Serum metabolomic characteristics and their predictive value for ninety-day prognosis in patients with acute-on-chronic liver failure

doi:10.3748/wjg.v31.i30.110401

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Aug 14, 2025 (publication date) through Aug 7, 2025

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Gastroenterol. Aug 14, 2025; 31(30): 110401
Published online Aug 14, 2025. doi: 10.3748/wjg.v31.i30.110401

Table 1 Baseline characteristics and laboratory indices by clinical outcome, mean ± SD

Characteristic	Survival group (n = 33)	Death group (n = 25)	Statistic	P value
Age (years)	44 ± 10	51 ± 11	t = -2.520	0.015
Male/female (n)	25/8	19/6	Z = -0.021	0.983
Liver disease etiology
HBV	15	9	NA	NA
Alcohol	13	10	NA	NA
Other	5	6	NA	NA
MELD	18.75 ± 6.65	22.89 ± 6.03	t = -2.440	0.018
MELD-Na	21.98 ± 8.01	28.36 ± 8.41	t = -2.940	0.005
ALBPS sessions	1.36 ± 2.09	1.61 ± 2.14	t = -0.494	0.623
Laboratory tests
WBC	6.26 (4.36-9.85)	8.23 (5.23-13.40)	Z = -1.382	0.167
NLR	5.98 ± 6.56	11.46 ± 9.78	t = -2.548	0.014
Hb	104.47 ± 25.31	95.92 ± 28.91	t = 1.198	0.236
PLT	132.96 ± 84.89	83.96 ± 58.93	t = 2.468	0.017
ALB	31.18 ± 6.20	30.35 ± 4.24	t = 0.575	0.567
ALT	55.00 (28.00-212.50)	47.00 (25.50-76.00)	Z = -0.864	0.388
AST	107.00 (61.00-275.00)	105.00 (55.00-150.00)	Z = -1.083	0.279
ALP	132.00 (105.50-186.50)	137.00 (119.00-213.00)	Z = -0.958	0.338
GGT	68.00 (49.00-145.50)	76.00 (40.50-164.50)	Z = -0.196	0.844
TBil	235.10 (198.40-310.15)	297.50 (235.45-378.50)	Z = -2.206	0.027
Scr	53.00 (47.50-72.50)	68.00 (56.00-89.50)	Z = -2.223	0.026
BUN	5.25 ± 3.84	10.16 ± 8.38	t = -2.978	0.004
Na⁺	134.33 ± 4.14	132.24 ± 6.19	t = 1.505	0.138
APTT	42.61 ± 8.49	45.97 ± 10.70	t = -1.334	0.188
INR	2.35 ± 0.59	2.53 ± 0.87	t = -0.977	0.333

HBV: Hepatitis B virus; MELD: Model for end-stage liver disease; MELD-Na: Model for end-stage liver disease with sodium; ALBPS: Artificial liver blood purification system; WBC: White blood cell; NLR: Neutrophil-to-lymphocyte ratio; Hb: Hemoglobin; PLT: Platelet; ALB: Albumin; ALP: Alkaline phosphatase; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; GGT: γ-glutamyl transferase; TBil: Total bilirubin; Scr: Serum creatinine; BUN: Blood urea nitrogen; Na⁺: Natrium; APTT: Activated partial thromboplastin time; INR: International normalized ratio; NA: Not available.

Table 2 Clinical baseline characteristics and laboratory indices between the artificial liver blood purification system and standardized medical treatment groups

