血清色氨酸用于乙肝相关慢加急性肝衰竭90 d死亡风险分层管理的潜在价值：一项多中心回顾性研究

doi:10.12122/j.issn.1673-4254.2025.01.08

南方医科大学学报 ›› 2025, Vol. 45 ›› Issue (1): 59-64.doi: 10.12122/j.issn.1673-4254.2025.01.08

血清色氨酸用于乙肝相关慢加急性肝衰竭90 d死亡风险分层管理的潜在价值：一项多中心回顾性研究

周超¹(), 张晶晶¹, 唐巧², 付双楠¹, 张宁¹, 何召云¹, 张瑾¹, 张田义¹, 刘鹏程¹, 宫嫚¹^,²()

^1.中国人民解放军总医院第五医学中心中医肝病科，北京 100039
^2.南方医科大学中医药学院，广东广州 510515

收稿日期:2024-02-12 出版日期:2025-01-20 发布日期:2025-01-20
通讯作者: 宫嫚 E-mail:379317021@qq.com;gongman302 @163.com
作者简介:周超，博士，主治医师，E-mail: 379317021@qq.com
基金资助:
国家科技重大专项项目(2018ZX10725506-002);国家自然科学基金(82305067)

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

Chao ZHOU¹(), Jingjing ZHANG¹, Qiao TANG², Shuangnan FU¹, Ning ZHANG¹, Zhaoyun HE¹, Jin ZHANG¹, Tianyi ZHANG¹, Pengcheng LIU¹, Man GONG¹^,²()

^1.Department of Traditional Chinese Medicine Liver Diseases, Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
^2.College of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China

Received:2024-02-12 Online:2025-01-20 Published:2025-01-20
Contact: Man GONG E-mail:379317021@qq.com;gongman302 @163.com
Supported by:
National Natural Science Foundation of China(82305067)

摘要/Abstract

摘要：

目的探索血清色氨酸与乙肝相关慢加急性肝衰竭（HBV-ACLF）死亡风险之间的相关性。方法回顾性纳入180例HBV-ACLF患者，根据确诊后90 d结局为患者分为存活组和死亡组；采用高效液相色谱法测定两组患者外周血中的血清色氨酸含量；比较两组患者基线血清色氨酸水平的差异；通过单因素及多因素回归分析基线血清色氨酸水平对于HBV-ACLF患者确诊后90 d病死率的影响；通过受试者曲线下面积探讨血清色氨酸对HBV-ACLF 90 d死亡风险的潜在预测价值。结果 90 d随访期内，53例（29.4%）HBV-ACLF患者因疾病死亡，127例（70.6%）存活。死亡患者的基线色氨酸水平低于存活患者（P<0.001）；经多因素回归分析校正混杂因素显示，色氨酸水平是HBV-ACLF死亡风险的独立预测因素。HBV-ACLF患者入组时低水平色氨酸（<10.14 pg/mL）与高水平色氨酸（≥10.14 pg/mL）相比具有更高的90 d死亡风险（43.3% vs 15.6%，HR：3.157，95% CI：1.713-5.817）；同时合并肾功能不全和低水平色氨酸的90 d死亡风险更高（73.3% vs 15.0%，HR：7.558，95% CI：3.369-16.960）；血清色氨酸水平用于预测HBV-ACLF患者的90 d死亡风险具有一定潜在价值（ROC=0.771，95% CI：0.699-0.844）。结论血清色氨酸与 HBV-ACLF预后密切相关；低水平的血清色氨酸预示90 d高死亡风险；尤其是同时合并肾功能不全的患者90 d死亡风险更高。

关键词: 肝衰竭, 预后, 色氨酸, 乙型肝炎病毒, 肾功能不全

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

周超, 张晶晶, 唐巧, 付双楠, 张宁, 何召云, 张瑾, 张田义, 刘鹏程, 宫嫚. 血清色氨酸用于乙肝相关慢加急性肝衰竭90 d死亡风险分层管理的潜在价值：一项多中心回顾性研究[J]. 南方医科大学学报, 2025, 45(1): 59-64.

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.

图/表 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

血清色氨酸用于乙肝相关慢加急性肝衰竭90 d死亡风险分层管理的潜在价值：一项多中心回顾性研究

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

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参考文献 27

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Parameters	Tryptophan		P
Parameters	≤10.14 pg/mL (n=90)	>10.14 pg/mL (n=90)	P
KD	15 (16.7%)	6 (6.7%)	0.037
Ascites	48 (53.3%)	45 (50.6%)	0.711
HE	10 (11.1%)	9 (10.0%)	0.808
Coagulation failure	22 (25.3%)	21 (23.6%)	0.794
Liver Failure	78 (86.7%)	74 (82.2%)	0.411

Models	Variable	HR (95% CI)	P
Estimation of Trp-by-KD interaction	Trp	3.416 (1.829-6.380)	<0.001
	KD	1.875 (1.425-5.800)	0.003
	Interaction Trp-by-KD	2.160 (0.251-8.566)	0.483
Evaluation of the influence of Trp and KD*	Trp	2.629 (1.362-5.078)	0.004
	KD	1.331 (1.174-5.943)	0.030
	Combination of independent effects: Trp/KD vs. no Trp/no KD	7.558 (3.369-16.960)	<0.001

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