合并代谢功能障碍的慢性HBV感染者的临床管理

羊璐萍; 施军平

doi:10.12449/JCH240304

合并代谢功能障碍的慢性HBV感染者的临床管理

DOI: 10.12449/JCH240304

羊璐萍¹,
施军平^2, , ,

1.
浙江中医药大学第四临床医学院，杭州 310053
2.
杭州师范大学附属医院感染与肝病科，杭州 310015

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：羊璐萍负责查阅及分析文献，撰写论文；施军平负责论文修改及指导撰写，并最终定稿。

详细信息

通信作者:
施军平， 20131004@hznu.edu.cn （ORCID： 0000-0001-9434-897X）

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出版历程
- 收稿日期: 2024-01-10
- 录用日期: 2024-02-01
- 出版日期: 2024-03-20

Clinical management of chronic hepatitis B virus infection comorbid with metabolic dysfunction

Luping YANG¹,
Junping SHI^{2
, ,
,}

1.
The Fourth Clinical Medical College of Zhejiang Chinese Medical University，Hangzhou 310053，China
2.
Department of Infectious Diseases & Hepatology，The Affiliated Hospital of Hangzhou Normal University，Hangzhou 310015，China

More Information

Corresponding author: SHI Junping， 20131004@hznu.edu.cn （ORCID： 0000-0001-9434-897X）

摘要

摘要: 随着代谢功能障碍相关疾病在全球范围内快速增长，慢性HBV感染合并代谢功能障碍的患者也逐年增加。高血糖、高血压和血脂异常等代谢功能障碍的合并存在可能会使慢性HBV感染者发生不良肝脏结局和心血管事件的风险增加，并影响抗HBV治疗的应答反应。合并代谢功能障碍的慢性HBV感染者的规范管理成为当前面临的一个挑战。进一步研究代谢功能障碍与HBV之间的相互作用以及针对性的管理策略，将有助于优化慢性HBV感染者的临床管理。
- 乙型肝炎病毒 /
- 代谢障碍 /
- 治疗学
Abstract: With the rapid growth of metabolic dysfunction （MD） worldwide， there is also a gradual increase in the number of patients with chronic hepatitis B virus （HBV） infection and MD. Comorbidity with metabolic disorders such as hyperglycemia， hypertension， and dyslipidemia may increase the risk of adverse liver outcomes and cardiovascular events in patients with chronic HBV infection and affect the response to anti-HBV therapy. The standardized management of patients with chronic HBV infection and MD has become a challenge at present， and further in-depth research on the interaction between MD and HBV and targeted management strategies will help to optimize the clinical management of patients with chronic HBV infection.
- Hepatitis B Virus /
- Metabolic Dysfunction /
- Therapeutics

HTML全文

肝细胞癌（HCC）是临床常见的恶性肿瘤之一。HCC早期治疗以手术切除为主，但侵袭性HCC的治疗策略目前选择有限，索拉非尼、仑伐替尼及程序性细胞死亡受体1及其配体免疫抑制剂治疗HCC的效果不佳，临床有效率不足30%。因此，亟需进一步探究HCC的发病机制与治疗靶点。随着基因组学研究的发展，对HCC肿瘤生物学的认识逐渐深入，但HCC的泛素化特征尚不明晰。本研究旨在揭示HCC的泛素化特征，并探寻可指导侵袭性HCC临床诊断和治疗的潜在生物标志物。

陆军军医大学第一附属医院（重庆西南医院）谢传明教授、张雷达教授与重庆医科大学侯宇教授等通过对85例HCC患者肿瘤及相邻正常肝组织进行蛋白质组学、磷酸化修饰组学和泛素化修饰组学测序与分析发现，COL4A1、LAMC1和LAMA4在无病生存期较差患者中高表达。磷酸化与泛素化修饰在代谢和转移相关信号通路中存在关联。利用泛素化组学和蛋白质组学数据对HCC进行分子分型，发现具有不同临床特征的3个亚型：S-‍Ⅰ、S-‍Ⅱ和S-Ⅲ。S-‍Ⅰ亚型以代谢相关蛋白高表达为特征，预后最好；S-Ⅲ亚型与增殖/转移信号通路密切相关，预后最差，表现为总生存期最短和复发率最高；而S-‍Ⅱ亚型则介于两者之间。研究发现，生物标志物TUBA1A、BHMT2、BHMT和ACY1的表达表现出不同的泛素化水平，与HCC患者预后不良密切相关，表明靶向这些蛋白质或其泛素化修饰蛋白可能对临床治疗有益。此外，研究证实TUBA1A K370去泛素化可驱动HCC发生与转移，这主要归因于AKT介导的USP14激活。TUBA1A K370去泛素化标志着一类高侵袭性HCC亚型。值得注意的是，靶向AKT-USP14-TUBA1A复合物可促进TUBA1A降解，并在体内阻断HCC发生。

总之，本研究从泛素化组学、磷酸化组学和蛋白质组学角度对HCC进行了全面的整合分析，该研究不仅加深了对HCC中泛素化特征的了解，并为开发新的HCC生物标志物和潜在的治疗靶点提供了依据。

摘译自LIN XT, LUO YD, MAO C, et al. Integrated ubiquitomics characterization of hepatocellular carcinomas[J]. Hepatology, 2024. DOI: 10.1097/HEP.0000000000001096. [Online ahead of print]

(陆军军医大学第一附属医院肝胆外科谢传明报道）

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