Plasma soluble CD 163 level as a marker of oesophageal varices in cirrhotic patients

Peer review under responsibility of Alexandria University Faculty of Medicine.

Available online 23 February 2018

Figures & data

Table 1 Comparison between the different studied groups according to demographic data.

	Group I (n = 20)		Group II (n = 20)		Group IIIa (n = 20)		IV (Control) (n = 20)		Test of sig.	p
	No.	%	No.	%	No.	%	No.	%
Sex
Female	9	45.0	8	40.0	3	15.0	8	40.0	χ^2 = 4.835	0.184^*
Male	11	55.0	12	60.0	17	85.0	12	60.0
Age
Min.–Max.	35.0–73.0		46.0–71.0		45.0–65.0		40.0–61.0		F = 0.969	0.412^*
Mean ± SD.	52.0 ± 7.89		54.45 ± 6.29		52.55 ± 5.29		50.95 ± 6.93
BMI (kg/m^2)
Min.–Max	22.0–28.10		24.0–30.70		23.0–31.90		22.0–27.0		F = 2.287	0.085^*
Mean ± SD.	26.01 ± 1.95		27.17 ± 2.30		27.40 ± 2.49		26.15 ± 1.42

χ²: Chi square test, F: ANOVA test, p: p value for comparing between the four groups.

* Statistically significant at p ≤ 0.05.

Table 2 Comparison between the three studied groups according to etiology of liver cirrhosis and fibrosis.

	Group I (n = 20)		Group II (n = 20)		Group IIIa (n = 20)		Control (n = 20)		χ^2	p
	No.	%	No.	%	No.	%	No.	%
HCV anti bodies
Negative	1	5.0	0	0.0	2	10.0	20	100.0	66.575	<0.001^*
Positive	19	95.0	20	100.0	18	90.0	0	0.0
HBS antigen
Negative	20	100.0	20	100.0	19	95.0	20	100.0	2.842	^MCp =  1.000
Positive	0	0.0	0	0.0	1	5.0	0	0.0
Schistosomal anti bodies titer
Negative	9	45.0	12	60.0	8	40.0	20	100	80.0	<0.001^*
Positive	11	55.0	8	40.0	12	60.0	0	0.0

χ²: Chi square test, MC: Monte Carlo for Chi square test, p: p value for comparing between the four groups,

* Statistically significant at p ≤ 0.05.

Table 3 Comparison between the three studied groups according to Local abdominal examination.

Local abdominal examination	Group I (n = 20)		Group II (n = 20)		Group IIIa (n = 20)		χ^2	p
	No.	%	No.	%	No.	%
Liver
Not enlarged	19	95.0	13	65.0	14	70.0	6.204	^MCp = 0.062
Enlarged	1	5.0	7	35.0	6	30.0
Spleen
Not enlarged	19	95.0	8	40.0	0	0.0	36.768^*	<0.001^*
Enlarged	1	5.0	12	60.0	20	100.0
Clinically detected ascites
Absent	16	80.0	6	30.0	5	25.0	14.949^*	0.001^*
Present	4	20.0	14	70.0	15	75.0

χ²: Chi square test, MC: Monte Carlo for Chi square test, p value.

* Statistically significant at p ≤ 0.05.

Table 4 Comparison between the different studied groups according to Child-Pugh classification.

Child-Pugh	Group I (n = 20)		Group II (n = 20)		Group III (n = 20)		Test of sig.	p
	No.	%	No.	%	No.	%
Classes
A	11	55.0	0	0.0	2	10.0	χ^2 = 27.972^*	^MCp  < 0.001^*
B	7	35.0	17	85.0	7	35.0
C	2	10.0	3	15.0	11	55.0
Scores
Mean ± SD.	6.70 ± 2.0		8.60 ± 1.54		9.60 ± 2.26		F = 11.358	<0.001^*
Sig. bet. grps	p1 = 0.003^*, p2 < 0.001^*, p3 = 0.111

χ²: Chi square test, MC: Monte Carlo for Chi square test, F: ANOVA test, Sig. bet. grps was done using test (LSD) for ANOVA.

p: p value for comparing between the three groups.

p₁: p value for comparing between group I and group II.

p₂: p value for comparing between group I and group III.

p₃: p value for comparing between group II and group III.

