Epstein-Barr virus infection is an independent risk factor for surgery in patients with moderate-to-severe ulcerative colitis

Table 1 Comparison of baseline demographic and clinical characteristics of patients with moderate to severe ulcerative colitis (surgery vs control group), n (%)

	Surgery group (n = 47)	Control group (n = 106)	P value
Sex			0.486
Male	29 (61.7)	59 (55.7)
Female	18 (38.3)	47 (44.3)
Age (year)	59 (47, 64)	47 (33, 59)	0.001a
Diseases course (month)	36 (12, 96)	28 (12, 84)	0.673
Smoking history	1 (2.1)	8 (7.5)	0.346
History of surgery	8 (17)	20 (18.9)	0.785
Cardiovascular and cerebrovascular risk factors	14 (29.8)	21 (19.8)	0.175
History of malignant tumor	4 (8.5)	3 (2.8)	0.202
Fever	23 (48.9)	15 (14.2)	0.000a
Complication	0 (0.0)	6 (5.7)	0.178
Extraintestinal manifestations	6 (12.8)	9 (8.5)	0.599
Intestinal stenosis	8 (17)	9 (8.5)	0.121
UCEIS ≥ 5	20 (42.6)	41 (38.7)	0.652
Nancy index ≥ 3	47 (100)	100 (94.3)	0.178
EBER positivity	19 (40.4)	5 (4.7)	0.000a
High EBER concentration	7 (14.9)	0 (0.0)	0.000a
Low EBER concentration	12 (25.5)	5 (4.7)	0.000a
Single EBV infection	11 (23.4)	5 (4.7)	0.001a
CMV positivity	14 (29.8)	1 (0.9)	0.000a
CMV high-grade infection	2 (4.3)	0 (0.0)	0.093
CMV low-grade infection	12 (25.5)	1 (0.9)	0.000a
Single CMV infection	6 (12.8)	1 (0.9)	0.004a
Combined infection of EBV and CMV	8 (17.0)	0 (0.0)	0.000a
Fungal infection	12 (25.5)	10 (9.4)	0.009a
WBC count ( 109/L)	6.49 (4.85, 8.64)	7.16 (5.76, 9.07)	0.158
Hemoglobin (g/L)	102 ± 21	118 ± 21	0.000a
Platelet count ( 109/L)	254 (196, 324)	289 (234, 383)	0.069
C-reactive protein (mg/L)	39.6 (15.6, 78.4)	5.5 (1.2, 20.1)	0.000a
ESR (mm/hour)	34 (15, 59)	24 (10, 38)	0.010a
Albumin (g/L)	30.4 (24.5, 34.9)	38.6 (33.5, 42.1)	0.000a
Prealbumin (g/L)	138.6 ± 72.1	173.9 ± 60.8	0.002a
Treatment with ≥ 3 types of immunosuppressive drugs before admission	17 (36.2)	8 (7.5)	0.000a
Antibiotic therapy with third-generation cephalosporins or more advanced antibiotics during admission	42 (89.4)	64 (60.4)	0.000a

^aP < 0.05.

UCEIS: Ulcerative colitis endoscopic index of severity; EBER: Epstein-Barr virus-encoded small RNA; CMV: Cytomegalovirus; WBC: White blood cell; ESR: Erythrocyte sedimentation rate.

Table 2 Results of univariate logistic analysis

	Univariate logistic analysis		AUC
	P value	OR (95%CI)
Sex	0.486	1.283 (0.636-2.590)
Age (year)	0.002a	1.040 (1.014-1.067)	0.6651
Disease course (month)	0.623	1.001 (0.996-1.007)
Smoking history	0.219	0.266 (0.032-2.193)
History of surgery	0.785	0.882 (0.358-2.176)
Cardiovascular and cerebrovascular risk factors	0.178	1.71 7 (0.782-3.771)
History of malignant tumor	0.139	3.194 (0.686-14.878)
Fever	0.000a	5.814 (2.636-12.821)	0.6741
Complication	NC
Extraintestinal manifestations	0.415	1.577 (0.527-4.718)
Intestinal stenosis	0.128	2.211 (0.795-6.145)
UCEIS ≥ 5	0.652	1.174 (0.584-2.360)
Nancy index ≥ 3	NC
EBER positivity	0.000a	13.707 (4.700-39.977)	0.6791
CMV positivity	0.000a	44.545 (5.643-351.647)	0.6441
Fungal infection	0.012a	3.291 (1.306-8.293)	0.580
WBC count ( 109/L)	0.410	0.954 (0.851-1.068)
Hemoglobin (g/L)	0.000a	0.966 (0.949-0.983)	0.279
Platelet count ( 109/L)	0.124	0.998 (0.994-1.001)
C-reactive protein (mg/L)	0.000a	1.025 (1.014-1.037)	0.8141
ESR (mm/hour)	0.019a	1.017 (1.003-1.031)	0.6301
Albumin (g/L)	0.000a	0.855 (0.806-0.908)	0.212
Prealbumin (g/L)	0.003a	0.991 (0.986-0.997)	0.328
Treatment with ≥ 3 types of immunosuppressive drugs before admission	0.000a	6.942 (2.726-17.674)	0.6431
Antibiotic therapy with third-generation cephalosporins or more advanced antibiotics during admission	0.001a	5.512 (2.017-15.069)	0.6451

^aP < 0.05.

¹AUC > 0.6.

