Spleen stiffness mirrors changes in portal hypertension after successful interferon-free therapy in chronic-hepatitis C virus patients

Table 1 Baseline characteristics of included patients

Variable	Overall (n = 134)	CSPH (LSM ≥ 21 kPa) (n = 60)	No CSPH (LSM < 21 kPa) (n = 74)
Age (yr)	60 (51-69)	57 (50.5-65)	61.5 (51-70)
Male	92 (68.7)	42 (70)	50 (67.6)
HCV-genotype
1	95 (70.9)	41 (68.3)	54 (72.5)
2	12 (8.9)	4 (6.7)	8 (10.8)
3	20 (14.9)	11 (18.3)	9 (12.2)
4	7 (5.3)	4 (6.7)	3 (4.5)
Treatment regimen
SOF/RBV	33 (24.6)	10 (16.7)	23 (31.1)
SOF/SMV	29 (21.6)	15 (25)	14 (18.9)
SOF/DCV	38 (28.4)	19 (31.6)	19 (25.6)
SOF/LDV	16 (12)	7 (11.7)	9 (12.2)
Other	18 (13.4)	9 (15)	9 (12.2)
Child Pugh Score
A	115 (85.8)	52 (86.7)	63 (85.1)
B	19 (14.2)	8 (13.3)	11 (14.9)
MELD Score	8 (7-10)	9 (8-10)	8 (7-10)
Spleen Diameter (cm)	14 (12.3-15.5)	14.7 (12.8-15.8)	13.9 (12.1-15)
Laboratory results
Platelets (cells × 109/L)	110 (79-150)	102 (74-132)	134 (92-159)
ALT (U/L)	58 (39-95)	55 (39-84)	60 (38-105)
Bilirubin (mg/dL)	0.9 (0.67-1.29)	1 (0.84-1.52)	0.8 (0.6-1.1)
Albumin (g/dL)	3.8 (3.6-4.1)	3.8 (3.5-4.1)	3.8 (3.6-4.1)
Creatinine (mg/dL)	0.8 (0.7-0.98)	0.8 (0.70-0.96)	0.85 (0.71-1.08)
INR	1.1 (1.06-1.2)	1.17 (1.1-1.21)	1.08 (1.04-1.13)
NITs
SSM (kPa)	58.8 (42.2-75)	69.9 (55.7-75)	46.2 (31.6-63.9)
LSM (kPa)	19.3 (14.1-27)	29.1 (23.9-39.7)	14.6 (12-17)
LSPS	2.78 (1.4-4.94)	5.1 (3.05-7.48)	1.58 (1.09-2.79)

Qualitative data were expressed as number and percentage (%); quantitative data were expressed as median (25%-75% quantiles). ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; CSPH: Clinically significant portal hypertension; DCV: Daclatasvir; HRV: High risk varices; INR: International normalized ratio; LDV: Ledipasvir; LSM: Liver stiffness measurement; LSPS: Liver stiffness to spleen/platelet score; MELD: Model for end-stage liver disease; NITs: Non-invasive tests; RBV: Ribavirin; SMV: Simeprevir; SOF: Sofosbuvir; SVR: Sustained virological response; SSM: Spleen stiffness measurement.

Table 2 Liver and Spleen stiffness measurement decreases after sustained viral response

Variable	Overall (n = 134)	CSPH (LSM ≥ 21 kPa) (n = 60)	No CSPH (LSM < 21 kPa) (n = 74)
Relative SSM decrease (%)	12.3 (0-36.3)	4.7 (0-32.5)	20.4 (0-39.7)
Overall SSM decrease	92 (68.7)	40 (66.7)	52 (70.3)
> 10%	73 (54.5)	31 (51.7)	42 (56.8)
> 20%	60 (44.8)	23 (38.3)	37 (50)
Relative LSM decrease (%)	30 (13.5-42.4)	28.3 (11.4-41.9)	30.8 (13.9-42.4)
Overall LSM decrease	114 (85.1)	51 (85)	63 (85.1)
> 10%	108 (80.6)	48 (80)	60 (81.1)
> 20%	88 (65.7)	40 (66.7)	48 (64.9)
PLT Increase (%)	12.4 (-10.1 to 29.6)	5.5 (-15.6 to 25.9)	17.4 (-0.67 to 35.6)

CSPH: Clinically significant portal hypertension; LSM: Liver stiffness measurement; PLT: Platelet count; SSM: Spleen stiffness measurement.

