Plasma Adiponectin Levels in Relation to Chronic Hepatitis B Infection Progression to Liver Cancer Milestones: A Prospective Study.

IF 9.1 1区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Liver Cancer Pub Date : 2024-06-21 eCollection Date: 2025-03-01 DOI:10.1159/000539909

Chi-Ling Chen, Wei-Shiung Yang, Hwai-I Yang, Chuen-Fei Chen, Li-Yu Wang, Sheng-Nan Lu, Jia-Horng Kao, Pei-Jer Chen, Chien-Jen Chen

{"title":"Plasma Adiponectin Levels in Relation to Chronic Hepatitis B Infection Progression to Liver Cancer Milestones: A Prospective Study.","authors":"Chi-Ling Chen, Wei-Shiung Yang, Hwai-I Yang, Chuen-Fei Chen, Li-Yu Wang, Sheng-Nan Lu, Jia-Horng Kao, Pei-Jer Chen, Chien-Jen Chen","doi":"10.1159/000539909","DOIUrl":null,"url":null,"abstract":"Introduction: Our previous nested-case-control study demonstrated elevated adiponectin increased liver cirrhosis and HCC risk in HBV carriers. We extended the analysis to the whole REVEAL-HBV cohort to prospectively evaluate whether adiponectin directly affected end-stage liver diseases, or through affecting HBV progression.Methods: Baseline plasma adiponectin was determined to investigate the association between adiponectin and subsequent HBeAg, HBsAg, and HBV DNA seroclearance, and the development of cirrhosis, HCC and liver-related death. Whether HBV characteristics modify the adiponectin-milestones associations was also examined.Results: Among 3,931 HBsAg(+)/anti-HCV(-) REVEAL-HBV participants, 3,684 had sufficient biosamples left for adiponectin assay. Elevated adiponectin was associated with a higher chance of HBeAg-seropositive, high HBV viral load (≥2 × 105 IU/mL) and high HBsAg titers (≥1,000 IU/mL) in a dose-response manner (OR = 2.25, 95% CI: 1.55-3.28; OR = 2.11, 95% CI: 1.47-3.04; and OR = 1.92, 95% CI: 1.47-2.52 for Q5 vs. Q1, respectively). Those with the highest quintile had a lower chance of achieving HBeAg (HR = 0.48, 95% CI: 0.27-0.85), HBsAg (HR = 0.69, 95% CI: 0.49-0.97), and HBV DNA seroclearance (HR = 0.63, 95% CI: 0.43-0.90) and a higher chance of developing liver cirrhosis (HR = 2.88, 95% CI: 1.98-4.20, HCC (HR = 2.38, 95% CI: 1.52-3.73), and died from liver-related causes (HR = 2.32, 95% CI: 1.51-3.54). HBV genotype significantly modified the adiponectin-HCC (Pinteraction = 0.005) and adiponectin-liver death associations (Pinteraction = 0.0157), with higher risk among genotype C.Conclusion: Elevated adiponectin is consistently associated with all important chronic HBV infection milestones toward progression to liver cancer. The exact mechanism of how adiponectin mediates HBV infection toward carcinogenesis remains unclear and warrants further investigation. Disentangling this may help us in finding new HBV treatment target, biomarker in HBV surveillance to identify high-risk patients, or even cancer prevention.","PeriodicalId":18156,"journal":{"name":"Liver Cancer","volume":"14 1","pages":"19-35"},"PeriodicalIF":9.1000,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11936446/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Liver Cancer","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1159/000539909","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/3/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Introduction: Our previous nested-case-control study demonstrated elevated adiponectin increased liver cirrhosis and HCC risk in HBV carriers. We extended the analysis to the whole REVEAL-HBV cohort to prospectively evaluate whether adiponectin directly affected end-stage liver diseases, or through affecting HBV progression.

Methods: Baseline plasma adiponectin was determined to investigate the association between adiponectin and subsequent HBeAg, HBsAg, and HBV DNA seroclearance, and the development of cirrhosis, HCC and liver-related death. Whether HBV characteristics modify the adiponectin-milestones associations was also examined.

