老年乙肝相关性原发性肝癌早期检测的标志物研究

倪宏　王林　李波



老年乙肝相关性原发性肝癌早期检测的标志物研究

倪宏王林李波

目的探讨血清甲胎蛋白(AFP)、α-L-岩藻糖苷酶(AFU)及恶性肿瘤特异性生长因子(TSGF)检测对老年乙肝相关性原发性肝癌的临床诊断价值。方法选取2014年1月至2015年6月期间在我院肝病科住院治疗的老年乙肝相关性原发性肝癌患者45例(Ⅰ组)，老年乙肝相关性肝硬化患者68例(Ⅱ组)，另选取健康老年人80例作为正常对照组。对3组研究对象肝功能、AFP、AFU、TSGF进行检测并进行相关性研究。结果本研究结果显示，Ⅰ组丙氨酸氨基转移酶(ALT)，天门氨酸氨基转移酶(AST)均高于Ⅱ组及对照组,白蛋白水平低于Ⅱ组及对照组,且差异具有统计学意义(P均<0.05),Ⅱ组AST、ALT均高于对照组,白蛋白水平低于对照组,差异亦具有统计学意义(P均<0.05);Ⅰ组血清AFP、AFU、TSGF均高于Ⅱ组及对照组,差异具有统计学意义(P均<0.05)。临床分期越高、分化程度越低、肿瘤大小≥5 cm、肿瘤个数<4,老年乙肝相关性原发性肝癌患者AFP水平越高(P<0.05);临床分期越高、分化程度越低、肿瘤大小<5 cm、肿瘤个数<4,老年乙肝相关性原发性肝癌患者AFU水平越高(P<0.05);临床分期越高,老年乙肝相关性原发性肝癌患者TSGF水平越高(P<0.05)。结论联合检测血清AFP、AFU、TSGF水平对老年乙肝相关性原发性肝癌具有重要的诊断价值。

原发性肝癌; 乙型肝炎; 血清标志物; 临床价值

伴随社会经济的飞速发展,人们生活水平日益提高,但是由于环境污染、黄曲霉毒素摄入、乙型肝炎病毒感染等因素的影响,原发性肝癌的发病率越来越高[1],我国是乙肝大国,我国原发性肝癌中有>90%的患者合并有乙型肝炎病毒感染[2]。随着人口老龄化的进展,老年原发性肝癌人群越来越受到关注,由于其合并糖尿病、心脑血管疾病等慢性疾病较多,自身机能降低,发病时多数已经是中晚期[3-5]。很多老年原发性肝癌患者初诊时就已经失去根治性手术的机会,导致生存期缩短,给生命带来巨大威胁,给社会带来极大的疾病负担。所以探索能早期检测出原发性肝癌的肿瘤标志物,对于制订治疗策略,提高治疗效果,改善预后,延长生存期具有至关重要的意义。本研究通过对甲胎蛋白(alpha-fetoprotein, AFP)、α-L-岩藻糖苷酶(alpha-L-fucosidase, AFU)、恶性肿瘤特异性生长因子(tumor specific growth factor, TSGF)进行检测并进行相关性研究分析,探讨其在老年乙肝相关性原发性肝癌中的诊断价值。

1　资料与方法

1.1临床资料选取2014年1月至2015年6月期间在我院肝病科住院治疗的老年乙肝相关性原发性肝癌患者45例,作为Ⅰ组,其中男31例,女14例,年龄62～75岁,平均(68.65±4.28)岁;同期肝病科住院治疗的老年乙肝相关性肝硬化患者68例,作为Ⅱ组,其中男45例,女23例,年龄61～75岁,平均(67.71±5.06)岁;另选取同期本院健康门诊参加体检的健康老年人80例作为正常对照组,其中男54例,女26例,年龄60～76岁,平均(68.32±4.91)岁。

1.2纳入与排除标准纳入标准:(1)年龄≥60岁;(2)乙肝相关性原发性肝癌由术后组织病理学检查确诊,乙肝相关性肝硬化诊断标准参考2002年版的乙肝相关性肝硬化诊断标准[6];(3)肝癌、肝硬化患者均为乙肝表面抗原阳性患者;(4)乙肝相关性原发性肝癌患者术前没有接受化疗或者射频消融等治疗;(5)病例资料详细完整;(6)签署书面知情同意书。排除标准:(1)合并有丙肝病毒(HCV)、丁肝病毒(HDV)、人类免疫缺陷病毒(HIV)感染或者酒精肝等其他肝病的患者;(2)患有心力衰竭的患者;(3)病例资料不完整者;(4)不配合者。

