APASL2017 [OP113] 早期生化和病毒学反应的相关性 在口服抗病毒

StephenW

APASL2017[OP113]
Correlation of early biochemical and virologic responses
during oral antiviral therapy for chronic hepatitis B
Sang Hoon Ahn1, Maurizia Brunetto2, Ting-Tsung Chang3, Seng
Gee Lim4, Adrian Streinu-Cercel5, John Flaherty6, Kyungpil
Kim7, Anuj Gaggar7, Mani Subramanian7, Wendy Chneg8,
Magdy Elkashab9, Namiki Izumi10
1Yonsei University College of Medicine, Seoul, South Korea;
2Azienda Ospedaliera Universitaria, Florence, Italy; 3National Cheng
Kung University Hospital, Tainan, Taiwan; 4National University of
Singapore, Singapore; 5National Institute for Infectious Diseases
Matei Bals, Bucharest, Romania; 6Gilead Sciences, Foster City, CA,
USA; 7Gilead Sciences, Foster City, USA; 8Department of
Gastroenterolgoy/Hepatology, Royal Perth Hospital, Perth, Western
Australia; 9Toronto Liver Centre, Toronto, Canada; 10Japan Red
Cross Musashino Hospital, Musashino, Japan
Background: The objective of this study was to evaluate factors
associated with rapid biochemical and virologic responses to
treatment with tenofovir alafenamide (TAF) or tenofovir diporoxil
(TDF), and predictors of discordance between ALT normalization and
viral suppression.
Methods: The study included HBV-infected adults enrolled in two
Phase 3 studies of TAF 25 mg QD vs. TDF 300 mg QD (Study GSUS-
321-0108 in HBeAg- and GS-US-321-110 in HBeAg + subjects).
At Week 12, virologic suppression was defined as HBV DNA
\29 IU/mL (Roche COBAS Taqman) and ALT normalization was
defined according to reference ranges recommended by AASLD
(B19 U/L for women, B30 U/L for men). The associations between
host, viral, and treatment-related predictors with combined virologic
suppression and ALT normalization at Week 12 were determined
using logistic regression analyses. Among patients with HBV DNA
suppression at Week 12, the characteristics of patients with normal vs.
elevated ALT were also compared.
Result: Based on AASLD criteria, 1,276 of 1,301 randomized subjects
(98%) had abnormal baseline (BL) ALT. The 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. In total, 194 patients (16%) normalized
ALT by Week 12; 96 of these patients (49%; 8% of the total) also
achieved virologic suppression. The proportion of subjects achieving
ALT normalization and virologic suppression at Week 12 was higher
among TAF- vs. TDF-treated subjects (9.0 vs. 5.0%; P = 0.013).
Among patients with suppressed HBV DNA at Week 12, 39% (75/
190) in the TAF group and 24% (21/89) in the TDF group normalized
serum ALT (P = 0.010). Patients with persistently elevated ALT
despite virologic suppression had a higher prevalence of diabetes (8.7
vs. 5.2%; P = 0.346), hypertension (16.9 vs. 6.3%; P = 0.015),
dyslipidemia (9.3 vs. 4.2%; P = 0.154), and overweight (37.7 vs.
27.1%; P = 0.085) compared with those with normal ALT. In a
multivariate analysis, treatment with TAF (odds ratio [OR] 2.78; 95%
CI 1.44–5.37; P = 0.002), HBeAg-negativity (OR 3.12; 95% CI
1.63–5.98; P = 0.001), lower BL HBV DNA (OR per log10 IU/mL:
0.53; 95% CI 0.43–0.64; P\0.001), male sex (OR 2.48; 95% CI
1.39–4.44; P = 0.002), and the absence of cirrhosis (OR 7.35; 95%
CI 1.70–31.87; P = 0.008), were independent predictors of achieving
biochemical normalization and virologic suppression at Week 12.
Conclusion: A minority of patients with CHB achieve ALT normalization
and virologic suppression after 12 weeks of oral antiviral
therapy. Treatment with TAF compared with TDF is independently
associated with achieving this endpoint.

