Cytomegalovirus Reactivation in Ulcerative Colitis Patients

Nguyen, Minh; Bradford, Kara; Zhang, Xiaolan; Shih, David Q.

doi:10.1155/2011/282507

Cited by 52 publications

(42 citation statements)

References 39 publications

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“…Indeed, whether CMV infection/reactivation represents an “innocent bystander” or “true player” in IBD disease has long been debated [19, 20], and data regarding CMV in this setting are quite conflicting [21-23]. Proponents of the “innocent bystander” hypothesis state that CMV virus has a propensity towards colonizing inflamed, granulated ulcer beds, and suggest that the presence of CMV represents tropism towards areas of inflammation, rather than a reflection of true disease [21, 24]. Nonetheless, there have been several studies presenting solid evidence to support testing for CMV in cases of moderate to severe colitis, and if CMV is present, treating with ganciclovir [15, 17].…”

Section: Discussionmentioning

confidence: 99%

“…For patients with IBD and other conditions at our institution, treatment for CMV is usually not given if only 1 - 2 cells stained, unless there is systemic viremia. In addition, most of the IBD patients with > 2 IHC positive cells and subsequent positive CMV viral loads were on systemic steroids (prednisone) at the time of detection, suggesting that the increased risk for CMV in IBD patients may in part be iatrogenic, mostly ascribed to steroid therapy [20, 24]. The proposal that CMV in IBD patients may represent transient CMV reactivation status/innocent bystander was further supported by negative CMV in follow-up biopsies without anti-viral treatment.…”

Section: Discussionmentioning

confidence: 99%

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Immunostaining Detection of Cytomegalovirus in Gastrointestinal Biopsies: Clinicopathological Correlation at a Large Academic Health System

2016

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BackgroundCytomegalovirus (CMV) infection can be asymptomatic in healthy individuals but may cause serious complications in immunocompromised patients. We investigated the clinicopathological correlation of CMV in gastrointestinal (GI) biopsies at our institute between January 1, 2013 and December 31, 2015.MethodsA total of 105 non-neoplastic GI biopsies tested positive for CMV by immunohistochemistry (IHC). The IHC results were stratified as “true positive” if > 2 cells stained, or “rare positive” if only 1 - 2 cells stained. Clinical information including comorbidities, serum CMV viral loads, and treatment was reviewed and correlated.ResultsOverall 1% of all GI biopsies were positive for CMV by immunostaining. The most frequently involved organ was colon, followed by esophagus, stomach, ileum and duodenum. When > 2 cells were stained positive, serum CMV viral loads were positive in 52.2%, negative in 17.2%, and not tested in 27.6% of cases. When only 1 - 2 cells stained positive, CMV viral loads were positive in 23.4%, negative in 25.5%, and not tested in 51.1% of cases. We further showed that clinical management of CMV differs based on both pathological findings and underlying diseases.ConclusionsThe role of CMV in GI biopsies remains controversial. We propose an algorithm of performing CMV immunostaining based on clinicopathological correlation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Immunostaining Detection of Cytomegalovirus in Gastrointestinal Biopsies: Clinicopathological Correlation at a Large Academic Health System

2016

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“…Decreased bile acids levels are found after ileal resection (66) or in patients with inflammatory bowel disease such as ulcerative colitis or Crohn's disease (67). In ulcerative colitis, CMV reactivation is more common than in healthy individuals (68,69). Beside the fact that these patients have an inflammatory disease that is treated with immunosuppressive drugs, reduced bile acid levels could be associated with CMV reactivation in these cases.…”

Section: Discussionmentioning

confidence: 99%

Bile Acids Act as Soluble Host Restriction Factors Limiting Cytomegalovirus Replication in Hepatocytes

