Development and validation of a new prognostic model for patients with acute-on-chronic liver failure in intensive care unit

doi:10.3748/wjg.v30.i20.2657

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World Journal of Gastroenterology

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Retrospective Cohort Study

World J Gastroenterol. May 28, 2024; 30(20): 2657-2676
Published online May 28, 2024. doi: 10.3748/wjg.v30.i20.2657

Table 1 Baseline characteristics of patients with Acute-on-chronic liver failure in different cohorts

Baseline characteristics	MIMIC cohort		External validation cohorts
Baseline characteristics	Derivation set (n = 938)	Validation set (n = 313)	eICU (n = 551)	SHHMU (n = 121)
Age (yr)	59 (52-68)	56 (53-66)	57 (50-64)	58 ± 13
Male, n (%)	617 (65.8)	202 (64.5)	334 (60.6)	81 (66.9)
Race, n (%)
White	613 (65.4)^a	209 (66.8)	448 (81.3)	Eastern Asian
Non white	325 (34.6)^a	104 (33.2)	103 (18.7)	Eastern Asian
Etiology of cirrhosis, n (%)
Alcohol	524 (55.9)^b	180 (57.5)	376 (68.2)	43 (35.5)
Non-alcohol	414 (44.1)^b	133 (42.5)	175 (31.8)	78 (64.5)
AD at admission, n (%)
Ascites	520 (55.4)^a^,^b	173 (55.3)	169 (30.7)	32 (26.4)
Hepatic encephalopathy	390 (41.6)^b	136 (43.5)	156 (28.3)	31 (25.6)
Bacterial infection	422 (45.0)^b	152 (48.6)	216 (39.2)	16 (13.2)
Acute variceal bleeding	75 (8.0)^a^,^b	34 (10.9)	127 (23.0)	42 (34.7)
Laboratory indicators
WBC (10⁹/L)	12 (8-18)^b	13 (9-18)	10 (6-14)	6 (5-11)
Hemoglobin	85 (73-100)^b	83 (72-98)	88 (75-103)	92 (77-107)
Platelet (10⁹/L)	81 (50-135)	72 (49-120)	78 (49-126)	75 (48-116)
Total bilirubin (mg/dL)	4.1 (1.6-11.7)	4.9 (1.8-12.3)	4.0 (1.5-12.9)	6.2 (1.6-17.5)
Albumin (g/dL)	2.9 (2.4-3.3)	2.9 (2.4-3.4)	2.8 (2.2-3.3)	2.9 ± 0.6
ALT (U/L)	39 (22-98)^b	39 (23-101)	36 (21-97)	34 (16-64)
AST (U/L)	83 (44-216)^b	94 (47-266)	91 (43-253)	62 (35-138)
INR	2.1 (1.6-2.8)^a^,^b	2.0 (1.6-2.7)	1.7 (1.4-2.4)	1.7 (1.2-2.6)
Prothrombin time (s)	22 (17-30)^b	22 (17-29)	21 (16-28)	19 (14-29)
Serum creatinine (mg/dL)	2.1 (1.3-3.4)	2.0 (1.2-3.2)	2.0 (1.1-3.2)	2.1 (1.1-3.0)
Serum sodium (mEq/L)	135 (131-139)	135 (131-139)	137 (133-142)	134 ± 7
Serum potassium (mEq/L)	4.6 (4.1-5.3)^a^,^b	4.6 (4.2-5.4)	4.0 (3.6-4.6)	4.2 (3.7-4.7)
Organ failure, n (%)
Circulatory failure	382 (40.7)^a^,^b	148 (47.3)	305 (55.4)	18 (14.9)
Respiratory failure	427 (45.5)^a^,^b	156 (49.8)	162 (29.4)	22 (18.2)
Cerebral failure	129 (13.8)^a^,^b	46 (14.7)	223 (40.5)	38 (31.4)
Renal failure	658 (70.1)^a^,^b	201 (64.2)	280 (50.8)	75 (62.0)
Coagulation failure	332 (35.4)^b	106 (33.9)	131 (23.8)	37 (30.6)
Liver failure	233 (24.8)^a^,^b	82 (26.2)	273 (49.5)	54 (44.6)
Prognostic scores at admission
MELD	28 (22-34)^a^,^b	27 (21-34)	25 ± 10	25 (18-31)
MELD-Na	31 (23-40)^b	31 (22-40)	27 (19-35)	30 (21-38)
CLIF-C ACLF	58 (51-64)^b	58 (52-64)	50 (45-57)	47 (42-54)
Liver transplantation, n (%)	44 (4.7)	11 (3.5)	24 (4.4)	2 (1.7)
ACLF grade, n (%)
Grade 1	266 (28.4)^a	86 (27.5)	263 (46.3)	30 (33.1)
Grade 2	317 (33.8)	105 (33.5)	177 (31.1)	50 (41.3)
Grade 3	355 (37.8)^a	122 (39.0)	128 (22.6)	41 (33.9)
28-day mortality, n (%)	376 (40.1)	122 (39.0)	--	46 (38.0)
90-day mortality, n (%)	465 (49.6)	144 (46.0)	--	59 (48.7)
In-ICU mortality, n (%)	--	--	112 (20.3)	--
In-hospital mortality, n (%)	--	--	179 (32.4)	--

^aP < 0.05 vs electronic intensive care unit cohort.

^bP < 0.05 vs the Second Hospital of Hebei Medical University cohort.

