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标题: AASLD2018[384] 治疗ALT正常化没有 对肝硬度的统计学显着性影响 [打印本页]

作者: StephenW    时间: 2018-10-10 20:42     标题: AASLD2018[384] 治疗ALT正常化没有 对肝硬度的统计学显着性影响

384
On-Treatment ALT Normalization Has No
Statistical Significant Impact on Liver Stiffness
Regression in Chinese Chronic Hepatitis B
Patients with Advanced Fibrosis or Cirrhosis
Receiving Tenofovir Disoproxil Fumarate
Therapy
Lai Wei, Peking University People’s Hospital, Peking
University Hepatology Institute, Beijing Key Laboratory for
Hepatitis C and Immunotherapy for Liver Disease, Jia Shang,
Henan Provincial People’s Hospital, Qing Xie, Department
of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong
University School of Medicine, Shanghai, China, Zhansheng
Jia, Center of Diagnosis and Treatment for Infectious Diseases
of Chinese PLA, Tangdu Hospital, the Fourth Military Medical
University,, Pujun Gao, Department of Hepatology, The First
Hospital of Jilin University, Junping Shi, Department of Liver
Disease, The Affiliated Hospital of Hangzhou Normal University,
Hangzhou, Xinyue Chen, International Medical Department,
Beijing Youan Hospital Capital Medical University, Jiefei
Wang, Department of Liver Intensive Care Unit, Shanghai
Public Health Clinical Center, Min Xu, Guangzhou Eighth
Municipal People’s Hospital, Liaoyun Zhang, Department
of Infectious Diseases, First Hospital of Shanxi Medical
University, Yingren Zhao, Department of Infectious Disease,
The First Affiliated Hospital, Xi’an Jiaotong University,Xi’an,
China, Maorong Wang, Department of Infectious Diseases,
No. 81 Hospital of People’s Liberation Army, Nanjing, Qing
Mao, Department of Infectious Diseases, Southwest Hospital,
Third Military Medical University, Wei Zhao, Department of
Hepatology, The Second Hospital of Nanjing, Zong Zhang,
Division of Liver Disease, Jinan Infectious Disease Hospital,
Shandong University, Jidong Jia, Liver Research Center,
Beijing Friendship Hospital, Capital Medical University, Beijing
Key Laboratory of Translational Medicine in Liver Cirrhosis,
National Clinical Research Center of Digestive Diseases,
Beijing, China;, Hong Tang, West China Hospital of Sichuan
University, Jiming Zhang, Department of Infectious Diseases,
Huashan Hospital Affiliated to Fudan University, Xin Zheng,
Department of Infectious Disease, Institute of Infection and
Immunology, Affiliated Union Hospital of Tongji Medical
College, Huazhong University of Science and Technology,
Cui Xiong, Statistics, Glaxosmithkline (China) R&D Company
Limited and Mingfen Zhu, Medical Affairs, Glaxosmithkline
(China) Investment Company Limited
Background: Liver stiffness measurement (LSM) change
and factors associated with improvement of fibrosis stage in
patients with chronic hepatitis B (CHB) with advanced fibrosis
or cirrhosis after tenofovir disoproxil fumarate (TDF) treatment
are rarely reported. Methods: This ongoing (since March
2015), prospective, open-label study (GSK [NCT02224456])
enrolled treatment-naïve CHB patients aged 18-60 years
with advanced fibrosis or compensated cirrhosis (diagnosed
clinically [LSM plus abnormal ultrasound or platelets
<100x10^9/L] or by liver biopsy) to receive TDF 300 mg/day
(240 weeks). Study assessments include changes in LSM
and fibrosis stage (measured by LSM) and factors associated
with fibrosis stage regression (gender, age, baseline HBV
DNA level, HBeAg sero-status, alanine aminotransferase
[ALT]), platelet count, LSM, 24- and 48-week virologic
response, and ALT normalization). Here, we report 96-week
results. Results: Of 195 enrolled patients (75.9% men; mean
age 43.3 years) 37.4% and 36.9% patients were diagnosed
with advanced fibrosis and cirrhosis, respectively. The LSM
declined significantly in first 24 weeks and showed a slow
but continuous decline through 96 weeks. Mean % change
in LSM (baseline to week 96) was -32.9% and -37.6% in
patients with advanced fibrosis and cirrhosis, respectively
(p<0.001). In total, 44% patients experienced fibrosis stage
regression ≥2 stages and did not have advanced fibrosis or
cirrhosis at week 96. Age ≤40 years (OR: 0.468, p=0.012)
and higher baseline LSM (OR: 1.063, p=0.020) were found
to be associated with fibrosis stage regression. Baseline ALT
level (OR: 1.007, p=0.053) and ALT normalization at week 24
(OR 1.986, p=0.114) or week 48 (OR: 2.061, p=0.088) had no
statistically significant impact on fibrosis regression. The trend
in LSM decline was similar between patients with normal
and elevated ALT. Virologic response (HBV DNA<20 IU/ml)
was achieved in 88.8% patients and ALT normalization was
seen in 66% patients. HBeAg loss and seroconversion was
seen in 33% and 14.9% patients, respectively. Three patients
(1.5%) developed HCC. Mean eGFR value was stable during
the 96-week treatment (Table 1). SAEs were reported in
20 patients. The most common adverse drug reaction was
hypophosphatemia (n=11). The safety and tolerability in
this study was consistent with the known safety profile.
Conclusion: Over 2 years, treatment with TDF significantly
decreased LSM. Younger age or higher baseline LSM were
positively associated with fibrosis regression.
Disclosures:
Cui Xiong – glaxosmithkline: Employment
Mingfen Zhu – GlaxoSmithKline (China) Investment Company Limited:
Employment
The following people have nothing to disclose: Lai Wei, Jia Shang, Qing Xie,
Zhansheng Jia, Pujun Gao, Junping Shi, Xinyue Chen, Min Xu, Liaoyun Zhang,
Maorong Wang, Qing Mao, Wei Zhao, Jidong Jia, Jiming Zhang, Xin Zheng
Disclosure information not available at the time of publication: Jiefei Wang,
Yingren Zhao, Zong Zhang, Hong Tang
作者: StephenW    时间: 2018-10-10 20:43

