PDF下载 ( 2602 KB)
HBV相关慢性肝病患者血清原卟啉Ⅸ检测的临床意义
DOI: 10.3969/j.issn.1001-5256.2021.05.020
利益冲突声明：本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突。
作者贡献声明：张璎、成若晨负责课题设计，资料分析，撰写论文；郭蕊、王霞参与收集数据与样本检测；刘凯歌负责拟定写作思路，指导撰写文章并最后定稿。
Clinical significance of serum protoporphyrin Ⅸ measurement in patients with HBV-related chronic liver diseases
-
摘要:
目的 探讨血清原卟啉Ⅸ(PPⅨ)检测在HBV相关慢性肝病患者肝损伤中的价值。 方法 纳入2018年10月—2019年10月于西安医学院第一附属医院诊断为HBV相关慢性肝病110例患者作为病例组[慢性乙型肝炎(CHB)组(n=50)、肝硬化(LC)组(n=40)、肝细胞癌(HCC)组(n=20)]，40例健康人群作为对照组。高效液相色谱法检测血清PPⅨ。符合正态分布的计量资料多组间比较采用单因素方差分析；非正态分布的计量资料两组间比较采用Mann-Whitney U检验，多组间比较采用Kruskal-Wallis H检验；计数资料多组间比较采用χ2检验；受试者工作特征曲线(ROC曲线)分析诊断价值；相关性采用Spearman相关分析法。 结果 CHB、LC、HCC患者的PPⅨ显著高于对照组[44.29(25.99~85.36) ng/dl、72.73(48.28~90.43) ng/dl、91.79(68.34~121.52) ng/dl vs 15.43(10.87~20.16) ng/dl]，差异均有统计学意义(P值均＜0.05)；与代偿期LC患者相比，失代偿期患者PPⅨ显著升高[54.50(29.14~85.65) vs 76.09(53.47~104.37)，Z=-2.176，P＜0.05]。PPⅨ诊断CHB、LC和HCC的敏感度均在85%以上，特异度均在60%以上。静止期CHB患者PPⅨ显著高于对照组(Z=-4.303，P＜0.05)。LC患者PPⅨ与TBil呈中等正相关(rs=0.587，P＜0.05)，与Alb呈中等负相关(rs=-0.408，P＜0.05)；HCC患者PPⅨ与TBil呈中等正相关(rs=0.470，P＜0.05)，与ChE呈中等负相关(rs=-0.459，P＜0.05)。 结论 HBV相关慢性肝病患者血清PPⅨ升高是肝损伤的早期事件，可作为肝损伤早期预警及病情评估的敏感参数。 Abstract:Objective To investigate the value of serum protoporphyrin Ⅸ (PPIX) measurement in evaluating liver damage in patients with HBV-related chronic liver diseases. Methods A total of 110 patients who were diagnosed with HBV-related chronic liver diseases in The First Affiliated Hospital of Xi'an Medical University from October 2018 to October 2019 were enrolled as case group [chronic hepatitis B (CHB) group with 50 patients, liver cirrhosis (LC) group with 40 patients, and hepatocellular carcinoma (HCC) group with 20 patients], and 40 healthy individuals were enrolled as control group. High-performance liquid chromatography was used to measure serum PPIX. A one-way analysis of variance was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test or the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups; the receiver operating characteristic (ROC) curve was plotted to analyze diagnostic value; a Spearman correlation analysis was also performed to investigate correlation. Results The CHB, HC, and HCC groups had a significantly higher level of PPIX than the control group [44.29 (25.99-85.36) ng/dl, 72.73 (48.28-90.43) ng/dl, and 91.79 (68.34-121.52) ng/dl vs 15.43 (10.87-20.16) ng/dl, all P < 0.05], and the patients with decompensated LC had a significant increase in the level of PPIX compared with those with compensated LC [54.50(29.14~85.65) vs 76.09(53.47~104.37), Z=-2.176, P < 0.05]. PPIX had a sensitivity of > 85% and a specificity of > 60% in the diagnosis of CHB, LC, and HCC. The patients in the latent stage of CHB had a significantly higher level of PPIX than those in the control group (Z=-4.303, P < 0.05). In the patients with LC, PPIX was moderately positively correlated with total bilirubin (TBil) (rs=0.587, P < 0.05) and moderately negatively correlated with albumin (rs=-0.408, P < 0.05); in the patients with HCC, PPIX was moderately positively correlated with TBil (rs=0.470, P < 0.05) and moderately negatively correlated with cholinesterase (rs=-0.459, P < 0.05). Conclusion Elevated serum PPIX is an early event of liver damage in patients with HBV-related chronic liver diseases and can thus be used as a sensitive parameter for the early warning and assessment of liver damage. -