AUC: Area under the curve; UCEIS: Ulcerative colitis endoscopic index of severity; EBER: Epstein-Barr virus-encoded small RNA; CMV: Cytomegalovirus; WBC: White blood cell; ESR: Erythrocyte sedimentation rate; OR: Odds ratio; NC: Not calculated (comparison not feasible for computational reasons).

Table 3 Stratified analysis

	Conditional independence tests (χ2, P value)	OR parity test (P value)	Estimated combined OR (95%CI)
Age (≤ 51, > 51), year	26.588, P = 0.000	0.208	10.850 (3.726-31.594)
Fever	19.673, P = 0.000	0.635	9.254 (2.998-28.569)
CMV positivity	21.170, P = 0.000	0.712	10.669 (3.361-33.867)
Fungal infection	30.291, P = 0.000	0.437	14.969 (4.875-45.962)
Hemoglobin (≤ 113, >113) g/L	22.047, P = 0.000	0.708	12.459 (3.726-41.661)
CRP (≤ 11.74, > 11.74) mg/L	16.495, P = 0.000	0.339	10.979 (3.071-39.245)
ESR (≤ 27, > 27) mm/hour	28.514, P = 0.000	0.369	12.056 (4.070-35.715)
Albumin (≤ 35.2, > 35.2) g/L	20.065, P = 0.000	0.598	9.897 (3.119-31.409)
Prealbumin (≤ 163, >163) g/L	28.164, P = 0.000	0.127	10.992 (3.822-31.612)
Treatment with ≥ 3 types of immunosuppressive drugs before admission	42.469, P = 0.000	0.825	25.583 (7.836-83.531)
Antibiotic therapy with third-generation cephalosporins or more advanced antibiotics during admission	23.298, P = 0.000	0.087	12.659 (4.035-39.719)

CMV: Cytomegalovirus; OR: Odds ratio; CRP: C-reactive protein; ESR: Erythrocyte sedimentation rate.

Table 4 Results of multivariate logistic analysis

	Multivariate logistic analysis
	P value	OR (95%CI)
Age (year)	0.004a	1.063 (1.020, 1.107)
Fever	0.288	2.038 (0.549, 7.568)
EBER positivity	0.003a	9.634 (2.137, 43.424)
CMV positivity	0.001a	118.825 (6.839, 2064.630)
C-reactive protein (mg/L)	0.116	1.013 (0.997, 1.029)
ESR (mm/hour)	0.429	1.010 (0.985, 1.037)
Treatment with ≥ 3 types of immunosuppressive drugs before admission	0.000a	17.959 (4.638, 69.540)
Antibiotic therapy with third-generation cephalosporins or more advanced antibiotics during admission	0.130	2.948 (0.728, 11.934)

^aP < 0.05.

EBER: Epstein-Barr virus-encoded small RNA; CMV: Cytomegalovirus; ESR: Erythrocyte sedimentation rate; OR: Odds ratio.

Table 5 Univariate logistic analysis and multivariate logistic analysis in the subgroup (n = 138)

	Univariate logistic analysis		Multivariate logistic analysis
	P value	OR (95%CI)	P value	OR (95%CI)
Sex	0.451	1.364 (0.609, 3.059)
Age (year)	0.004a	1.045 (1.014, 1.076)	0.009a	1.067 (1.017-1.120)
Disease course (month)	0.134	1.005 (0.999, 1.011)
History of surgery	0.912	0.944 (0.344, 2.593)
Cardiovascular and cerebrovascular risk factors	0.117	2.000 (0.840, 4.762)
History of malignant tumor	0.051	4.690 (0.993, 22.156)
Fever	0.000a	6.375 (2.659, 15.286)	0.705	1.366 (0.272-6.854)
Extraintestinal manifestations	0.281	1.905 (0.590, 6.146)
Intestinal stenosis	0.055	2.872 (0.977, 8.445)
UCEIS ≥ 5	0.208	1.659 (0.755, 3.644)
EBER positivity	0.000a	10.000 (3.155, 31.692)	0.027a	6.698 (1.243-36.083)
Fungal infection	0.013a	3.562 (1.303, 9.739)	0.050	5.092 (1.001-25.914)
WBC count (× 109/L)	0.534	0.962 (0.850, 1.088)
Hemoglobin (g/L)	0.000a	0.964 (0.945, 0.983)	0.057	0.963 (0.927-1.001)
Platelet count (× 109/L)	0.379	0.998 (0.995, 1.002)
C-reactive protein (mg/L)	0.000a	1.023 (1.011, 1.035)	0.043a	1.022 (1.001-1.044)
ESR (mm/hour)	0.040a	1.017 (1.001, 1.033)	0.392	0.988 (0.960-1.016)
Albumin (g/L)	0.000a	0.858 (0.804, 0.916)	0.060	0.867 (0.747-1.006)
Prealbumin (g/L)	0.004a	0.990 (0.984, 0.997)	0.124	1.013 (0.997-1.029)
Treatment with ≥ 3 types of immunosuppressive drugs before admission	0.000a	7.881 (2.889, 21.502)	0.000a	27.158 (5.515-133.724)
Antibiotic therapy with third-generation cephalosporins or more advanced antibiotics during admission	0.007a	4.645 (1.521, 14.185)	0.907	1.098 (0.229-5.261)

^aP < 0.05.

UCEIS: Ulcerative colitis endoscopic index of severity; EBER: Epstein-Barr virus-encoded small RNA; WBC: White blood cell; ESR: Erythrocyte sedimentation rate; OR: Odds ratio.