. China
- Correspondence to: Dr Cheng-Yan Ma, Department of Critical Care Medicine, Linyi People's Hospital, 27 Jiefang Road, Linyi, Shandong 276003, P.R. China, E-mail:
| | - Jian-Guo Zhang
- Department of Critical Care Medicine, Linyi People's Hospital, Linyi, Shandong 276003, P.R. China
| | - Feng He
- Department of Critical Care Medicine, Linyi People's Hospital, Linyi, Shandong 276003, P.R. China
| | - Qing-Min Liu
- Department of Critical Care Medicine, Linyi People's Hospital, Linyi, Shandong 276003, P.R. China
| | - Aibin Cheng
- Department of Critical Care Medicine, Linyi People's Hospital, Linyi, Shandong 276003, P.R. China
| | - Tiejun Liu
- Department of Critical Care Medicine, Linyi People's Hospital, Linyi, Shandong 276003, P.R. China
| | - Junwei Zhang
- Department of Critical Care Medicine, Linyi People's Hospital, Linyi, Shandong 276003, P.R. China
| | - Jianjun Wang
- Department of Critical Care Medicine, Linyi People's Hospital, Linyi, Shandong 276003, P.R. China
| | - Xuan Bu
- Department of Critical Care Medicine, Linyi People's Hospital, Linyi, Shandong 276003, P.R. China
| | - Yuxi Xie
- Department of Critical Care Medicine, Linyi People's Hospital, Linyi, Shandong 276003, P.R. China
| | - Zengli Diao
- Department of Critical Care Medicine, Linyi People's Hospital, Linyi, Shandong 276003, P.R. China
| | - Jing Bai
- Department of Critical Care Medicine, Linyi People's Hospital, Linyi, Shandong 276003, P.R. China
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Abstract
Human cytomegalovirus (CMV) is a common cause of opportunistic infection leading to severe and fatal disease in immune-compromised individuals. In inflammatory bowel disease patients, particularly those with ulcerative colitis (UC), CMV is often reactivated because these patients are frequently treated with immunosuppressive agents. Many reports have described the relationship between CMV reactivation and UC exacerbation, however, a therapeutic strategy for CMV infection in UC patients has not been established. Area covered: This review highlights therapeutic strategies for UC patients with CMV infection. Recent findings have suggested a benefit from antiviral therapy in patients with histologically proven CMV colitis and/or a high colonic CMV load as determined by quantitative PCR. Expert commentary: To decide who requires antiviral therapies and when we start antiviral therapies, prospective studies of large numbers of UC patients with CMV infection are needed. However, we should know that the bottom-line therapy for UC patients with CMV infection is to optimally control mucosal inflammation.
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Affiliation(s)
- Hiroshi Nakase
- a Department of Gastroenterology, and Hepatology , Sapporo Medical University School of Medicine , Sapporo , Japan
| | - Kei Onodera
- a Department of Gastroenterology, and Hepatology , Sapporo Medical University School of Medicine , Sapporo , Japan
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Thörn M, Rorsman F, Rönnblom A, Sangfelt P, Wanders A, Eriksson BM, Bondeson K. Active cytomegalovirus infection diagnosed by real-time PCR in patients with inflammatory bowel disease: a prospective, controlled observational study (.). Scand J Gastroenterol 2016; 51:1075-80. [PMID: 27142339 DOI: 10.3109/00365521.2016.1156154] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE It is assumed that cytomegaloviral (CMV) infection in inflammatory bowel disease (IBD) is caused by reactivation due to the immunosuppressive therapy, but the role of CMV as a pathophysiological factor and prognostic marker in IBD is unclear. The aim of this study was to investigate CMV infection in IBD, with real-time polymerase chain reaction (PCR) and immunohistochemistry, with emphasis on newly diagnosed disease. MATERIALS AND METHODS In this prospective, controlled study, 67 patients with IBD and 34 control patients with irritable bowel syndrome (IBS) or rectal bleeding were included. Serology for CMV was analysed along with CMV DNA in plasma, mucosal biopsies, and faeces. Mucosal biopsies were further analysed with histopathology and CMV immunohistochemistry. RESULTS Detection of CMV IgM was more common in patients with IBD, compared to controls, 21% versus 3%. CMV DNA was found in 16% of patients with newly diagnosed, untreated IBD and in 38% of steroid-treated patients. Four of the five patients that needed urgent surgery were CMV-DNA positive in at least one of three sample types. None of the controls had detectable CMV DNA. CONCLUSIONS Active CMV infection was found in high proportions of newly diagnosed untreated patients with IBD, in patients on immunosuppression and in patients in the need of surgery. Low CMV-DNA levels in non-immunosuppressed patients were not a risk factor for the development of more severe IBD, while the detection of CMV DNA in patients on immunosuppressive therapy may foresee disease progression.
