Development and validation of a nomogram for predicting in-hospital mortality of intensive care unit patients with liver cirrhosis

Table 1 Baseline characteristics of two cohorts

Variables		MIMIC-IV cohort			P value		eICU cohort			P value
		All	Survivors	Non-survivors			All	Survivors	Non-survivors
		(n = 2730)	0 (n = 2161)	1 (n = 569)			(n = 841)	0 (n = 666)	1 (n = 175)
Demographics
Age, median [IQR], year		59.043 [51.654, 67.468]	58.865 [51.466, 67.150]	60.412 [52.537, 69.440]	0.012		56.000 [50.000, 64.000]	56.000 [50.000, 64.000]	56.000 [50.000, 64.000]	0.820
Gender, n (%)	Female (0)	1027 (37.619)	813 (37.621)	214 (37.610)	0.996	Female (0)	324 (38.526)	265 (39.790)	59 (33.714)	0.142
	Male (1)	1703 (62.381)	1348 (62.379)	355 (62.390)		Male (1)	517 (61.474)	401 (60.210)	116 (66.286)
Etiology and complications
Etiology, n (%)	Alcoholic (0)	1448 (53.040)	1129 (52.244)	319 (56.063)	0.104	Alcoholic (0)	290 (34.483)	231 (34.685)	59 (33.714)	0.81
	Others (1)	1282 (46.960)	1032 (47.756)	250 (43.937)		Others (1)	551 (65.517)	435 (65.315)	116 (66.286)
HE, n (%)	No (0)	2171 (79.524)	1752 (81.074)	419 (73.638)	< 0.001	No (0)	605 (71.938)	503 (75.526)	102 (58.286)	< 0.001
	Yes (1)	559 (20.476)	409 (18.926)	150 (26.362)		Yes (1)	236 (28.062)	163 (24.474)	73 (41.714)
VH, n (%)	No (0)	2407 (88.168)	1896 (87.737)	511 (89.807)	0.174	No (0)	740 (87.990)	585 (87.838)	155 (88.571)	0.79
	Yes (1)	323 (11.832)	265 (12.263)	58 (10.193)		Yes (1)	101 (12.010)	81 (12.162)	20 (11.429)
AKI_stage_max, n (%)	Without (0)	646 (23.663)	625 (28.922)	21 (3.691)	< 0.001	Without (0)	431 (51.249)	391 (58.709)	40 (22.857)	< 0.001
	Stage Ⅰ (1)	333 (12.198)	296 (13.697)	37 (6.503)		Stage Ⅰ (1)	164 (19.501)	114 (17.117)	50 (28.571)
	Stage Ⅱ (2)	779 (28.535)	683 (31.606)	96 (16.872)		Stage Ⅱ (2)	29 (3.448)	23 (3.453)	6 (3.429)
	Stage Ⅲ (3)	972 (35.604)	557 (25.775)	415 (72.935)		Stage Ⅲ (3)	217 (25.803)	138 (20.721)	79 (45.143)
Comorbidities
Renal_disease, n (%)	No (0)	2096 (76.777)	1688 (78.112)	408 (71.705)	0.001	No (0)	688 (81.807)	552 (82.883)	136 (77.714)	0.115
	Yes (1)	634 (23.223)	473 (21.888)	161 (28.295)		Yes (1)	153 (18.193)	114 (17.117)	39 (22.286)
Diabetes, n (%)	No (0)	1872 (68.571)	1479 (68.441)	393 (69.069)	0.774	No (0)	642 (76.338)	507 (76.126)	135 (77.143)	0.778
	Yes (1)	858 (31.429)	682 (31.559)	176 (30.931)		Yes (1)	199 (23.662)	159 (23.874)	40 (22.857)
COPD, n (%)	No (0)	2563 (93.883)	2027 (93.799)	536 (94.200)	0.722	No (0)	752 (89.417)	598 (89.790)	154 (88.000)	0.493
	Yes (1)	167 (6.117)	134 (6.201)	33 (5.800)		Yes (1)	89 (10.583)	68 (10.210)	21 (12.000)
