病毒性肝炎 Open Access
Copyright ©The Author(s) 2003. Published by Baishideng Publishing Group Inc. All rights reserved.
世界华人消化杂志. 2003-07-15; 11(7): 963-965
在线出版日期: 2003-07-15. doi: 10.11569/wcjd.v11.i7.963
乙型肝炎肝纤维化及癌变时脾脏超声影像, HBV e系统及APF水平
柯伟民, 林国莉, 叶一农, 赖箐, 李建国
柯伟民, 林国莉, 叶一农, 赖箐, 李建国, 中山大学第三附属医院传染病科广东省广州市 510630 |柯伟民, 男, 1957-09-05生, 广东省南澳县人. 1983年中山医学院本科毕业, 1988年中山医科大学临床硕士研究生毕业, 现任中山大学附属第三医院传染病科副教授, 副主任. 从事传染病学的临床医疗、教学和研究工作. 发表论文和专著30篇.
通讯作者: 柯伟民, 510630, 广东省广州市, 中山大学附属第三医院传染病科. kwmkwm@21cn.com
电话: 020-85516867-2033 传真: 020-85515940
收稿日期: 2002-11-12
修回日期: 2002-11-20
接受日期: 2002-11-28
在线出版日期: 2003-07-15

目的

探讨慢性乙型肝炎肝纤维化分期以及癌变时脾脏超声影像与HBeAg至抗-HBe自发血清转换以及甲胎蛋白水平的关系.

方法

对慢性乙型肝炎不同肝纤维化分期以及癌变时脾脏超声影像指标, HBeAg与抗-HBe的阳性率和甲胎蛋白的水平进行比较.

结果

慢性乙型肝炎肝纤维化的不同分期S1, S2, S3, S4组以及肝细胞癌组(HCC): 脾脏长径(mm)分别为104.6±13.1, 108.7±13.6, 110.5±15.4, 123.0±16.8和116.9±28.2, S4组与S1, S2或S3组比较存在差异(P<0.042-0.001). 脾脏厚度(mm)分别为35.2±6.3, 37.0±7.7, 37.8±9.6, 43.3±10.8和40.8±11.2, 仅S4组与S1组比较存在差异(P<0.017). 脾静脉内径(mm)分别为6.0±1.4, 6.5±1.4, 6.8±1.7, 7.8±1.7和 6.8±2.6, S4组与S1或S2组比较存在差异(P<0.05). HBeAg的阳性率分别为92%(23/25), 75.6%(31/41), 68.8%(22/32), 51.9%(14/27)和13.5%(5/37); 抗-HBe的阳性率分别为4%(1/25), 19.5%(8/41), 25%(8/32), 33.3%(9/27)和70.3%(26/37); HBeAg和抗-HBe的阳性率在S1-S4组和HCC组五组之间两两比较均存在差异(P<0.05). AFP的水平(μg/L)分别为11.0±6.7, 49.4±74.5, 112.1±159.0, 179.3±210.8和367.4±617.1; HCC组与S1或S2组比较, S4, S3或S2组与S1组比较存在差异(P<0.05).

结论

随着慢性乙型肝炎肝纤维化从S1至S4的逐渐加重, 脾脏的长径, 厚度和静脉内径也逐渐增大, 其中, 以脾脏的长径间接反映肝纤维化程度更为灵敏. 伴随HBeAg至抗-HBe自发血清转换率的逐步增加, AFP水平逐渐升高, 脾脏也不断增大. 乙型肝炎不同肝纤维化分期均有发生乙型肝炎相关肝细胞癌的危险.

关键词: N/A
引文著录: 柯伟民, 林国莉, 叶一农, 赖箐, 李建国. 乙型肝炎肝纤维化及癌变时脾脏超声影像, HBV e系统及APF水平. 世界华人消化杂志 2003; 11(7): 963-965
Correlation of splenic ultrasonography, HBV e system and AFP levels in hepatitis B with hepatic fibrosis and carcinogenesis
Wei-Min Ke, Guo-Li Lin, Yi-Nong Ye, Qin Lai, Jian-Guo Li
Wei-Min Ke, Guo-Li Lin, Yi-Nong Ye, Qin Lai, Jian-Guo Li, Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, Guangdong Province, China
Correspondence to: Dr.Wei-Min Ke, Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, Guangdong Province, China. kwmkwm@21cn.com
Received: November 12, 2002
Revised: November 20, 2002
Accepted: November 28, 2002
Published online: July 15, 2003

AIM

To clarify the relationship of splenic ultrasonography in liver fibrosis and carcinogenesis associated with hepatitis B, the spontaneous conversion of HBeAg to Anti-HBe and AFP level.