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Affiliation(s)
- Mari Thörn
- a Department of Medical Sciences, Section of Gastroenterology and Hepatology , Uppsala University , Uppsala , Sweden
| | - Fredrik Rorsman
- a Department of Medical Sciences, Section of Gastroenterology and Hepatology , Uppsala University , Uppsala , Sweden
| | - Anders Rönnblom
- a Department of Medical Sciences, Section of Gastroenterology and Hepatology , Uppsala University , Uppsala , Sweden
| | - Per Sangfelt
- a Department of Medical Sciences, Section of Gastroenterology and Hepatology , Uppsala University , Uppsala , Sweden
| | - Alkwin Wanders
- b Department of Immunology, Genetics and Pathology , Uppsala University , Uppsala , Sweden
| | - Britt-Marie Eriksson
- c Department of Medical Sciences, Section of Infectious Diseases , Uppsala University , Uppsala , Sweden
| | - Kåre Bondeson
- d Department of Medical Sciences, Clinical Microbiology and Infectious Medicine , Uppsala University , Uppsala , Sweden
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Abegunde AT, Muhammad BH, Bhatti O, Ali T. Environmental risk factors for inflammatory bowel diseases: Evidence based literature review. World J Gastroenterol 2016; 22:6296-6317. [PMID: 27468219 PMCID: PMC4945988 DOI: 10.3748/wjg.v22.i27.6296] [Citation(s) in RCA: 142] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2016] [Revised: 05/19/2016] [Accepted: 06/28/2016] [Indexed: 02/06/2023] Open
Abstract
AIM: Advances in genetics and immunology have contributed to the current understanding of the pathogenesis of inflammatory bowel diseases (IBD).
METHODS: The current opinion on the pathogenesis of IBD suggests that genetically susceptible individuals develop intolerance to dysregulated gut microflora (dysbiosis) and chronic inflammation develops as a result of environmental insults. Environmental exposures are innumerable with varying effects during the life course of individuals with IBD. Studying the relationship between environmental factors and IBD may provide the missing link to increasing our understanding of the etiology and increased incidence of IBD in recent years with implications for prevention, diagnosis, and treatment. Environmental factors are heterogeneous and genetic predisposition, immune dysregulation, or dysbiosis do not lead to the development of IBD in isolation.
RESULTS: Current challenges in the study of environmental factors and IBD are how to effectively translate promising results from experimental studies to humans in order to develop models that incorporate the complex interactions between the environment, genetics, immunology, and gut microbiota, and limited high quality interventional studies assessing the effect of modifying environmental factors on the natural history and patient outcomes in IBD.
CONCLUSION: This article critically reviews the current evidence on environmental risk factors for IBD and proposes directions for future research.
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Coutermarsh-Ott S, Eden K, Allen IC. Beyond the inflammasome: regulatory NOD-like receptor modulation of the host immune response following virus exposure. J Gen Virol 2016; 97:825-838. [PMID: 26763980 PMCID: PMC4854363 DOI: 10.1099/jgv.0.000401] [Citation(s) in RCA: 85] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
A complex interaction exists between elements of the host innate immune system and viral pathogens. It is essential that the host mount a robust immune response during viral infection and effectively resolve inflammation once the pathogen has been eliminated. Members of the nucleotide-binding domain leucine-rich repeat [NBD-LRR; known as NOD-like receptor (NLR)] family of cytosolic pattern-recognition receptors are essential components of these immunological processes and have diverse functions in the host antiviral immune response. NLRs can be subgrouped based on their general function. The inflammasome-forming subgroup of NLRs are the best-characterized family members, and several have been found to modulate the maturation of IL-1β and IL-18 following virus exposure. However, the members of the regulatory NLR subgroups are significantly less characterized. These NLRs uniquely function to modulate signalling pathways initiated by other families of pattern-recognition receptors, such as Toll-like receptors and/or Rig-I-like helicase receptors. Regulatory NLRs that augment pro-inflammatory pathways include nucleotide-binding oligomerization domain-containing protein 1 (NOD1) and NOD2, which have been shown to form a multiprotein complex termed the NODosome that significantly modulates IFN and NF-κB signalling following viral infection. Conversely, a second subgroup of regulatory NLRs functions to negatively regulate inflammation. These inhibitory NLRs include NLRX1, NLRP12 and NLRC3, which have been shown to interact with TRAF molecules and various kinases to modulate diverse cellular processes. Targeting NLR signalling following infection with a virus represents a novel and promising therapeutic strategy. However, significant effort is still required to translate the current understanding of NLR biology into effective therapies.
