临床研究 Open Access
Copyright ©The Author(s) 2003. Published by Baishideng Publishing Group Inc. All rights reserved.
世界华人消化杂志. 2003-11-15; 11(11): 1720-1722
在线出版日期: 2003-11-15. doi: 10.11569/wcjd.v11.i11.1720
肝硬化患者血清和腹水CA125升高
肖文斌, 刘玉兰
肖文斌, 刘玉兰, 北京大学人民医院消化科 北京市 100044
肖文斌, 博士, 男, 1975-12-16生, 江西泰和人, 汉族. 1998年北京大学医学部毕业. 主要从事消化系统疾病的诊断和治疗.
通讯作者: 刘玉兰, 100044, 北京市, 北京大学人民医院消化科. lanhong@public.bta.net.cn
电话: 010-68314422-5448 传真: 010-68318386
收稿日期: 2002-11-29
修回日期: 2002-12-20
接受日期: 2002-12-25
在线出版日期: 2003-11-15

目的

研究肝硬化患者血清和腹水CA125升高的情况、原因及临床意义.

方法

共有70例患者入选, 分成3组: 组1(Group I), 肝硬化伴或不伴腹水患者30例, 组2 (Group II), 消化系统肿瘤伴或不伴腹水患者30例, 组3(Group III), 除肝硬化外其他良性疾病引起的腹水患者10例. 检测所有患者血清CA125(15例患者同时检测腹水CA125), 并与病因、腹水、Child分级等指标作相关分析. 同时检测AFP、CEA和CA19-9等肿瘤标记物.

结果

87%的Group I患者存在血清CA125异常升高, 伴腹水的患者血清CA125异常发生率显著高于不伴腹水的患者(95% vs 38%, P<0.01). 血清CA125的水平与Child-Pugh评分相关(但不具显著性, r = 0.38, P = 0.06), 而与肝硬化的病因无关. Group II伴腹水和Group III的患者血清CA125明显升高, 但Group I伴腹水患者、Group II伴腹水患者和 Group III患者之间的血清CA125水平无显著差异(P>0.05), 分别为275±175 kU/L、368±190 kU/L和396±287 kU/L, 均显著高于Group I和 Group II不伴腹水的患者的血清CA125水平(分别为72±83 kU/L和83±42 kU/L, P<0.05). 血清CA125显著低于腹水CA125 (198±108 kU/L vs 460±234 kU/L), 二者呈线性相关(r = 0.58, P = 0.026); 90%的恶性腹水患者血清CA125的升高伴有其他肿瘤标记物的异常, 而良性腹水患者极少伴其他指标的异常(仅2%, P<0.01). 38例患者仅血清CA125异常, 其中有36例(95%)为良性腹水.

结论

肝硬化患者血清CA125的异常升高很常见, 其水平与腹水有关, 也可能与肝功能不全有关, 但与腹水的病因、良恶性等无关. 血清CA125可能来源于腹水. 血清CA125单项异常多提示良性、而非恶性疾病.

关键词: N/A
引文著录: 肖文斌, 刘玉兰. 肝硬化患者血清和腹水CA125升高. 世界华人消化杂志 2003; 11(11): 1720-1722
Elevation of serum and ascites CA125 levels in liver cirrhosis
Wen-Bin Xiao, Yu-Lan Liu
Wen-Bin Xiao, Yu-Lan Liu, Department of Gastroenterology, Peking University People's Hospital, Beijing 100044, China
Corresponding author: Dr. Yu-Lan Liu, Department of Gastroenterology, Peking University People's Hospital, Beijing 100044, China. lanhong@public.bta.net.cn
Received: November 29, 2002
Revised: December 20, 2002
Accepted: December 25, 2002
Published online: November 15, 2003

AIM

To evaluate the range of serum and ascitic cancer antigen(CA) 125 levels in patients with liver cirrhosis and to explore possible factors associated with CA 125 elevation.

METHODS

A total of 70 patients were studied. Group I consisted of 30 patients with liver cirrhosis with or without ascites. Group II consisted of 30 patients with digestive malignant tumors with or without asictes. And group III consisted of 10 patients with benign (but not cirrhotic) ascites. CA 125 levels were measured in sera of all the patients and also simultaneously in ascitic fluids of 15 patients.

