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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 |
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发表于 2018-10-10 20:42