AASLD2020[808]回顾HBEAG状态对抗病毒药的影响 肝细胞癌的风险治

StephenW

808
REVISITING THE IMPACT OF HBEAG-STATUS OF ANTIVIRAL
TREATMENT ON RISK OF HEPATOCELLULAR CARCINOMA
DEVELOPMENT: A NATIONWIDE MULTICENTER STUDY
Heejoon Jang1, Jun Sik Yoon2, Hwi Young Kim3, Soo Young
Park4, Seung Up Kim5, Dong Hyun Sinn6, Yeon Seok Seo7,
Han Ah Lee8, Sung Eun Kim9, Dae Won Jun10, Eileen Yoon11,
Joo Hyun Sohn12, Sang Bong Ahn13, Jae-Jun Shim14, Soung
Won Jeong15, Yong Kyun Cho16, Hyoung Su Kim17, Yun Bin
Lee1, Eun Ju Cho1, Su Jong Yu1, Yoon Jun Kim18, Jung-Hwan
Yoon1 and Jeong-Hoon Lee19, (1)Department of Internal
Medicine and Liver Research Institute, Seoul National
University Hospital, (2)Department of Internal Medicine, Busan
Paik Hospital, Inje University College of Medicine, Busan,
Korea;, (3)Department of Internal Medicine, Ewha Womans
University College of Medicine, (4)Department of Internal
Medicine, Kyungpook National University Hospital, Daegu,
Republic of Korea, (5)Department of Internal Medicine, Yonsei
University College of Medicine, Seoul, Republic of Korea, (6)
Department of Internal Medicine, Samsung Medical Center,
Sungkyunkwan University School of Medicine, Seoul, Korea,
(7)Internal Medicine, Korea University College of Medicine,
(8)Department of Internal Medicine, Korea University College
of Medicine, (9)Department of Internal Medicine, Hallym
University Sacred Heart Hospital, (10)Department of Internal
Medicine, Hanyang University Hospital, Hanyang University
College of Medicine, (11)Department of Internal Medicine,
Sanggye Paik Hospital, Inje University College of Medicine,
(12)Department of Internal Medicine, Hanyang University,
College of Medicine, Guri Hospital, (13)Department of
Internal Medicine, Eulji University School of Medicine, (14)
Kyung Hee University Hospital, (15)Department of Internal
Medicine, College of Medicine, Soonchunhyang University,
(16)Kangbuk Samsung Hospital, Sungkyunkwan University
School of Medicine, (17)Department of Internal Medicine,
Kangdong Sacred Heart Hospital, Hallym University College
of Medicine, (18)Department of Internal Medicine and Liver
Research Institute, Seoul National University Hospital, Seoul,
Republic of Korea, (19)Department of Internal Medicine and
Liver Research Institute, Seoul National University College of
Medicine, Seoul, Korea
Background: Recent studies indicate that the integration of
hepatitis B virus (HBV) into host genome, which may directly
develop hepatocellular carcinoma (HCC), occurs during HBV
envelope antigen (HBeAg)-positive phase of chronic hepatitis
B (CHB) This study aimed to investigate whether early
antiviral treatment from HBeAg-positive phase is associated
with lower risk of HCC Methods: We performed a multicenter
study involving consecutive CHB patients who treated with
entecavir or tenofovir for >6 months in Korea. The primary
endpoint was development of HCC Baseline characteristics
were adjusted or balanced by combination of three methods:
multivariable Cox analyses, propensity score matching
(PSM), and inverse probability of treatment weighting (IPTW)
Results: A total of 9,143 patients (mean age=49 2 years,
male=60 3%) were included: 4,492 (49 1%) were HBeAgpositive
at baseline The prevalence of cirrhosis was 49 2%
During median 5 1 years (interquartile range, 3 1–6 8 years)
of follow-up, 916 patients (10 0%) developed HCC Baseline
HBeAg-positivity was not associated with HCC risk in the entire
cohort (adjusted hazard ratio [aHR]=1.00, 95% confidence
interval [CI]=0 87–1 15; P=0 97) or in the cirrhotic subcohort
(n=4,499; aHR=1 10, 95% CI=0 95–1 26; P=0 21) However,
in the non-cirrhotic subcohort (n=4,644), baseline HBeAgpositivity
was an independent negative-risk factor of HCC
development (aHR=0 46, 95% CI=0 29–0 72; P<0 001) after
adjustment for confounding variables including sex, age, and
fibrosis grade (by FIB-4 score). This result within non-cirrhotic
subcohort was maintained in both PSM (aHR=0 52, 95%
CI=0 31–0 86; P=0 01) and IPTW analyses (aHR=0 48, 95%
CI=0 30–0 75; P=0 001) Conclusion: This large nationwide
cohort study implicates that an earlier antiviral treatment
before spontaneous HBeAg-seroclearance might reduce the
risk of HCC occurrence more profoundly independent of age
and fibrosis in non-cirrhotic CHB patients.