1.3血清标本采集所有研究对象均采集入院初诊没有任何治疗的清晨空腹静脉血3 ml,离心机离心出血清,并置于-30 ℃冰箱内低温保存备测,集中测定前拿出标本自然复融。

1.4血清学指标检测方法血清天冬氨酸氨基转移酶(aspartate aminotransterase, AST)、丙氨酸氨基转移酶(alanine transaminase, ALT)、白蛋白检测采用美国贝克曼库尔特有限公司的Beckman全自动生化分析仪进行检测;AFP、TSGF检测均采用酶联免疫吸附法,AFU采用速率法检测,检测仪器为Beckman全自动生化分析仪。

1.5老年乙肝相关性原发性肝癌患者临床病理特征术中记录老年乙肝相关性原发性肝癌患者临床病理特征,包括性别、年龄、肿瘤分化程度、肿瘤大小及个数,并判断临床分期。

2　结果

2.13组研究对象一般情况比较Ⅰ组、Ⅱ组及对照组3组研究对象的性别、年龄、BMI比较差异无统计学意义(P均>0.05),具有可比性。3组AST、ALT、白蛋白及血清AFP、AFU、TSGF差异均具有统计学意义(P均<0.05),Ⅰ组AST、ALT均高于Ⅱ组及对照组,差异具有统计学意义(P均<0.05),Ⅰ组白蛋白水平低于Ⅱ组及对照组,差异具有统计学意义(P均<0.05),Ⅱ组AST、ALT均高于对照组,差异具有统计学意义(P均<0.05),Ⅱ组白蛋白水平低于对照组,差异具有统计学意义(P均<0.05);Ⅰ组血清AFP、AFU、TSGF均高于Ⅱ组及对照组,差异具有统计学意义(P均<0.05),Ⅱ组血清AFP、AFU、TSGF与对照组比较,差异无统计学意义(P均>0.05)。见表1。

2.2老年乙肝相关性原发性肝癌患者临床病理特征和血清AFP、AFU、TSGF的关系本研究结果显示,临床分期高、分化程度低、肿瘤大小≥5 cm、肿瘤个数<4的患者，AFP水平高,差异均有统计学意义(P<0.05);临床分期高、分化程度低、肿瘤大小<5 cm、肿瘤个数<4的患者，AFU水平高,差异均有统计学意义(P<0.05);临床分期高的患者TSGF水平高,差异有统计学意义(P<0.05)。未发现性别、年龄与患者血清AFP、AFU、TSGF水平有关。见表2。

3　讨论

原发性肝癌严重威胁我国人民生命健康,乙型肝炎病毒感染是原发性肝癌的主要病原学因素,由慢性乙型肝炎进展为肝硬化,最后发生癌变是原发性肝癌发病最常见的“三部曲”模式[7]。本研究通过对老年乙肝相关性原发性肝癌、乙肝相关性肝硬化患者的AFP、AFU、TSGF水平进行检测,探讨其对肝癌的诊断价值。

表1　3组研究对象术前一般情况比较±s)

注：与对照组比较,*P<0.05;与Ⅱ组比较,△P<0.05

表2　肝癌患者临床病理特征和血清AFP、AFU、TSGF的关系研究

注：同项目内不同子项目间比较,*P<0.05

3.1术前肝脏功能情况本研究对术前的肝脏功能进行检测,目的是了解患者的身体情况,并有助于对疾病的诊断。本研究发现术前Ⅰ组、Ⅱ组及对照组3组研究对象AST、ALT、白蛋白差异均具有统计学意义(P均<0.05)。提示随着慢性乙型肝炎病情的恶化及进展,肝脏细胞破坏程度逐渐加重,表现为AST、ALT升高,以肝癌患者的AST、ALT为最高。由于肝癌患者的慢性消耗,导致白蛋白降低,这与周琦等[8]的研究结果一致。

