超氧化物歧化酶检测在乙型肝炎病毒相关性肝病中的应用价值

doi:10.3877/cma.j.issn.2095-5820.2023.01.005

目的

评估超氧化物歧化酶（SOD）检测在HBV相关性肝病中的临床应用价值，为HBV相关性肝病的诊疗提供参考。

方法

收集HBV相关性肝病患者300例和健康体检者110例，检测血清中SOD活性、甲胎蛋白（AFP）、总胆红素（TBIL）、总蛋白（TP）、白蛋白（ALB）、谷丙转氨酶（ALT）、谷草转氨酶（AST）、谷氨酰转肽酶（GGT）及HBV-DNA，分析比较各指标的组间差异，同时分析SOD与各指标间的相关性，采用受试者工作特征（ROC）曲线分析SOD对HBV相关性慢性肝炎（CHB）、肝硬化（HBV-LC）和肝癌（HBV-HCC)的诊断效能。

结果

HBV相关性肝病患者血清AFP、AST、ALT、GGT、TBIL水平均较健康对照组高，且AFP、GGT、TBIL随着疾病的进展逐渐升高；而HBV相关性肝病患者血清SOD、TP、ALB水平均较健康对照组降低，其中TP、ALB随着疾病的进展而降低。SOD活性比较发现，与健康对照组相比，HBV-LC患者和HBV-HCC患者血清SOD水平显著降低（P＜0.05）；与CHB患者相比，HBV-LC患者和HBV-HCC患者血清SOD水平显著降低（P＜0.05）。相关分析显示HBV-LC患者SOD活性与TP、ALB呈正相关（均P＜0.05），与AFP、AST、TBIL呈负相关（均P＜0.05）；HBV-HCC患者SOD活性与TP、ALB呈正相关（均P＜0.05），与AFP、AST、GGT、TBIL、HBV-DNA呈负相关（均P＜0.05）。SOD对HBV相关性肝病诊断效能分析，HBV-LC患者和HBV-HCC患者血清SOD曲线下面积具有统计学意义。

结论

SOD活性降低可反映HBV相关性肝病患者的肝脏损害，用于HBV相关性肝病患者疾病进展的监测，为鉴别慢性肝炎是否向肝硬化、肝癌发展提供依据，联合其它实验室检查可辅助诊断HBV相关性肝硬化、肝癌。

关键词: 超氧化物歧化酶, 乙型肝炎病毒, 慢性乙型肝炎, 肝硬化, 肝细胞癌

Objective

To estimate application value of superoxide dismutase (SOD) test in hepatitis B virus (HBV) related liver disease, and to provide reference for the diagnosis and treatment of HBV related liver disease.

Methods

A total of 300 patients with HBV related liver disease and 110 healthy controls were enrolled in our study. The serum enzyme activity of SOD, alpha-fetoprotein (AFP), total bilirubin (TBIL), total protein (TP), albumin (ALB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT) and HBV-DNA were detected. The difference of tested indexes in difference groups, and the correlations between SOD and the other biomarkers were analyzed. The receiver operating characteristic (ROC) curve were applied to analyze the diagnosis efficacy of SOD in chronic hepatitis B (CHB), hepatitis B virus related liver cirrhosis (HBV-LC), and hepatocellular carcinoma (HBV-HCC).

Results

In patients with HBV related liver disease, the levels of AFP, AST, ALT, GGT, TBIL were significantly higher than those in healthy people, and AFP, GGT and TBIL increased gradually with the progression of the disease. However, the levels of SOD, TP and ALB were decreased in patients with HBV related liver disease, the levels of TP and ALB were decreased with the progression of the disease. The SOD activity in HBV-LC and HBV-HCC patients were significantly lower than that in healthy group (P＜0.05), the level of SOD in HBV-LC and HBV-HCC patients was markedly lower than that in CHB patients (P＜0.05). Correlation analysis showed that the serum enzyme activity of SOD in HBV-LC patients was positively correlated with the value of TP, ALB (P＜0.05), and negatively correlated with AFP, AST, TBIL(P＜0.05). SOD activity in HBV-HCC patients was positively correlated with TP, ALB (P＜0.05), and negatively correlated with AFP, AST, GGT, TBIL, HBV-DNA (P＜0.05). Analysis of the efficacy of SOD in the diagnosis of HBV related liver diseases showed that the SOD area under the curve of HBV-LC patients and HBV-HCC patients had statistical significance (P＜0.05).