StephenW

APASL2017 [OP113]
早期生化和病毒学反应的相关性
在口服抗病毒治疗慢性乙型肝炎
Sang Hoon Ahn1，Maurizia Brunetto2，Ting-Tsung Chang3，Seng
Gee Lim4，Adrian Streinu-Cercel5，John Flaherty6，Kyungpil
Kim7，Anuj Gaggar7，Mani Subramanian7，Wendy Chneg8，
Magdy Elkashab9，Namiki Izumi10
1柳州大学医学院，韩国首尔;
2Azienda Ospedaliera Universitaria，Florence，Italy; 3国立程
台湾台南市大学医院; 4国立大学
新加坡，新加坡;国家传染病研究所
Matei Bals，布加勒斯特，罗马尼亚; 6Gilead Sciences，Foster City，CA，
美国; 7Gilead Sciences，Foster City，USA; 8部
Gastroenterolgoy / Hepatology，Royal Perth Hospital，Perth，Western
澳大利亚; 9多伦多肝脏中心，多伦多，加拿大; 10日本红
Cross Musashino医院，武藏野市，日本
背景：本研究的目的是评价因素
与快速生化和病毒学应答相关
用替诺福韦艾拉酚胺（TAF）或替诺福韦酯二氧化物治疗
（TDF），和ALT正常化之间的不一致的预测因子
病毒抑制。
方法：本研究纳入HBV感染的成年人
TAF 25mg QD与TDF 300mg QD的3期研究（研究GSUS-
321-0108在HBeAg-和GS-US-321-110在HBeAg +受试者中）。
在第12周，病毒学抑制定义为HBV DNA
\ 29IU / mL（Roche COBAS Taqman）和ALT标准化
根据AASLD推荐的参考范围定义
（女性B19 U / L，男性B30 U / L）。之间的关联
主机，病毒和治疗相关的预测因子与组合的病毒学
抑制和ALT标准化
使用逻辑回归分析。在HBV DNA的患者中
抑制在第12周，患者的特征与正常vs.
升高的ALT也进行了比较。
结果：根据AASLD标准，1,301名随机受试者中的1,276名
（98％）具有异常基线（BL）ALT。中位数BL ALT
和HBV DNA分别为82U / L（IQR 56-126）和7.4log10 IU / mL
（IQR 5.8-8.3）。总共有194名患者（16％）正常化
ALT到第12周;其中96例（49％，占总数的8％）
实现病毒学抑制。受试者达到的比例
在第12周的ALT标准化和病毒抑制更高
在TAF-与TDF-治疗的受试者中（9.0对5.0％; P = 0.013）。
在第12周时抑制HBV DNA的患者中，39％（75 /
190）和24％（21/89）的TDF组标准化
血清ALT（P = 0.010）。 ALT持续升高的患者
尽管病毒学抑制具有更高的糖尿病流行率（8.7
vs. 5.2％; P = 0.346），高血压（16.9对6.3％; P = 0.015），
血脂异常（9.3vs.2.2％; P = 0.154）和超重（37.7vs。
27.1％; P = 0.085）。在一个
多变量分析，用TAF治疗（优势比[OR] 2.78; 95％
CI 1.44-5.37; P = 0.002），HBeAg阴性（OR 3.12; 95％CI
1.63-5.98; P = 0.001），低BL HBV DNA（OR / log10IU / mL：
0.53; 95％CI 0.43-0.64; P <0.001），男性（OR 2.48; 95％CI
1.39-4.44; P = 0.002）和无肝硬化（OR 7.35; 95％
CI 1.70-31.87; P = 0.008）是实现的独立预测因素
生化标准化和病毒学抑制。
结论：少数CHB患者实现ALT正常化
和12周口服抗病毒后的病毒抑制
治疗。 TAF与TDF相比的治疗是独立的
与实现此端点相关联。