Results: Among 3,931 HBsAg(+)/anti-HCV(-) REVEAL-HBV participants, 3,684 had sufficient biosamples left for adiponectin assay. Elevated adiponectin was associated with a higher chance of HBeAg-seropositive, high HBV viral load (≥2 × 10⁵ IU/mL) and high HBsAg titers (≥1,000 IU/mL) in a dose-response manner (OR = 2.25, 95% CI: 1.55-3.28; OR = 2.11, 95% CI: 1.47-3.04; and OR = 1.92, 95% CI: 1.47-2.52 for Q5 vs. Q1, respectively). Those with the highest quintile had a lower chance of achieving HBeAg (HR = 0.48, 95% CI: 0.27-0.85), HBsAg (HR = 0.69, 95% CI: 0.49-0.97), and HBV DNA seroclearance (HR = 0.63, 95% CI: 0.43-0.90) and a higher chance of developing liver cirrhosis (HR = 2.88, 95% CI: 1.98-4.20, HCC (HR = 2.38, 95% CI: 1.52-3.73), and died from liver-related causes (HR = 2.32, 95% CI: 1.51-3.54). HBV genotype significantly modified the adiponectin-HCC (P_interaction = 0.005) and adiponectin-liver death associations (P_interaction = 0.0157), with higher risk among genotype C.

Conclusion: Elevated adiponectin is consistently associated with all important chronic HBV infection milestones toward progression to liver cancer. The exact mechanism of how adiponectin mediates HBV infection toward carcinogenesis remains unclear and warrants further investigation. Disentangling this may help us in finding new HBV treatment target, biomarker in HBV surveillance to identify high-risk patients, or even cancer prevention.

查看原文本刊更多论文

血浆脂联素水平与慢性乙型肝炎感染进展到肝癌里程碑的关系：一项前瞻性研究。

我们之前的巢式病例对照研究表明，脂联素升高会增加HBV携带者肝硬化和HCC的风险。我们将分析扩展到整个REVEAL-HBV队列，以前瞻性评估脂联素是否直接影响终末期肝病，或通过影响HBV进展。方法：测定基线血浆脂联素，探讨脂联素与随后的HBeAg、HBsAg和HBV DNA血清清除率以及肝硬化、HCC和肝脏相关性死亡的关系。是否HBV特征改变脂联素里程碑关联也被检查。结果：在3,931名HBsAg(+)/anti-HCV(-) REVEAL-HBV参与者中，3,684人有足够的生物样本用于脂联素检测。脂联素升高与hbeag -血清阳性、高HBV病毒载量（≥2 × 105 IU/mL）和高HBsAg滴度（≥1000 IU/mL）的发生率呈剂量-反应方式相关(OR = 2.25, 95% CI: 1.55-3.28；Or = 2.11, 95% ci: 1.47-3.04；OR = 1.92, 95% CI: 1.47-2.52 （Q5 vs. Q1）。最高五分位数的患者实现HBeAg （HR = 0.48, 95% CI: 0.27-0.85）、HBsAg （HR = 0.69, 95% CI: 0.49-0.97）和HBV DNA血清清除率（HR = 0.63, 95% CI: 0.43-0.90）的几率较低，发生肝硬化(HR = 2.88, 95% CI: 1.98-4.20, HCC （HR = 2.38, 95% CI: 1.52-3.73）的几率较高，并死于肝脏相关原因（HR = 2.32, 95% CI: 1.51-3.54）。HBV基因型显著改变了脂联素- hcc （p相互作用= 0.005）和脂联素-肝死亡相关性（p相互作用= 0.0157），其中基因型c的风险更高。结论：脂联素升高与所有重要的慢性HBV感染进展为肝癌的里程碑一致相关。脂联素介导HBV感染致癌变的确切机制尚不清楚，值得进一步研究。解开这一谜团可能有助于我们寻找新的HBV治疗靶点，HBV监测中的生物标志物，以识别高危患者，甚至预防癌症。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Liver Cancer Medicine-Oncology

CiteScore

20.80

自引率

7.20%

发文量

审稿时长

16 weeks

期刊介绍： Liver Cancer is a journal that serves the international community of researchers and clinicians by providing a platform for research results related to the causes, mechanisms, and therapy of liver cancer. It focuses on molecular carcinogenesis, prevention, surveillance, diagnosis, and treatment, including molecular targeted therapy. The journal publishes clinical and translational research in the field of liver cancer in both humans and experimental models. It publishes original and review articles and has an Impact Factor of 13.8. The journal is indexed and abstracted in various platforms including PubMed, PubMed Central, Web of Science, Science Citation Index, Science Citation Index Expanded, Google Scholar, DOAJ, Chemical Abstracts Service, Scopus, Embase, Pathway Studio, and WorldCat.