Characteristic	Total (n = 35)	SMT group		Total (n = 23)	ALBPS group		P value^a
Characteristic	Total (n = 35)	Survival (n = 22)	Death (n = 13)	Total (n = 23)	Survival (n = 11)	Death (n = 12)	P value^a
Age (years)	45 ± 11	42 ± 10	50 ± 11	50 ± 11	47 ± 9	52 ± 12	0.128
Male/female (n)	27/8	17/5	10/3	17/6	8/3	9/3	0.780
Liver disease etiology
HBV	10	8	2	17	7	7	NA
Alcohol	18	10	8	5	3	2	NA
Other	7	4	3	1	1	3	NA
MELD	18.83 ± 6.13	17.42 ± 5.86	21.21 ± 6.03	23.13 ± 6.74	21.41 ± 7.60	24.70 ± 5.73	0.015
MELD-Na	24.92 ± 10.00	21.61 ± 8.15	30.51 ± 10.65	24.44 ± 6.47	22.71 ± 8.05	26.02 ± 4.37	0.841
ALBPS sessions	-	-	-	3.74 ± 1.60	4.09 ± 1.30	3.42 ± 1.83	NA
Laboratory tests
WBC	6.75 (4.57-11.05)	6.51 (4.31-9.47)	7.96 (4.32-13.47)	7.32 (5.15-12.81)	6.03 (4.17-12.81)	9.38 (5.76-13.68)	0.465
NLR	5.88 (2.68-9.15)	5.18 (2.03-7.80)	9.15 (4.40-25.11)	7.09 ± 6.31	5.55 ± 5.82	8.50 ± 6.66	0.541
Hb	94.64 ± 28.37	97.83 ± 26.77	87.54 ± 30.64	110.13 ± 22.28	115.73 ± 18.33	105.00 ± 25.04	0.031
PLT	106.24 ± 81.53	127.02 ± 91.56	71.08 ± 45.07	120.35 ± 73.66	144.82 ± 72.28	97.92 ± 70.38	0.506
ALB	28.73 ± 5.31	29.34 ± 6.02	27.71 ± 3.82	34.00 ± 3.87	34.86 ± 4.97	33.21 ± 2.46	0.000
ALT	40.00 (20.00-70.00)	36.50 (19.50-124.50)	44.00 (22.50-70.00)	79.00 (47.00-203.00)	124.00 (79.00-222.00)	64.00 (30.25-81.50)	0.004
AST	75.00 (43.00-161.00)	77.50 (44.75-384.25)	75.00 (30.50-141.50)	148.00 (71.00-176.00)	167.00 (95.00-179.00)	126.50 (65.00-152.00)	0.048
ALP	149.69 ± 55.04	146.19 ± 54.91	155.62 ± 56.98	133.00 (115.00-203.00)	127.00 (107.00-203.00)	133.00 (117.00-210.75)	0.899
GGT	68.00 (36.00-165.00)	89.50 (36.75-171.25)	53.00 (30.50-164.50)	76.00 (49.00-108.00)	65.00 (50.00-108.00)	88.00 (44.25-172.25)	0.844
TBil	249.98 ± 80.28	237.03 ± 79.44	271.89 ± 79.93	287.00 (223.30-353.70)	225.00 (208.00-317.20)	312.25 (279.38-392.23)	0.046
Scr	70.00 ± 37.37	58.14 ± 20.57	90.08 ± 50.22	62.00 (52.00-79.00)	53.00 (51.00-78.00)	66.50 (60.25-83.50)	0.426
BUN	5.01 (3.75-9.00)	4.43 (3.46-5.71)	6.73 (4.50-17.04)	6.64 ± 5.57	4.54 ± 2.22	8.57 ± 7.16	0.830
Na⁺	132.34 ± 6.29	134.23 ± 5.31	129.15 ± 6.72	135.09 ± 2.66	134.55 ± 1.75	135.58 ± 3.29	0.053
APTT	43.22 ± 8.91	41.93 ± 8.70	45.39 ± 9.17	45.33 ± 10.58	43.96 ± 8.31	46.59 ± 12.55	0.415
INR	2.33 ± 0.59	2.26 ± 0.52	2.46 ± 0.69	2.57 ± 0.88	2.53 ± 0.69	2.61 ± 1.05	0.216

^aP value compares total artificial liver blood purification system vs total standardized medical treatment groups for each parameter.

SMT: Standardized medical treatment; ALBPS: Artificial liver blood purification system; HBV: Hepatitis B virus; MELD: Model for end-stage liver disease; MELD-Na: Model for end-stage liver disease with sodium; ALBPS: Artificial liver blood purification system; WBC: White blood cell; NLR: Neutrophil-to-lymphocyte ratio; Hb: Hemoglobin; PLT: Platelet; ALB: Albumin; ALP: Alkaline phosphatase; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; GGT: γ-glutamyl transferase; TBil: Total bilirubin; Scr: Serum creatinine; BUN: Blood urea nitrogen; Na⁺: Natrium; APTT: Activated partial thromboplastin time; INR: International normalized ratio; NA: Not available.