Key words:
- Hepatitis B Virus /
- Liver Diseases /
- Protoporphyrins
-
表 1 患者基本资料的比较
组别 例数 男/女(例) 年龄(岁) 对照组 40 24/16 48.65±15.98 CHB组 50 30/20 46.92±10.01 LC组 40 27/13 52.95±13.54 HCC组 20 14/6 54.10±10.83 统计值 χ2=1.112 F=2.471 P值 0.774 0.064 
下载: 导出CSV
表 2 CHB与LC患者组内PPⅨ水平
分期 例数 PPⅨ(ng/dl) CHB 静止期 26 40.45(19.25~59.80) 活动期 24 59.61(28.41~99.19) Z值 -1.321 P值 0.187 LC 代偿期 18 54.50(29.14~85.65) 失代偿期 22 76.09(53.47~104.37) Z值 -2.176 P值 0.030
下载: 导出CSV
表 3 CHB患者静止期与对照组PPⅨ及肝功能指标比较
指标 CHB静止期(n=26) 对照组(n=40) Z值 P值 PPIX 42.45(21.26~61.80) 15.43(10.87~20.16) -4.303 ＜0.001 TBil 12.85(10.57~16.24) 11.37(8.52~14.44) -1.536 0.125 ChE 9280(8112~10 092) 8045(7599~9234) -2.139 0.032 AST 22.00(19.75~27.25) 21.00(17.00~26.50) -1.046 0.296 ALT 22.00(17.75~29.25) 18.50(12.25~25.00) -1.774 0.076 ALP 82.00(64.00~97.50) 76.00(60.50~86.50) -1.313 0.189 GGT 18.00(12.75~25.25) 14.50(12.00~23.75) -1.105 0.269 Alb 44.90(42.43~47.28) 43.20(38.05~45.98) -1.510 0.131
下载: 导出CSV
表 4 PPⅨ与各指标的相关性分析
指标 CHB LC HCC P值 rs值 P值 rs值 P值 rs值 PLT 0.980 0.004 0.028 -0.347 0.114 -0.365 HBV DNA 0.259 0.163 0.078 0.282 0.929 0.021 AFP 0.758 0.045 0.021 0.365 0.076 0.405 TBil 0.450 0.109 ＜0.001 0.587 0.036 0.470 ChE 0.195 -0.186 0.031 -0.342 0.042 -0.459 AST 0.149 0.207 0.044 0.320 0.811 -0.057 ALT 0.137 0.214 0.675 0.068 0.304 -0.242 ALP 0.054 0.274 0.079 0.281 0.322 0.233 GGT 0.562 -0.084 0.129 0.244 0.707 -0.090 Alb 0.567 -0.083 0.009 -0.408 0.232 -0.280 PT 0.861 0.025 0.082 0.278 0.661 0.105
下载: 导出CSV
-
[1] Chinese Society of Infectious Diseases and Chinese Society of Hepatology, Chinese Medical Association. Guidelines for the prevention and treatment of chronic hepatitis B (version 2019)[J]. J Clinl Hepatol, 2019, 35(12): 2648-2669. DOI: 10.3969/j.issn.1001－5256.2019.12.007.中华医学会感染病学分会, 中华医学会肝病学分会. 慢性乙型肝炎防治指南(2019年版)[J]. 临床肝胆病杂志, 2019, 35(12): 2648-2669. DOI: 10.3969/j.issn.1001－5256.2019.12.007. [2] FUJIWARA T, HARIGAE H. Biology of heme in mammalian erythroid cells and related disorders[J]. Biomed Res Int, 2015, 2015: 278536. DOI: 10.1155/2015/278536. [3] Chinese Society of Hepatology and Chinese Society of Infectious Diseases, Chinese Medical Association. The guideline of prevention and treatment for chronic hepatitis B: A 2015 update[J]. J Clin Hepatol, 2015, 31(12): 1941-1960. DOI: 10.3969/j.issn.1001－5256.2015.12.002.中华医学会肝病学分会, 中华医学会感染病学分会. 慢性乙型肝炎防治指南(2015年更新版)[J]. 临床肝胆病杂志, 2015, 31(12): 1941-1960. DOI: 10.3969/j.issn.1001－5256.2015.12.002. [4] MANSOURI A, GATTOLLIAT CH, ASSELAH T. Mitochondrial dysfunction and signaling in chronic liver diseases[J]. Gastroenterology, 2018, 155(3): 629-647. DOI: 10.1053/j.gastro. 2018.06.083 [5] SACHAR M, ANDERSON KE, MA X. Protoporphyrin Ⅸ: The good, the bad, and the ugly[J]. J Pharmacol Exp Ther, 2016, 356(2): 267-275. DOI: 10.1124/jpet.115.228130. [6] ZHU FC, BI HQ, ZHAO Y, et al. How hepatitis B virus core protein triggers abnormal metabolism of porphyrin in human liver cancer cells[J]. Chin J Virol, 2019, 35(4): 592-598. DOI: 10.13242/j.cnki.bingduxuebao.003577.朱芳成, 毕华强, 赵毅, 等. 