Conclusions

The decrease of SOD activity can reflect the liver damage of patients with HBV related liver disease, which can be used to monitor the development of the disease in patients with HBV related liver disease, and provide a basis for identifying whether there was transformation from chronic hepatitis B to LC or HCC. Combined with other laboratory examination, it can assist in the diagnosis of HBV-LC and HBV-HCC.

Key words: SOD, hepatitis B virus, chronic hepatitis B, liver cirrhosis, hepatocellular carcinoma

表1 HBV相关性肝病患者与健康对照组临床资料比较（

x ˉ

±s）

项目	健康对照组	CHB组	HBV-LC组	HBV-HCC组	P值
总例数/例	110	116	111	73	-
SOD/（U/ml）， $x ¯$ ±s	259.45±24.90	243.73±48.36	156.10±54.63	156.90±51.16	＜0.001
AFP/（ng/ml）， $x ¯$ ±s	3.43±1.24	5.31±7.87	10.22±13.29	4709.10±12 688.04	＜0.001
AST/（IU/L）， $x ¯$ ±s	22.13±5.47	72.26±157.06	52.68±46.27	100.37±101.07	＜0.001
ALT/（IU/L）， $x ¯$ ±s	22.26±10.84	116.76±292.09	41.74±32.00	85.08±149.29	＜0.001
GGT/（U/L）， $x ¯$ ±s	21.73±9.80	59.68±108.97	102.85±253.02	164.52±208.82	＜0.001
TP/（g/L）， $x ¯$ ±s	74.20±4.36	71.92±5.82	67.87±8.35	66.25±7.18	＜0.001
ALB/（g/L）， $x ¯$ ±s	44.95±2.98	42.08±5.29	35.62±7.53	34.40±7.65	＜0.001
TBIL/（μmol/L）， $x ¯$ ±s	16.45±4.64	28.48±41.54	41.64±45.67	58.52±123.75	＜0.001
HBV-DNA，log10/（IU/ml）， $x ¯$ ±s	-	1.37±2.02	0.57±1.44	1.93±2.49	＜0.001

表1 HBV相关性肝病患者与健康对照组临床资料比较（

x ˉ

±s）

项目	健康对照组	CHB组	HBV-LC组	HBV-HCC组	P值
总例数/例	110	116	111	73	-
SOD/（U/ml）， $x ¯$ ±s	259.45±24.90	243.73±48.36	156.10±54.63	156.90±51.16	＜0.001
AFP/（ng/ml）， $x ¯$ ±s	3.43±1.24	5.31±7.87	10.22±13.29	4709.10±12 688.04	＜0.001
AST/（IU/L）， $x ¯$ ±s	22.13±5.47	72.26±157.06	52.68±46.27	100.37±101.07	＜0.001
ALT/（IU/L）， $x ¯$ ±s	22.26±10.84	116.76±292.09	41.74±32.00	85.08±149.29	＜0.001
GGT/（U/L）， $x ¯$ ±s	21.73±9.80	59.68±108.97	102.85±253.02	164.52±208.82	＜0.001
TP/（g/L）， $x ¯$ ±s	74.20±4.36	71.92±5.82	67.87±8.35	66.25±7.18	＜0.001
ALB/（g/L）， $x ¯$ ±s	44.95±2.98	42.08±5.29	35.62±7.53	34.40±7.65	＜0.001
TBIL/（μmol/L）， $x ¯$ ±s	16.45±4.64	28.48±41.54	41.64±45.67	58.52±123.75	＜0.001
HBV-DNA，log10/（IU/ml）， $x ¯$ ±s	-	1.37±2.02	0.57±1.44	1.93±2.49	＜0.001

