AASLD2016[1852]代谢综合征的特征与之相关 治疗期间缺乏血清ALT

StephenW

1852
Features of the metabolic syndrome are associated with
lack of serum ALT normalization during therapy for
chronic hepatitis B
Scott Fung2, Hiroshi Yatsuhashi3, Won Young Tak4, Mustafa K.
Celen5, John F. Flaherty1, Kyungpil Kim1, Robert P. Myers1, Mani
Subramanian1, Stephen D. Ryder6, Manoj Sharma7, Mindie H.
Nguyen8; 1Gilead Sciences, Inc., Foster City, CA; 2University of
Toronto, Toronto, ON, Canada; 3National Hospital Organization
Nagasaki Medical Center, Nagasaki, Japan; 4Kyungpook
National University Hospital, Daegu, Korea (the Republic of);
5Dicle University, Diyabakir, Turkey; 6Nottingham University Hospitals
NHS Trust, Nottingham, United Kingdom; 7Institute of Liver
and Biliary Sciences, New Delhi, India; 8Stanford University Medical
Center, Palo Alto, CA
Background: Despite complete suppression of HBV DNA
with antiviral agents, serum alanine aminotransferase (ALT)
levels fail to normalize in some patients with chronic hepatitis
B (CHB). Our objective was to evaluate factors associated
with persistent ALT elevation during treatment with tenofovir
alafenamide (TAF) or tenofovir disoproxil fumarate (TDF).
Methods: Adults with CHB enrolled in two Phase 3 studies
of TAF 25 mg QD vs. TDF 300 mg QD (Study GS-US-320-
0108 in HBeAg- and GS-US-320-0110 in HBeAg+ subjects)
were included. Rates of ALT normalization at Weeks 12 and
48 were determined using reference ranges recommended
by AASLD (≤19 U/L for women, ≤30 for men). A sensitivity
analysis examined ALT normalization according to central
laboratory (Covance) criteria (<69 yrs: ≤34 U/L for women,
≤43 for men; ≥69 yrs: ≤32 U/L for women, ≤35 for men).
Associations between host, viral and treatment-related factors,
including virologic suppression (HBV DNA <29 IU/mL; Roche
COBAS Taqman), with persistent ALT elevation at Week 48
were determined using logistic regression. Results: Based on
AASLD criteria, 1,276 of 1,301 subjects (98%) had abnormal
baseline (BL) ALT. Median BL ALT and HBV DNA were
82 U/L (IQR 56-126) and 7.4 log10 IU/mL (IQR 5.8-8.3),
respectively. Compared with patients treated with TDF, ALT
normalization by AASLD criteria at Week 12 (11% vs. 18%;
P=0.003) and Week 48 (36% vs. 49%; P<0.001) were more
common among patients treated with TAF. Similarly, ALT normalization
by central laboratory criteria was greater in TAF
vs. TDF-treated subjects at Week 12 (43% vs. 35%; P=0.015)
and Week 48 (78% vs. 72%; P=0.012). Patients with elevated
ALT at Week 48 had a higher prevalence of overweight (45%
vs. 29%; P<0.001), hypertension (15% vs. 10%; P=0.007),
dyslipidemia (11% vs. 6%; P=0.003), and diabetes (8% vs.
5%; P=0.062) compared with those with normal ALT. In a
multivariate analysis, TAF treatment (odds ratio [OR] 0.60;
95% CI 0.44-0.82; P=0.002) and virologic suppression (OR
0.33; 0.22-0.49; P<0.001) were associated with a lower likelihood
of ALT elevation at Week 48. Additional independent
predictors of ALT elevation included female sex (OR 1.79;
1.29-2.47; P<0.001), higher BMI (OR 1.14; 95% CI 1.09-
1.19; P<0.001), diabetes (OR 2.27; 1.11-4.63; P=0.024),
cirrhosis (OR 2.64; 1.53-4.57; P<0.001), and lower BL ALT
(OR 0.995; 95% CI 0.993-0.997; P<0.001). Conclusions: In
patients with CHB, treatment with TAF compared with TDF is
associated with a greater likelihood of ALT normalization independent
of virologic suppression. Patients with metabolic risk
factors are less likely to normalize ALT, which could occur due
to underlying hepatic steatosis.
Disclosures:
Scott Fung - Advisory Committees or Review Panels: Gilead Sciences, Merck,
Abbvie; Speaking and Teaching: BMS, Gilead, AbbVie, Merck
Won Young Tak - Advisory Committees or Review Panels: Gilead Korea; Grant/
Research Support: SAMIL Pharma
John F. Flaherty - Employment: Gilead Sciences; Stock Shareholder: Gilead Sciences
Robert P. Myers - Employment: Gilead Sciences, Inc.; Stock Shareholder: Gilead
Sciences, Inc.
Stephen D. Ryder - Advisory Committees or Review Panels: Abbvie, Gilead,
MSD, MBS, Norgine
Mindie H. Nguyen - Advisory Committees or Review Panels: Bristol-Myers
Squibb, Gilead; Consulting: Gilead Sciences, Inc.; Grant/Research Support:
Gilead Sciences, Inc., Bristol-Myers Squibb
The following people have nothing to disclose: Hiroshi Ya