乙型肝炎病毒核心蛋白触发人肝癌细胞异常卟啉代谢的机制[J]. 病毒学报, 2019, 35(4): 592-598. DOI: 10.13242/j.cnki.bingduxuebao.003577. [7] LIU X, LI SH, GAO SL, et al. Preliminary study on changes of hematoporphyrin in patients with chronic liver disease[J]. J Harbin Med Univ, 1992, 26(2): 99-101. https://www.cnki.com.cn/Article/CJFDTOTAL-HYDX199202008.htm刘桪, 李少华, 高善玲, 等. 慢性肝病患者血卟啉变化初探[J]. 哈尔滨医科大学学报, 1992, 26(2): 99-101. https://www.cnki.com.cn/Article/CJFDTOTAL-HYDX199202008.htm [8] GIBSON PR, GRANT J, CRONIN V, et al. Effect of hepatobiliary disease, chronic hepatitis C and hepatitis B virus infections and interferon-alpha on porphyrin profiles in plasma, urine and faeces[J]. J Gastroenterol Hepatol, 2000, 15(2): 192-201. DOI: 10.1046/j.1440-1746.2000.02065.x. [9] GAO SL, GUO HC, YIN JM, et al. Clinical significance of changes of hematoporphyrin in primary liver cancer[J]. J Harbin Med Univ, 1997, 31(2): 142-144. https://www.cnki.com.cn/Article/CJFDTOTAL-HYDX702.018.htm高善玲, 郭惠春, 殷积美, 等. 原发性肝癌血卟啉变化的临床意义[J]. 哈尔滨医科大学学报, 1997, 31(2): 142-144. https://www.cnki.com.cn/Article/CJFDTOTAL-HYDX702.018.htm [10] NAKANO T, MORIYA K, KOIKE K, et al. Hepatitis C virus core protein triggers abnormal porphyrin metabolism in human hepatocellular carcinoma cells[J]. PLoS One, 2018, 13(6): e0198345. DOI: 10.1371/journal.pone.0198345. [11] YANG Z, PHILIPS JD, DOTY RT, et al. Kinetics and specificity of feline leukemia virus subgroup C receptor (FLVCR) export function and its dependence on hemopexin[J]. J Biol Chem, 2010, 285(37): 28874-28882. DOI: 10.1074/jbc.M110.119131. [12] KHAN AA, QUIGLEY JG. Control of intracellular heme levels: heme transporters and heme oxygenases[J]. Biochim Biophys Acta, 2011, 1813(5): 668-682. DOI: 10.1016/j.bbamcr.2011.01.008. [13] KRISHNAMURTHY PC, DU G, FUKUDA Y, et al. Identification of a mammalian mitochondrial porphyrin transporter[J]. Nature, 2006, 443(7111): 586-589. DOI: 10.1038/nature05125. [14] GAO WY, LI D, CAI DE, et al. Hepatitis B virus X protein sensitizes HL-7702 cells to oxidative stress-induced apoptosis through modulation of the mitochondrial permeability transition pore[J]. Oncol Rep, 2017, 37(1): 48-56. DOI: 10.3892/or.2016.5225. [15] GRAZIANI M, SARTI P, ARESE M, et al. Cardiovascular mitochondrial dysfunction induced by cocaine: Biomarkers and possible beneficial effects of modulators of oxidative stress[J]. Oxid Med Cell Longev, 2017, 2017: 3034245. DOI: 10.1155/2017/3034245. [16] KRIVOSHEEV AB, KONDRATOVA MA, KRIVOSHEEVA TA, et al. The porphyrin metabolism in liver cirrhosis[J]. Ter Arkh, 2013, 85(1): 48-55. http://www.ncbi.nlm.nih.gov/pubmed/23536946 [17] ESMAT S, ELGENDY D, ALI M, et al. Prevalence of photosensitivity in chronic hepatitis C virus patients and its relation to serum and urinary porphyrins[J]. Liver Int, 2014, 34(7): 1033-1039. DOI: 10.1111/liv.12513. [18] WANG RM, ZHU YF, HE YF, et al. Structures and functions of metalloporphyrin protein conjugates[J]. Prog Chem, 2010, 22(10): 1952-1963. https://www.cnki.com.cn/Article/CJFDTOTAL-HXJZ201010009.htm王荣民, 朱永峰, 何玉凤, 等. 金属卟啉蛋白质结合体的结构与功能[J]. 化学进展, 2010, 22(10): 1952-1963. https://www.cnki.com.cn/Article/CJFDTOTAL-HXJZ201010009.htm -
本文二维码
图(3) / 表(4)
计量
- 文章访问数: 341
- HTML全文浏览量: 107
- PDF下载量: 30
- 被引次数: 0
