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Code  ›  慢性乙型肝炎患者肝脏良性占位的发病率及其特点：基于39 450例彩色多普勒超声的病例对照研究 - PMC
癌症 占位性病变 pubmed 肝血管瘤
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6867945/
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Nan Fang Yi Ke Da Xue Xue Bao. 2019 Oct 20; 39(10): 1149–1154.
Chinese. doi: 10.12122/j.issn.1673-4254.2019.10.03
PMCID: PMC6867945
PMID: 31801719

Language: Chinese | English

慢性乙型肝炎患者肝脏良性占位的发病率及其特点：基于39 450例彩色多普勒超声的病例对照研究

Incidence and characteristics of benign liver space-occupying mass in 17 721 patients with chronic hepatitis B: a color Doppler ultrasound-based case-control study

任 彦瑜 , 1, * 袁 国盛 , 1 周 宇辰 , 2 胡 承光 , 1 刘 俊维 , 1 ANWAR Muhammad Ikram , 1 唐 淬蓉 , 1 李 园 , 1 于 文轩 , 1 周 元平 , 1, * and 戴 琳 1, *

任 彦瑜

南方医科大学南方医院感染内科，广东 广州 510515, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China

Find articles by 任 彦瑜

袁 国盛

南方医科大学南方医院感染内科，广东 广州 510515, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China

Find articles by 袁 国盛

周 宇辰

南方医科大学中西医结合医院外科，广东 广州 510315, Department of Surgery, TCM-Integrated Hospital, Southern Medical University, Guangzhou 510315, China

Find articles by 周 宇辰

胡 承光

南方医科大学南方医院感染内科，广东 广州 510515, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China

Find articles by 胡 承光

刘 俊维

南方医科大学南方医院感染内科，广东 广州 510515, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China

Find articles by 刘 俊维

ANWAR Muhammad Ikram

南方医科大学南方医院感染内科，广东 广州 510515, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China

Find articles by ANWAR Muhammad Ikram

唐 淬蓉

南方医科大学南方医院感染内科，广东 广州 510515, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China

Find articles by 唐 淬蓉

李 园

南方医科大学南方医院感染内科，广东 广州 510515, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China

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于 文轩

南方医科大学南方医院感染内科，广东 广州 510515, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China

Find articles by 于 文轩

周 元平

南方医科大学南方医院感染内科，广东 广州 510515, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China

Find articles by 周 元平

戴 琳

南方医科大学南方医院感染内科，广东 广州 510515, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China 南方医科大学南方医院感染内科，广东 广州 510515, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China 南方医科大学中西医结合医院外科，广东 广州 510315, Department of Surgery, TCM-Integrated Hospital, Southern Medical University, Guangzhou 510315, China *Fisher's exact test was used if the theoretical frequency was less than 5. Benign occupation of the liver7206 (40.6%)2712 (12.5%)4087.0260.000Hepatic cyst2098 (11.8%)1872 (8.7%)108.8610.000Hepatic hemangioma1457 (8.2%)349 (1.6%)971.3860.000Liver cirrhosis nodule3649 (20.6%)524 (2.4%)3391.6470.000Focal nodular hyperplasia1 (0.006%)9 (0.042%)-0.028*Hepatocellular adenoma1 (0.006%)0(0)-0.450*

2.3. CHB患者肝脏良性占位的特点分析

2.3.1. CHB患者中肝脏良性占位性病变的构成

在17 721例CHB患者中，有7206例发生肝脏良性占位性病变，其中肝囊肿2098例，肝血管瘤1457例，肝硬化结节3649例，FNH 1例，HCA 1例。

2.3.2. 肝脏良性占位的年龄、性别特点

将CHB患者按每10岁进行年龄分层，随着年龄的增长，肝囊肿和肝硬化结节的发病率逐渐升高，且均表现为男性高于女性（分别12.5% vs 9.2%，22.6% vs 14.2%，均 P < 0.001），肝血管瘤则呈现先升后降的趋势，30~49岁年龄段发病率最高（9.5%[1037/10 961]），男、女性发病率之间无统计学差异（ 表 2 、 3 、 图 1 ）。为排除肝血管瘤发病率的性别表现是由于各年龄层人数分布不均所造成，将肝血管瘤患者按照年龄分层发现，30~39岁年龄段的573例肝血管瘤患者中，男性的发病率高于女性（χ 2 =10.718， P =0.001， 表 3 ）。FNH与HCA病例数分别仅1例，故未对其进行分析。

2

不同年龄的CHB患者的良性占位性病变发病率

Incidence of benign liver space-occupying mass in patients with CHB at different ages

Age group (year) Hepatic cyst ( n =2098) Hepatic hemangioma ( n =1457) Liver cirrhosis nodule ( n =3649)
< 20 0.04% (1/250) 1.6% (4/1457) 2.0% (5/250)
20~ 1.9% (63/3263) 6.7% (217/3263) 4.6% (150/3263)
30~ 8.7% (519/5959) 9.6% (573/5959) 13.3% (794/5959)
40~ 15.9% (795/5002) 9.3% (464/5002) 32.2% (1310/5002)
50~ 19.5% (439/2251) 6.6% (148/2251) 39.9% (898/2251)
> 60 28.2% (281/996) 5.1% (21/996) 49.7% (492/996)
χ 2 855.455 68.707 1181.38
P 0.000 0.000 0.000