METHODS

The indexes of spleen ultrasonography of liver fibrosis along with carcinogenensis related with hepatitis B, positive rates of HBeAg or Anti-HBe and AFP levels were compared in different liver fibrosis stages and hepatocellular carcinoma (HCC) related with hepatitis B.

RESULTS

The lengths of spleen (mm) in stages of liver fibrosis S1, S2, S3, S4 and HCC with hepatitis B were 104.6±13.1, 108.7±13.6, 110.5±15.4, 123.0±16.8 and 116.9±28.2, respectively; differences of splenic length between group S4 and groups S1, S2 or S3 were significant statistically (P<0.05). The thicknesses of spleen (mm) in groups S1, S2, S3, S4 and HCC were 35.2±6.3, 37.0±7.7, 37.8±9.6, 43.3±10.8 and 40.811.2, respectively; difference in splenic thickness between group S4 and S1 was significant statistically (P<0.05). The widths of splenic vein (mm) in groups S1, S2, S3, S4 and HCC were 6.0±1.4, 6.5±1.4, 6.8±1.7, 7.8±1.7 and 6.82.6 respectively; there were differences among groups S4 and S1 or S2 (P<0.05) statistically. The positive rates of HBeAg were 92%(23/25), 75.6%(31/41), 68.8%(22/32), 51.9%(14/27) and 13.5%(5/37); and the positive rates of anti-HBe were 4%(1/25), 19.5%(8/41), 25%(8/32), 33.3%(9/27) and 70.3%(26/37) in group S1, S2, S3, S4 and HCC, respectively; difference between each two group among group S1, S2, S3, S4 and HCC was significant(P<0.05). The AFP levels(μg/L) were 11.0±6.7, 49.4±74.5, 112.11±59.0, 179.32±0.8 and 367.46±17.1 in group S1, S2, S3, S4 and HCC, respectively; there were differences among groups HCC and S1 or S2; S4, S3 or S2 and S1 (P<0.05), statistically.

CONCLUSION

The length and thickness of spleen and width of splenic vein were increased as the deterioration of severity of hepatic fibrosis. The length of spleen is more sensitive in indicating the severity of liver fibrosis. Both AFP level and splenic size were elevated as the increase rate of spontaneous conversion from HBeAg to anti-HBe. The risk of hepatocellular carcinoma associated with hepatitis B exists in any stages of liver fibrosis.

Key Words: N/A
0 引言

慢性乙型肝炎病毒(HBV)感染造成肝脏炎症、坏死、再生和纤维化病变的持续活动[1-4], 伴随脾脏的逐渐增大[5], 有时甚至出现癌变[6,7]. 尽管, 肝脏病理组织学检查是评价肝脏病变的金指标, 但是, 肝活检是一种创伤性的检查, 普遍应用受到限制[8,9]. 故此, 有必要弄清慢性乙型肝炎不同肝纤维化分期以及癌变时脾脏超声改变与HBeAg至抗-HBe自发血清转换以及APF水平的关系, 进一步阐明脾脏超声改变在慢性乙型肝炎及其癌变发病机制和临床诊断的作用.

1 材料和方法
1.1 材料

慢性乙型肝炎组: 125例, 男119例, 女6例, 年龄为30±8岁, 未用过拉米夫定、干扰素和胸腺素等抗病毒治疗, 并排除重叠甲、丁、丙或戊型肝炎病毒感染, 去除抗病毒治疗[10-14]以及重叠感染[15,16]对肝脏纤维化分期和AFP水平的影响. 每例均在彩色B型超声波仪的引导下使用自动活检装置切割活检肝组织, 肝活检标本用40 g/L甲醛固定, 石蜡切片, HE染色及网状纤维染色, 进行肝纤维化分期[17,18]. 乙型肝炎病原学诊断和肝纤维化分期标准根据文献[19]进行. 乙型肝炎相关肝细胞癌组: 37例, 男35例, 女2例, 年龄48±18岁, 也无拉米夫定、干扰素和胸腺素等抗病毒药物的使用史, HBsAg阳性, 经手术获得病理标本, 经病理组织学检查诊断为肝细胞癌.

1.2 方法

血清AFP: 采用放射免疫法测定, 试剂盒由潍达3V公司提供, 检测方法按照说明书进行. 血清甲、乙、丙、丁和戊型肝炎病毒标志物: 采用国内或合资厂家的商品化试剂, 用酶联免疫黏附试验方法检测, 血清采集与贮存, 检测程序和结果测定按照产品说明书的要求进行. 脾脏超声检查: 使用BIOSOUD AU4彩色多普勒超声诊断仪, 探头3.5MHz测量脾脏的长径、厚度和脾静脉的内径.