HF, n (%)	No (0)	2148 (78.681)	1724 (79.778)	424 (74.517)	0.006	No (0)	751 (89.298)	595 (89.339)	156 (89.143)	0.94
	Yes (1)	582 (21.319)	437 (20.222)	145 (25.483)		Yes (1)	90 (10.702)	71(10.661)	19(10.857)
MI, n (%)	No (0)	2462 (90.183)	1968 (91.069)	494 (86.819)	0.002	No (0)	806 (95.838)	639(95.946)	167(95.429)	0.76
	Yes (1)	268 (9.817)	193 (8.931)	75 (13.181)		Yes (1)	35 (4.162)	27(4.054)	8(4.571)
Treatment
Vasopressor, n (%)	No (0)	1569 (57.473)	1432 (66.266)	137 (24.077)	< 0.001	No (0)	630 (74.911)	535 (80.330)	95 (54.286)	< 0.001
	Yes (1)	1161 (42.527)	729 (33.734)	432 (75.923)		Yes (1)	211 (25.089)	131 (19.670)	80 (45.714)
Invasive_ventilation, n (%)	No (0)	1499 (54.908)	1333 (61.684)	166 (29.174)	< 0.001	No (0)	651 (77.408)	538 (80.781)	113 (64.571)	< 0.001
	Yes (1)	1231 (45.092)	828 (38.316)	403 (70.826)		Yes (1)	190 (22.592)	128 (19.219)	62 (35.429)
RRT, n (%)	No (0)	2314 (84.762)	1940 (89.773)	374 (65.729)	< 0.001	No (0)	730 (86.801)	578 (86.787)	152 (86.857)	0.98
	Yes (1)	416 (15.238)	221 (10.227)	195 (34.271)		Yes (1)	111 (13.199)	88 (13.213)	23 (13.143)
Laboratory tests
Bicarbonate, median [IQR], mmol/L		22.000 [19.000, 25.000]	22.000 [19.000, 25.000]	20.000 [17.000, 24.000]	< 0.001		22.000 [18.000, 25.000]	22.700 [19.000,26.000]	21.000 [17.000, 24.000]	< 0.001
Calcium, median [IQR], mg/dL		8.300 [7.700, 8.900]	8.300 [7.700, 8.800]	8.300 [7.700, 9.000]	0.328		8.200 [7.700, 8.700]	8.200 [7.700, 8.700]	8.200 [7.700, 8.700]	0.953
Chloride, median [IQR], mmol/L		102.000 [97.000, 107.000]	103.000 [97.000, 107.000]	101.000 [95.000, 106.000]	< 0.001		102.000 [98.000, 107.000]	102.000 [98.000, 107.000]	102.000 [97.000, 108.000]	0.938
Sodium, median [IQR], mmol/L		137.000 [133.000, 140.000]	137.000 [133.000, 140.000]	136.000 [132.000, 140.000]	0.015		136.000 [131.000, 140.000]	136.000 [131.000, 139.700]	135.000 [130.000, 140.000]	0.768
Potassium, median [IQR], mmol/L		4.200 [3.700, 4.800]	4.200 [3.700, 4.700]	4.200 [3.700, 4.900]	0.149		4.100 [3.600, 4.600]	4.020 [3.500, 4.600]	4.300 [3.800, 4.900]	0.003
BUN, median [IQR], mg/dL		26.000 [15.000, 45.000]	24.000 [14.000, 40.000]	36.000 [20.000, 60.000]	< 0.001		25.000 [14.000, 45.000]	24.000 [13.000, 43.000]	32.000 [19.000, 54.000]	< 0.001
Creatinine, median [IQR], mg/dL		1.200 [0.800, 2.100]	1.100 [0.800, 1.800]	1.800 [1.000, 3.100]	< 0.001		1.250 [0.800, 2.200]	1.100 [0.760, 2.040]	1.600 [1.100, 2.800]	< 0.001
Albumin, median [IQR], g/dL		3.000 [2.600, 3.400]	3.000 [2.600, 3.400]	2.900 [2.400, 3.400]	< 0.001		2.500 [2.100, 3.067]	2.500 [2.100, 3.100]	2.300 [1.900, 2.800]	< 0.001