RESULTS

Serum CA125 levels in 87% patients from group I were elevated, especially in those with ascites (95% vs 38% in patients without ascites, P<0.01) irrespective of the etiology of cirrhosis. Serum CA 125 levels were correlated with Child-Pugh scores (r = 0.38) but it was marginally significant (P = 0.06). All the patients with ascites from group II and group III had elevated serum CA 125 levels. There was no difference in serum CA 125 levels among patients with ascites from group I (275±175 kU/L), group II (368±190 kU/L) and group III (396±287 kU/L), neither did ascitic CA 125 levels (P>0.05), but serum CA 125 levels were significantly higher than those of patients without ascites from group I (72±83 kU/L) and group II (83±42 kU/L). The levels of serum CA 125 were lower than, but correlated with that of ascites CA 125 (198±108 kU/L vs 460±234 kU/L, r = 0.58, P = 0.026). The elevation of serum CA 125 in malignant ascites was more often accompanied with abnormalities of other tumor markers compared with that in benign ascites(90% vs 6%, P<0.01). Among the 38 patients with only serum CA125 elevation but not accompanied with a rise of other tumor markers, 36 (95%) were diagnosed as benign ascites.

CONCLUSION

The elevation of serum CA 125 is common in liver cirrhosis patients. It is correlated with the amount of ascites, and possibly insufficiency of liver function. Serum CA 125 probably derives from ascites. It usually predicts benign disease if the elevation of serum or ascites CA 125 is not accompanied with a rise of other tumor markers.

Key Words: N/A
0 引言

癌抗原CA125在妇科肿瘤、尤其是卵巢癌的诊断和预后中的作用已经得到公认[1-9]. 有学者发现, 非肿瘤疾病如肝硬化患者也可出现血清CA125升高[10-15]. 我们研究肝硬化患者血清和腹水CA125的变化情况, 以探讨其升高的原因和临床意义.

1 材料和方法
1.1 材料

I组: 1999/2001年住院肝硬化患者30 (男15, 女15)例, 平均年龄65±16岁, 其中乙型肝炎后肝硬化20例, 丙型肝炎后肝硬化5例, 酒精性肝硬化5例. Ia: 无腹水, 8例; Ib: 中少量腹水, 9例; Ic: 大量腹水, 13例. II组: 恶性肿瘤伴或不伴腹水患者30 (男16, 女14)例, 平均年龄50±15岁, 其中: IIa: 原发性肝癌10例, 均有大量腹水; IIb: 胃癌和胰腺癌10例, 有大量腹水; IIc: 胃癌和胰腺癌10例, 无腹水. III组: 良性腹水患者10 (男4, 女6例), 平均年龄45±9岁, 其中嗜酸性胃肠炎3例, 布加综合征3例, 低白蛋白血症4例. 所有患者均同时行妇科查体、B超和CT除外妇科肿瘤疾病.

1.2 方法

对所有患者进行B超检查, 按腹水的深度划分为大量、中少量. 液性暗区厚度小于3 cm为中少量, 大于3 cm为大量. 对有腹水的患者在做腹水穿刺时, 同时检测腹水和血清CA125, 并查其他肿瘤指标, 包括癌胚抗原CEA, 甲胎蛋白AFP和糖抗原CA19-9, 采用酶联免疫黏附法(ELISA), 试剂盒均购自Roche. 以大于正常值上限2倍者为异常升高.

统计学处理 分别采用t检验, x2检验和线性相关回归分析.

2 结果
2.1 肝硬化患者血清CA125与Child分级和腹水的关系

肝硬化患者30例Child A级9例, B级12例, C级9例. 血清CA125异常升高者占26例(87%), 其中A级7/9 (78%), B级10/12 (83%), C级9/9 (100%), 三者相比, 无显著性差异(P>0.05). 按血清CA125水平的高低排列, C级(330±287 kU/L)大于B级(207±152 kU/L)大于A级(169±158 kU/L), 但三者之间无显著性差异(P>0.05). 血清CA125与Child评分具有一定的相关性(r = 0.38, P = 0.06), 但不具显著性. 我们同时将肝硬化患者血清CA125分别与其相应的血清转氨酶、血氨水平、前胶原III肽和IV型胶原、胆固醇、转肽酶、凝血酶原时间、血清白蛋白等指标做相关分析, 结果均无统计学意义. Ia组中血清CA125异常升高者占38%, Ib＋Ic组中占95%, 具有显著性差异(P<0.01). Ia组(72±83 kU/L, n = 8)血清CA125的水平显著低于Ib组(328±238 kU/L, n = 9, P<0.01)和Ic组(255±152 kU/L, n = 13, P<0.01), 而Ib组和Ic组之间的血清CA125水平无显著性差异(P>0.05).

