AASLD2020[21]縱向估計的真實世界研究 腎小球濾過率（EGFR）的

StephenW

21
LONGITUDINAL REAL-WORLD STUDY ON ESTIMATED
GLOMERULAR FILTRATION RATE (EGFR) CHANGES IN
ENTECAVIR (ETV) VERSUS TENOFOVIR DISOPROXIL
FUMARATE (TDF)-TREATED CHRONIC HEPATITIS B (CHB)
PATIENTS: A REAL-B STUDY
Lung Yi Mak1, Joseph Hoang2, Dae Won Jun3, Chien Hung
Chen4, Cheng-Yuan Peng5, Ming-Lun Yeh6, Sung Eun Kim7,
Jae Yoon Jeong8, Eileen Yoon9, Hyunwoo Oh10, Pei-Chien
Tsai11, Chung-Feng Huang12, Sang Bong Ahn13, Qing Xie14,
Grace Lai-Hung Wong15, Masaru Enomoto16, Huy Trinh17,
Jae-Jun Shim18, Dong Hyun Lee19, Li Liu20, Ritsuzo Kozuka16,
Yong Kyun Cho21, Soung Won Jeong22, Hyoung Su Kim23,
Rui Huang24, Rex Wan-Hin Hui1, Vivien Tsui1, Eiichi Ogawa25,
Chia-Yen Dai12, Jee-Fu Huang26, Ramsey Cheung27, Chao
Wu28, Wan-Long Chuang29, Ming-Lung Yu12, Man Fung Yuen1
and Mindie H. Nguyen30, (1)Medicine, The University of
Hong Kong, (2)Division of Gastroenterology and Hepatology,
Stanford University Medical Center, (3)Hanyang University,
(4)Division of Hepatogastroenterology, Department of Internal
Medicine, Kaohsiung Chang Gung Memorial Hospital, (5)
Division of Hepatology and Gastroenterology, Department
of Internal Medicine, China Medical University Hospital,
(6)Department of Internal Medicine, Kaohsiung Medical
University Hospital, (7)Department of Internal Medicine,
Hallym University Sacred Heart Hospital, (8)Department of
Internal Medicine, Hanyang University College of Medicine,
Guri Hospital, (9)Inje University Sanggye Paik Hospital,
(10)Department of Internal Medicine,, Hanyang University
Hospital, (11)Hepatobiliary Division, Department of Internal
Medicine, Kaohsiung Medical University Hospital, Kaohsiung
Medical University, (12)Hepatobiliary Division, Department
of Internal Medicine, Kaohsiung Medical University Hospital,
Kaohsiung Medical University, Kaohsiung, Taiwan, (13)
Department of Internal Medicine, Eulji University School
of Medicine, (14)Shanghai Jiaotong University School of
Medicine, Ruijin Hospital, China, (15)Department of Medicine
and Therapeutics, Medical Data Analytic Centre (MDAC),
Institute of Digestive Disease, The Chinese University of Hong
Kong, (16)Department of Hepatology, Osaka City University
Graduate School of Medicine, (17)San Jose Gastroenterology,
(18)Department of Internal Medicine, Kyung Hee University
Hospital, (19)Gastroenterology, Good Gang-an Hospital,
(20)Hepatology, The Third Hospital of Kumming City, (21)
Department of Internal Medicine, Sungkyunkwan University
School of Medicine, (22)Department of Internal Medicine,
College of Medicine, Soonchunhyang University, (23)Internal
Medicine, Hallym University Kangdong Sacred Heart Hospital,