ALT, median [IQR], IU/L		31.000 [20.000, 59.500]	31.000 [20.000, 58.000]	34.000 [20.000, 65.000]	0.115		36.000 [23.000, 60.000]	34.000 [23.000, 57.000]	38.000 [24.000, 70.000]	0.045
AST, median [IQR], IU/L		63.000 [38.000, 125.000]	60.000 [37.000, 117.000]	79.000 [42.000, 149.000]	< 0.001		70.000 [43.000, 130.000]	67.000 [42.000, 118.000]	86.000 [48.000, 150.000]	0.004
Bilirubin_total, median [IQR], mg/dL		2.500 [1.100, 6.200]	2.100 [1.000, 5.000]	4.800 [1.900, 15.100]	< 0.001		3.100 [1.400, 7.000]	2.800 [1.300, 5.700]	5.700 [2.400, 14.000]	< 0.001
Inr, median [IQR]		1.600 [1.300, 2.100]	1.600 [1.300, 2.000]	2.000 [1.600, 2.700]	< 0.001		1.600 [1.300, 2.100]	1.500 [1.300, 2.000]	1.900 [1.500, 2.500]	< 0.001
Pt, median [IQR], sec		17.800 [14.600, 22.700]	17.000 [14.200, 21.100]	21.850 [17.800, 28.400]	< 0.001		18.300 [15.500, 23.400]	17.800 [15.200, 22.000]	21.700 [17.400, 27.633]	< 0.001
Hemoglobin, median [IQR], g/dL		9.500 [8.100,11.100]	9.600 [8.200,11.200]	9.100 [7.800, 10.600]	< 0.001		9.500 [8.000, 11.300]	9.400 [7.800, 11.300]	9.600 [8.200, 11.200]	0.434
Platelets, median [IQR], 109/L		108.000 [68.000, 170.000]	109.000 [70.000, 171.000]	100.000 [62.000, 161.000]	0.012		97.000 [63.000, 154.000]	99.000 [66.000, 155.000]	89.000 [58.000, 145.000]	0.094
WBC, median [IQR], 109/L		9.000 [5.800, 13.600]	8.400 [5.600, 12.700]	11.500 [7.600, 16.900]	< 0.001		9.400 [5.900, 14.300]	8.700 [5.600, 13.100]	12.100 [8.400, 17.800]	< 0.001
RDW, median [IQR], %		16.800 [15.100, 18.900]	16.600 [15.000, 18.700]	17.800 [15.800, 20.000]	< 0.001		17.300 [15.500, 19.600]	17.100 [15.280, 19.300]	18.000 [16.400, 20.100]	< 0.001
Vital signs
HR_mean, median [IQR]		86.800 [76.237, 98.769]	85.360 [75.040, 96.875]	93.304 [80.826, 103.724]	< 0.001		89.029 [78.045, 100.000]	87.105 [76.676, 99.333]	94.796 [84.556, 102.423]	< 0.001
SBP_mean, median [IQR], mmHg		110.120 [101.694, 122.500]	112.292 [103.125, 124.917]	104.828 [97.667, 113.741]	< 0.001		108.920 [99.750, 121.000]	109.963 [100.654, 122.314]	103.855 [97.103, 115.954]	< 0.001
DBP_mean, median [IQR], mmHg		60.320 [53.963, 68.038]	61.520 [55.000, 69.080]	57.095 [50.625, 63.045]	< 0.001		59.310 [53.225, 67.000]	60.231 [53.638, 67.970]	56.455 [51.579, 63.857]	< 0.001
RR_mean, median [IQR]		18.243 [15.958, 21.200]	17.872 [15.774, 20.577]	19.900 [16.846, 23.318]	< 0.001		18.640 [16.533, 21.896]	18.321 [16.277, 20.964]	20.649 [17.852, 23.911]	< 0.001
Prognostic scoring system
SOFA, median [IQR]		8.000 [5.000, 10.000]	7.000 [5.000, 9.000]	11.000 [8.000, 14.000]	< 0.001		7.000 [5.000, 10.000]	7.000 [4.000, 9.000]	9.000 [7.000, 12.000]	< 0.001