3.2术前AFP、AFU、TSGF水平AFP是由胎儿的肝脏细胞合成的,其正常状态是存在于胎儿血清中的[9],发生肝癌时血清中AFP会异常升高[10]。在有效排除了妊娠、活动性肝炎、肝硬化炎症活动期及生殖腺胚胎瘤以后,AFP可以作为诊断原发性肝癌的“金标准”[11-13]。AFU在肝、肾等组织中活性最高,发生肝癌时,AFU会合成增多并进入血液,导致血清中AFU异常增加[14]。TSGF存在于各种恶性肿瘤细胞中,且是和其他的常见肿瘤标志物不相关的独立物质,而且在肿瘤形成早期就可以进入血液当中,导致血清中TSGF异常升高[15],所以对于恶性肿瘤具有早期诊断价值。本研究发现,Ⅰ组血清AFP、AFU、TSGF均高于Ⅱ组及对照组,差异具有统计学意义(P均<0.05),Ⅱ组血清AFP、AFU、TSGF与对照组比较差异无统计学意义,由此可见老年乙肝相关性原发性肝癌患者的血清AFP、AFU、TSGF与老年乙肝相关性肝硬化患者有明显不同,所以对老年乙肝患者加强血清AFP、AFU、TSGF定期监测,可以做到对老年乙肝相关性原发性肝癌的早发现、早诊断、早治疗。

3.3老年乙肝相关性原发性肝癌患者临床病理特征和血清AFP、AFU、TSGF的关系本研究发现临床分期越高,AFP、AFU、TSGF水平均越高;分化程度越低、肿瘤个数<4,AFP、AFU水平越高,提示肿瘤分化程度低,肿瘤个数还较少时,AFP、AFU就可以检测出来;肿瘤大小≥5 cm,AFP水平越高;肿瘤大小<5 cm,AFU水平越高,这与Kaseb等[16]的研究结果一致,提示肝癌早期,AFP浓度还较低时,AFU浓度即可较高,所以AFU可以对肝癌进行早期诊断。未发现性别、年龄与AFP、AFU、TSGF水平有关。

综上所述,血清AFP、AFU、TSGF对老年乙肝相关性原发性肝癌具有重要的诊断价值,定期监测血清AFP、AFU、TSGF水平对早期发现老年乙肝相关性原发性肝癌,指导临床制订治疗策略,提高治疗效果,改善预后,延长生存期具有至关重要的意义。

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Study on the markers for early diagnosis of hepatitis B related primary hepatic carcinoma in the elderly patients

NIHong,LIBo.DepartmentofGeneralSurgery,ShanxiZhen’anCountyHospital,Shangluo711500,China;WANGLin.

DepartmentofHepatobiliarySurgery,theFirstAffiliatedHospitalofXi’anJiaoTongUniversity,Xi’an710061,China

ObjectiveTo investigate the clinical value of serum alpha-feloprotein(AFP), alpha-L-fucosidase(AFU) and tumor specific growth factor(TSGF) in the elderly patients with hepatitis B related primary hepatic carcinoma.MethodsFrom January 2014 to June 2015, 45 patients with primary hepatic carcinoma in our hospital were selected as groupⅠ, and 68 patients with liver cirrhosis were selected as groupⅡ and 80 healthy old people were selected as control group. The liver function, AFU, TSGF, AFP were detected and the correlation study were carried out in three groups.ResultsThe levels of ALT, AST in group Ⅰ were significantly higher than those in group Ⅱ and the control group (P<0.05). The albumin in group Ⅰ and group Ⅱ was significantly lower than that of the control group (P<0.05). The levels of AST, ALT in group Ⅱ were higher than those in the control group (P<0.05), and the level of serum albumin was lower than that in the control group (P<0.05); The levels of AFP, TSGF and AFU in groupⅠ were higher than those in group Ⅱ and control group with statistically significant difference (P<0.05). Higher clinical stage, lower degree of differentiation, tumor size≥5 cm, tumor number < 4 were associated with higher level of AFP (P<0.05) in group Ⅱ. The higher clinical stage, lower degree of differentiation, tumor size<5 cm, tumor number < 4 were associated with higher level of AFU (P<0.05);The higher clinical stage, the higher TSGF level were found in group Ⅱ(P<0.05).ConclusionsSerum levels of AFP, AFU and TSGF have important diagnostic value for hepatitis B related primary liver cancer in elderly patients.

primary hepatic carcinoma; hepatitis B; serum marker; clinical value

711500陕西省商洛市，陕西省镇安县医院普外科(倪宏，李波)；710061陕西省西安市，西安交通大学第一附属医院肝胆外科(王林)

R 735.7

Adoi:10.3969/j.issn.1003-9198.2016.07.016

2015-09-06)