StephenW

808
回顾HBEAG状态对抗病毒药的影响
肝细胞癌的风险治疗
发展：全国多中心研究
Heejoon Jang1，Jun Sik Yoon2，Hwi Young Kim3，Soo Young
Park4，Seung Up Kim5，Dong Hyun Sinn6，Yen Seok Seo7，
韩亚利8，成恩金9，大元俊10，艾琳允11，
Joo Hyun Sohn12，Sang Bong Ahn13，Jae-Jun Shim14，宋
元正15，容坤祖16，孝素金17，允彬
Lee1，Eun Ju Cho1，Su Jong Yu1，Yoon Jun Kim18，郑焕
Yoon1和Lee Jeong-Hoon19，（1）内部部门
首尔国立医学与肝脏研究所
釜山大学医院（2）内科
釜山仁济大学医学院白克医院
韩国；（3）梨花女子内科
大学医学院，（4）内部系
大邱庆北国立大学医院医学
大韩民国（5）延世市内科
大韩民国首尔大学医学院（6）
三星医疗中心内科
成均馆大学医学院，韩国首尔
（7）高丽大学医学院内科，
（8）高丽大学学院内科
医学（9）哈里姆内科
大学圣心医院，（10）内科
汉阳大学汉阳大学医院医学
医学院，（11）内科，
仁济大学医学院Sanggye Paik医院
（12）汉阳大学内科
九里医院医学院，（13）
乙支大学医学院内科，（14）
庆熙大学医院（15）内科
淳春市大学医学院医学部，
（16）成均馆大学江北三星医院
医学院，（17）内科，
哈林大学学院康东圣心医院
医学部（18）内科学与肝脏学系
首尔国立首尔大学医院研究所
大韩民国（19）内科与内科
首尔国立大学医学院肝脏研究所
医药，首尔，韩国
背景：最近的研究表明
乙型肝炎病毒（HBV）进入宿主基因组，可能直接
发生肝细胞癌（HCC），在HBV期间发生
慢性肝炎的包膜抗原（HBeAg）阳性阶段
B（CHB）本研究旨在调查是否早期
HBeAg阳性阶段的抗病毒治疗相关
肝癌风险较低的方法：我们进行了多中心
连续CHB患者接受治疗的研究
恩替卡韦或替诺福韦在韩国使用超过6个月。首要的
终点是肝癌基线特征的发展
通过以下三种方法进行调整或平衡：
多变量Cox分析，倾向得分匹配
（PSM）和治疗加权的逆概率（IPTW）
结果：总共9,143例患者（平均年龄= 49 2岁，
男性= 60 3％）包括在内：4,492（49 1％）是HBe阳性
基线时肝硬化的患病率为49 2％
在中位数5 1年（四分位数范围，3 1–6 8年）
随访的916例患者（10 0％）形成了HCC基线
整个过程中，HBeAg阳性与肝癌风险无关
队列（调整后的危险比[aHR] = 1.00，置信度为95％
间隔[CI] = 0 87–1 15; P = 0 97）或在肝硬化亚人群中
（n = 4,499； aHR = 1 10，95％CI = 0 95–1 26； P = 0 21），但是，
在非肝硬化亚人群（n = 4,644）中，基线HBe阳性
是肝癌的独立负风险因素
（aHR = 0 46，95％CI = 0 29-0 72; P <0 001）
调整混杂变量，包括性别，年龄和
纤维化等级（按FIB-4评分）。非肝硬化内的这一结果
在两个PSM中均维持亚队列（aHR = 0 52，95％
CI = 0 31–0 86； P = 0 01）和IPTW分析（aHR = 0 48，95％
CI = 0 30–0 75； P = 0 001）结论：全国范围较大
队列研究表明较早的抗病毒治疗
自发性HBeAg血清清除可能会降低
肝癌发生的风险与年龄无关
和非肝硬化性CHB患者的纤维化。