MELD, median [IQR]		16.060 [10.225, 23.595]	14.287 [9.338, 21.346]	23.674 [16.662, 30.045]	< 0.001		17.887 [12.060, 26.087]	16.699 [10.941, 24.147]	24.499 [16.194, 32.895]	< 0.001

HE: Hepatic encephalopathy; VH: Variceal hemorrhage; AKI: Acute kidney injury; COPD: Chronic obstructive pulmonary disease; HF: Heart failure; MI: Myocardial infarct; BUN: Blood urea nitrogen; ALT: Aminotransferase alanine; AST: Aminotransferase aspartate; INR: International Normalized Ratio; Pt: Prothrombin Time; WBC: White blood cells; RDW: Red cell distribution width; RRT: Renal replacement therapy; HR: Heart rate; SBP: Systolic blood pressure; DBP: Diastolic blood pressure; RR: Respiratory rate; SOFA: Sequential Organ Failure Assessment; max: Maximum; MELD: Model for end-stage liver disease; IQR: Interquartile range; MIMIC-IV: Medical Information Mart for Intensive Care IV.

Table 2 Baseline comparison between the two databases

Variables		All	MIMIC	eICU	P value
		(n = 3571)	0 (n = 2730)	1 (n = 841)
Hospital_expire_flag, n (%)	0	2827 (79.165)	2161 (79.158)	666 (79.191)	0.983
	1	744 (20.835)	569 (20.842)	175 (20.809)
Demographics
Age, median [IQR], yr		58.641 [51.114, 66.693]	59.043 [51.654, 67.468]	56.000 [50.000, 64.000]	< 0.001
Gender, n (%)	Female (0)	1351 (37.833)	1027 (37.619)	324 (38.526)	0.636
	Male (1)	2220 (62.167)	1703 (62.381)	517 (61.474)
Etiology and complications
Etiology, n (%)	Alcoholic (0)	1738 (48.670)	1448 (53.040)	290 (34.483)	< 0.001
	Others (1)	1833 (51.330)	1282 (46.960)	551 (65.517)
HE, n (%)	No (0)	2776(77.737)	2171 (79.524)	605 (71.938)	< 0.001
	Yes (1)	795(22.263)	559 (20.476)	236 (28.062)
VH, n (%)	No (0)	3147(88.127)	2407 (88.168)	740 (87.990)	0.889
	Yes (1)	424(11.873)	323 (11.832)	101 (12.010)
AKI_stage_max, n (%)	Without (0)	1077 (30.160)	646 (23.663)	431 (51.249)	< 0.001
	Stage Ⅰ (1)	497 (13.918)	333 (12.198)	164 (19.501)
	Stage Ⅱ (2)	808 (22.627)	779 (28.535)	29 (3.448)
	Stage Ⅲ (3)	1189 (33.296)	972 (35.604)	217 (25.803)
Comorbidities
Renal_disease, n (%)	No (0)	2784 (77.961)	2096 (76.777)	688 (81.807)	0.002
	Yes (1)	787 (22.039)	634 (23.223)	153 (18.193)
Diabetes, n (%)	No (0)	2514 (70.400)	1872 (68.571)	642 (76.338)	< 0.001
	Yes (1)	1057 (29.600)	858 (31.429)	199 (23.662)
COPD, n (%)	No (0)	3315 (92.831)	2563 (93.883)	752 (89.417)	< 0.001
	Yes (1)	256 (7.169)	167 (6.117)	89 (10.583)
HF, n (%)	No (0)	2899 (81.182)	2148 (78.681)	751 (89.298)	< 0.001
	Yes (1)	672 (18.818)	582 (21.319)	90 (10.702)
MI, n (%)	No (0)	3268 (91.515)	2462 (90.183)	806 (95.838)	< 0.001
	Yes (1)	303 (8.485)	268 (9.817)	35 (4.162)
Treatment
