Value of serum tryptophan in stratified management of 90-day mortality risk in patients with hepatitis B virus-related acute-on-chronic liver failure: a multicenter retrospective study

doi:10.12122/j.issn.1673-4254.2025.01.08

Abstract

Abstract:

Objective To explore the correlation of serum tryptophan level with 90-day mortality risk in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). Methods This retrospective study was conducted among 108 patients with HBV-ACLF, whose survival outcomes within 90 days after diagnosis were recorded. The correlation of baseline serum tryptophan levels measured by high-performance liquid chromatography with 90-day mortality of the patients was analyzed, and the predictive value of serum tryptophan for 90-day mortality was explored. Results Within 90 days after diagnosis, 53 (29.4%) of the patients died and 127 (70.6%) survived. The deceased patients had significantly lower baseline serum tryptophan levels than the survivors (7.31±3.73 pg/mL vs 13.32±7.15 pg/mL, P<0.001). Multivariate analysis suggested that serum tryptophan level was an independent factor correlated with mortality of HBV-ACLF after adjustment for confounding variables. The patients with serum tryptophan levels below the median level (10.14 pg/mL) at admission had significantly higher 90-day mortality risks than those with higher tryptophan levels (43.3% vs 15.6%, HR: 3.157, 95% CI: 1.713-5.817), and the complication by kidney dysfunction further increased the risk to 73.3% as compared with patients with higher serum tryptophan levels with normal kidney function (15.0%; HR: 7.558, 95% CI: 3.369-16.960). Serum tryptophan levels had an area under the receiver operating characteristic curve of 0.771 (95% CI: 0.699-0.844) for predicting 90-day mortality. Conclusion Serum tryptophan level is closely correlated with the survival outcomes of patients with HBV-ACLF, and a decreased tryptophan level indicates a high 90-day mortality risk, which can be further increased by the complication by kidney dysfunction.

Key words: liver failure, prognosis, tryptophan, hepatitis B virus, kidney dysfunction

Chao ZHOU, Jingjing ZHANG, Qiao TANG, Shuangnan FU, Ning ZHANG, Zhaoyun HE, Jin ZHANG, Tianyi ZHANG, Pengcheng LIU, Man GONG. Value of serum tryptophan in stratified management of 90-day mortality risk in patients with hepatitis B virus-related acute-on-chronic liver failure: a multicenter retrospective study[J]. Journal of Southern Medical University, 2025, 45(1): 59-64.

Figures/Tables 7

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Parameter	All subjects (n=180)	Survivors (n=127)	Deceased (n=53)	P
Age (year)	44.6±10.6	39.6±11.2	44.3±9.6	0.008
Male [n (%)]	162 (90.0)	114 (89.8)	48 (90.6)	0.870
Serum albumin (g/L)	32.4±6.3	33.1±7.0	30.8±4.0	0.032
Serum globulin (g/L)	29.9±8.2	30.2±8.0	29.4±8.8	0.538
Total bilirubin (mg/dL)	19.7±7.1	18.1±6.2	23.6±7.8	<0.001
ALT (U/L)	145 (63-360)	151(63-353)	183(74-458)	0.255
AST (U/L)	153 (86-299)	143(85-285)	189(110-363)	0.100
Creatinine (mg/dL)	0.84±0.23	0.82±0.19	0.86±0.32	0.437
International normalized ratio	2.2±0.6	2.1±0.5	2.5±0.8	<0.001
Leukocyte (×10⁹/L)	7.2±3.2	7.2±3.0	7.2±3.5	0.889
Hemoglobin content (g/L)	122±29	122±28	120±29	0.608
Thrombocyte (×10⁹/L)	109±57	118±58	88±49	0.001
Ammonia(mmol/L)	61.6±7.2	70.4±7.9	57.1±7.7	0.120
HBV DNA (log₁₀ IU/mL)	3.4±2.2	3.5±2.1	3.2±2.4	0.505
HBsAg (>250 KIU/mL)	112 (62.2)	83 (65.4)	29 (54.7)	0.180
MELD	24.2±4.8	23.6±4.4	25.7±5.3	0.011
MELD-Na	25.9±6.8	24.8±5.3	28.7±9.1	0.005
AARC score	7.8±1.3	7.5±1.1	8.3±1.5	0.001
HE [n (%)]	19 (10.6)	9 (7.1)	10 (18.9)	0.001
SBP [n (%)]	44 (24.6)	28 (22.0)	16 (30.8)	0.219
Hyponatremia [n (%)]	50 (28.2)	32 (25.6)	18 (34.6)	0.225
KD [n (%)]	21 (11.7)	9 (7.1)	12 (22.6)	0.003
Trp (pg/mL)	11.67±6.83	13.32±7.15	7.31±3.73	<0.001
HBV reactivation [n (%)]	162 (90.0)	113(89.0)	49 (92.5)	0.479