* Statistically significant at p ≤ 0.05.

Table 5 Comparison between the different studied groups according to lab investigations.

	Group I	Group II (n = 20)	Group IIIa (n = 20)	IV Control (n = 20)	Test of Sig.	p
HB(g/dl)
Mean ± SD.	12.06 ± 1.91	11.83 ± 1.63	9.57 ± 1.17	14.27 ± 1.03	F = 33.714^*	<0.001^*
pCont.	<0.001^*	<0.001^*	<0.001^*
Sig. bet. grps	p1 = 0.960, p2 < 0.001^*,p3 < 0.001^*
RBCs
Mean ± SD.	3.96 ± 0.82	4.14 ± 0.71	3.45 ± 0.67	4.31 ± 0.39	F = 6.228^*	0.001^*
pCont.	0.350	0.846	0.001^*
Sig. bet. grps	p1 = 0.831, p2 = 0.082, p3 = 0.009^*
WBCs
Mean ± SD.	5.14 ± 1.68	5.21 ± 1.81	4.45 ± 1.55	7.43 ± 1.78	H = 24.813^*	<0.001^*
pCont.	<0.001^*	<0.001^*	<0.001^*
Sig. bet. grps	p1 = 0.860, p2 = 0.140, p3 = 0.074
Platelets
Mean ± SD.	135.10 ± 53.74	97.30 ± 48.65	89.25 ± 33.57	327.85 ± 70.72	H = 48.823	<0.001^*
pCont.	<0.001^*	<0.001^*	<0.001^*
Sig. bet. grps	p1 = 0.037^*, p2 = 0.003^*, p3 = 0.797
Fasting insulin level
Mean ± SD.	11.63 ± 2.12	18.14 ± 1.55	22.92 ± 3.72	7.94 ± 2.10	F = 141.752	<0.001^*
pCont.	<0.001^*	<0.001^*	<0.001^*
Sig. bet. grps	p1 < 0.001^*,p2 < 0.001^*, p3 < 0.001^*
FBS g/dl
Mean ± SD.	88.37 ± 13.73	89.27 ± 11.46	91.12 ± 13.40	90.27 ± 14.84	F = 0.159	0.924
HOMA IR
Mean ± SD.	2.49 ± 0.37	3.03 ± 0.81	3.64 ± 1.20	1.82 ± 0.70	17.636	<0.001^*
pCont.	0.059	<0.001^*	<0.001^*
Sig. bet. grps	p1 = 0.173,p2 < 0.001^*,p3 = 0.098

F: ANOVA test, Sig. bet. grps was done using test (Tukey) for ANOVA.

H: Kruskal Wallis test, Sig. bet. grps was done using Mann Whitney test.

p: p value for comparing between the four groups.

p_Cont.: p value for comparing between control and each other periods.

p₁: p value for comparing between group I and group II.

p₂: p value for comparing between group I and group III.

p₃: p value for comparing between group II and group III.

* Statistically significant at p ≤ 0.05.

Table 6 Comparison between the different studied groups according to liver profiles.