Data were described as means ± SD, median (interquartile range) or number (percentage) of patients and compared by Kruskal-Wallis test and chi-square test where appropriate. AD: Acute decompensation; ACLF: Acute-on-chronic liver failure; INR: International normalized ratio; MIMIC: Medical Information Mart for Intensive Care; MELD: Model for End-stage Liver; CLIF-C: Chronic Liver Failure Consortium; eICU: Electronic intensive care unit; ICU: Intensive care unit; SHHMU: The Second Hospital of Hebei Medical University; WBC: White blood cell; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase.

Table 2 Risk factors for 28-day mortality in acute-on-chronic liver failure patients from Medical Information Mart for Intensive Care-derivation set

Variable	Univariate analysis		Multivariate analysis
Variable	HR (95%CI)	P value	HR (95%CI)	P value
Female	1.08 (0.88-1.33)	0.47
Ln (age)	2.18 (1.32-3.61)	0.002	9.14 (5.16-16.19)	< 0.001
Race (Non-white)	1.15 (0.93-1.41)	0.20
Cirrhosis etiology (non-alcohol)	1.00 (0.82-1.23)	0.998
Ln (MAP)	0.03 (0.01-0.06)	< 0.001	0.06 (0.03-0.14)	< 0.001
Organ failures
Circulatory failure	1.87 (1.53-2.29)	< 0.001
Respiratory failure	1.56 (1.27-1.93)	< 0.001	1.84 (1.48-2.29)	< 0.001
Cerebral failure	1.63 (1.26-2.11)	< 0.001	1.36 (1.05-1.77)	0.02
Renal failure	1.89 (1.53-2.34)	< 0.001	1.68 (1.36-2.09)	< 0.001
Liver failure	2.31 (1.67-2.50)	< 0.001
Coagulation failure	2.04 (1.87-2.84)	< 0.001
Laboratory indicators
Ln (WBC)	1.58 (1.33-1.88)	< 0.001	1.25 (1.05-2.10)	0.01
Ln (hemoglobin)	0.65 (0.44-0.97)	0.04
Ln (platelet)	0.84 (0.73-0.97)	0.02
Ln (TB)	1.50 (1.38-1.63)	< 0.001	1.57 (1.42-1.73)	< 0.001
Ln (Albumin)	0.68 (0.45-1.04)	0.07
Ln (ALT)	1.04 (0.97-1.12)	0.29
Ln (AST)	1.09 (1.02-1.17)	0.01
Ln (INR)	1.27 (1.20-1.33)	< 0.001	1.82 (1.43-2.32)	< 0.001
Ln (sodium)	0.04 (0.01-0.23)	< 0.001
Ln (potassium)	2.05 (1.23-3.41)	0.006	1.84 (1.10-3.07)	0.02

Bold font indicates statistical differences. MAP: Mean arterial pressure; WBC: White blood cell; TB: Total bilirubin; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; INR: International normalized ratio.

Table 3 Predictive values of prognostic scores for 28-day mortality in patients with acute-on-chronic liver failure

Scores	Youden index	Cutoff value	SEN (%)	SPE (%)	PPV (%)	NPV (%)	Brier score	R² value	P in H-L test
Derivation set in MIMIC cohort	Development of MIMIC ACLF score
MIMIC ACLF	0.48	0.57	71.81	75.98	66.7	80.1	0.17	0.36	0.73
CLIF-C ACLF	0.40	59	65.43	74.56	63.2	76.3	0.19	0.26	0.70
MELD	0.38	27	73.14	65.12	58.4	78.4	0.20	0.20	0.04
MELD-Na	0.36	29	75.53	59.96	55.8	78.6	0.21	0.18	0.11
Validation set in MIMIC cohort	Internal validation
MIMIC ACLF	0.46	0.32	81.97	64.40	69.5	84.8	0.17	0.36	0.26
CLIF-C ACLF	0.40	61	55.74	84.29	69.4	74.9	0.19	0.26	0.92
MELD	0.37	27	72.13	64.40	56.4	78.3	0.20	0.21	0.67
MELD-Na	0.35	30	72.95	62.30	55.3	78.3	0.20	0.23	0.09
SHHMU cohort	External validation
MIMIC ACLF	0.49	1.51	65.22	84.00	71.4	79.7	0.17	0.34	0.84
CLIF-C ACLF	0.54	49	71.74	82.67	71.7	82.7	0.17	0.35	0.14
MELD	0.30	33	36.96	93.33	77.3	70.7	0.21	0.13	0.08
MELD-Na	0.44	34	60.87	82.67	68.3	77.5	0.20	0.22	0.52

SEN: Sensitivity; SPE: Specificity; PPV: Positive predictive value; NPV: Negative predictive value; H-L test: Hosmer-Lemeshow goodness-of-fit test; MIMIC: Medical Information Mart for Intensive Care; MELD: Model for End-stage Liver; CLIF-C: Chronic Liver Failure Consortium; ACLF: Acute-on-chronic liver failure; SHHMU: The Second Hospital of Hebei Medical University.

Citation: Zhu ZY, Huang XH, Jiang HQ, Liu L. Development and validation of a new prognostic model for patients with acute-on-chronic liver failure in intensive care unit. World J Gastroenterol 2024; 30(20): 2657-2676
URL: https://www.wjgnet.com/1007-9327/full/v30/i20/2657.htm
DOI: https://dx.doi.org/10.3748/wjg.v30.i20.2657