β-arrestin-2 predicts the clinical response to β-blockers in cirrhotic portal hypertension patients: A prospective study

Table 1 Baseline clinical and laboratory data of the study population

	PPA (n = 91)	NSBB responders (n = 60)	NSBB non-responders (n = 31)	P value
Male sex n (%)	65 (71.4)	44 (73.3)	21 (67.7)	0.371
Age (years)	55.16 ± 4.0	55.43 ± 3.74	54.64 ± 4.57	0.382
Ascites n (%)	29 (31.9)	19 (31.7)	10 (32.3)	0.571
HB (g/dL)	11.07 ± 1.44	11.10 ± 1.66	11.02 ± 0.91	0.812
Platelets (× 103/mm3)	83.13 ± 12.33	85.32 ± 15.46	78.90 ± 12.19	0.022
WBCs (× 103/mm3)	4.85 ± 1.05	4.88 ± 1.11	4.78 ± 0.96	0.662
ALT (IU/L)	40.01 ± 9.74	40.75 ± 9.98	38.58 ± 9.23	0.322
AST (IU/L)	54.40 ± 14.00	55.48 ± 14.24	52.29 ± 13.47	0.312
APRI-score	1.94 ± 0.46	1.92 ± 0.30	1.97 ± 0.56	0.632
Albumin (g/dL)	2.94 ± 0.18	2.93 ± 0.17	2.97 ± 0.18	0.252
Bilirubin (mg/dL)	1.73 ± 0.62	1.65 ± 0.55	1.89 ± 0.72	0.112
INR	1.35 ± 0.18	1.34 ± 0.17	1.39 ± 0.16	0.192
CTP A/B/C	48/36/7	34/22/4	14/14/3	0.563
Baseline PVCI	0.533 ± 0.10	0.545 ± 0.11	0.509 ± 0.09	0.112
Baseline esophageal varices grade: n (%)
Small	17(18.7)	10 (16.7)	7 (22.6)	0.061
Medium	48 (52.7)	28 (46.6)	20 (64.5)
large	26 (28.6)	22 (36.7)	4 (12.9)
Baseline portal hypertensive gastropathy grade: n (%)
No	26 (28.6)	13 (21.7)	13 (41.9)	0.0121
Mild	32 (35.2)	19(31.7)	13 (41.9)
Severe	33 (36.2)	28 (46.6)	5 (16.2)
GV presence n (%)	14 (15.4)	12 (20.0)	2 (6.5)	0.083
NSBB dose (min-max): (mg/d)	64.84 ± 14.63 (30-100)	65.33 ± 15.45 (30-100)	63.87 ± 13.08 (40-80)	0.652

¹Chi-square test.

²Independent sample t-test.

³Fisher’s exact test.

ALT: Alanine aminotransferase; APRI: Aspartate aminotransferase/platelet ratio index; AST: Aspartate aminotransferase; β-Arr-2: β-Arrestin-2; CI: Congestion index; CTP: Child-Turcotte-Pugh class; GV: Gastric varices; HB: Hemoglobin; INR: International normalization ratio; ITA: Intention to treat analysis; Max: Maximum; Min: Minimum; NSBB: Nonselective beta-blocker; PPA: Per-protocol analysis; WBCs: White blood cells.

Table 2 Univariate and multivariate analysis for predictors of diminished β-Arrestin-2 expression after nonselective β-blockers

Parameters	Univariate analysis		Multivariate analysis
	P value	OR	P value	OR	95%CI
ALT	0.51	-	-	-	-
AST	0.20	-	-	-	-
Platelets	0.26	-	-	-	-
APRI	0.06	-	-	-	-
Albumen	0.25	-	-	-	-
Bilirubin	0.69	-	-	-	-
Child-Turcotte-Pugh class	0.73	-	-	-	-
Baseline EV grade	0.003	1.35	-	-	-
Baseline β-Arr-2 expression	< 0.001	2.41	-	-	-
NSBB dose	0.049	6.5	0.02	1.01	0.91-1.05
ΔPVCI	< 0.001	10.34	0.005	1.58	0.001- 0.002

ALT: Alanine aminotransferase; APRI: Aspartate aminotransferase/platelet ratio index; AST: Aspartate aminotransferase; β-Arr-2: β-Arrestin-2; ΔPVCI: Delta (change in) portal vein congestion index; EV: Esophageal varices; NSBB: Nonselective beta-blockers.

Table 3 Correlations between serum and antral expression of β-arrestin-2 and different study parameters

	Serum β-Arr-2 level		β-Arr-2 expression in the gastric antrum
	rs	P value	rs	P value
Age	0.101	0.43	0.16	0.14
Child-Pugh class	0.11	0.34	0.08	0.45
INR	0.121	0.19	0.11	0.34
Serum albumin	-0.191	0.07	-0.12	0.26
Serum bilirubin	0.121	0.19	0.03	0.77
Presence of ascites	0.11	0.30	0.14	0.18
Platelets count	-0.381	< 0.001	-0.28	0.008
Baseline EV grade	0.48	< 0.001	0.30	0.004
Baseline PHG grade	0.33	0.002	0.38	< 0.001
Baseline congestion index	0.361	< 0.001	0.32	0.002
Antral β-Arr-2expression	0.72	< 0.001	-	-
Corpus β-Arr-2 expression	0.17	0.10	0.11	0.28
Duodenal β-Arr-2 expression	0.19	0.07	0.13	0.23
AST	-0.231	0.03	-0.25	0.019
APRI score	0.341	< 0.001	0.25	0.039
Non-selective B-blocker dose	0.151	0.15	0.03	0.73

¹Pearson’s correlation. APRI: Aspartate aminotransferase/platelet ratio index; AST: Aspartate aminotransferase; β-Arr-2: β-Arrestin-2; EV: Esophageal varices; INR: International normalization ratio; PHG: Portal hypertensive gastropathy.

Table 4 Cox-regression analysis for predictors of variceal bleeding among patients

Baseline parameters	P value	OR	95%CI
Alanine aminotransferase	0.32	-	-
Aspartate aminotransferase	0.19	-	-
Platelets count	0.006	0.93	0.85- 0.99
APRI score	0.11	-	-
Child-Turcotte-Pugh class	0.54	-	-
Baseline esophageal varices grade	0.29	-	-
Baseline portal vein congestion index	0.49	-	-
Β-arrestin-2 antral expression	< 0.001	0.15	0.1- 0.3
Serum β-arrestin-2	< 0.001	0.13	0.09-0.13

APRI: AST/platelet ratio score; CI: Confidence interval; OR: Odd’s ratio.