Parameter	All subjects (n=180)	Survivors (n=127)	Deceased (n=53)	P
Age (year)	44.6±10.6	39.6±11.2	44.3±9.6	0.008
Male [n (%)]	162 (90.0)	114 (89.8)	48 (90.6)	0.870
Serum albumin (g/L)	32.4±6.3	33.1±7.0	30.8±4.0	0.032
Serum globulin (g/L)	29.9±8.2	30.2±8.0	29.4±8.8	0.538
Total bilirubin (mg/dL)	19.7±7.1	18.1±6.2	23.6±7.8	<0.001
ALT (U/L)	145 (63-360)	151(63-353)	183(74-458)	0.255
AST (U/L)	153 (86-299)	143(85-285)	189(110-363)	0.100
Creatinine (mg/dL)	0.84±0.23	0.82±0.19	0.86±0.32	0.437
International normalized ratio	2.2±0.6	2.1±0.5	2.5±0.8	<0.001
Leukocyte (×10⁹/L)	7.2±3.2	7.2±3.0	7.2±3.5	0.889
Hemoglobin content (g/L)	122±29	122±28	120±29	0.608
Thrombocyte (×10⁹/L)	109±57	118±58	88±49	0.001
Ammonia(mmol/L)	61.6±7.2	70.4±7.9	57.1±7.7	0.120
HBV DNA (log₁₀ IU/mL)	3.4±2.2	3.5±2.1	3.2±2.4	0.505
HBsAg (>250 KIU/mL)	112 (62.2)	83 (65.4)	29 (54.7)	0.180
MELD	24.2±4.8	23.6±4.4	25.7±5.3	0.011
MELD-Na	25.9±6.8	24.8±5.3	28.7±9.1	0.005
AARC score	7.8±1.3	7.5±1.1	8.3±1.5	0.001
HE [n (%)]	19 (10.6)	9 (7.1)	10 (18.9)	0.001
SBP [n (%)]	44 (24.6)	28 (22.0)	16 (30.8)	0.219
Hyponatremia [n (%)]	50 (28.2)	32 (25.6)	18 (34.6)	0.225
KD [n (%)]	21 (11.7)	9 (7.1)	12 (22.6)	0.003
Trp (pg/mL)	11.67±6.83	13.32±7.15	7.31±3.73	<0.001
HBV reactivation [n (%)]	162 (90.0)	113(89.0)	49 (92.5)	0.479

Model	Parameters	HR	95% CI	P
1	Tryptophan (pg/mL)	0.853	0.796-0.914	<0.001
	MELD	1.054	1.017-1.093	0.004
2	Tryptophan (pg/mL)	0.858	0.801-0.920	<0.001
	MELD-Na	1.053	1.023-1.084	<0.001
3	Tryptophan (pg/mL)	0.847	0.792-0.906	<0.001
	AARC	1.840	1.448-2.339	<0.001
4	Tryptophan (pg/mL)	0.861	0.801-0.926	<0.001
	Age (year)	1.034	0.999-1.070	0.055
	Serum albumin (g/L)	1.012	0.965-1.061	0.625
	Bilirubin (mg/dL)	1.097	1.054-1.142	<0.001
	Thrombocyte (×10⁹/L)	0.991	0.984-0.999	0.027
	International normalized ratio	1.947	1.269-2.987	0.002
	Presence of HE	1.627	1.049-2.523	0.030
	Presence of KD	3.121	1.635-5.955	0.001

Model	Parameters	HR	95% CI	P
1	Tryptophan (pg/mL)	0.853	0.796-0.914	<0.001
	MELD	1.054	1.017-1.093	0.004
2	Tryptophan (pg/mL)	0.858	0.801-0.920	<0.001
	MELD-Na	1.053	1.023-1.084	<0.001
3	Tryptophan (pg/mL)	0.847	0.792-0.906	<0.001
	AARC	1.840	1.448-2.339	<0.001
4	Tryptophan (pg/mL)	0.861	0.801-0.926	<0.001
	Age (year)	1.034	0.999-1.070	0.055
	Serum albumin (g/L)	1.012	0.965-1.061	0.625
	Bilirubin (mg/dL)	1.097	1.054-1.142	<0.001
	Thrombocyte (×10⁹/L)	0.991	0.984-0.999	0.027
	International normalized ratio	1.947	1.269-2.987	0.002
	Presence of HE	1.627	1.049-2.523	0.030
	Presence of KD	3.121	1.635-5.955	0.001

Parameters	90-day mortality		28-day mortality
Parameters	AUROC	Pvs tryptophan	AUROC	Pvs tryptophan
Tryptophan	0.771 (0.699-0.844)		0.570 (0.429-0.710)
AARC	0.684 (0.584-0.784)	0.001	0.823 (0.725-0.920)	<0.001
MELD	0.656 (0.555-0.757)	<0.001	0.745 (0.647-0.844)	0.005
MELD-Na	0.665 (0.567-0.763)	<0.001	0.829 (0.745-0.913)	<0.001