统计学处理应用统计软件SPSS 10.0版, 使用Dunnett T3方差检验对不同纤维化分期及癌变时脾脏超声改变和AFP水平进行两两比较; 使用多组之间χ2检验对不同纤维化分期及癌变时HBV e系统进行两两比较.

2 结果

乙型肝炎肝纤维化及癌变时脾脏超声改变, HBV e系统及APF水平见表1. 乙型肝炎肝纤维化分期及癌变时脾脏超声改变, HBV e系统及AFP水平两两比较的统计学分析结果见表2.

表1 乙型肝炎肝纤维化及癌变时脾脏超声改变, HBV e系统及APF水平.
参数S1(25)S2(41)S3(32)S4(27)HCC(37)
脾脏长径(mm)104.6±13.1108.7±13.6110.5±15.4123.0±16.8116.9±28.2
脾脏厚度(mm)35.2±6.337.0±7.737.8±9.643.3±10.840.8±11.2
脾静脉内径(mm)6.0±1.46.5±1.46.8±1.77.8±1.76.8±2.6
HBeAg(+)抗-HBe(-)92%(23/25)75.6%(31/41)68.8%(22/32)51.9%(14/27)13.5%(5/37)
HBeAg(-)抗-HBe(-)4%(1/25)4.9%(2/41)6.3%(2/32)14.8%(4/27)16.2%(6/37)
HBeAg(-)抗-HBe(+)4%(1/25)19.5%(8/41)25%(8/32)33.3%(9/27)70.3%(26/37)
AFP(μg/L)11.0±6.749.4±74.5112.1±159.0179.3±210.8367.4±617.1
表2 乙型肝炎肝纤维化分期及癌变时脾脏超声改变, HBV e系统以及AFP水平两两比较.
脾脏长径脾脏厚度脾静脉内径HBeAg(+) 抗-HBe(-)HBeAg(-)抗-HBe(+)AFP
S1与S20.9250.9700.827<0.05<0.050.021
S1与S30.7310.9060.339<0.05<0.050.011
S1与S40.0010.0170.001<0.05<0.050.003
S1与HCC0.2190.1250.622<0.05<0.050.008
S2与S31.0001.0000.984<0.05<0.050.335
S2与S40.0050.1070.020<0.05<0.050.042
S2与HCC0.6750.5550.997<0.05<0.050.026
S3与S40.0420.3630.325<0.05<0.050.844
S3与HCC0.9230.9141.000<0.05<0.050.152
S4与HCC0.9570.9910.608<0.05<0.050.581
3 讨论

部分急性乙型肝炎病变迁延超过6 mo转变为慢性乙型肝炎, 引起肝脏纤维化进展以及门静脉压力的逐渐升高[20,21]; 加上肝脏Kupffer细胞对来自门脉系统抗原处理能力下降促使免疫系统增生, 共同导致肝纤维化从S1至S4逐步发展, 脾脏的长径, 厚度和脾静脉内径逐渐增大(见表1). 脾脏的长径在S4与S1, S2或S3的比较均有统计学差异(P<0.042-0.001), 比脾脏的厚度和脾静脉的内径反映肝纤维化更为敏感. 一般认为, 乙型肝炎肝硬化比慢性乙型肝炎更容易并发肝细胞癌, HBV可通过基因的整合[22]、HBx反式激活[23,24]、转化生长因子α或抑癌基因P53的变异[25,26]等机制引起癌变. 但是, HCC组脾脏的长径, 厚度和脾静脉内径均大于S1, S2和S3组而小于S4组, 与S1-S4四组之间比较均无统计差异, 说明乙型肝炎相关HCC的发病启动机制复杂[27,28], 在慢性乙型肝炎不同分期均有发生HCC的可能.

肝纤维化从S1组至S4组, 再到HCC组, HBeAg阳性率逐步下降, 反而, 抗-HBe阳性率逐步升高, AFP的水平也逐渐升高. 统计学分析(见表2)HBV e系统状态各组之间的两两比较均存在差异(P<0.05); AFP水平在S1组与S2, S3, S4或 HCC组, S2与S4或HCC组之间的比较存在差异(P<0.042-0.003). 本组162例患者均没有拉米夫定、干扰素和胸腺素等抗病毒药物的使用史, 并且排除重叠甲、丙、丁或戊型肝炎的重叠感染, 在机体慢性免疫清除压力下, HBV前C区出现变异, 逐渐出现HBeAg的自发血清转换, 导致HBeAg阳性率逐步下降和抗-HBe阳性率逐步升高, 伴随肝脏的炎症、坏死、再生和纤维生成的累积, 造成脾脏进行性增大, APF水平逐步升高, 肝纤维化不断发展, 有时甚至发生癌变.

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