Liver function	Group I (n = 20)	Group II (n = 20)	Group IIIa (n = 20)	IV Control (n = 20)	Test of sig.	p
ALT(U/L)					H = 27.516	<0.001^*
Mean ± SD.	55.95 ± 21.48	53.55 ± 26.35	44.20 ± 25.53	26.50 ± 7.58
pCont.	<0.001^*	<0.001^*	0.001^*
Sig. bet. grps	p1 = 0.379,p2 = 0.025^*,p3 = 0.099
AST(U/L)					H = 30.470	<0.001^*
Mean ± SD.	47.70 ± 23.04	71.45 ± 43.32	58.60 ± 32.77	29.75 ± 7.68
pCont.	0.001^*	<0.001^*	<0.001^*
Sig. bet. grps	p1 = 0.010^*,p2 = 0.343, p3 = 0.168
Albumin (g/dl)					F = 39.465	<0.001^*
Mean ± SD.	3.30 ± 0.52	2.67 ± 0.41	2.47 ± 0.78	4.12 ± 0.26
pCont.	<0.001^*	0.627	<0.001^*
Sig. bet. grps	p1 = 0.002^*,p2 < 0.001^*,p3 = 0.002^*
Total bilirubin (mg/dl)					H = 24.375	<0.001^*
Mean ± SD.	1.63 ± 0.80	1.82 ± 0.99	2.58 ± 1.56	0.93 ± 0.12
pCont.	0.005^*	<0.001^*	<0.001^*
Sig. bet. grps	p1 = 0.440,p2 = 0.032^*, p3 = 0.129
Direct bilirubin (mg/dl)					H = 33.656	<0.001^*
Mean ± SD.	0.68 ± 0.42	0.91 ± 0.58	1.29 ± 1.16	0.19 ± 0.05
pCont.	<0.001^*	<0.001^*	<0.001^*
Sig. bet. grps	p1 = 0.328,p2 = 0.131, p3 = 0.684
Alkaline phosphatase (u/l)					25.261	<0.001^*
Mean ± SD.	146.20 ± 34.68	141.06 ± 27.31	157.93 ± 38.23	81.60 ± 16.75
pCont.	<0.001^*	<0.001^*	<0.001^*
Sig. bet. grps	p1 = 0.950,p2 = 0.616, p3 = 0.303

F: ANOVA test, Sig. bet. grps was done using test (Tukey) for ANOVA.

H: Kruskal Wallis test, Sig. bet. grps was done using Mann Whitney test.

p: p value for comparing between the four groups.

p_Cont.: p value for comparing between control and each other periods.

p₁: p value for comparing between group I and group II.

p₂: p value for comparing between group I and group III.

p₃: p value for comparing between group II and group III.

* Statistically significant at p ≤ 0.05.

Table 7 Comparison between the different studied groups according to prothrombin activity, prothrombin time and INR.

Prothrombin	Group I (n = 20)	Group II (n = 20)	Group IIIa (n = 20)	IV Control (n = 20)	F	p
Activity (%)					45.312^*	<0.001^*
Mean ± SD.	69.13 ± 15.69	52.62 ± 9.10	59.64 ± 14.97	93.94 ± 4.72
pCont.	<0.001^*	<0.001^*	<0.001^*
Sig. bet. grps	p1 < 0.001^*,p2 = 0.068, p3 = 0.258
Time (sec.)					10.423^*	<0.001^*
Mean ± SD.	14.91 ± 3.27	17.42 ± 6.69	16.0 ± 2.84	10.60 ± 1.67
pCont.	0.007^*	0.689	<0.001^*
Sig. bet. grps	p1 = 0.216,p2 = 0.832, p4 = 0.216
INR					20.847^*	<0.001^*
Mean ± SD.	1.46 ± 0.34	1.55 ± 0.19	1.65 ± 0.40	0.99 ± 0.14
pCont.	<0.001^*	<0.001^*	<0.001^*
Sig. bet. grps	p1 = 0.736,p2 = 0.178, p3 = 0.733

F: ANOVA test, Sig. bet. grps was done using test (Tukey) for ANOVA, p: p value for comparing between the four groups.

p_Cont.: p value for comparing between control and each other periods.

p₁: p value for comparing between group I and group II.

p₂: p value for comparing between group I and group III.

p₃: p value for comparing between group II and group III.

* Statistically significant at p ≤ 0.05.

Table 8 Comparison between the studied groups according to ultra-sonographic data.

