HBsAg血清清除后发展为肝细胞癌的患者肝内HBV DNA整合的持久

StephenW

Persistence of intrahepatic HBV DNA integration in patients developing hepatocellular carcinoma after HBsAg seroclearance
Jeong Won Jang  1   2 , Jin Seoub Kim  1   2 , Hye Seon Kim  1   2 , Kwon Yong Tak  1   2 , Heechul Nam  1   2 , Pil Soo Sung  1   2 , Si Hyun Bae  1   2 , Jong Young Choi  1   2 , Seung Kew Yoon  1   2 , Lewis R Roberts  3
Affiliations
Affiliations

    1
    Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
    2
    The Catholic University Liver Research Center, USA.
    3
    Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA.

    PMID: 33317255 DOI: 10.3350/cmh.2020.0115

Abstract

Background/aim: The role of hepatitis B virus (HBV) integration into the host genome in hepatocarcinogenesis following HBsAg seroclearance remains unknown. The aim of our study was to investigate and characterize HBV integration events in patients with chronic hepatitis B (CHB) who developed hepatocellular carcinoma (HCC) after HBsAg seroclearance.

Methods: Using probe-based HBV capturing followed by next generation sequencing technology, HBV integration was examined in 10 samples (seven HCC tumors and three nontumor tissues) from 7 chronic carriers who developed HCC after HBsAg loss. Genomic locations and patterns of HBV integration were investigated.

Results: HBV integration was observed in six (85.7%) patients and 8 (80.0%) of 10 tested samples. HBV integration breakpoints were detected in all of the non-tumor (3/3, 100%) and five of the seven (71.4%) tumor samples, with an average number of breakpoints of 4.00 and 2.43, respectively. Despite the lower total number of tumoral integration breakpoints, HBV integration sites in the tumors were more enriched within the genic area. In contrast, non-tumor tissues more often showed intergenic integration. Regarding functions of the affected genes, tumoral genes with HBV integration were mostly associated with carcinogenesis. At enrollment, patients who did not remain under regular HCC surveillance after HBsAg seroclearance had a large HCC, while those on regular surveillance had a small HCC.

Conclusions: The biological functions of HBV integration are almost comparable between HBsAg-positive and HBsAg-serocleared HCCs, with continuing pro-oncogenic effects of HBV integration. Thus, ongoing HCC surveillance and clinical management should continue even after HBsAg seroclearance in patients with CHB.

Keywords: Cancer surveillance; HBsAg seroclearance; Hepatitis B virus; Liver cancer; Virus integration.

StephenW

HBsAg血清清除后发展为肝细胞癌的患者肝内HBV DNA整合的持久性
郑元章1 2，金世ou金1 2，惠善金1 2，权龙德1 2，Heechul Nam 1 2，P秀成1 2，施贤培1 2，钟荣彩1 2，成邱Yo 1 2，刘易斯·罗伯茨3
隶属关系
隶属关系

    1个
    大韩民国首尔天主教大学医学院内科系。
    2
    美国天主教大学肝脏研究中心。
    3
    美国明尼苏达州罗切斯特市梅奥诊所医学院，消化内科和肝病科。

    PMID：33317255 DOI：10.3350 / cmh.2020.0115

抽象

背景/目的：乙肝病毒（HBsAg）血清清除后，乙型肝炎病毒（HBV）整合入宿主基因组在肝癌发生中的作用仍然未知。我们研究的目的是调查和表征在HBsAg血清清除后发展为肝细胞癌（HCC）的慢性乙型肝炎（CHB）患者中的HBV整合事件。

方法：使用基于探针的HBV捕获技术和下一代测序技术，对来自7个在HBsAg丢失后发展为HCC的慢性携带者的10个样品（七个HCC肿瘤和三个非肿瘤组织）中的HBV整合进行了检测。研究了HBV整合的基因组位置和模式。

结果：六名（85.7％）患者和10个测试样本中的8名（80.0％）观察到HBV整合。在所有非肿瘤（3 / 3，100％）和七个（71.4％）肿瘤样品中的五个中检测到HBV整合断裂点，平均断裂点数分别为4.00和2.43。尽管肿瘤整合断裂点总数较低，但肿瘤中的HBV整合位点在基因区域内更为丰富。相反，非肿瘤组织更经常表现出基因间整合。关于受影响基因的功能，HBV整合的肿瘤基因大多与癌变有关。在入组时，HBsAg血清清除后仍未接受常规HCC监测的患者具有较大的HCC，而接受常规监测的患者则具有较小的HCC。

结论：HBV整合的生物学功能在HBsAg阳性和HBsAg血清清除的HCC之间几乎具有可比性，并具有持续的促癌作用。因此，即使在CHB患者中进行HBsAg血清清除后，仍应继续进行持续的HCC监测和临床管理。

关键字：癌症监测； HBsAg血清清除；乙型肝炎病毒;肝癌;病毒集成。

小宁想痊愈

也就是说hbsag清除后还是有肝癌风险呗，真累。hbv整合能治好吗

newchinabok

来到这世上，就没打算活着回去