吸烟与乙型肝炎病毒相关的肝细胞癌风险：病毒载量和丙氨

StephenW

Hepatology. 2018 Nov 1. doi: 10.1002/hep.30339. [Epub ahead of print]
Smoking and Hepatitis B Virus-Related Hepatocellular Carcinoma Risk: The Mediating Roles of Viral Load and Alanine Aminotransferase.
Wang YH1,2, Chuang YH3, Wu CF1, Jan MC1,4, Wu WJ1, Lin CL5, Liu CJ6, Yang YC3, Chen PJ6, Lin SM7, Tsai MH8, Huang YW9, Yu MW1.
Author information

1
    Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
2
    Medical Research Center, Cardinal Tien Hospital and School of Medicine, College of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan.
3
    Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan.
4
    Department of Laboratory Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
5
    Department of Gastroenterology, Ren-Ai Branch, Taipei City Hospital, Taipei, Taiwan.
6
    Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital and Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
7
    Division of Hepatology, Liver Research Unit, Department of Gastroenterology and Hepatology, College of Medicine, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan.
8
    Institute of Biotechnology, National Taiwan University, Taipei, Taiwan.
9
    Division of Gastroenterology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.

Abstract

Smoking interacts with hepatitis B virus (HBV) to increase risk of hepatocellular carcinoma (HCC) that might be explained by its role in antiviral immunity. We aimed to evaluate the potential mediating role of viral load and/or alanine aminotransferase (ALT) in the relation of smoking with HBV-associated HCC risk. Using multiple mediation analyses to analyze data from 209 HCC cases and 1256 controls nested within a cohort of 4841 male HBV carriers, we found that the effect of smoking on the risk of subsequent HCC was substantially mediated through viral load (percent mediated= 31.7%; P=0.0054), and a significant mediation effect by both viral load and ALT was also evidenced. Among the 1143 subjects with repeated measures of viral load and ALT over periods of up to 16 years, we further observed that higher pack-years of smoking was associated with higher viral load, maintenance of a high viral load (>4.39 log copies/mL), severer hepatotoxicity grades, and increased likelihood of ALT ≥80 U/L (odds ratio [95% CI]: 3.14 [1.03-9.64] and 6.06 [1.10-33.25], respectively, for 10-19 and ≥20 pack-years vs. nonsmokers) during follow-up. Furthermore, plasma interferon-γ levels were reduced in smokers compared with nonsmokers (interferon-γ-positive rate: 14.9% vs. 28.7%, P<0.0001) at baseline. Smoking was also associated with a reduced natural killer (NK) cell frequency in peripheral blood, characterized by reduced NK function through a systems immunology approach, after long-term follow-up in a subsample (N=171). The combination of smoking and reduced NK cell frequency further increased viral load and the likelihood of occurring ALT ≥80 U/L. Conclusion The data highlight a role of smoking on HBV viral load, underlining the importance of smoking prevention and cessation in hepatitis B management. This article is protected by copyright. All rights reserved.
KEYWORDS:

longitudinal study; mediation analysis; natural killer cells; plasma interferon-γ levels; transcriptome

PMID:
    30382583
DOI:
    10.1002/hep.30339

StephenW

肝病。 2018年11月1日：doi：10.1002 / hep.30339。 [提前打印]
吸烟与乙型肝炎病毒相关的肝细胞癌风险：病毒载量和丙氨酸氨基转移酶的中介作用。
Wang YH1,2，Chuang YH3，Wu CF1，Jan MC1,4，Wu WJ1，Lin CL5，Liu CJ6，Yang YC3，Chen PJ6，Lin SM7，Tsai MH8，Huang YW9，Yu MW1。
作者信息

1
    台湾台北大学公共卫生学院流行病学与预防医学研究生院。
2
    台湾新北市辅仁大学医学院医学研究中心，红衣主教医院和医学院。
3
    台湾台北大学医学院临床检验科学与医学生物技术系。
4
    台湾桃园长庚纪念医院检验科
五
    台北市台北市医院仁爱分院消化内科
6
    台湾大学医学院国立台湾大学医院内科，消化内科，台湾台北大学医学院临床医学研究所。
7
    台湾桃园长庚纪念医院和长庚大学医学院肝病研究室，肝病研究室，肝病研究室。
8
    台湾大学台湾大学生物技术研究所。
9
    台北医科大学医学院医学院内科，消化内科，台湾台北

抽象

吸烟与乙型肝炎病毒（HBV）相互作用可增加肝细胞癌（HCC）的风险，这可能是由于其在抗病毒免疫中的作用所致。我们的目的是评估病毒载量和/或丙氨酸氨基转移酶（ALT）在吸烟与HBV相关HCC风险之间的关系中的潜在中介作用。使用多个中介分析来分析来自209个HCC病例的数据和嵌套在4841个男性HBV携带者队列中的1256个对照，我们发现吸烟对后续HCC风险的影响基本上是通过病毒载量介导的（介导百分比= 31.7％; P = 0.0054），并且还证明了病毒载量和ALT的显着中介作用。在重复测量病毒载量和ALT超过16年的1143名受试者中，我们进一步观察到，较高的包年吸烟与较高的病毒载量相关，维持较高的病毒载量（> 4.39 log copies / mL） ），更严重的肝毒性等级，ALT≥80U/ L的可能性增加（比值比[95％CI]：3.14 [1.03-9.64]和6.06 [1.10-33.25]，分别为10-19和≥20包 - 在随访期间，与非吸烟者相比。此外，与非吸烟者相比，吸烟者血浆干扰素-γ水平降低（干扰素-γ阳性率：14.9％对比28.7％，P <0.0001）。吸烟还与外周血中自然杀伤（NK）细胞频率降低相关，其特征是通过系统免疫学方法降低NK功能，在子样本中长期随访（N = 171）。吸烟和NK细胞频率降低的组合进一步增加了病毒载量和ALT≥80U/ L的可能性。结论数据突出了吸烟对HBV病毒载量的作用，强调了吸烟预防和戒烟对乙型肝炎管理的重要性。本文受版权保护。版权所有。
关键词：

纵向研究;调解分析;自然杀伤细胞;血浆干扰素-γ水平;转录

结论：
    30382583
DOI：
    10.1002 / hep.30339

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