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Affiliation(s)
| | | | - Irving Coy Allen
- Department of Biomedical Sciences and Pathobiology, Virginia Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24061, USA
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Zhang C, Krishna SG, Hinton A, Arsenescu R, Levine EJ, Conwell DL. Cytomegalovirus-Related Hospitalization Is Associated With Adverse Outcomes and Increased Health-Care Resource Utilization in Inflammatory Bowel Disease. Clin Transl Gastroenterol 2016; 7:e150. [PMID: 26963000 PMCID: PMC4822090 DOI: 10.1038/ctg.2016.10] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2015] [Accepted: 02/03/2016] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVES Impact of cytomegalovirus (CMV)-related hospitalization in inflammatory bowel disease (IBD) patients is unknown. The aim of this study was to determine hospital outcomes of CMV-related hospitalization in IBD patients in a large national in-patient administrative data set. METHODS This was a cross-sectional study using data from the Nationwide In-patient Sample database. IBD- and CMV-related hospitalizations between 2003 and 2011 were identified using appropriate ICD-9-CM (International Classification of Diseases, Ninth Revision, Clinical Modification) codes. Impact of CMV-related hospitalization on in-hospital mortality, length of stay (LOS), and hospital charges were quantified. RESULTS CMV-related hospitalization was associated with higher in-hospital mortality (odds ratio (OR) 7.09, 95% confidence interval (CI) 3.38-14.85), prolonged LOS (7.77 days, P<0.0001), and more hospital charge (US$66,495, P<0.0001) in IBD patients. CONCLUSIONS CMV-related hospitalization in IBD is associated with high in-hospital mortality, prolonged LOS, and hospital care costs.
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Affiliation(s)
- Cheng Zhang
- Section of Inflammatory Bowel Disease, Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University, Wexner Medical Center, Columbus, Ohio, USA
| | - Somashekar G Krishna
- Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University, Wexner Medical Center, Columbus, Ohio, USA
| | - Alice Hinton
- Department of Biostatistics, College of Public Health, The Ohio State University, Columbus, Ohio, USA
| | - Razvan Arsenescu
- Section of Inflammatory Bowel Disease, Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University, Wexner Medical Center, Columbus, Ohio, USA
| | - Edward J Levine
- Section of Inflammatory Bowel Disease, Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University, Wexner Medical Center, Columbus, Ohio, USA
| | - Darwin L Conwell
- Division of Gastroenterology, Hepatology and Nutrition, The Ohio State University, Wexner Medical Center, Columbus, Ohio, USA
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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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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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Pillet S, Jarlot C, Courault M, Del Tedesco E, Chardon R, Saint-Sardos P, Presles E, Phelip JM, Berthelot P, Pozzetto B, Roblin X. Infliximab Does Not Worsen Outcomes During Flare-ups Associated with Cytomegalovirus Infection in Patients with Ulcerative Colitis. Inflamm Bowel Dis 2015; 21:1580-1586. [PMID: 25933392 DOI: 10.1097/mib.0000000000000412] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Immunosuppressive therapies used for treating ulcerative colitis are known to favor chronic and latent viral diseases. This study aimed at evaluating prospectively the association between colonic cytomegalovirus (CMV) reactivation and anti-tumor necrosis factor (TNF) monoclonal antibodies (mabs) by comparison to azathioprine (AZA) in a series of flare-ups occurring in consecutive ulcerative colitis patients. METHODS A total of 109 flare-ups were recorded in 73 patients receiving a maintenance therapy by anti-TNF mabs (n = 69) or AZA (n = 40). The CMV DNA load in colonic tissue was determined by reverse transcription polymerase chain reaction on a pair of biopsies. RESULTS The number of CMV reactivation was of 35% and 38% in patients receiving anti-TNF mabs and AZA, respectively. The median of CMV DNA load was 378 [10-29,800] and 8300 [10-3,25,000] copies/mg of tissue in patients treated by anti-TNF mabs and AZA, respectively (P = 0.11 by Mann-Whitney U test). In a subgroup of 45 patients under anti-TNF mabs requiring an optimized treatment by infliximab, clinical remission (partial Mayo score <3) was not significantly impacted by the presence of CMV reactivation at the time of flare-up (P = 0.52). Twenty of these patients underwent a second colonic biopsy 8 weeks after the initiation of flare-up therapy; except for 3 patients, the colonic CMV DNA load was stable or decreased. CONCLUSIONS Patients under anti-TNF maintenance therapy are not at higher risk of CMV reactivation in case of flare-up. No reciprocal adverse influence was observed between anti-TNF mabs and CMV infection, suggesting that these drugs must be considered for treating flare-ups associated to CMV reactivation.