384
治疗ALT正常化没有
对肝硬度的统计学显着性影响
中国慢性乙型肝炎的回归分析
晚期纤维化或肝硬化患者
接受替诺福韦地索普西富马酸盐
治疗
北京北京大学人民医院赖伟
大学肝病研究所,北京市重点实验室
丙型肝炎和肝病免疫治疗,贾尚,
河南省人民医院,谢谢,系
上海交通大学瑞金医院传染病研究所
中国上海大学医学院,湛生
贾,传染病诊断与治疗中心
中国人民解放军,唐都医院,第四军医大学
大学,高普军,肝病学系,第一
吉林大学医院,Junping Shi,肝脏科
疾病,杭州师范大学附属医院,
杭州陈新月国际医疗部
北京佑安医院首都医科大学,解飞
王,上海市肝脏重症监护室
公共卫生临床中心,徐敏,广州八
市人民医院张辽云系
山西医科大学第一医院感染科
大学,赵英仁,传染病系,
西安交通大学第一附属医院,西安,
中国,王茂荣,传染病科,
清华南京人民解放军第81医院
毛泽东,西南医院感染科,
第三军医大学赵薇系
南京市第二医院肝病科,张宗,
济南市传染病医院肝病科,
山东大学,吉东佳,肝脏研究中心,
首都医科大学附属北京友谊医院
肝硬化转化医学重点实验室,
国家消化疾病临床研究中心,
中国北京;四川华西医院康唐
大学,张继明,传染病科,
复旦大学附属华山医院,新郑,
传染病研究所,感染与传染病研究所
同济医学院附属协和医院免疫学
华中科技大学学院
崔雄,统计,葛兰素史克(中国)研发公司
有限公司和朱明芬,医疗事务,Glaxosmithkline
(中国)投资有限公司
背景:肝硬度测量(LSM)变化
和与纤维化阶段改善有关的因素
患有晚期纤维化的慢性乙型肝炎(CHB)患者
或替诺福韦地索普西富马酸盐(TDF)治疗后的肝硬化
很少报道。方法:这是持续的(从3月开始
2015),前瞻性,开放标签研究(GSK [NCT02224456])
入组治疗 - 初治CHB患者年龄18-60岁
伴有晚期纤维化或代偿性肝硬化(确诊为
临床[LSM加异常超声或血小板
<100x10 ^ 9 / L]或通过肝脏活组织检查)接受TDF 300 mg /天
(240周)。研究评估包括LSM的变化
和纤维化阶段(通过LSM测量)和相关因素
纤维化阶段消退(性别,年龄,基线HBV
DNA水平,HBeAg血清状态,丙氨酸氨基转移酶
[ALT]),血小板计数,LSM,24周和48周病毒学
响应和ALT标准化)。在这里,我们报告96周
结果。结果:195名入选患者(75.9%的男性;平均值
年龄43.3岁)37.4%和36.9%的患者被诊断出来
分别为晚期纤维化和肝硬化。 LSM
前24周显着下降并显示缓慢
但持续下降96周​​。平均%变化
在LSM(基线到第96周)中,-32.9%和-37.6%
分别为晚期纤维化和肝硬化的患者
(p <0.001)。总共有44%的患者出现纤维化阶段
回归≥2阶段并没有晚期纤维化
第96周肝硬化。年龄≤40岁(OR:0.468,p = 0.012)
可以找到更高的基线LSM(OR:1.063,p = 0.020)
与纤维化阶段回归有关。基线ALT
水平(OR:1.007,p = 0.053)和第24周的ALT正常化
(OR 1986,p = 0.114)或第48周(OR:2.061,p = 0.088)没有
对纤维化消退的统计学显着影响。趋势
LSM下降与正常患者相似
和升高的ALT。病毒学应答(HBV DNA <20 IU / ml)
在88.8%的患者中实现了ALT正常化
见于66%的患者。 HBeAg丢失和血清转换是
分别见于33%和14.9%的患者。三名患者
(1.5%)发展为HCC。平均eGFR值在期间稳定
96周的治疗(表1)。报道了SAE
20名患者。最常见的药物不良反应是
低磷血症(n = 11)。安全性和耐受性
该研究与已知的安全性概况一致。
结论:2年以上,TDF治疗效果显着
LSM下降。更年轻或更高的基线LSM
与纤维化消退呈正相关。
披露:
崔雄 - glaxosmithkline:就业
朱明芬 - 葛兰素史克(中国)投资有限公司:
雇用
下面的人没有什么可透露的:赖伟,贾尚,谢谢,
贾占生,高普军,史俊平,陈新月,徐敏,张辽云,
王茂荣,毛青,赵薇,贾继东,张继明,郑铮
发布时无法提供的披露信息:王杰飞,
赵英仁,张宗,唐红




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