血清高迁移率族蛋白B1 与肝硬化并发肝性脑病严重程度的相关性及诊断价值

doi:10.3877/cma.j.issn.2095-2015.2025.03.013

目的

探究血清高迁移率族蛋白B1（HMGB1）水平与肝硬化并发肝性脑病（HE）严重程度的相关性及诊断价值。

方法

回顾性选取2021 年1 月至2024 年7 月邵阳市中心医院收治的276 例肝硬化患者，根据纳入、排除标准最终筛选203 例患者为研究对象。根据患者是否合并HE分为HE 组（n=97）和非HE 组（n=106），进一步根据West Haven 分级标准将HE 组分为轻微肝性脑病（MHE）组（n=58）和显性肝性脑病（OHE）组（n=39）。收集患者基线资料，采用酶联免疫吸附试验（ELISA）检测血清HMGB1 水平，采用Spearman 系数分析血清HMGB1 水平与肝性脑病心理测量评分（PHES）、Child-Pugh 及终末期肝病模型（MELD）评分的相关性。并建立多因素Logistic回归模型分析肝硬化患者并发HE 的影响因素。绘制ROC 曲线分析血清HMGB1 水平在HE 诊断和病情评估中的应用价值。

结果

OHE 组患者血清HMGB1 水平显著高于MHE 组和非HE 组患者，MHE 组患者血清HMGB1 水平显著高于非HE 组（均P＜0.001）。血清HMGB1 水平与Child-Pugh及MELD 评分呈显著正相关（r=0.510，r=0.662，均P＜0.001），与PHES 评分呈负相关（r=－0.415，P＜0.001）。MELD 评分、血氨、总胆红素及血清HMGB1 水平升高是肝硬化患者并发HE 的独立危险因素（均P＜0.05）。血清HMGB1 辅助诊断HE 的AUC 为0.829，敏感度为83.96%，特异度为69.07%；在MHE 和OHE 的病情评估中，血清HMGB1 的AUC 为0.845，敏感度为79.49%，特异度为86.21%。

结论

HE 患者血清HMGB1 水平显著升高，其水平变化在HE 诊断和病情评估中具有较高的应用价值。

关键词: 肝硬化, 肝性脑病, 高迁移率族蛋白B1, 相关性, 诊断价值

Objective

To explore the correlation of serum high mobility group protein B1(HMGB1) level with the severity of liver cirrhosis complicated with hepatic encephalopathy (HE) and its diagnostic value.

Methods

A total of 276 patients with liver cirrhosis admitted to Shaoyang Central Hospital from January 2021 to July 2024 were retrospectively selected, and 203 patients were finally selected as the research objects according to the inclusion and exclusion criteria.According to the presence or absence of HE, the patients were divided into HE group (n=97) and non-HE group (n=106).According to the West Haven classification criteria, the HE group was further divided into minimal hepatic encephalopathy (MHE) group (n=58) and overt hepatic encephalopathy (OHE) group (n=39).The baseline data of the patients were selected.Serum HMGB1 level was detected by enzyme-linked immunosorbent assay (ELISA).Spearman coefficient was used to analyze the correlation between serum HMGB1 level and psychometric scores of hepatic encephalopathy (PHES), Child-Pugh and model for end-stage liver disease(MELD) scores.Multivariate logistic regression model was established to analyze the influencing factors of HE in patients with liver cirrhosis.ROC curve was drawn to analyze the application value of serum HMGB1 level in the diagnosis and disease evaluation of HE.

Results

The serum level of HMGB1 in the OHE group was significantly higher than that in the MHE group and the non-HE group, and the serum level of HMGB1 in the MHE group was significantly higher than that in the non-HE group (all P<0.001).Serum HMGB1 level was positively correlated with Child-Pugh score and MELD score (r=0.510, r=0.662, all P<0.001), and negatively correlated with PHES score (r=-0.415, all P<0.001).MELD score, elevated blood ammonia, total bilirubin (TBIL) and serum HMGB1 levels were independent risk factors for HE in patients with liver cirrhosis (all P<0.05).The AUC of serum HMGB1 in the auxiliary diagnosis of HE was 0.829, the sensitivity was 83.96%, and the specificity was 69.07%.In the assessment of MHE and OHE, the AUC of serum HMGB1 was 0.845, the sensitivity was 79.49%, and the specificity was 86.21%.