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Affiliation(s)
- Sylvie Pillet
- *EA-3064, Groupe Immunité des Muqueuses et Agents Pathogènes (GIMAP), Faculty of Medicine of Saint-Etienne, University of Lyon, Lyon, France; †Laboratory of Infectious Agents and Hygiene, University Hospital of Saint-Etienne, France; ‡Department of Gastroenterology, University Hospital of Saint-Etienne, France; and §Inserm, CIE3, F-42055 Saint-Etienne, France
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Metagenomic analysis of microbiome in colon tissue from subjects with inflammatory bowel diseases reveals interplay of viruses and bacteria. Inflamm Bowel Dis 2015; 21:1419-27. [PMID: 25939040 PMCID: PMC4450971 DOI: 10.1097/mib.0000000000000344] [Citation(s) in RCA: 66] [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] [Indexed: 12/18/2022]
Abstract
Inflammatory bowel diseases (IBD), Crohn's disease and ulcerative colitis, are poorly understood disorders affecting the intestinal tract. The current model for disease suggests that genetically susceptible patients develop intolerance to gut microflora, and chronic inflammation develops as a result of environmental insults. Although interest has mainly focused on studying genetic variants and gut bacterial flora, little is known about the potential of viral infection to contribute to disease. Accordingly, we conducted a metagenomic analysis to document the baseline virome in colonic biopsy samples from patients with IBD in order to assess the contribution of viral infection to IBD. Libraries were generated from colon RNA to create approximately 2 GB sequence data per library. Using a bioinformatic pipeline designed to detect viral sequences, more than 1000 viral reads were derived directly from tissue without any coculture or isolation procedure. Herein, we describe the complexity and abundance of viruses, bacteria/bacteriophage, and human endogenous retroviral sequences from 10 patients with IBD and 5 healthy subjects undergoing surveillance colonoscopy. Differences in gut microflora and the abundance of mammalian viruses and human endogenous retroviruses were readily detected in the metagenomic analyses. Specifically, patients with herpesviridae sequences in their colon demonstrated increased expression of human endogenous viral sequences and differences in the diversity of their microbiome. This study provides a promising metagenomic approach to describe the colonic microbiome that can be used to better understand virus-host and phage-bacteria interactions in IBD.
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Zidar N, Ferkolj I, Tepeš K, Štabuc B, Kojc N, Uršič T, Petrovec M. Diagnosing cytomegalovirus in patients with inflammatory bowel disease--by immunohistochemistry or polymerase chain reaction? Virchows Arch 2015; 466:533-9. [PMID: 25701481 DOI: 10.1007/s00428-015-1741-8] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2014] [Revised: 01/31/2015] [Accepted: 02/08/2015] [Indexed: 12/16/2022]
Abstract
Cytomegalovirus (CMV) reactivation is a common complication in patients with inflammatory bowel diseases (IBD), particularly in those with steroid-resistant ulcerative colitis. It is usually diagnosed by histopathologic and immunohistochemical examination of the colon biopsy. The introduction of quantitative, real-time polymerase chain reaction (qPCR) has been recommended to improve the sensitivity, but there is little consensus on how to use it. We compared the two methods in samples from resected bowel of patients with IBD. Twelve patients with IBD who had undergone bowel resection were analysed for CMV, using qPCR and immunohistochemistry. In all cases, tissue samples from the base and the edge of ulcers and from uninvolved mucosa were obtained. The highest densities of CMV-positive cells were found in samples from the base of ulcers (immunohistochemistry 0-0.47 positive cells/mm(2); qPCR 10-3809 viral copies/mg) or the edge of ulcers (immunohistochemistry 0.06-0.32 positive cells/mm(2); qPCR 35-1049 viral copies/mg). In samples of uninvolved mucosa, immunohistochemistry was negative, whereas qPCR was either negative or showed very low values (0-3 viral copies/mg). We conclude that both immunohistochemistry and qPCR can be successfully used for diagnosing CMV reactivation in patients with IBD. The base and the edge of ulcers are the optimal sites for endoscopic biopsies. The density of CMV-positive cells was low and their distribution within the colon uneven. It therefore seems that the number of sampled biopsies and/or the number of investigated levels is more important that the choice of diagnostic method.
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Affiliation(s)
- Nina Zidar
- Institute of Pathology, Faculty of Medicine, University of Ljubljana, Korytkova 2, 1000, Ljubljana, Slovenia,
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