Effect of Entecavir Treatment on Regression and Disease Outcome in HBV-induced Liver Fibrosis and Cirrhosis Patients

Effect of Entecavir Treatment on Regression and Long-term Disease Outcome in Patients With HBV-induced Liver Fibrosis and Cirrhosis (Regress Extension Study)

Patients who have completed 2 years follow-up of the past National 12th Five-Year Major Project on Infectious Diseases will receive another 8 years treatment with entecavir (10 years in total). Collect serology, imaging, and other clinical data to evaluate the incidence and mortality of decompensated cirrhosis and hepatocellular carcinoma. Understand the effects of long-term antiviral therapy on HBV-induced liver fibrosis/cirrhosis.

Study Overview

• Status: Active, not recruiting
• Conditions: Liver Cirrhosis; Hepatitis B
• Intervention / Treatment: Drug: Entecavir

Detailed Description

Patients who have completed 2-years entecavir-based treatment in Regress Study will receive another 8 years of entecavir extension therapy. Patients will be assessed at baseline and every six months for blood cell count, liver function test, HBV-DNA, AFP, prothrombin time, liver ultrasonography, and Fibroscan; A third liver biopsy will be performed at the 5th year of treatment in patients who have significant fibrosis at second biopsy. CT /MRI and endoscopy will be performed at baseline and the 5th and 10th year of treatment.

• Study Type: Interventional
• Enrollment (Anticipated): 800
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Tianjin, China, 300170
    • Tianjin Third Central Hospital
  • Beijing
    • Beijing, Beijing, China, 100034
      • Peking University First Hospital
    • Beijing, Beijing, China, 100050
      • Beijing Friendship Hospital, Capital Medical University
    • Beijing, Beijing, China, 100039
      • 302 Military Hospital of China
    • Beijing, Beijing, China, 100050
      • Beijing Tiantan Hospital, Capital Medical University
    • Beijing, Beijing, China, 100050
      • Peking University People's Hospital
    • Beijing, Beijing, China, 100069
      • Beijing Youan Hospital, Capital Medical University
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • NanfangHospital,Southern Medical University
  • Hebei
    • Shijiazhuang, Hebei, China, 050051
      • The Third Hospital of Hebei Medical University
    • Shijiazhuang, Hebei, China, 50021
      • Shijiazhuang Fifth Hospital
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Tongji Hospital, Tongji Medical College , Huazhong University of Science and Technology
  • Jilin
    • Yanji, Jilin, China, 133000
      • The Affiliated Hospital of Yanbian University
  • Shanghai
    • Shanghai, Shanghai, China, 200080
      • Shanghai General Hospital
    • Shanghai, Shanghai, China, 201508
      • Shanghai Public Health Clinical Center
    • Shanghai, Shanghai, China, 200040
      • Zhongshan Hospital Fudan University
    • Shanghai, Shanghai, China, 200032
      • Renji Hospital, Shanghai Jiao Tong University, School of Medicine
  • Shanxi
    • Taiyuan, Shanxi, China, 30001
      • The First Hospital of Shanxi Medical University
    • Xi'an, Shanxi, China, 710032
      • Xijing Hospital, Fourth Military Medical University
  • Tianjin
    • Tianjin, Tianjin, China, 300380
      • Tianjin Xiqing Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310016
      • Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

- Subjects who completed the 2 years of entecavir-based therapy in Regress study; Subjects who are willing to participate the extension study.

Exclusion Criteria:

- Any complication of severe heart, lung, kidney, brain, blood diseases or other important systematic diseases; Pregnant women; Subjects who could not compliance with the protocol judged by investigators; Subjects who are not suitable for the study judged by investigators.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment group; entecavir oral，0.5mg daily for 8 years	Drug: Entecavir; oral entecavir 0.5mg daily for 8 years