Ultra Sonographic data	Group I (n = 20)			Group II (n = 20)			Group IIIa (n = 20)			IV Control (n = 20)		Test of sig.	p
	No.	%		No.	%		No.	%		No.	%
No liver cirrhosis	0	0.0		0	0.0		0	0.0		20	100.0	χ^2= 80.0	<0.001^*
Liver cirrhosis	20	100.0		20	100.0		20	100.0		0	0.0
No SHF	8	40.0		12	60.0		8	40.0		20	100.0	χ^2= 20.000	<0.001^*
SHF	12	60.0		8	40.0		12	60.0		0	0.0
Ascites
No	16	80.0		6	30.0		6	30.0		20	100.0	χ^2= 38.546	^MCp < 0.001^*
Mild	4	20.0		10	50.0		6	30.0		0	0.0
Moderate	0	0.0		4	20.0		7	35.0		0	0.0
Tense	0.0	0		0	0.0		1	5.0		0	0.0
Direction of portal blood flow
Hepatopetal	20	100.0		10	50.0	7		35.0	20		100.0	χ^2= 33.379	<0.001^*
Non hepatopetal	0	0.0		10	50.0	13		65.0	0		0.0
Portal blood volume
Mean ± SD.	843.75 ± 182.40		672.65 ± 185.32			559.75 ± 97.75			1222.70 ± 66.75			F = 82.356	<0.001^*
pCont.	<0.001^*		<0.001^*			<0.001^*
Sig. bet. grps	p1 = 0.002^*,p2 < 0.001^*, p3 = 0.068
Liver right lobe diameter(cm)
Mean ± SD.	13.56 ± 0.78		12.83 ± 0.84			10.87 ± 1.02			15.01 ± 0.82			F = 77.888	<0.001^*
pCont.	<0.001^*		<0.001^*			<0.001^*
Sig. bet. grps	p1 = 0.047*,p2 < 0.001^*, p3 < 0.001^*
Spleen bipolar diameter (cm)
Mean ± SD.	13.84 ± 1.23		15.44 ± 1.37			19.59 ± 2.09			10.30 ± 1.29			F = 125.746	<0.001^*
pCont.	<0.001^*		<0.001^*			<0.001^*
Sig. bet. grps	p1 = 0.008^*,p2 < 0.001^*p3 < 0.001^*
Portal vein diameter (mm)
Mean ± SD.	12.71 ± 0.93		13.35 ± 1.90			16.38 ± 1.76			9.84 ± 1.34			F = 61.668	<0.001^*
pCont.	<0.001^*		<0.001^*			<0.001^*
Sig. bet. grps	p1 = 0.549, p2 < 0.001^*p3 < 0.001^*

F: ANOVA test, Sig. bet. grps was done using test (Tukey) for ANOVA.

χ²: Chi square test.

p: p value for comparing between the four groups.

p_Cont.: p value for comparing between control and each other periods.

p₁: p value for comparing between group I and group II.

p₂: p value for comparing between group I and group III.

p₃: p value for comparing between group II and group III.

* Statistically significant at p ≤ 0.05.

Table 9 Comparison between the different studied groups according to predictive scores.

	Group I (n = 20)	Group II (n = 20)	Group III (n = 20)	Control (n = 20)	Test of Sig.	p
AST to platelets ratio index (APRI)					H = 50.971	<0.001^*
Mean ± SD.	1.11 ± 0.72	2.47 ± 1.75	1.93 ± 0.92	0.24 ± 0.09
pCont.	<0.001^*	<0.001^*	<0.001^*
Sig. bet. grps	p1 = 0.003^*,p2 = 0.004^*, p3 = 0.525
FIB4					H = 54.983	<0.001^*
Mean ± SD.	2.77 ± 1.31	6.88 ± 4.04	5.49 ± 2.05	0.95 ± 0.33
pCont.	<0.001^*	<0.001^*	<0.001^*
Sig. bet. grps	p1 < 0.001^*,p2 < 0.001^*,p3 = 0.482
Lok score					F = 157.928	<0.001^*
Mean ± SD.	0.78 ± 0.23	0.96 ± 0.04	0.93 ± 0.10	0.15 ± 0.08
pCont.	<0.001^*	<0.001^*	<0.001^*
Sig. bet. grps	p1 < 0.001^*,p2 = 0.002^*,p3 = 0.909
Platelet count /spleen diameter (mm) ratio					H = 54.992	<0.001^*
Mean ± SD.	997.65 ± 436.48	647.03 ± 349.53	462.80 ± 181.91	3233.10 ± 838.74
pCont.	<0.001^*	<0.001^*	<0.001^*
Sig. bet. grps	p1 = 0.009^*,p2 < 0.001^*, p3 = 0.144
AST/ALT Ratio					H = 18.246	<0.001^*
Mean ± SD.	0.94 ± 0.53	1.36 ± 0.54	1.40 ± 0.55	1.10 ± 0.11
pCont.	=0.004^*	0.045^*	0.007^*
Sig. bet. grps	p1 = 0.001^*,p2 = 0.003^*, p3 = 0.957
Right lobe liver diameter (cm)/albumin ratio					F = 7.855	<0.001^*
Mean ± SD.	4.17 ± 0.73	4.94 ± 1.03	4.76 ± 1.36	3.65 ± 0.29
pCont.	0.309	<0.001^*	0.002^*
Sig. bet. grps	p1 = 0.052,p2 = 0.201, p3 = 0.924