3

CHB患者良性占位性病变发病率的性别分布

Incidence of benign liver space-occupying mass male and femal patients with CHB

Gender Hepatic cyst Hepatic hemangioma Liver cirrhosis nodule Hepatic hemangioma (30〜39 year old)
Male 12.5% (1687/13468) 8.0% (1081/13468) 22.6% (3049/13468) 7.1% (421/5959)
Female 9.7% (411/4253) 8.6% (367/4253) 14.2% (600/4253) 2.6% (152/5959)
χ 2 25.370 1.565 143.871 10.718
P 0.000 0.211 0.000 0.001
An external file that holds a picture, illustration, etc. Object name is nfykdxxb-39-10-1149-1.jpg

各年龄层CHB患者的良性占位病变发病率及变化趋势

Changes in incidence of benign liver space-occupying mass with age in patients with CHB

2.4. 肝脏良性占位病变的彩超特征

2098例肝囊肿病例共检出3377个病灶，1984个位于肝右叶，1393个位于左叶，最小者直径为2 mm×2 mm，最大者为67 mm×55 mm，均表现为无回声区，伴后壁增强效应，边界清晰，形态规则。

1457例肝血管瘤病例共检出1895个病灶，1650个位于肝右叶，245个位于左叶，最小者直径为2 mm×1 mm，最大者为67 mm×48 mm，1579个表现为强回声（83.32%，1579/1895），226个为低回声（11.19%，226/1895），90个为混合回声（8.65%，90/1895），边界清楚，形态规则。彩超显示周边和内部未见血流信号者1429个（75.41%，1429/1895），点状、条块状血流信号者466个（24.59%，466/1895），固有动脉最小流速≤30 cm/s，最大流速≤ 75 cm/s，门静脉流速≥10 cm/s。

肝硬化结节9595个，最小者直径为4 mm×3 mm，最大者为49 mm × 42 mm，表现为强回声者380个（3.96%，380/9595），低回声者1372个（14.30%，1372/ 9595），等回声者144个（1.50%，144/9595），混合回声者7637个（79.60%，7637/9595），其中，31个呈现不均质回声（0.32%，31/9595），其余皆表现为内部回声均匀。彩超显示周边和内部未见血流信号者8753个（91.22%，8753/9595）。

肝血管瘤、肝囊肿、肝硬化结节，以及较少见的FNH、HCA的典型二维超声和彩超图像分别见 图 2 、 3 。

An external file that holds a picture, illustration, etc. Object name is nfykdxxb-39-10-1149-2.jpg

肝血管瘤、肝囊肿、肝硬化结节的二维超声和彩色多普勒超声图像

B model ultrasound and color Doppler flow imaging (CDFI) of hemangioma, hepatic cyst and cirrhotic nodules. A , B : Hepatic hemangioma shows homogeneous echo inside the lesion with clear boundary and regular shape with blood pool in the B mode ultrasound imaging, while presented with hyperechoic, stripy peripheral and internal blood flow signals in CDFI; C , D : Hepatic hemangioma is hypoechoic with stripy blood flow signals surrounding the lesion in CDFI; E , F : A liver cirrhosis nodules is hypoechoic with relatively homogeneous echo, clear boundary and regular shape without blood flow signal inside or around the nodule in CDFI; G , H : Hepatic cysts display no echo or blood signal inside the lesion, but the echo can be enhanced posteriorly

An external file that holds a picture, illustration, etc. Object name is nfykdxxb-39-10-1149-3.jpg

局灶性结节性增生和肝细胞腺瘤的二维超声和彩色多普勒超声图像

B mode ultrasound and CDFI images of focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA). A , B : FNH shows homogeneous echo inside the lesion with clear boundaries, a regular shape, and stripy internal blood flow signal in CDFI; C , D : HCA shows a regular shape with strong but uneven echoes and blood flow signal within the lesion in CDFI

3. 讨论

我国每年HCC的新发病例数和病死率在恶性肿瘤中居前三位，华南尤其突出 [ 3 - 4 , 15 ] 。早期诊断和及时治疗HCC，特别是小肝癌（SHCC），对提高患者生存率和生活质量有重要意义 [ 16 ] 。腹部超声因具有简单、经济、直观、快捷、无创、无辐射的综合优势，被广泛应用于HCC的早期筛查 [ 17 - 18 ] 。近年来随着CHB门诊随访的规范化和超声影像学的进步，我们在临床中观察到肝脏占位性病变的检出率明显增高，以良性者居多。然而，对中国人肝脏良性占位性病变的发病率未见文献报道。部分肝脏良性占位性病变，如肝硬化结节具有恶性转化为HCC的风险；肝血管瘤因与SHCC同样具有丰富的血供，易造成后者的漏诊、误诊。因此，识别肝脏占位性病变的性质，对于肝癌的早期诊断、早期治疗至关重要。我们对肝脏良性占位性病变的发病率与慢性乙型肝炎、性别、年龄的关系进行了分析，并归纳它们的超声影像学特征，以期为临床提供大样本的肝脏良性占位发病率的数据，为通过超声影像学鉴别其与恶性占位提供依据。