图1 HBV相关性肝病患者与健康对照组血清SOD活性比较注：图中o为试验异常值，213和161为异常值具体数值。

表2 病例组SOD活性与其它血清学指标的相关性分析

项目	CHB组		HBV-LC组		HBV-HCC组
项目	R值	P值	R值	P值	R值	P值
AFP	0.004	0.969	-0.187	0.049	-0.517	＜0.001
AST	0.018	0.848	-0.327	＜0.001	-0.367	0.001
ALT	0.096	0.305	0.013	0.895	-0.162	0.171
GGT	-0.066	0.482	0.020	0.834	-0.386	0.001
TP	0.022	0.815	0.522	＜0.001	0.404	＜0.001
ALB	0.037	0.694	0.688	＜0.001	0.727	＜0.001
TBIL	0.106	0.256	-0.388	＜0.001	-0.317	0.006
HBV-DNA	0.311	0.001	-0.173	0.069	-0.360	0.002

表2 病例组SOD活性与其它血清学指标的相关性分析

项目	CHB组		HBV-LC组		HBV-HCC组
项目	R值	P值	R值	P值	R值	P值
AFP	0.004	0.969	-0.187	0.049	-0.517	＜0.001
AST	0.018	0.848	-0.327	＜0.001	-0.367	0.001
ALT	0.096	0.305	0.013	0.895	-0.162	0.171
GGT	-0.066	0.482	0.020	0.834	-0.386	0.001
TP	0.022	0.815	0.522	＜0.001	0.404	＜0.001
ALB	0.037	0.694	0.688	＜0.001	0.727	＜0.001
TBIL	0.106	0.256	-0.388	＜0.001	-0.317	0.006
HBV-DNA	0.311	0.001	-0.173	0.069	-0.360	0.002

图2 SOD活性对HBV相关性肝病的诊断价值注：2A. CHB组SOD的ROC曲线；2B. HBV-LC组SOD的ROC曲线；2C. HBV-HCC组SOD的ROC曲线。