(24)Department of Infectious Diseases, Nanjing Drum Tower
Hospital, the Affiliated Hospital of Nanjing University Medical
School, (25)Department of General Internal Medicine, Kyushu
University Hospital, (26)Faculty of Internal Medicine and
Hepatitis Research Center, College of Medicine, and Center
for Cohort Study, Kaohsiung Medical University, Kaohsiung,
Taiwan, (27)Division of Gastroenterology and Hepatology,
Department of Medicine, Stanford University Medical Center
(28)Department of Infectious Diseases, Nanjing Drum Tower
Hospital, (29)Hepatobiliary Division, Department of Internal
Medicine, Kaohsiung Medical University Hospital, Kaohsiung,
Taiwan, (30)Gastroenterology and Hepatology, Stanford
University Medical Center
Background: Decreased renal function is sometimes
observed in CHB patients maintained on long-term oral
antiviral therapy, and it is controversial whether TDF is more
renal toxic than ETV We aimed to compare the longitudinal
eGFR changes of ETV vs TDF patients and to identify factors
associated with eGFR changes
Methods: We performed
a retrospective study of 4983 adult treatment-naïve CHB
patients who were initiated on TDF (n=1790) or ETV
(n=3193) then observed for ≥12 months at 22 centers from
the US, HK, Korea, Taiwan, Japan and Mainland China We
assessed eGFR (mL/min/1 73m2) using the CKD-EPI formula
at baseline and about every 6 months ETV and TDF patients
were balanced via propensity score matching (PSM) on age,
gender, DM, HTN, cirrhosis, baseline eGFR, and follow-up
duration We used multivariable generalized linear modeling
(GLM) to adjust mean eGFR during follow up for cirrhosis,
HTN, and DM, and multivariable Cox regression to identify
factors associated with decreased renal function by at least
one CKD stage as per KDIGO staging (eGFR >90 for stage 1,
60-89 stage 2, 45-59 stage 3a, 30-44 stage 3b, and <30 stage
4/5) .
Results: In the total cohort (mean age 48 9 years, 66 7%
male), DM, HTN, and cirrhosis were respectively present in
13 1%, 21 2%, and 43 9% of the ETV group as compared to
10 7%, 17%, 29 7% for the TDF group (P<0 05) The baseline
eGFR was higher for the TDF vs ETV group (76 9 vs 74 1,
P=0 018) PSM yielded 1406 pairs of ETV or TDF patients
with baseline eGFR ≥60 and 357 pairs for the eGFR<60
group Multivariable GLM analysis of the total (unmatched)
cohort as well as the matched eGFR ≥60 and matched
eGFR <60 cohorts revealed lower adjusted mean eGFRs in
TDF (vs ETV) patients (all P<0 01; Figures 1A-C), though
the mean eGFR difference was small in all comparisons
(1 2-3 1 mL/min/1 73m2). Among PSM eGFR≥60 patients,
the 5-year cumulative incidence of renal impairment were
45 08% for ETV and 49 8% for TDF (P=0 0039; Figure 1D) In
