Splenic stiffness measurement to predict decompensation in compensated advanced chronic liver disease

Table 1 Baseline parameters of patients with compensated advanced chronic liver disease of different etiology, n (%)/mean ± SD

Parameters	Overall (n = 231)	MASLD (n = 52)	ArLD (n = 43)	HCV (n = 75)	HBV (n = 60)
Age (years)	45.18 ± 9.73	47 ± 10.7	39.09 ± 7.17	47 ± 8.88	44 ± 9.33
Male:female	96:135	22:31	42:1	14: 61	18:42
Hemoglobin	11.66 ± 1.87	11.53 ± 1.75	11.82 ± 1.76	11.92 ± 1.95	11.37 ± 1.94
Total leukocyte count	5077.0 ± 1622	4857 ± 1436	5154 ± 1454	5322 ±1837	4905 ± 1582
Platelet	1.1 ± 0.43	1.49 ± 0.49	1.14 ± 0.47	1.43 ± 0.49	1.08 ±0.41
Total bilirubin	1.01 ± 0.54	1.6 ± 0.56	0.92 ± 0.67	1.0 ± 0.46	1.11 ± 0.55
Conjugated bilirubin	0.61 ± 0.33	0.7 ± 0.31	0.50 ± 0.33	0.62 ± 0.21	0.64 ± .13
AST	64 ± 30	63 ± 23	71 ± 37	70 ± 33	54.20 ± 21
ALT	49.18 ± 26	48 ± 20	56 ± 37	52 ± 29.5	40.8 ± 16
ALP	117 ± 43	121 ± 56	127 ± 36	121.6 ± 38	127 ± 34
Albumin	4.10 ± 2.6	3.87 ± 0.41	3.84 ± 0.50	3.82 ± 1.38	4.4 ± 2.76
Protein	8.8 ± 5.3	8.7 ± 3.1	8.45 ± 2.47	7.74 ± 0.61	8.1 ± 3.23
INR	1.12 ± 0.19	1.14 ± 0.20	1.09 ± 0.21	1.11 ± 0.16	1.15 ± 0.20
Urea	28.8 ± 9.27	31 ± 10.3	24.5 ± 8.75	28.42 ± 7.96	29.8 ± 9.21
Creatinine	0.88 ± 0.19	0.89 ± 0.19	0.50 ± 0.33	0.86 ± 0.19	0.89 ± 0.18
LSM	23.5 ± 7.9	23 ± 7.3	21.9 ± 8.17	24.5 ± 8.06	23.7 ± 8.12
SSM	46.4 ± 16.8	47.26 ± 16.47	47.26 ± 17.9	45.6 ± 15.9	49.9 ± 17.42
FIB-4	4.45 ± 2.5	4.78 ± 2.63	3.88 ± 2.34	4.90 ± 2.80	4.03 ± 2.11
APRI	1.73 ± 1.14	1.76 ± 1.02	1.89 ± 1.29	1.49 ± 0.94	1.83 ± 1.26
Decompensation	19 (8.22)	7 (13.4)	5 (11.62)	4 (5.3)	3 (5)
Death	5 (2.17)	2 (3.8)	2 (4.6)	0	1 (1.6)

ArLD: Alcohol related liver disease; HCV: Hepatitis C virus; HBV: Hepatitis B virus; MASLD: Metabolic dysfunction-associated steatotic liver disease; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; ALP: Alkaline phosphatase; INR: International normalized ratio; SSM: Splenic stiffness measurement; LSM: Liver stiffness measurement; FIB-4: Fibrosis-4 index; APRI: Aspartate aminotransferase to platelet ratio index.

Table 2 Comparison of baseline laboratory parameters in patients with decompensation as compared to patients who did not have any decompensation within the follow-up period, mean ± SD

Parameters	No decompensation (n = 212)	Decompensation (n = 19)	P value
Haemoglobin	11.73 ± 1.84	11.25 ± 2.17	0.245
Total leukocyte count	5117.77 ± 1606.44	4727.5 ± 1748.51	0.266
Platelet	1.15 ± 0.44	0.74 ± 0.16	< 0.001
Albumin	4.12 ± 2.81	3.41 ± 0.22	0.218
Protein	8.39 ± 6.03	7.68 ± 5.36	0.132
INR	1.11 ± 0.19	1.24 ± 0.17	0.002
Total bilirubin	0.99 ± 0.54	1.22 ± 0.59	0.054
Conjugated bilirubin	0.6 ± 0.34	0.69 ± 0.35	0.226
AST	64.73 ± 31.15	62.75 ± 19.48	0.761
ALT	49.1 ± 26.18	49.92 ± 25.43	0.884
ALP	124.3 ± 32.7	127 ± 37.4	0.971
Urea	28.66 ± 9.24	30.08 ± 9.67	0.477
Creatinine	0.88 ± 0.19	0.95 ± 0.22	0.086

INR: International normalized ratio; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; ALP: Alkaline phosphatase.