1	WHO. Hepatitis B[DB/OL]. 2022(2022-06-24)[2023-02-16]. URL
2	XIA C F, DONG X S, LI H, et al. Cancer statistics in China and United States, 2022: profiles, trends, and determinants[J]. Chinese Medical Journal, 2022, 135(5): 584-590.
3	CHIMED T, SANDAGDORJ T, ZNAOR A, et al. Cancer incidence and cancer control in Mongolia: results from the national cancer registry 2008-12[J]. International Journal of Cancer, 2017, 140(2): 302-309.
4	SUNG H, FERLAY J, SIEGEL R L, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA: A Cancer Journal for Clinicians, 2021, 71(3): 209-249.
5	D'SOUZA S, LAU K C, COFFIN C S, et al. Molecular mechanisms of viral hepatitis induced hepatocellular carcinoma[J]. World Journal of Gastroenterology, 2020, 26(38): 5759-5783.
6	LIU Y Q, XIE L, ZHAO J Y, et al. Association between catalase gene polymorphisms and risk of chronic hepatitis B, hepatitis B virus-related liver cirrhosis and hepatocellular carcinoma in Guangxi population: a case-control study[J]. Medicine, 2015, 94(13): e702.
7	BARADARAN A, NASRI H, RAFIEIAN-KOPAEI M. Oxidative stress and hypertension: possibility of hypertension therapy with antioxidants[J]. Journal of Research in Medical Sciences : The Official Journal of Isfahan University of Medical Sciences, 2014, 19(4): 358-367.
8	VISCONTI R, GRIECO D. New insights on oxidative stress in cancer[J]. Current Opinion in Drug Discovery and Development, 2009, 12(2): 240-245.
9	ZHANG X L, LU Y, YANG S, et al. An updated meta-analysis between the association of XRCC1 Arg399Gln polymorphism and hepatocellular carcinoma risk[J]. Asian Pacific Journal of Cancer Prevention : APJCP, 2014, 15(7): 3273-3278.
10	NISHIDA N, KUDO M. Oxidative stress and epigenetic instability in human hepatocarcinogenesis[J]. Digestive Diseases (Basel, Switzerland), 2013, 31(5-6): 447-453.
11	陆兴热, 陈凤羽, 刘孝文, 等. 肝病患者AFP、TP、ALB、SOD检测的临床价值[J]. 分子诊断与治疗杂志, 2017, 9(1): 37-40.
12	王贵强, 段钟平, 王福生, 等. 慢性乙型肝炎防治指南(2019年版)[J]. 实用肝脏病杂志, 2020, 23(1): 9-32.
13	袁牧, 王昌留, 王一斐, 等. 超氧化物歧化酶的研究进展[J]. 中国组织化学与细胞化学杂志, 2016, 25(6): 550-558.
14	AZADMANESH J, BORGSTAHL G E O. A review of the catalytic mechanism of human manganese superoxide dismutase[J]. Antioxidants (Basel, Switzerland), 2018, 7(2): 25.
15	BRESCIANI G, CRUZ I BDA, GONZÁLEZ-GALLEGO J. Manganese superoxide dismutase and oxidative stress modulation[J]. Advances in Clinical Chemistry, 2015, 68: 87-130.
16	GRIESS B, TOM E, DOMANN F, et al. Extracellular superoxide dismutase and its role in cancer[J]. Free Radical Biology and Medicine, 2017, 112: 464-479.
17	朱秀敏. 超氧化物歧化酶的生理活性[J]. 当代医学, 2011, 17(15): 26-27.
18	王君明, 崔瑛, 王峥涛, 等. 超氧化物歧化酶参与肝损伤的研究进展[J]. 中国实验方剂学杂志, 2011, 17(7): 265-269.
19	LIU S, HOU W, YAO P, et al. Quercetin protects against ethanol-induced oxidative damage in rat primary hepatocytes[J]. Toxicology in Vitro: An International Journal Published in Association with BIBRA, 2010, 24(2): 516-522.
20	郭光辉, 谭德明, 胡志亮. 慢性丙型肝炎患者血液微量元素、氧应激水平及与病毒载量的关系[J]. 中国医师杂志, 2008(8): 1126-1127.
21	肖宇宏, 冯静波, 苗勤, 等. 肝病患者AFP、TP、ALB、SOD检测分析[J]. 临床合理用药杂志, 2018, 11(31): 140-141.
22	SCHINZARI V, BARNABA V, PICONESE S. Chronic hepatitis B virus and hepatitis C virus infections and cancer: synergy between viral and host factors[J]. Clinical Microbiology and Infection : The Official Publication of The European Society of Clinical Microbiology and Infectious Diseases, 2015, 21(11): 969-974.
23	孙镜洁, 肖敏, 周志祥. 锰超氧化物歧化酶(MnSOD)表达与活性调控及其与肿瘤的关系[J]. 生理科学进展, 2019, 50(2): 117-121.
24	易力, 刘宏雷. 超氧化物歧化酶2与肿瘤关系的研究进展[J]. 山东医药, 2021, 61(29): 109-112.
25	CHROBOT A M, SZAFLARSKA-SZCZEPANIK A, DREWA G. Antioxidant defense in children with chronic viral hepatitis B and C[J]. Medical Science Monitor: International Medical Journal Of Experimental And Clinical Research, 2000, 6(4): 713-718.
26	高佳, 李佳, 严翠娥, 等. 健康成人血清超氧化物歧化酶的参考范围及其与性别、年龄的关系[J]. 标记免疫分析与临床, 2017, 24(4): 366-368.
27	ZHANG X L, LU Y, RONG C Z, et al. Role of superoxide dismutase in hepatitis B virus-related hepatocellular carcinoma[J]. Journal of Research in Medical Sciences : The Official Journal of Isfahan University of Medical Sciences, 2016, 21: 94.
28	徐艳秋, 刘斌, 常媛, 等. 超氧化物歧化酶在乙型肝炎和肝细胞癌中的应用价值[J]. 中国现代普通外科进展, 2017, 20(11): 841-844.
29	胡春华, 罗洁, 李济金. 肝硬化患者血清SOD和VWF水平变化及意义[J]. 现代诊断与治疗, 2015, 26(11): 2594-2596.
30	MORIYA K, NAKAGAWA K, SANTA T, et al. Oxidative stress in the absence of inflammation in a mouse model for hepatitis C virus-associated hepatocarcinogenesis[J]. Cancer Research, 2001, 61(11): 4365-4370.
31	SASAKI Y. Does oxidative stress participate in the development of hepatocellular carcinoma?[J]. Journal of Gastroenterology, 2006, 41(12): 1135-1148.