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fibrosis regression rate	Ishak fibrosis score decrease after long-term treatment	year 3
Cumulative incidence of liver decompensation	Cumulative incidence of liver decompensation (including ascites, hepatic encephalopathy, esophageal varices bleeding and Hepatocellular Carcinoma) and death after long-term treatment	year 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Virological response	Percentage of patients achieving hepatitis B virus (HBV) DNA < 20IU/mL at year 3, 5, 7 and 10	year 3, 5, 7 and 10
Aminotransferase response	The percentage of patients with alanine aminotransferase (ALT) normalization at year 3, 5, 7 and 10	year 3, 5, 7 and 10
HBeAg loss or HBeAg seroconversion	Percentage of patients with HBeAg loss or HBeAg seroconversion at year 2, 5, 7 and 10	year 2, 5, 7 and 10
HBsAg loss or HBsAg seroconversion rate	Percentage of patients with HBsAg loss or HBsAg seroconversion at year 2, 5, 7 and 10	year 2, 5, 7 and 10
Dynamic changes of Child-Pugh score	Dynamic changes of Child-Pugh score after 3, 5, 7 and 10 years of treatment	year 3, 5, 7 and 10
Dynamic changes of MELD score	Dynamic changes of MELD score after 3, 5, 7 and 10 years of treatment	year 3, 5, 7 and 10
Dynamic changes of liver stiffness values measured by Transient Elastography	Dynamic changes of liver stiffness values after 3, 5, 7 and 10 years of treatment	year 3, 5, 7 and 10
Improvement of life quality (SF36 and EQ-5D)	Improvement of life quality after 3, 5, 7 and 10 years of treatment	year 3, 5, 7 and 10

Collaborators and Investigators

• Sponsor: Beijing Friendship Hospital
• Collaborators: Peking University People's Hospital; Fudan University; Beijing YouAn Hospital; Nanfang Hospital of Southern Medical University; Shanghai Public Health Clinical Center; Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine; Affiliated Hospital of Yanbian University
• Investigators: Principal Investigator: Xiaojuan Ou, Beijing Friendship Hospital

Publications and helpful links

General Publications

• Wu X, Zhou J, Sun Y, Ding H, Chen G, Xie W, Piao H, Xu X, Jiang W, Ma H, Ma A, Chen Y, Xu M, Cheng J, Xu Y, Meng T, Wang B, Chen S, Shi Y, Kong Y, Ou X, You H, Jia J. Prediction of liver-related events in patients with compensated HBV-induced cirrhosis receiving antiviral therapy. Hepatol Int. 2021 Feb;15(1):82-92. doi: 10.1007/s12072-020-10114-1. Epub 2021 Jan 18.
• Arvaniti V, D'Amico G, Fede G, Manousou P, Tsochatzis E, Pleguezuelo M, Burroughs AK. Infections in patients with cirrhosis increase mortality four-fold and should be used in determining prognosis. Gastroenterology. 2010 Oct;139(4):1246-56, 1256.e1-5. doi: 10.1053/j.gastro.2010.06.019. Epub 2010 Jun 14.
• Liaw YF, Sung JJ, Chow WC, Farrell G, Lee CZ, Yuen H, Tanwandee T, Tao QM, Shue K, Keene ON, Dixon JS, Gray DF, Sabbat J; Cirrhosis Asian Lamivudine Multicentre Study Group. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med. 2004 Oct 7;351(15):1521-31. doi: 10.1056/NEJMoa033364.
• Wu X, Hong J, Zhou J, Sun Y, Li L, Xie W, Piao H, Xu X, Jiang W, Feng B, Chen Y, Xu M, Cheng J, Meng T, Wang B, Chen S, Kong Y, Ou X, You H, Jia J. Health-related quality of life improves after entecavir treatment in patients with compensated HBV cirrhosis. Hepatol Int. 2021 Dec;15(6):1318-1327. doi: 10.1007/s12072-021-10240-4. Epub 2021 Nov 29.
• Yang JM, Chen LP, Wang YJ, Lyu B, Zhao H, Shang ZY, Li J, Fan ZY, Wu SD, Ming X, Li X, Huang SP, Cheng JL. Entecavir add-on Peg-interferon therapy plays a positive role in reversing hepatic fibrosis in treatment-naive chronic hepatitis B patients: a prospective and randomized controlled trial. Chin Med J (Engl). 2020 Jul 20;133(14):1639-1648. doi: 10.1097/CM9.0000000000000857.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2016
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2025

Study Registration Dates

• First Submitted: July 22, 2016
• First Submitted That Met QC Criteria: July 26, 2016
• First Posted (Estimate): July 29, 2016

Study Record Updates

• Last Update Posted (Actual): April 28, 2021
• Last Update Submitted That Met QC Criteria: April 25, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis; Fibrosis; Hepatitis B; Liver Cirrhosis; Anti-Infective Agents; Antiviral Agents; Entecavir
• Other Study ID Numbers: 2016ZX10002011