vasopressor, n (%)	No (0)	2199 (61.579)	1569 (57.473)	630 (74.911)	< 0.001
	Yes (1)	1372 (38.421)	1161 (42.527)	211 (25.089)
invasive_ventilation, n (%)	No (0)	2150 (60.207)	1499 (54.908)	651 (77.408)	< 0.001
	Yes (1)	1421 (39.793)	1231 (45.092)	190 (22.592)
RRT, n (%)	No (0)	3044 (85.242)	2314 (84.762)	730 (86.801)	0.145
	Yes (1)	527 (14.758)	416 (15.238)	111 (13.199)
Laboratory tests
Bicarbonate, median [IQR], mmol/L		22.000 [19.000, 25.000]	22.000 [19.000, 25.000]	22.000 [18.000, 25.000]	0.291
Calcium, median [IQR], mg/dL		8.300 [7.700, 8.800]	8.300 [7.700, 8.900]	8.200 [7.700, 8.700]	0.005
Chloride, median [IQR], mmol/L		102.000 [97.000, 107.000]	102.000 [97.000, 107.000]	102.000 [98.000, 107.000]	0.108
Sodium, median [IQR], mmol/L		137.000 [133.000, 140.000]	137.000 [133.000, 140.000]	136.000 [131.000, 140.000]	< 0.001
Potassium, median [IQR], mmol/L		4.100 [3.700, 4.700]	4.200 [3.700, 4.800]	4.100 [3.600, 4.600]	< 0.001
BUN, median [IQR], mg/dL		26.000 [15.000, 45.000]	26.000 [15.000, 45.000]	25.000 [14.000, 45.000]	0.49
Creatinine, median [IQR], mg/dL		1.200 [0.800, 2.100]	1.200 [0.800, 2.100]	1.250 [0.800, 2.200]	0.193
Albumin, median [IQR], g/dL		2.900 [2.400, 3.350]	3.000 [2.600, 3.400]	2.500 [2.100, 3.067]	< 0.001
ALT, median [IQR], IU/L		32.000 [20.000, 60.000]	31.000 [20.000, 59.500]	36.000 [23.000, 60.000]	0.001
AST, median [IQR], IU/L		65.000 [39.000, 126.000]	63.000 [38.000, 125.000]	70.000 [43.000, 130.000]	0.007
Bilirubin_total, median [IQR], mg/dL		2.623 [1.200, 6.400]	2.500 [1.100, 6.200]	3.100 [1.400, 7.000]	< 0.001
INR, median [IQR]		1.600 [1.300, 2.100]	1.600 [1.300, 2.100]	1.600 [1.300, 2.100]	0.272
Pt, median [IQR], sec		18.000 [14.800, 22.900]	17.800 [14.600, 22.700]	18.300 [15.500, 23.400]	0.005
Hemoglobin, median [IQR], g/dL		9.500 [8.000, 11.100]	9.500 [8.100, 11.100]	9.500 [8.000, 11.300]	0.88
Platelets, median [IQR], 109/L		105.000 [67.000, 166.000]	108.000 [68.000, 170.000]	97.000 [63.000, 154.000]	< 0.001
WBC, median [IQR], 109/L		9.100 [5.800, 13.700]	9.000 [5.800, 13.600]	9.400 [5.900, 14.300]	0.113
RDW, median [IQR], %		17.000 [15.200, 19.100]	16.800 [15.100, 18.900]	17.300 [15.500, 19.600]	< 0.001
Bicarbonate, median [IQR], mmol/L
Hr_mean, median [IQR]		87.182 [76.588, 99.122]	86.800 [76.237, 98.769]	89.029 [78.045, 100.000]	0.002
SBP_mean, median [IQR], mmHg		109.842 [101.208, 122.292]	110.120 [101.694, 122.500]	108.920 [99.750, 121.000]	0.002
Dbp_mean, median [IQR], mmHg		60.143 [53.750, 67.810]	60.320 [53.963, 68.038]	59.310 [53.225, 67.000]	0.031
Rr_mean, median [IQR], mmHg		18.363 [16.047, 21.286]	18.243 [15.958, 21.200]	18.640 [16.533, 21.896]	< 0.001