[1]	史学兵, 谢迎东, 谢霓, 徐超丽, 杨斌, 孙帼. 声辐射力弹性成像对不可切除肝细胞癌门静脉癌栓患者放射治疗效果的评价[J/OL]. 中华医学超声杂志（电子版）, 2024, 21(08): 778-784.
[2]	诸琴红, 夏典平, 葛芳娣, 崔大伟. 抗氧化和炎症指标在糖尿病肾病患者中的临床意义[J/OL]. 中华危重症医学杂志(电子版), 2024, 17(04): 307-311.
[3]	胡森焱, 徐冬, 方健, 谢冬冬, 王财庆. ICG荧光显影Laennec膜入路腹腔镜解剖性肝切除的临床研究[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(05): 513-516.
[4]	贺健, 张骊, 王洪海, 蒋文涛. 肝移植术后脾功能亢进转归及治疗研究进展[J/OL]. 中华移植杂志(电子版), 2024, 18(05): 310-314.
[5]	王浩源, 汪海洋, 孙建明, 陈以宽, 祁小桐, 唐博. 腹腔镜与开放修补对肝硬化腹外疝患者肝功能及凝血的影响[J/OL]. 中华疝和腹壁外科杂志(电子版), 2024, 18(06): 654-659.
[6]	蔡艺丹, 方坚, 张志强, 陈莉, 张世安, 夏磊, 阮梅, 李东良. 经颈静脉肝内门体分流术对肝硬化门脉高压患者肠道菌群及肝功能的影响[J/OL]. 中华细胞与干细胞杂志(电子版), 2024, 14(05): 285-293.
[7]	刘敏思, 李荣, 李媚. 基于GGT与Plt比值的模型在HBV相关肝细胞癌诊断中的作用[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(06): 831-835.
[8]	邓万玉, 陈富, 许磊波. 肝硬化与非肝硬化乙肝相关性肝癌患者术后无复发生存比较及其影响因素分析[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(05): 670-674.
[9]	刘起帆, 蒋安. 肝硬化门静脉高压症门静脉压力无创测量进展[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(03): 270-275.
[10]	董佳, 王坤, 张莉. 预后营养指数结合免疫球蛋白、血糖及甲胎蛋白对HBV 相关慢加急性肝衰竭患者治疗后预后不良的预测价值[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(06): 555-559.
[11]	崔健, 夏青, 林云, 李光玲, 李心娜, 王位. 血小板与淋巴细胞比值、免疫球蛋白、心肌酶谱及心电图对中老年肝硬化患者病情及预后的影响[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(05): 400-406.
[12]	秦相清, 朱陈, 张海银. 构建诺模图模型预测肝硬化食管胃底静脉曲张出血的风险[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(04): 330-335.
[13]	刘燚隆, 党荣广, 艾蓉, 张凯. 肝硬化合并静脉曲张出血患者内镜治疗后再出血风险的模型建立与验证[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(04): 336-342.
[14]	胡静, 杨秀锦, 侯志云. HBV感染患者外周血ISGs表达水平变化及其与干扰素治疗疗效的关系[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(04): 343-347.
[15]	王子阳, 王宏宾, 刘晓旌. 血清标志物对甲胎蛋白阴性肝细胞癌诊断的研究进展[J/OL]. 中华临床医师杂志(电子版), 2024, 18(07): 677-681.

阅读次数

全文

摘要

选择文件类型/文献管理软件名称

选择包含的内容

Application value of superoxide dismutase test in hepatitis B virus related liver disease

模态框（Modal）标题

选择文件类型/文献管理软件名称

选择包含的内容

Application value of superoxide dismutase test in hepatitis B virus related liver disease