Schupp

Trilling

Rattay

et al. 2016

J Virol

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The liver constitutes a prime site of cytomegalovirus (CMV) replication and latency. Hepatocytes produce, secrete, and recycle a chemically diverse set of bile acids, with the result that interactions between bile acids and cytomegalovirus inevitably occur. Here we determined the impact of naturally occurring bile acids on mouse CMV (MCMV) replication. In primary mouse hepatocytes, physiological concentrations of taurochenodeoxycholic acid (TCDC), glycochenodeoxycholic acid, and to a lesser extent taurocholic acid significantly reduced MCMV-induced gene expression and diminished the generation of virus progeny, while several other bile acids did not exert antiviral effects. The anticytomegalovirus activity required active import of bile acids via the sodium-taurocholate-cotransporting polypeptide (NTCP) and was consistently observed in hepatocytes but not in fibroblasts. Under conditions in which alpha interferon (IFN-␣) lacks antiviral activity, physiological TCDC concentrations were similarly effective as IFN-␥. A detailed investigation of distinct steps of the viral life cycle revealed that TCDC deregulates viral transcription and diminishes global translation in infected cells. IMPORTANCECytomegaloviruses are members of the Betaherpesvirinae subfamily. Primary infection leads to latency, from which cytomegaloviruses can reactivate under immunocompromised conditions and cause severe disease manifestations, including hepatitis. The present study describes an unanticipated antiviral activity of conjugated bile acids on MCMV replication in hepatocytes. Bile acids negatively influence viral transcription and exhibit a global effect on translation. Our data identify bile acids as site-specific soluble host restriction factors against MCMV, which may allow rational design of anticytomegalovirus drugs using bile acids as lead compounds. C ytomegaloviruses (CMV) are members of the Betaherpesvirinae subfamily and persist for life in infected individuals during alternating phases of latency and productive reactivation. Seroprevalence studies indicate that the large majority of the global human population is currently infected with human cytomegalovirus (HCMV) (human herpesvirus 5 [HHV-5]; taxonomy ID 10359). Although HCMV-related fatalities in apparently healthy individuals sporadically occur (1, 2), HCMV replication usually remains subclinical. This drastically changes under immunocompromising conditions, where untreated CMV infections often cause overt disease, including hepatitis (3) and dysfunction, bleeding, ulceration, and perforation of organs of the upper as well as lower gastrointestinal tract (4). HCMV hepatitis is particularly common in liver transplant recipients and is associated with organ dysfunction and graft failure (5-9).The species specificity of CMV precludes meaningful in vivo experimentation with HCMV in small animal models. Therefore, the homologous mouse CMV (MCMV) (Murid herpesvirus 1, taxonomy ID 10366), which infects Mus musculus (taxonomy ID 10090) as its natural host, has been estab...

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“…A number of cohort studies have been performed; while the incidence of CMV disease has not been clearly demonstrated to be associated with anti-tumour necrosis factor or thiopurine therapy, patients who are on long-term steroids have at least a 10-fold increased risk of developing the condition 1. The majority of the patients with CMV colitis treated promptly with intravenous antiviral therapy are able to go into disease remission, although it remains controversial whether an episode of CMV colitis changes the course of ulcerative colitis in terms of colectomy rates or disease prognosis 2. The gold standard for diagnosing the condition is the histological examination of diseased colon as CMV PCR levels correlate poorly with disease activity.…”

Section: Discussionmentioning

confidence: 99%

Ulcerative colitis: a case of steroid refractory disease

et al. 2013

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A 21-year-old lady was admitted to a hospital with an 8-week history of bloody diarrhoea. She had been diagnosed with ulcerative colitis 2 years previously and had remained in remission until the gradual onset of bloody diarrhoea. Her bowel frequency was 20 times per day and associated with significant abdominal pain and weight loss. She was started on intravenous steroids, topical therapy and anti-tumour necrosis factor therapy; however, this failed to achieve symptom control. Histology of tissue obtained from flexible sigmoidoscopy eventually demonstrated cytomegalovirus (CMV)-associated colitis. Intravenous anti-viral valganciclovir was initiated and the patient made a rapid recovery. This case discusses the differentials for steroid-refractory ulcerative colitis, including the common pitfall of inflammatory bowel disease management and CMV infection. This case also discusses CMV pathophysiology including histological features, appropriate investigations and current management guidelines.

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Cytomegalovirus Reactivation in Ulcerative Colitis Patients

Cited by 52 publications

References 39 publications

Immunostaining Detection of Cytomegalovirus in Gastrointestinal Biopsies: Clinicopathological Correlation at a Large Academic Health System

Immunostaining Detection of Cytomegalovirus in Gastrointestinal Biopsies: Clinicopathological Correlation at a Large Academic Health System

Bile Acids Act as Soluble Host Restriction Factors Limiting Cytomegalovirus Replication in Hepatocytes

Ulcerative colitis: a case of steroid refractory disease

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