Table 3 Univariate and multivariate analysis of factors associated with a SSM decrease > 20%

Entire Population (n = 134)
Variable	Univariate analysis				Multivariate analysis
					LR Chi-2 = 16.48	AIC = 171.8
					AUROC = 0.6821	BIC = 177.6
	SSM Decrease >20% (n = 60)	No SSM Decrease >20% (n = 74)	OR (95%CI)	P value	OR (95%CI)	P value
Age (yr)	62 (52-69)	56 (50-68)	1.005 (0.975-1.037)	0.727
Sex (male)	21 (28.4)	21 (35)	1.359 (0.653-2.828)	0.412
Presence of varices (n = 67) (yes)	9 (34.2)	24 (82.8)	0.110 (0.031-0.388)	0.001
Spleen diameter (cm)	13.6 (11.65-15.15)	14.5 (13-16)	0.800 (0.660-0.970)	0.023
Child Pugh Score	5 (5-6)	5 (5-6)	0.885 (0.601-1.303)	0.535
Child Pugh Score B (yes)	8 (13.3)	11 (14.9)	0.881 (0.330-2.352)	0.801
MELD score	8 (7-10)	9 (8-10)	0.786 (0.648-0.954)	0.015
MELD > 10	12 (20)	30 (40.5)	0.367 (0.167-0.804)	0.012
AST (U/L)	54.5 (38-85)	56 (35.5-87)	0.996 (0.987-1.004)	0.322
ALT (U/L)	62 (37-105)	53 (40-90)	1.002 (0.995-1.008)	0.620
ALT ≥ 2 × ULN at BL	59.5 (37.5-101)	54 (40-91.5)	1.326 (0.597-2.944)	0.489
INR	1.09 (1.05-1.17)	1.12 (1.09-1.21)	0.127 (0.001-0.551)	0.023
Bilirubin (mg/dl)	0.85 (0.65-1.16)	1.02 (0.71-1.52)	0.903 (0.535-1.525)	0.703
Albumin (g/dl)	3.8 (3.52-4.12)	3.78 (3.52-4.12)	2.096 (0.959-4.581)	0.063
Creatinine (mg/d)	0.8 (0.7-1)	0.81 (0.69-0.93)	0.327 (0.674-1.585)	0.165
Platelet count (10^9/L)	118 (92-154)	91 (74-137)	1.002 (0.996-1.007)	0.579
LSM BL (kPa)	18 (14.6-25.7)	21.1 (14-38.5)	0.988 (0.962-1.015)	0.391
LSM SVR24 (kPa)	12.4 (9.4-18)	17.5 (10.4-32.4)	0.944 (0.908-0.981)	0.004
SSM BL (kPa)	60.4 (45.7-70.7)	53.2 (37.4-75)	1.012 (0.992-1.032)	0.225
LSPS BL	2.17 (1.33-3.77)	4.15 (1.65-6.26)	0.817 (0.684-0.975)	0.025
LSM decrease (Delta, %)	33 (18.1–44.6)	19.4 (0–31.3)	0.0332 (0.005-0.225)	< 0.0001	0.0332 (0.005-0.225)	< 0.0001
LSM decrease > 10% (yes)	54 (90)	54 (73)	3.333 (1.242-8.946)	0.017
LSM decrease > 20% (yes)	47 (78.3)	41 (55.4)	2.910 (1.352-6.262)	0.006

Qualitative data were expressed as number and percentage (%); quantitative data were expressed as median (25%-75% quantiles). AIC: Akaike information criterion; ALT: Alanine aminotransferase; AUROC: Area under curve ROC; AST: Aspartate aminotransferase; BIC: Bayesian information criterion; CSPH: Clinically significant portal hypertension; DCV: Daclatasvir; HRV: High risk varices; INR: International normalized ratio; LDV: Ledipasvir; LR: Like-hood ratio; LSM: Liver stiffness measurement; LSPS: Liver stiffness to spleen/platelet score; MELD: Model for end-stage liver disease; NITs: Non-invasive tests; RBV: Ribavirin; SMV: Simeprevir; SOF: Sofosbuvir; SVR: Sustained virological response; SSM: Spleen stiffness measurement.