Conclusion

Serum HMGB1 level is significantly increased in patients with HE, and its changes have a high application value in the diagnosis and disease evaluation of HE.

Key words: Liver cirrhosis, Hepatic encephalopathy, High mobility group protein B1, Correlation, Diagnostic value

表1 各组肝硬化患者一般资料比较

临床资料	非HE 组(n=106)	MHE 组(n=58)	OHE 组(n=39)	F/H/χ²	P
年龄(岁)	61.92±6.24	62.66±5.89	63.31±5.49	0.843	0.432
性别(男/女,例)	56/50	31/27	22/17	0.149	0.928
体重指数(kg/m², $\overset{ˉ}{x}$ ± s )	22.40±2.08	21.98±2.05	22.24±2.15	0.753	0.472
病因[例(%)]
乙型肝炎肝硬化	58(54.72)	34(58.62)	22(56.41)
酒精性肝硬化	45(42.45)	19(32.76)	15(38.46)	3.566	0.468
其他	3(2.83)	5(8.62)	2(5.13)
MELD 分数[M ( Q₁,　 Q₃ )]	6.49(4.28,12.05)	9.08(8.26,12.86)	15.75(10.12,21.14)	155.601	＜0.001
Child-Pugh 分级(A/B/C 级,例)	78/28/0	14/44/0	1/14/24	162.752	＜0.001
Child-Pugh 分数[M ( Q₁,　 Q₃ )]	6(5,9)	8(5,9)	10(6,13)	105.820	＜0.001
West Haven 分级(0/1/2 级,例)	-	58/0/0	0/22/17	97.000	＜0.001
PHES 分数[M ( Q₁,　 Q₃ )]	0(-1,2)	-5(-7,-4)	-	114.329	＜0.001
合并肝肾综合征[例(%)]	32(30.19)	28(48.28)	24(61.54)	13.144	＜0.001
合并肝硬化腹水[例(%)]	43(40.57)	30(51.72)	25(64.10)	6.712	0.035
合并电解质紊乱[例(%)]	22(20.75)	25(43.10)	20(51.28)	15.761	＜0.001
实验室指标( $\overset{ˉ}{x}$ ± s )
血钠(mmol/L)	135.65±8.95	134.79±9.02	135.09±8.47	0.189	0.828
血氨(μmol/L)	70.54±9.40	91.12±10.84^*	89.85±11.05^*	99.134	＜0.001
血红蛋白(g/L)	91.05±8.31	91.58±6.85	92.45±7.63	0.468	0.627
PT(s)	19.69±1.87	19.38±1.75	19.37±1.68	0.796	0.452
TBIL(μmol/L)	39.93±8.70	66.95±9.24^*	83.36±10.85^*#	367.360	＜0.001
DBIL(μmol/L)	25.25±6.59	34.11±7.96^*	45.15±8.77^*#	106.350	＜0.001
AST(U/L)	48.29±8.33	48.72±7.22	47.05±6.68	0.572	0.566
ALT(U/L)	46.59±9.86	46.28±10.23	46.31±8.75	0.024	0.977
TP(g/L)	62.35±6.91	61.72±7.94	59.35±8.42	2.281	0.105

