Osteopontin: A non-invasive parameter of portal hypertension and prognostic marker of cirrhosis

Table 1 Characteristics of patients with liver cirrhosis in the study

Parameter	All patients (n = 154)	Compensated patients (without ascites) (n = 91)	Decompensated patients (with ascites) (n = 63)	P value1
Age (yr)	54.7 ± 11.1	54.5 ± 11.2	55.4 ± 11.3	0.276
Gender (M/F) (%)	74/26	73/27	77/23	0.340
Etiology of cirrhosis (alcohol/viral/other incl. NASH) Number of patients	112/22/20	63/15/13	47/9/7	0.490
Child-Pugh A/B/C (%)	41/34/25	69/27/4	14/39/47	< 0.001
MELD score	12.5 ± 4.9	10.9 ± 4.5	14.3 ± 4.8	< 0.001
Bleeding from varices (%)	30	28	33	0.288
Bilirubin (µmol/L)	31 (18-55)	25 (15-44)	40 (23-62)	0.011
Albumin (g/L)	33.6 ± 7.4	39.9 ± 6.7	30.1 ± 6.6	< 0.001
Creatinine (µmol/L)	83 ± 29	81.6 ± 27.2	97.8 ± 22.3	< 0.001
ALT (μkat/L)	0.65 (0.5-1.4)	0.71 (0.6-1.7)	0.58 (0.4-0.8)	0.282
AST (μkat/L)	0.96 (0.7-1.6)	1.11 (0.8-1.6)	0.75 (0.6-1)	0.193
Platelets (× 109/L)	107 (74-163)	98 (68-142)	130 (82-203)	0.015
Arterial mean blood pressure (mmHg)	91 ± 11.5	92 ± 13	90 ± 10	0.483
Ascites (%)	41	-	-	-
Encephalopathy (%)	12	6	19	< 0.001
HVPG (mmHg)	16.0 ± 5.4	14.2 ± 5.1	26.9 ± 6.1	< 0.001
Varices (none/small/large) (%)	18/35/47	25/30/45	10/40/50	< 0.001
Spleen length (mm)	143 ± 22	142 ± 19	146 ± 26	0.534
Diameter of the portal vein (mm)	13.3 ± 2.1	13.2 ± 1.8	13.5 ± 2.4	0.729
Portal flow velocity (cm/s)	16 ± 5.8	18.8 ± 6	13.5 ± 4	< 0.001
Diameter of the lienal vein (mm)	10.1 ± 3	10.25 ± 2.7	9.8 ± 3.5	0.348
Follow-up (yr)	3.7 ± 2.6	4.13 ± 2.4	2.88 ± 2.6	0.004
Osteopontin (ng/mL)	107 (73.7-154)	85.7 (65.7-129)	138 (106-194)	< 0.001

¹Statistical difference between compensated and decompensated patients. Data are expressed as mean ± SD or as a median and 25-75 percentile, when non-normally distributed. HVPG: Hepatic venous pressure gradient.

Table 2 Presence of clinically significant portal hypertension in relation to osteopontin and other parameters

Parameter	P value
Osteopontin	0.04
Platelet count	0.05
AST/ALT ratio	0.49

Multiple linear regression with hepatic venous pressure gradient (HVPG) > 10 mmHg as a variable carried out with OPN, platelet count, and AST/ALT ratio as independent variables. AST: Aspartate aminotransferase; ALT: Alanine aminotransferase.

Table 3 Risk for death of patients with liver cirrhosis based on the cut-off values of hemodynamic evaluation of portal hypertension and osteopontin

Parameter	Odds ratio	95%CI	P value
HVPG > 10 mmHg	2.92	1.09-7.76	0.032
OPN > 80 ng/mL	2.23	1.06-4.68	0.034
HVPG or OPN above cut-off1	2.34	1.16-4.75	0.018
Both HVPG and OPN above cut-off2	5.09	1.29-20.15	0.020

¹Only one parameter above cut-off values (10 mmHg for HVPG, 80 ng/mL for OPN);

²Both parameters above cut-off. HVPG: Hepatic venous pressure gradient; OPN: Osteopontin.

Table 4 Laboratory and clinical parameters in different Child-Pugh groups of patients

Parameter	Child-Pugh A	Child-Pugh B	Child-Pugh C	P value
Age (yr)	55.6 ± 10.7	52.9 ± 11.2	56.3 ± 10.7	NS
Osteopontin (ng/mL)	84.8 ± 34.9	158.8 ± 98.2	205.2 ± 142.8	A vs B, P < 0.001, A vs C, P < 0.001, B vs C, NS
HVPG (mmHg)	14.1 ± 5.1	17.1 ± 4.8	19.5 ± 4.5	A vs B, P < 0.001, A vs C, P < 0.001, B vs C, NS
Survival (yr)	4.6 ± 2.3	3.3 ± 2.5	2.5 ± 2.6	A vs C, P < 0.001, A vs B, NS, B vs C, NS

HVPG: Hepatic venous pressure gradient; NS: Not significant.

Table 5 Correlation of hemodynamic evaluation of portal hypertension and osteopontin to clinical parameters in patients with liver cirrhosis

Parameter	HVPG		Osteopontin
	r	P value	r	P value
Survival	0.220	0.009	0.230	0.006
Platelet counts	0.247	0.005	0.231	0.009
Size of varices	0.352	< 0.001	0.009	0.927
History of bleeding from varices		< 0.001		0.506
Presence of ascites		< 0.001		< 0.001

r: Correlation coefficient; HVPG: Hepatic venous pressure gradient.