本研究调查分析发现，CHB患者的肝血管瘤、肝囊肿和肝硬化结节的发病率均高于普通人群。分析可能的原因如下：（1）HBV通过机体免疫攻击引起肝细胞损伤，加速肝脏组织退行性改变，形成肝囊肿；肝细胞不断损伤后反复再生，引起肝脏纤维化，形成肝硬化结节；（2）肝组织发生局部炎症、坏死，致使局部血液循环异常，周围血管扩张形成肝血管瘤；（3）受损的肝脏灭活雌激素的能力下降，高雌激素水平促进肝血管瘤发生 [ 19 ] 。其中，肝囊肿和肝硬化结节均多见于中、老年男性CHB患者，与既往报道基本一致 [ 5 ] ；而肝血管瘤多发于30~49岁患者，发病率无显著的性别差异，与普通人群中女性高发的特点不同 [ 20 - 21 ] ，提示CHB男性患者可能比普通男性更易发生肝血管瘤，考虑与前者的雌激素灭活能力下降有关。同时，为了排除该结果是由于各年龄层人数分布不均造成，进行年龄分层发现，30~39岁女性的肝血管瘤发病率高于男性（男:女=1:1.3， P =0.001），而该年龄段女性的内源性雌激素分泌旺盛，且怀孕、口服避孕药者较多，符合高雌激素水平促发肝血管瘤这一观点 [ 19 ] 。FNH在CHB患者中的发病率为0.02%，低于普通人群，而HCA的发病率在CHB患者与普通人群中并无明显统计学差异，两者与其他良性占位病变的不同表现，可能受超声诊断效能所限 [ 22 - 25 ] ，也可能提示HBV在FNH形成过程中起到抑制作用。

在常见的肝脏良性占位性病变中，肝硬化结节作为肝硬化进展为HCC过程中（即肝硬化再生结节-肝硬化不典型增生结节-肝细胞癌）的早期阶段 [ 26 ] ，具有一定特殊性。如果能够及时发现结节的恶变趋势，并给予监测和根治性治疗，对于降低肝癌发病率有重要意义。本研究发现：肝脏良性占位性病变具有共同的超声声像特征，即内部回声均匀，边界清晰，形态规则。其中，肝硬化结节多为混合回声（79.60%，7637/9595），亦有低回声者（14.30%，1372/9595）；内部多无肿瘤新生血管出现，与周围肝硬化组织的血流动力学表现相似，周边一般无血流信号（91.22%，8753/9595）。当再生结节向不典型增生结节转化，结节内新生血管迅速生长，造成动脉供血先减少后增加，同时门静脉供血趋于下降，因此，当肝硬化结节，特别是低回声结节增大，伴内部回声发生不均匀改变，彩超显示内部和周边血流信号增强时，提示恶变概率升高。肝血管瘤与SHCC都有丰富的血供，且发病年龄相似，故常需要对两者进行鉴别，尤其是肝血管瘤中有低回声者 [ 27 ] 。本研究发现：肝血管瘤的彩超多为高回声（83.32%，1519/1895），低回声者多数直径较大，病灶周边有带状高强回声。SHCC则表现为内部回声不均匀，边界不清，形态不规则，呈现膨胀、侵袭性生长，同时，SHCC肿块显示出更丰富的四周与内部血流信号，固有动脉的最小流速和最大流速均远高于肝血管瘤，门静脉流速低于肝血管瘤。肝囊肿的超声图像常表现为内部无回声，后方回声增强，较容易与SHCC区别。

本研究存在的不足：为单中心研究，若能进行多中心调查分析，扩大FNH和HCA患者例数，将为原发性肝癌与良性占位的鉴别提供更充足的临床证据。

综上所述，CHB患者比普通人群更易发生肝囊肿、肝血管瘤和肝硬化结节这三种良性占位性病变；肝囊肿多发于老年、男性CHB患者；肝血管瘤多发于青、中年CHB患者，特别是30~39岁女性；肝硬化结节多见于中老年、男性CHB患者。本研究归纳的肝脏良性占位的发病特点和彩超检查的声像特征，旨在为鉴别常见的肝脏良性占位性病变与小肝癌提供重要依据或进一步精准检查的线索。

Biography

•

任彦瑜，在读硕士研究生，E-mail: moc.361@228neruynay

Funding Statement

国家自然科学基金（81772923）

Supported by National Natural Science Foundation of China (81772923)

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Articles from Journal of Southern Medical University are provided here courtesy of Editorial Department of Journal of Southern Medical University
 
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