Development and validation of a prognostic model for patients with hepatorenal syndrome: A retrospective cohort study

Table 1 Characteristics of patients with hepatorenal syndrome, n (%)

Variables	Derivation cohort (n = 248)			Validation cohort (n = 123)			1P value
	Non-survivor (n = 188)	Survivor (n = 60)	P value	Non-survivor (n = 90)	Survivor (n = 33)	P value
Age (y)	59.11 ± 12.61	55.43 ± 12.04	0.048	56.94 ± 12.17	57.21 ± 11.81	0.913	0.379
Gender (male/female)	138/50	52/8	0.031	69/21	26/7	0.995	0.795
Causes of cirrhosis			0.046			0.741	0.096
HBV/HBV plus others	124 (66.0)	34 (56.7)		45 (50.0)	19 (57.6)
Alcoholic	27 (14.4)	17 (28.3)		21 (23.3)	7 (21.2)
Others	37 (19.7)	9 (15.0)		24 (26.7)	7 (21.2)
MAP (mmHg)	95.16 ± 16.42	100.31 ± 18.44	0.041	93.1 ± 15.01	100.58 ± 18.33	0.023	0.483
INR	1.90 (1.70-2.60)	1.60 (1.30-1.90)	< 0.001	1.96 (1.54-2.40)	1.50 (1.31-1.90)	< 0.001	0.305
Neutrophil	75.68 ± 11.99	71.21 ± 13.03	0.015	76.03 ± 10.98	72.95 ± 10.97	0.170	0.647
RBC (× 109/L)	3.15 ± 0.85	3.04 ± 0.85	0.404	3.16 ± 1.05	2.99 ± 0.78	0.388	0.950
Hemoglobin (g/L)	103.13 ± 25.48	95.14 ± 26.89	0.044	102.55 ± 29.63	95.41 ± 25.60	0.229	0.840
MCV (fl)	94.20 ± 9.16	92.21 ± 8.07	0.146	95.28 ± 11.72	94.00 ± 9.71	0.580	0.267
MCH (pg)	33.19 ± 3.78	31.45 ± 3.21	0.002	33.17 ± 3.93	32.21 ± 3.66	0.233	0.756
MCHC (g/L)	351.81 ± 18.15	341.77 ± 19.35	< 0.001	349.14 ± 19.13	342.83 ± 18.25	0.104	0.355
Platelet (× 109/L)	66.5 (42.0-97.5)	69.0 (45.5-98.0)	0.419	64.0 (36.0-103.0)	75.0 (46.0-118.0)	0.250	0.737
Albumin (g/L)	29.12 ± 5.48	28.77 ± 5.37	0.668	29.22 ± 5.41	30.99 ± 5.61	0.115	0.274
A/G	1.00 (0.78-1.40)	0.92 (0.73-1.30)	0.267	1.13 ± 0.56	1.19 ± 0.51	0.620	0.400
ALT	60.00 (31.00-137.00)	32.50 (18.25-66.00)	0.001	59.00 (26.50-135.00)	36.00 (16.00-104.00)	0.035	0.673
Serum bilirubin	15.00 (5.32-27.50)	3.92 (1.10-12.80)	< 0.001	18.30 (6.75-25.30)	2.30 (1.17-23.30)	0.003	0.779
Cholinesterase (U/L)	1963.00 (1399.00-2559.00)	2264.00 (1410.50-3081.50)	0.197	1937.50 (1585.75-2637.20)	2376.00 (1716.00-3903.00)	0.152	0.198
Creatinine (mg/dL)	1.60 (0.92-2.70)	1.84 (1.14-2.80)	0.206	1.43 (0.85-2.20)	2.10 (1.10-2.90)	0.046	0.291
Sodium (mmol/L)	133.74 ± 6.79	135.66 ± 6.34	0.053	132.88 ± 5.89	136.02 ± 4.90	0.009	0.499
Potassium (mmol/L)	4.35 ± 1.01	4.18 ± 0.74	0.217	4.16 ± 0.80	4.31 ± 0.65	0.352	0.288
Number of failed organs	1 (0.75-2.00)	0 (0-1.00)	< 0.001	1 (0-2.00)	0 (0-1.00)	< 0.001	0.433
One organ failed	65 (34.6)	19 (31.7)	0.797	28 (31.1)	11 (33.3)	0.987	0.764
Two organs failed	50 (26.6)	1 (1.7)	< 0.001	26 (28.9)	3 (9.1)	0.040	0.596
≥ Three organs failed	26 (13.8)	1 (1.7)	0.017	12 (13.3)	1 (3.0)	0.188	0.990
MELD	29.50 ± 9.06	22.97 ± 8.00	< 0.001	28.04 ± 8.74	23.46 ± 9.47	0.013	0.276
CLIF-SOFA	10.79 ± 3.29	8.18 ± 3.08	< 0.001	10.86 ± 3.75	8.09 ± 3.37	< 0.001	0.912
COSSH-ACLF	7.57 ± 1.84	6.05 ± 1.27	< 0.001	7.57 ± 1.86	6.14 ± 1.49	< 0.001	0.958
Treatment			0.261			0.842	0.125
Terlipressin plus albumin	41 (21.8)	18 (30.0)		15 (16.7)	5 (15.2)
Albumin only	147 (78.2)	42 (70.0)		75 (83.3)	28 (84.8)

P non-survivor vs survivor.