Table 3 Differences in baseline non-invasive parameters in patients who developed decompensation, mean ± SD

Parameters	No decompensation (n = 212)	Decompensation (n = 19)	P value
LSM (kPa)	22.68 ± 7.02	30.77 ± 11.26	< 0.001
SSM (kPa)	43.99 ± 14.81	69.61 ± 16.27	< 0.001
FIB-4	4.28 ± 2.52	5.97 ± 2.31	0.002
APRI	1.68 ± 1.16	2.24 ± 0.95	0.022
Spleen size (cm)	13.41 ± 1.37	14.59 ± 1.02	< 0.001
Liver size (cm)	12.31 ± 1.14	12.2 ± 1.57	0.676
PV diameter (mm)	12.83 ± 0.82	13.11 ± 0.86	0.123

LSM: Liver stiffness measurement; SSM: Splenic stiffness measurement; FIB-4: Fibrosis-4 index; APRI: Aspartate aminotransferase to platelet ratio index; PV: Portal vein.

Table 4 Predictors of decompensation based on the Cox proportional hazard ratio model and adjusted hazard ratio based on beta-blocker therapy

Parameters	HR (95%CI)	Adjusted HR	P value
SSM	1.073 (1.049-1.097)	0.54 (0.28-1.62)	< 0.001
LSM	1.084 (1.047-1.122)	0.97 (0.14-1.67)	< 0.001
Platelet	0.056 (0.056-0.014)	-	< 0.001
INR	1.045 (1.34-1.57)	-	< 0.001
FIB-4	1.203 (1.065-1.359)	-	0.003
APRI	1.357 (1.035-1.778)	-	0.027

HR: Hazard ratio; CI: Confidence interval; LSM: Liver stiffness measurement; SSM: Splenic stiffness measurement; INR: International normalized ratio; FIB-4: Fibrosis-4 index; APRI: Aspartate aminotransferase to platelet ratio index.

Table 5 Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of splenic stiffness measurement compared to other parameters

Parameters	SSM > 57.5 kPa	LSM > 27 kPa	APRI > 1.6	FIB-4 > 4.01	SIP score
Sensitivity	82.04	78.16	59.22	61	87.5%
Specificity	87.50	62.50	79.17	82	82.5%
Area under the curve	0.848	0.703	0.70	0.76	0.89
Positive predictive value	98.26	94.70	96.06	97	36.8%
Negative predictive value	36.21	25.00	18.45	21.5	98.3%
Diagnostic accuracy	82.61	76.50	61.30	64	83.0

SSM: Splenic stiffness measurement; LSM: Liver stiffness measurement; APRI: Aspartate aminotransferase to platelet ratio index; FIB-4: Fibrosis-4 index; SIP: Splenic stiffness measurement-international normalized ratio-platelet score.

Table 6 Splenic stiffness measurement-based decompensation predictive model: Splenic stiffness measurement-international normalized ratio-platelet score and risk of decompensation

Variable	Cut-off	Points
SSM	< 40 kPa	0
	40-59.9 kPa	2
	≥ 60 kPa	4
Platelets	≥ 150 × 109/L	0
	100-149 × 109/L	1
	< 100 × 109/L	2
INR	< 1.20	0
	1.20-1.49	1
	≥ 1.50	2
SIP score	Total score	0-8
Score	Risk stratification	Estimated risk
0-2	Low	< 10%
3-5	Moderate	10%-30%
6-8	High	> 30%

SSM: Splenic stiffness measurement; INR: International normalized ratio; SIP: Splenic stiffness measurement-international normalized ratio-platelet.

Table 7 Predictors of death among patients with compensated advanced chronic liver diseases

Parameters	HR (95%CI)	P value
SSM	1.021 (0.977- 1.067)	0.347
LSM	1.049 (0.964-1.142)	0.263
Platelet	0.361(0.043-3.026)	0.347
FIB-4	1.088 (0.569-2.081)	0.799
APRI	0.96 (0.69-1.334)	0.806

HR: Hazard ratio; CI: Confidence interval; SSM: Splenic stiffness measurement; LSM: Liver stiffness measurement; FIB-4: Fibrosis-4 index; APRI: Aspartate aminotransferase to platelet ratio index.