2.2 恶性腹水患者血清、腹水CA125的比较

IIa组(375±192 kU/L)与IIb组(346±187 kU/L)的血清CA125水平无显著性差异(P＝0.16), 但均显著高于IIc组(83±42 kU/L, P<0.01). 将IIa、IIb组合并后, 分别与III组以及Ib+Ic组患者相比较(表1), 血清、腹水CA125水平均无显著性差异(P>0.05). IIa+IIb组(恶性腹水)患者血清CA125均有升高, 但同时有CA19-9, CEA和AFP至少一项异常升高者18例(90%), 而Ib+Ic＋III组(良性腹水)患者中仅有2例同时伴有CA19-9升高(6%), 具有显著性差异(P<0.01). 38例血清CA125单项升高的患者中, 有36例(95%)为良性疾病.

表1 腹水患者血清、腹水CA125(mean±SD, kU/L)的比较.
分组别血清CA125腹水CA125a
IIa+IIb368±190 (n =20)434±278 (n =4)
III396±287 (n =10)462±254 (n =4)
Ib+Ic275±175 (n =22)435±207 (n =7)
aP<0.05, vs 血清.
2.3 腹水CA125与血清CA125的关系

有15例患者同时测定腹水和血清CA125, 腹水CA125显著高于血清CA125 (460±234 kU/L vs 198±108 kU/L, P = 0.0 005), 二者之间显著相关(r = 0.58, P = 0.026, 见图1).

图1
图1 血清CA125与腹水CA125的相关.
3 讨论

本研究显示, 87%的肝硬化患者血清CA125异常升高, 有腹水的患者高达95%. 我们还发现, 肝硬化患者血清CA125的升高与腹水的存在相关, 而与肝硬化的病因、腹水的原因以及良恶性无关. 肝硬化患者血清CA125升高的具体机制尚不清楚, 肝硬化时常伴肝功能不全, 结果导致肝脏对血清CA125的清除能力下降, 可能成为血清CA125异常升高的原因之一. 本研究中有38%的无腹水的肝硬化患者血清CA125异常升高, 而且血清CA125水平与Child-Pugh分级轻度相关, 均支持此假说. 但另一方面, 肝硬化患者伴腹水时血清CA125异常发生率和异常水平显著高于无腹水患者; 肝硬化患者血清CA125水平低于腹水, 与腹水CA125呈正相关. 我们曾对3例大量腹水的肝硬化患者进行腹水穿刺, 同时检测穿刺前后的血清CA125的变化, 发现腹水穿刺后, 血清CA125的水平有明显下降. 肝硬化患者血清CA125的水平随腹水的长消而增减, 腹水完全消退后, 血清CA125也恢复正常[16]. 以上结果均支持血清CA125可能来源于腹水. 免疫组化研究发现腹膜间皮细胞CA125呈现高表达[17-19], 因此, 腹水可能刺激腹膜, 使其产生CA125增加, 通过腹膜屏障, 以一定的比例吸收进入血循环, 引起血清CA125升高.

各种原因的腹水均可导致血清CA125升高, 而与腹水的良恶性无关. 良恶性腹水的患者之间血清CA125水平并无差异, 而且结核性腹水、心功能不全以及创伤造成的腹水患者血清CA125同样明显增加[20-24], 因此, 血清CA125的异常升高并不一定提示恶性肿瘤, 尤其是在肝硬化患者. 传统认为血清CA125是一种妇科肿瘤标记物, 因此, 肝硬化腹水尤其是女性患者, 血清 CA125的异常升高会误导临床诊断, 有时甚至会造成不必要的剖腹探查. 我们的研究发现, 如果在检测CA125的同时检测其他几种肿瘤标记物, 如CEA、AFP和CA19-9等, 则很容易区分良恶性腹水. 血清CA125单项异常常提示良性腹水, 而恶性腹水常伴有其他更特异性的肿瘤标记物的异常.

此外, 考虑到肝硬化患者血清CA125的升高与腹水有关, 并且血清CA125的升高早于腹水的出现, 故有学者认为血清CA125的升高可预测腹水的发生, 其敏感性甚至高于B超[16], 提示血清CA125有可能成为监测肝硬化患者腹水消长的一项有用指标.

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