¹P derivation cohort vs validation cohort. A/G: Albumin/globulin; ALT: Alanine aminotransferase; CLIF-SOFA: Chronic Liver Failure-Sequential Organ Failure Assessment; COSSH-ACLF: Chinese Group on the Study of Severe Hepatitis B-Acute-on-Chronic Liver Failure; HBV: Hepatitis B virus; INR: International normalized ratio; MAP: Mean arterial pressure; MCH: Mean cell hemoglobin; MCHC: Mean corpuscular hemoglobin concentration; MCV: Mean cell volume; MELD: Model for End-Stage Liver Disease; RBC: Red blood cells.

Table 2 Univariate and multivariate Cox regression.

Variables	Univariate Cox regression		Multivariate Cox regression
	HR (95%CI)	P value	HR (95%CI)	P value
Age	1.007 (0.995-1.019)	0.244
Gender	0.586 (0.425-0.807)	0.001	0.532 (0.384-0.737)	< 0.001
Causes of cirrhosis	0.946 (0.785-1.140)	0.557
MAP	0.990 (0.981-0.999)	0.024
INR	1.842 (1.599-2.122)	< 0.001	1.408 (1.173-1.691)	< 0.001
Neutrophil	1.028 (1.015-1.041)	< 0.001	1.031 (1.018-1.044)	< 0.001
RBC	1.137 (0.959-1.348)	0.139
Hemoglobin	1.007 (1.002-1.012)	0.012
MCV	1.004 (0.988-1.021)	0.599
MCH	1.066 (1.022-1.111)	0.003
MCHC	1.019 (1.010-1.027)	< 0.001	1.014 (1.005-1.022)	0.002
Platelet	0.997 (0.994-1.000)	0.090
Albumin	1.000 (0.973-1.028)	0.999
A/G	1.257 (1.093-1.445)	0.001
ALT	1.000 (1.000-1.001)	0.094
Serum bilirubin	1.002 (1.001-1.003)	< 0.001
Cholinesterase	1.000 (0.999-1.000)	0.160
Creatinine	1.000 (0.999-1.001)	0.704
Sodium	0.960 (0.939-0.982)	< 0.001
Potassium	1.215 (1.032-1.430)	0.019
Stage	3.805 (2.800-5.170)	< 0.001	2.724 (1.877-3.952)	< 0.001
MELD	1.077 (1.058-1.096)	< 0.001
CLIF-SOFA	1.221 (1.166-1.278)	< 0.001
COSSH-ACLF	1.467 (1.361-1.581)	< 0.001

A/G: Albumin/globulin; ALT: Alanine aminotransferase; CI: Confidence interval; CLIF-SOFA: Chronic liver failure-sequential organ failure assessment; COSSH-ACLF: Chinese Group on the study of severe hepatitis B-acute-on-chronic liver failure; HR: Hazard ratio; INR: International normalized ratio; MAP: Mean arterial pressure; MCH: Mean cell hemoglobin; MCHC: Mean corpuscular hemoglobin concentration; MCV: Mean cell volume; MELD: Model for end-stage liver disease; RBC: Red blood cells.

Table 3 Mortality at 28 d in patients with hepatorenal syndrome stratified according to the GIMNS score

GIMNS score	28-d mortality in HRS patients (%)
≥ 2	100.0
1-2	73.8
0-1	57.1
< 0	30.3

HRS: Hepatorenal syndrome.

Table 4 Accuracy of different scoring systems in derivation and validation cohorts

Models	Cut-off	Sensitivity (%)	Specificity (%)	Youden	AUROC (95%CI)	P value	P value
							compared with GIMNS
Derivation cohort (n = 248)
GIMNS	0.4	73.5	78.7	0.522	0.830 (0.778-0.882)	< 0.001	-
MELD	24.8	61.4	76.6	0.380	0.759 (0.670-0.821)	< 0.001	0.029
CLIF-SOFA	9.0	72.7	68.1	0.408	0.767 (0.706-0.827)	< 0.001	0.045
COSSH-ACLF	7.5	56.8	84.0	0.408	0.759 (0.696-0.821)	< 0.001	0.026
Validation cohort (n = 123)
GIMNS	0.7	57.8	79.6	0.374	0.732 (0.642-0.821)	< 0.001	-
MELD	26.6	65.6	63.0	0.286	0.623 (0.520-0.726)	< 0.050	0.013
CLIF-SOFA	11.0	29.7	94.4	0.241	0.661 (0.563-0.758)	< 0.010	0.049
COSSH-ACLF	7.9	51.6	81.5	0.331	0.674 (0.577-0.770)	< 0.001	0.122

AUROC: Area under the receiver operating characteristic curve; CLIF-SOFA: Chronic liver failure-sequential organ failure assessment; COSSH-ACLF: Chinese Group on the study of severe hepatitis B-acute-on-chronic liver failure; MELD: Model for end-stage liver disease; CI: Confidence interval.