Cytomegalovirus in inflammatory bowel disease: A systematic review

Table 1 Eligibility criteria for inclusion

Adults

Diagnosis of IBD, according to international guidelines

English language

Prevalence and/or diagnostics CMV infection or intestinal disease reported

Minimal sample size 10 patients

IBD: Inflammatory bowel disease; CMV: Cytomegalovirus.

Table 2 Prevalence by definition of cytomegalovirus-infection

Definition	Studies, n	Median	Range
Antigenemia[17-21]	5	32%	6%-34%
Tissue PCR[22-25]	4	11%	1%-32%
IHC1[26-29]	4	13%	9%-23%
HE[30-32]	3	17%	5%-36%
HE or IHC[33,34]	2	8%	5%-11%
HE and IHC[35,36]	2	19%	12%-27%
IgM or HE or IHC2[37,38]	2	9%	5%-13%
Antigenemia or Tissue PCR[39]	1	NA	NA
Serum PCR[40]	1	84%	-
(HE and IHC) or tissue PCR[41]	1	4%	-
Tissue PCR 10 copies/µg; OR histology OR Antigenemia[42]	1	54%	-
Antigenemia (2 tests: C7-HRP OR C10/C11) OR histology[43]	1	9%	-
Antigenemia or blood PCRquantitative[44]	1	36%	-
IgM or serum PCR or HE[45]	1	78%	-
IgM or tissue PCRqualitative or HE[46]	1	16%	-
IgG and (blood culture, antigenemia or histology or IgM or urine culture)[47]	1	6%	-
IgM or serum PCRqualitative or feces PCR[48]	1	5%	-
Inclusions: HE[49]	1	13%	-
Active infection: tissue PCR[50]	1	13%	-
Active replication: (HE or IHC) and antigenemia[51]	1	36%	-
Blood dissemination: (viremia, antigenemia, RNAemia) or (viremia or tissue culture)[52]	1	16%	-
Total: 21	Total: 36

¹One study defined a clinically relevant infection as > 10 IHC + cells/section but also recognized “scattered” positivity as 1-9 cells per section[29]; ²Once mentioned as “acute infection”. PCR: Polymerase chain reaction; HE: Hematoxylin and eosin staining; IHC: Immunohistochemistry; IgM: Immunoglobulin M; IgG: immunoglobulin G; NA: Not applicable.

Table 3 Prevalence by definition of cytomegalovirus-intestinal disease

Definition	Studies, n	Median	Range
HE or IHC1,2[38,44,53,54]	4	6%	2%-29%
HE[20,55]	2	9%	0%-17%
Tissue PCRquantitative > 10 copies/mg[56,57]	2	34%	30%-38%
Serology and (IHC or antigenemia or serum PCR or tissue PCR)[58]	1	6%	-
IHC[59]	1	0%	-
HE or IHC or tissue PCR[51]	1	33%	-
(Pp65 antigenemia or tissue PCRquantitative) and IHC and intestinal symptoms[39]	1	NA3	-
IHC positive when inflammation present[52]	1	1%	-
Total: 8	Total: 13

¹One study tested both before and after iv-steroid administration; ²No data on prevalence: definition is used as the gold standard to compare other diagnostics;

³No prevalence is reported in this study. PCR: Polymerase chain reaction; HE: Hematoxylin and eosin staining; IHC: Immunohistochemistry.

Table 4 Prevalence by definition of cytomegalovirus-reactivation

Definition	Studies, n	Median	Range
IgM or HE or PCR1[60]	1	10%	-
Serum PCR in IgG positive patients[61]	1	0%	-
Antigenemia or plasma PCR[62]	1	36%	-
Total: 3	Total: 3

¹Not specified what material is used for PCR testing. PCR: Polymerase chain reaction; HE: Hematoxylin and eosin staining; IgM: Immunoglobulin M; IgG: Immunoglobulin G.

Table 5 Test characteristics different diagnostic tools for cytomegalovirus

Test	Pro	Con	Sens	Spec
Serology	Fast, quantification possible	Systemic, not proving intestinal disease;	98%-100%	96%-99%
Antigenemia	Fast, quantification possible	Systemic, not proving intestinal disease labor intensive	60%-100%	83%-100%
Serum PCR	Fast, quantification possible	Systemic, not proving intestinal disease	65%-100%	40%-94%
HE Histology (gold standard?)	Specific, proofs intestinal disease	Slow; low sensitivity	10%-87%	92%-100%
Histology with IHC	Specific, proofs intestinal disease	Slow	93%	92%-100%
Tissue PCR	Quantification possible	Cut-off point unclear, uncertain clinical significance	65%-100%	40%-100%
Stool PCR	Quantification possible	Little experience	83%%	93%
Viral Culture	Very specific	Very slow	45%-78%	89%-100%
Rapid Vial culture	Very specific	Little experience	68%-100%	89%-100%

Sens: Sensitivity; Spec: Specificity; PCR: Polymerase chain reaction; HE: Hematoxylin and eosin staining; IHC: Immunohistochemistry.