StephenW

AASLD2016 [1852]代谢综合征的特征与之相关
治疗期间缺乏血清ALT正常化
代谢综合征的特征与之相关
治疗期间缺乏血清ALT正常化
慢性乙型肝炎
Scott Fung2，Hiroshi Yatsuhashi3，Won Young Tak4，Mustafa K.
Celen5，John F.Flherty1，Kyungpil Kim1，Robert P.Myers1，Mani
Subramanian1，Stephen D.Ryder6，Manoj Sharma7，Mindie H.
Nguyen8; 1Gilead Sciences，Inc.，Foster City，CA; 2大学
Toronto，Toronto，ON，Canada; 3国家医院组织
长崎医疗中心，长崎，日本; 4Kyungpook
国立大学医院，大邱，韩国（共和国）;
土耳其Diyabakir 5Dicle大学;诺丁汉大学医院
NHS信托，诺丁汉，英国; 7肝脏研究所
和Biliary Sciences，新德里，印度; 8斯坦福大学医学
Center，Palo Alto，CA
背景：尽管完全抑制HBV DNA
与抗病毒剂，血清丙氨酸氨基转移酶（ALT）
水平不能在一些慢性肝炎患者中正常化
B（CHB）。我们的目标是评估相关因素
在用替诺福韦治疗期间具有持续的ALT升高
（TAF）或替诺福韦地索普西富马酸盐（TDF）。
方法：CHB的成年人参加两个3期研究
的TAF 25mg QD对TDF 300mg QD（研究GS-US-320-
0108在HBeAg-和GS-US-320-0110在HBeAg +受试者中）
包括。在第12周和第12周ALT标准化的速率
48使用推荐的参考范围确定
（女性≤19U / L，男性≤30）。灵敏度
分析根据中心检查ALT正常化
实验室（Covance）标准（<69岁：女性≤34U / L，
男性≤43; ≥69岁：女性≤32U / L，男性≤35岁）。
宿主，病毒和治疗相关因素之间的关联，
包括病毒学抑制（HBV DNA <29IU / mL; Roche
COBAS Taqman），在第48周时具有持续的ALT升高
使用逻辑回归确定。结果：基于
AASLD标准，1,301名受试者中的1,276名（98％）有异常
基线（BL）ALT。中位BL ALT和HBV DNA
82 U / L（IQR 56-126）和7.4log 10 IU / mL（IQR 5.8-8.3）
分别。与用TDF治疗的患者相比，ALT
在第12周通过AASLD标准进行归一化（11％对18％;
P = 0.003）和第48周（36％对49％; P <0.001）更多
在用TAF治疗的患者中是常见的。类似地，ALT标准化
通过中心实验室标准在TAF中更大
与TDF治疗的受试者在第12周（43％对35％; P = 0.015）
和第48周（78％对72％; P = 0.012）。患者升高
ALT在第48周具有更高的超重流行率（45％
vs. 29％; P <0.001），高血压（15％对10％; P = 0.007），
血脂异常（11％对6％; P = 0.003）和糖尿病（8％vs.
5％; P = 0.062）。在一个
多变量分析，TAF治疗（优势比[OR] 0.60;
95％CI 0.44-0.82; P = 0.002）和病毒抑制（OR
0.33; 0.22-0.49; P <0.001）与较低的可能性相关
的ALT升高
ALT升高的预测因素包括女性（OR 1.79;
1.29-2.47; P <0.001），更高的BMI（OR 1.14; 95％CI 1.09-
1.19; P <0.001），糖尿病（OR 2.27; 1.11-4.63; P = 0.024），
肝硬化（OR 2.64; 1.53-4.57; P <0.001），和低BL ALT
（OR 0.995; 95％CI 0.993-0.997; P <0.001）。结论：
患者CHB，用TAF治疗与TDF相比
与ALT标准化的可能性更大无关
的病毒抑制。患有代谢风险的患者
因素不太可能使ALT正常化，这可能发生
到基础性肝脂肪变性。
披露：
Scott Fung - 咨询委员会或审查小组：G​​ilead Sciences，Merck，
Abbvie;口语和教学：BMS，Gilead，AbbVie，Merck
Won Young Tak - 咨询委员会或审查小组：G​​ilead韩国;赠款/
研究支持：SAMIL Pharma
约翰·弗莱厄蒂 - 就业：吉利德科学;股票股东：Gilead Sciences
就业：吉利德科学公司股票股东：Gilead
科学公司
Stephen D. Ryder - 咨询委员会或审查小组：Abbvie，Gilead，
MSD，MBS，Norgine
Mindie H. Nguyen - 咨询委员会或审查小组：Bristol-Myers
Squibb，Gilead;咨询：吉利德科学有限公司;资助/研究支持：
吉利德科学公司，Bristol-Myers Squibb
以下人士没有透露：Hiroshi Ya