H: Kruskal Wallis test, Sig. bet. grps was done using Mann Whitney test.

F: ANOVA test, Sig. bet. grps was done using test (Tukey) for ANOVA.

p: p value for comparing between the four groups.

p_Cont.: p value for comparing between control and each other periods.

p₁: p value for comparing between group I and group II.

p₂: p value for comparing between group I and group III.

p₃: p value for comparing between group II and group III.

* Statistically significant at p ≤ 0.05.

Fig. 1 Comparison between the different studied groups according to serum soluble CD163.

Fig. 2 ROC curve for Soluble CD163, HOMA IR and Platelets to predict presence of oesophageal varices between (Group II + Group IIIa) vs Group I.

Fig. 3 ROC curve for Soluble CD163 to differentiate small oesophageal varices from large oesophageal varices (Group IIIa vs Group II).

Table 10 Agreement (sensitivity, specificity and accuracy) for different parameters to predict presence of oesophageal varices between (Group II + Group III) vs Group I.

(Group II + Group III) vs Group I	AUROC	p	Cut off	Sensitivity	Specificity	PPV	NPV
Soluble CD163	0.820^*	<0.001^*	>191.71	77.50	75.0	86.1	62.5
HOMA IR	0.763^*	0.001^*	>2.83	67.50	90.0	93.1	58.1
Platelets count	0.734^*	0.003^*	≤93	62.50	80.0	86.2	51.6
Soluble CD163 and HOMA IR	0.863^*	<0.001^*		87.50	45.0	76.09	64.29
Soluble CD163 and Platelets	0.845^*	<0.001^*		85.0	65.0	82.93	68.42
Soluble CD163, HOMA IR and Platelets	0.915^*	<0.001^*		90.0	80.0	90.0	80.0
Soluble CD163, platelet count /spleen diameter (mm) and FIB4	0.910^*	<0.001^*		90.0	85.0	92.31	80.95
Soluble CD163, AST ALT ratio and ABRI	0.892^*	<0.001^*		90.0	70.0	85.71	77.78
Soluble CD163, Lok score and PLT	0.882^*	<0.001^*		92.50	75.0	88.10	83.33
Platelet count /spleen diameter (mm)	0.822^*	<0.001^*	≤643	75.0	85.0	90.9	63.0
FIB4	0.862^*	<0.001^*	>4.01	77.50	90.0	93.9	66.7
AST/ALT Ratio	0.785^*	<0.001^*	>0.9	77.50	75.0	86.1	62.5
AST to platelets ratio index (APRI)	0.770^*	<0.001^*	>1.54	67.50	95.0	96.4	59.4
Lok score	0.735^*	0.003^*	>0.85	87.50	55.0	79.5	68.8

Table 11 Agreement (sensitivity, specificity and accuracy) for soluble CD163 to differentiate small oesophageal varices from large oesophageal varices (Group IIIa vs Group II).

Gp IIIa vs Gp II	AUROC	p	Cut off	Sensitivity	Specificity	PPV	NPV
Soluble CD163	0.863^*	<0.001^*	>199.19	85.0	90.0	89.5	85.7