Prognostic scoring system
Meld, median [IQR]		16.588 [10.602, 24.153]	16.060 [10.225, 23.595]	17.887 [12.060, 26.087]	< 0.001
SOFA, median [IQR]		7.000 [5.000, 10.000]	8.000 [5.000, 10.000]	7.000 [5.000, 10.000]	0.017

HE: Hepatic encephalopathy; VH: Variceal hemorrhage; AKI: Acute kidney injury; COPD: Chronic obstructive pulmonary disease; HF: Heart failure; MI: Myocardial infarct; BUN: Blood urea nitrogen; ALT: Aminotransferase alanine; AST: Aminotransferase aspartate; INR: International Normalized Ratio; Pt: Prothrombin Time; WBC: White blood cells; RDW: Red cell distribution width; RRT: Renal replacement therapy; HR: Heart rate; SBP: Systolic blood pressure; DBP: Diastolic blood pressure; RR: Respiratory rate; SOFA: Sequential Organ Failure Assessment; max: Maximum; MELD: Model for end-stage liver disease; IQR: Interquartile range; MIMIC-IV: Medical Information Mart for Intensive Care IV.

Table 3 Multivariate logistic regression model of in-hospital mortality

	Multivariable analysis based on LASSO regression result			Multivariable logistics model
Predictor	β	P value	Odds ratio (95%CI)	β	P value	Odds Ratio
SOFA	0.074	0	1.076 (1.037-1.118)	0.078	0	1.082 (1.044-1.121)
RR_mean	0.05	0	1.052 (1.022-1.082)	0.054	0	1.055 (1.026-1.085)
DBP_mean	-0.009	0.226	0.991 (0.976-1.006)
SBP_mean	-0.014	0.006	0.986 (0.976-0.996)	-0.019	0	0.982 (0.973-0.99)
HR_mean	0.02	0	1.021 (1.012-1.029)	0.017	0	1.017 (1.009-1.024)
RDW	0.029	0.161	1.029 (0.988-1.072)
WBC	0.027	0	1.027 (1.012-1.042)	0.029	0	1.029 (1.015-1.044)
INR	0.203	0	1.226 (1.102-1.366)	0.207	0	1.230 (1.106-1.371)
Bilirubin_total	0.043	0	1.044 (1.029-1.059)	0.046	0	1.047 (1.033-1.062)
ALT	0	0.029	1 (0.999-1)
BUN	0.004	0.049	1.004 (1-1.008)
Age	0.033	0	1.034 (1.022-1.045)	0.039	0	1.039 (1.029-1.051)
AKI_stage_max 1	0.588	0.052	1.801 (1.002-3.3)	0.616	0.041	1.851 (1.031-3.387)
AKI_stage_max 2	0.683	0.01	1.981 (1.2-3.398)	0.709	0.007	2.031 (1.237-3.472)
AKI_stage_max 3	1.701	0	5.48 (3.402-9.231)	1.746	0	5.729 (3.585-9.585)
RRT1	0.002	0.987	1.002 (0.743-1.35)
Invasive_ventilation1	0.653	0	1.922 (1.456-2.543)	0.599	0	1.820 (1.385-2.397)
Vasopressor1	0.536	0	1.709 (1.279-2.288)	0.541	0	1.718 (1.291-2.290)
MI1	0.299	0.113	1.349 (0.928-1.949)
HF1	0.206	0.169	1.229 (0.915-1.646)

SOFA: Sequential Organ Failure Assessment; RR: Respiratory rate; SBP: Systolic blood pressure; HR: Heart rate; WBC: White blood cells; RDW: Red cell distribution width; INR: International Normalized Ratio; BUN: Blood urea nitrogen; HE: Hepatic encephalopathy; MI: Myocardial infarct; HF: Heart failure; max: Maximum.