Table 3 Candidate metabolites for assessing ninety-day prognosis in patients with acute-on-chronic liver failure

Metabolite	Survival	Death	\|Log₂FC\|	P value	VIP
Carnitine	50.55 ± 27.06	78.89 ± 35.86	1.51	0	1.94
Creatinine	61.75 ± 25.55	92.07 ± 49.32	1.74	0	1.62
Ala	405.67 ± 110.92	465.51 ± 211.05	5.04	0.08	1.49
Arg	14.56 ± 8.41	22.81 ± 11.93	1.55	0	1.43
Pro	266.13 ± 78.89	322.25 ± 133.30	3.62	0.03	1.21
Choline	57.26 ± 27.04	76.70 ± 37.78	2.37	0.01	1.17
C18:1	182.34 ± 221.42	279.69 ± 322.04	1.62	0.09	1.05

FC: Fold change; VIP: Variable importance in projection; Ala: Alanine; Arg: Arginine; Pro: Proline; C18:1: Oleic acid.

Table 4 Logistic regression analysis of factors influencing ninety-day mortality risk in patients with acute-on-chronic liver failure

Variable	Coefficient	SE	Wald χ²	P value	OR value	95%CI
Age	0.135	0.069	3.893	0.048	1.145	1.001-1.31
NLR	0.156	0.076	4.22	0.04	1.169	1.007-1.356
MELD	0.189	−0.140	1.824	0.177	1.208	0.918-1.589
PLT	-0.017	0.009	3.492	0.062	0.983	0.965-1.001
BUN	0.244	0.137	3.201	0.074	1.277	0.977-1.669
Choline	-0.012	0.019	0.384	0.536	0.988	0.951-1.026
Creatinine	-0.017	0.023	0.536	0.464	0.983	0.940-1.029
L-Carnitine	0.022	0.022	0.973	0.324	1.022	0.979-1.068
Pro	0.004	0.006	0.5	0.479	1.004	0.993-1.016
Arg	0.203	0.079	6.648	0.01	1.225	1.05-1.429
Ala	-0.003	0.004	0.723	0.395	0.997	0.990-1.004
C18:1	0.001	0.002	0.18	0.672	1.001	0.997-1.004
Constant	-15.481	6.044	6.561	0.01	0	-

OR: Odds ratio; CI: Confidence interval; NLR: Neutrophil-to-lymphocyte ratio; MELD: Model for end-stage liver disease; PLT: Platelet; BUN: Blood urea nitrogen; Pro: Proline; Arg: Arginine; Ala: Alanine; C18:1: Oleic acid.

Table 5 Predictive value of models and parameters for ninety-day mortality in patients with acute-on-chronic liver failure

Parameter	AUC	Sensitivity (%)	Specificity (%)	Optimal cut-off	95%CI	P value
Age	0.682	68	66.7	0.347	0.541-0.823	0.019
NLR	0.704	64	66.3	0.337	0.569-0.840	0.008
Arg	0.721	76	69.7	0.457	0.584-0.858	0.004
MELD	0.663	60	75.8	0.358	0.521-0.805	0.035
MELD-Na	0.714	80	60.6	0.406	0.580-0.847	0.006
ANA	0.945	88	87.9	0.759	0.893-0.997	0

AUC: Area under the curve; CI: Confidence interval; NLR: Neutrophil-to-lymphocyte ratio; Arg: Arginine; MELD: Model for end-stage liver disease; MELD-Na: Model for end-stage liver disease with sodium; ANA: Age-neutrophil-to-lymphocyte ratio-arginine.

Table 6 Changes in differential metabolites before and after artificial liver blood purification system treatment

Metabolite	ALBPS		P value	VIP
Metabolite	Before	After	P value	VIP
Ala	370.58 ± 143.66	548.53 ± 339.56	0.025	1.88
L-carnitine	69.79 ± 40.90	101.68 ± 70.24	0.067	1.36
Arg	22.48 ± 9.56	22.95 ± 9.57	0.87	0.91
Creatinine	90.21 ± 44.44	112.29 ± 69.86	0.208	0.88
Pro	303.03 ± 106.05	324.23 ± 171.56	0.617	0.79
C18:1	459.80 ± 304.72	350.58 ± 243.92	0.186	0.7
Choline	81.41 ± 39.88	89.30 ± 61.74	0.609	0.41

VIP: Variable importance in projection; ALBPS: Artificial liver blood purification system; Ala: Alanine; Arg: Arginine; C18:1: Oleic acid.

Citation: Liu Y, Xiao Y, Ai LF, Zhang JJ, Zhang JD, Qi ZQ, Dong L, Wang YD. Serum metabolomic characteristics and their predictive value for ninety-day prognosis in patients with acute-on-chronic liver failure. World J Gastroenterol 2025; 31(30): 110401
URL: https://www.wjgnet.com/1007-9327/full/v31/i30/110401.htm
DOI: https://dx.doi.org/10.3748/wjg.v31.i30.110401