multivariable Cox regression, TDF (HR 1 41), higher baseline
eGFR (HR 0 99), older age (HR 1 02), male (HR 2 16),
presence of DM or HTN (HR 1 4), and higher FIB-4 score
(HR 1 02) were all associated with worsening renal function
by at least one CKD stage Conclusion: TDF was associated
with lower mean eGFR throughout the 5-year on-treatment
follow-up and independently associated with incident renal
impairment, suggesting cautious use especially in those at
high risk for renal injury

StephenW

21
縱向估計的真實世界研究
腎小球濾過率（EGFR）的變化
恩替卡韋（ETV）與替諾福韋酯
富馬酸鹽（TDF）治療的慢性乙型肝炎（CHB）
患者：真實研究
麥龍儀1，黃浩然2，大元君3，建雄
Chen4，Peng-Yuan Peng5，Ying-LunYh6，Sung Eun Kim7，
Jae Yoon Jeong8，Eileen Yoon9，Hyunwoo Oh10，Pei-Chien
蔡11，黃忠峰12，桑峰安13，輕鞋14，
黃麗紅（Grace Lai-Hung Wong）15，江本正（Masaru Enomoto）16，惠特琳（Huy Trinh）17
Shie-Jun Shim18，Dong Hyun Lee19，Li Liu20，Rittsuzo Kozuka16，
Yong Kyun Cho21，Soung Won Jeong22，Hyoung Su Kim23，
黃瑞24，許婉軒1，徐若Vi 1，小川榮一25，
戴家仁12，黃潔夫26，張美蘭27
Wu28，Wan-Long Chuang29，Ming-Lung Yu12，Man Fung Yuen1
和Mindie H. Nguyen 30，（1）醫學，
香港（2）消化內科和肝病科，
斯坦福大學醫學中心，（3）漢陽大學，
（4）內科肝消化科
高雄長庚紀念醫院醫學部（5）
肝病消化科
中國醫科大學附屬醫院內科
（6）高雄市內科
大學醫院（7）內科
哈林大學聖心醫院（8）
漢陽大學醫學院內科，
古里醫院，（9）仁濟大學山溪派克醫院，
（10）漢陽大學內科
醫院內科肝膽科（11）
高雄醫科大學附屬醫院醫學
醫科大學（12）肝膽科
高雄醫科大學附屬醫院內科
台灣高雄市高雄醫科大學（13）
乙支大學醫學院內科
（14）上海交通大學醫學院
中國瑞金醫院醫學部（15）
和治療學，醫學數據分析中心（MDAC），
香港中文大學消化系統疾病研究所
Kong，（16）大阪市立大學肝病學系
醫學研究生院，（17）聖何塞胃腸病學，
（18）慶熙大學內科學系
醫院（19）江安好醫院消化內科
（20）昆明市第三醫院肝病科，（21）
成均館大學內科
醫學院，（22）內科，
淳淳大學的醫學院，（23）內部
哈里姆大學康東聖心醫院醫學
（24）南京鼓樓傳染病科
南京大學醫學院附屬醫院
學校（25）九州普通內科
大學醫院（26）內科與內科
醫學院肝炎研究中心和中心
高雄醫科大學隊列研究
台灣（27）腸胃病學和肝病學，
斯坦福大學醫學中心醫學系
（28）南京鼓樓傳染病科
醫院內科肝膽科（29）
高雄醫科大學附屬醫院醫學
台灣（30）斯坦福大學胃腸病學和肝病學
大學醫學中心
背景：有時腎功能下降
在長期口服CHB的患者中觀察到
抗病毒治療，TDF是否更多仍存在爭議
腎毒性比ETV我們的目的是比較縱向
ETV與TDF患者的eGFR變化及確定因素
與eGFR變化相關
方法：我們執行
4983名成人初治CHB的回顧性研究
在TDF（n = 1790）或ETV上啟動的患者
（n = 3193），然後在22個中心觀察了≥12個月
美國，香港，韓國，台灣，日本和中國大陸
使用CKD-EPI公式評估eGFR（mL / min / 1 73m2）
在基線以及大約每6個月ETV和TDF患者
通過年齡傾向匹配（PSM）獲得平衡，
性別，糖尿病，HTN，肝硬化，基線eGFR和隨訪
持續時間我們使用了多變量廣義線性建模
（GLM）來調整肝硬化隨訪期間的平均eGFR，
HTN和DM，以及多變量Cox回歸來識別
與腎功能下降至少相關的因素
根據KDIGO分期進行一個CKD階段（對於階段1，eGFR> 90
60-89階段2、45-59階段3a，30-44階段3b和<30階段
4/5）。
結果：在總隊列中（平均年齡48 9歲，66 7％
男性，DM，HTN和肝硬化分別存在於
ETV組的13 1％，21 2％和43 9％
TDF組為10 7％，17％，29 7％（P <0 05）基線
TDF組與ETV組的eGFR較高（76 9 vs 74 1，
P = 0 018）PSM產生了1406對ETV或TDF患者
eGFR≥60的基線eGFR≥60和357對
組多變量GLM總分析（不匹配）
隊列以及匹配的eGFR≥60和匹配
eGFR <60個隊列顯示，較低的調整後平均eGFR
儘管是TDF（vs ETV）患者（所有P <0 01；圖1A-C）
在所有比較中，平均eGFR差異均很小
（1 2-3 1 mL / min / 1 73平方米）。在PSM eGFR≥60的患者中，
腎功能損害的5年累積發生率是
ETV為45 08％，TDF為49 8％（P = 0 0039;圖1D）
多變量Cox回歸，TDF（HR 1 41），較高基線
eGFR（HR 0 99），老年（HR 1 02），男性（HR 2 16），
DM或HTN（HR 1 4）的存在，以及FIB-4評分更高
（HR 1 02）均與腎功能惡化有關
通過至少一個CKD階段得出結論：TDF與
整個治療5年的平均eGFR較低
隨訪並獨立於腎臟事件
損害，建議謹慎使用，尤其是在那些
腎損傷的高風險