表1 各组肝硬化患者一般资料比较

临床资料	非HE 组(n=106)	MHE 组(n=58)	OHE 组(n=39)	F/H/χ²	P
年龄(岁)	61.92±6.24	62.66±5.89	63.31±5.49	0.843	0.432
性别(男/女,例)	56/50	31/27	22/17	0.149	0.928
体重指数(kg/m², $\overset{ˉ}{x}$ ± s )	22.40±2.08	21.98±2.05	22.24±2.15	0.753	0.472
病因[例(%)]
乙型肝炎肝硬化	58(54.72)	34(58.62)	22(56.41)
酒精性肝硬化	45(42.45)	19(32.76)	15(38.46)	3.566	0.468
其他	3(2.83)	5(8.62)	2(5.13)
MELD 分数[M ( Q₁,　 Q₃ )]	6.49(4.28,12.05)	9.08(8.26,12.86)	15.75(10.12,21.14)	155.601	＜0.001
Child-Pugh 分级(A/B/C 级,例)	78/28/0	14/44/0	1/14/24	162.752	＜0.001
Child-Pugh 分数[M ( Q₁,　 Q₃ )]	6(5,9)	8(5,9)	10(6,13)	105.820	＜0.001
West Haven 分级(0/1/2 级,例)	-	58/0/0	0/22/17	97.000	＜0.001
PHES 分数[M ( Q₁,　 Q₃ )]	0(-1,2)	-5(-7,-4)	-	114.329	＜0.001
合并肝肾综合征[例(%)]	32(30.19)	28(48.28)	24(61.54)	13.144	＜0.001
合并肝硬化腹水[例(%)]	43(40.57)	30(51.72)	25(64.10)	6.712	0.035
合并电解质紊乱[例(%)]	22(20.75)	25(43.10)	20(51.28)	15.761	＜0.001
实验室指标( $\overset{ˉ}{x}$ ± s )
血钠(mmol/L)	135.65±8.95	134.79±9.02	135.09±8.47	0.189	0.828
血氨(μmol/L)	70.54±9.40	91.12±10.84^*	89.85±11.05^*	99.134	＜0.001
血红蛋白(g/L)	91.05±8.31	91.58±6.85	92.45±7.63	0.468	0.627
PT(s)	19.69±1.87	19.38±1.75	19.37±1.68	0.796	0.452
TBIL(μmol/L)	39.93±8.70	66.95±9.24^*	83.36±10.85^*#	367.360	＜0.001
DBIL(μmol/L)	25.25±6.59	34.11±7.96^*	45.15±8.77^*#	106.350	＜0.001
AST(U/L)	48.29±8.33	48.72±7.22	47.05±6.68	0.572	0.566
ALT(U/L)	46.59±9.86	46.28±10.23	46.31±8.75	0.024	0.977
TP(g/L)	62.35±6.91	61.72±7.94	59.35±8.42	2.281	0.105

图1 血清HMGB1 水平与疾病严重程度的相关性分析注： r 相关系数；HMGB1 迁移率族蛋白B1；PHES 肝性脑病心理测量评分；MELD 终末期肝病模型评分

表2 肝硬化患者并发肝性脑病的多因素Logistic 回归分析

因素	P值	OR 值	95% CI
MELD 评分	0.007	5.574	1.586～19.595
Child-Pugh 分数	0.299	2.050	0.528～7.954
合并肝肾综合征(有=1,无=0)	0.532	2.470	0.145～42.196
合并肝硬化腹水(有=1,无=0)	0.836	1.349	0.079～23.081
合并电解质紊乱(有=1,无=0)	0.480	2.909	0.151～56.163
血氨(μmol/L)	0.049	1.138	1.000～1.295
TBIL(μmol/L)	0.009	1.364	1.081～1.721
DBIL(μmol/L)	0.368	1.156	0.843～1.585
HMGB1(μg/L)	0.045	3.553	1.027～12.292

表2 肝硬化患者并发肝性脑病的多因素Logistic 回归分析

因素	P值	OR 值	95% CI
MELD 评分	0.007	5.574	1.586～19.595
Child-Pugh 分数	0.299	2.050	0.528～7.954
合并肝肾综合征(有=1,无=0)	0.532	2.470	0.145～42.196
合并肝硬化腹水(有=1,无=0)	0.836	1.349	0.079～23.081
合并电解质紊乱(有=1,无=0)	0.480	2.909	0.151～56.163
血氨(μmol/L)	0.049	1.138	1.000～1.295
TBIL(μmol/L)	0.009	1.364	1.081～1.721
DBIL(μmol/L)	0.368	1.156	0.843～1.585
HMGB1(μg/L)	0.045	3.553	1.027～12.292

图2 血清HMGB1 水平在HE 诊断和病情评估中的ROC 曲线分析注：2A 非HE 组、HE 组（MHE＋OHE）中，绘制ROC 曲线分析血清HMGB1 对HE 的诊断效能；2B 绘制ROC 曲线分析血清HMGB1 在在MHE和OHE 的病情评估中的应用价值。HMGB1 迁移率族蛋白B1；HE 肝性脑病；MHE 轻微肝性脑病；OHE 显性肝性脑病

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Correlation of serum HMGB1 level with the severity of hepatic encephalopathy in liver cirrhosis and its diagnostic value

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Correlation of serum HMGB1 level with the severity of hepatic encephalopathy in liver cirrhosis and its diagnostic value