Study of Entecavir for Reducing the Risk of Hepatocellular Carcinoma in Chronic Hepatitis B Patients

Efficacy of Entecavir for Reducing the Risk of Hepatocellular Carcinoma in Chronic Hepatitis B Patients With Compensated Cirrhosis and Low Viral Load: a Multicenter, Prospective Study

To analyze the incidence of liver cancer after entecavir administration among patients with low viral load and cirrhosis due to chronic hepatitis B infection.

Study Overview

• Status: Unknown
• Conditions: Chronic Hepatitis B

Detailed Description

To analyze the incidence of liver cancer after entecavir administration among patients with low viral load (HBV DNA titer<2,000 IU/mL (104 copies/mL)) and cirrhosis due to chronic hepatitis B infection.

• Study Type: Observational
• Enrollment (Anticipated): 245

Contacts and Locations

Study Locations

• Korea, Republic of
  • Bucheon, Korea, Republic of
    • Recruiting
    • Soon Chun Hyang University Hospital Bucheon
  • Cheonan, Korea, Republic of
    • Recruiting
    • Soon Chun Hyang University Hospital Cheonan
  • Gyeonggi-do, Korea, Republic of
    • Recruiting
    • Seoul National University Bundang Hospital
  • Gyeonggi-do, Korea, Republic of
    • Recruiting
    • Bundang Jesaeng Hospital
  • Gyeonggi-do, Korea, Republic of
    • Recruiting
    • Catholic University of Korea, Uijeongbu St. Mary's Hospital
  • Gyeonggi-do, Korea, Republic of
    • Recruiting
    • CHA Bundang Medical Center
  • Seoul, Korea, Republic of
    • Recruiting
    • Seoul National University Hospital
  • Seoul, Korea, Republic of
    • Recruiting
    • Samsung Medical Center
  • Suwon, Korea, Republic of
    • Recruiting
    • The Catholic university of Korea, St. Vincent's Hospital
  • Suwon, Korea, Republic of
    • Recruiting
    • Ajou University Hospital
  • Sŏngnam, Korea, Republic of
    • Recruiting
    • Gachon University, Donginchoen Gil Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Subject with Hepatitis B and liver cirrhosis displaying low viral load (HBV DNA titer <2,000 IU/mL (104 copies/mL))

Description

Inclusion Criteria:

• A subject who has consented to participate in this clinical trial
• A subject aged between ≥20 to ≤75 years old
• A subject with positive HBsAg for more than 24 weeks (may be confirmed by medical history)
• HBV DNA ≥26 IU/mL or ≤ 2,000 IU/mL at the time of screening

• A subject diagnosed with cirrhosis with one of the following:

  1. Subject with confirmed liver cirrhosis in the screening period or liver biopsy performed within 1 year from the time of screening (METAVIR score> 3, ISHAK score> 4)
  2. Two or more confirmed typical findings suggesting liver cirrhosis from imaging such as liver ultrasound and CT performed within 24 weeks of screening or during screening period (nodularity of the liver surface, atrophy of the inner right and left lobes, thickening of the left and tail lobes, hepatic portal system expansion of surrounding space, expansion of hepatic portal system (>1.3 cm) and splenomegaly (>12 cm))
  3. One or more confirmed typical findings suggesting liver cirrhosis from imaging such as liver ultrasound and CT performed within 24 weeks of screening or during screening period (nodularity of the liver surface, atrophy of the inner right and left lobes, thickening of the left and tail lobes, hepatic portal system expansion of surrounding space, expansion of hepatic portal system (>1.3 cm) and splenomegaly (>12 cm)) or findings including the following:
• Confirmed thrombocytopenia (<150,000/mm3) at the screening period or blood tests conducted within 24 weeks from the time of screening
• Confirmed identification of esophageal varicose veins or gastric varicose veins by endoscopy or CT performed within one year from the screening period or at screening
• Liver stiffness measurement (LSM)> 11.5 kilopascal (kPa) (F4) as a result of liver fibrosis scan, performed within 1 year from screening period or at screening

Exclusion Criteria:

• A subject with non compensated cirrhosis and any of the following:

  1. Serum bilirubin> 3 mg/dL
  2. Prothrombin time> 6 seconds prolonged or International Normalized Ratio (INR) >1.6
  3. Serum albumin <2.8 g/dL
  4. History of ascites, varicose bleeding, hepatorenal syndrome, hepatic encephalopathy (hepatic coma) requiring treatment within 5 years from screening
  5. Child-Pugh score ≥ 8
• A subject who have received interferon or other oral nucleic acid analogues (nucleos(t)ide analogues) (However, if the treatment duration was less than 30 days in the past and the treatment was treated 24 weeks before the screening, participation is possible)
• A subject diagnosed with liver cancer in the past or present
• Renal function decline (creatinine clearance <50 mL/min, estimated by the Cockcroft-Gault formula)
• A subject with serious concomitant diseases such as congestive heart failure, chronic kidney disease, blood disease, or malignant tumors in the past or present
• A subject infected with hepatitis C virus (HCV) or human immunodeficiency virus (HIV)
• A subject who consume excessive alcohol (men: 30g/day or more, women: 20g/day or more)
• A subject with liver diseases such as autoimmune hepatitis, hemochromatosis, or Wilson's disease
• Pregnant or breastfeeding women
• Previous organ transplant recipients
• A subject unable to complete the clinical trial or to have any medical condition that may interfere with the evaluation of the efficacy of this clinical trial

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
5-year Cumulative hepatocellular carcinoma incidence	Compare the difference in the 5-year cumulative incidence of hepatocellular carcinoma in patients with chronic hepatitis B and cirrhosis with entecavir and control	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Compare the difference in the 5-year incidence overall survival in patients with chronic hepatitis B and cirrhosis with entecavir and control	5 years
Incidence of ascites, esophageal, gastric variceal bleeding, hepatic encephalopathy (hepatic coma)	Compare the difference in the 5-year incidence of ascites/esophageal/gastric variceal bleeding/hepatic encephalopathy (hepatic coma) in patients with chronic hepatitis B and cirrhosis with entecavir and control	5 years
Incidence of virologic response, virologic breakthrough	Compare the difference in the 5-year incidence incidence of virologic response and virologic breakthrough in patients with chronic hepatitis B and cirrhosis with entecavir and control	5 years
Incidence of cirrhosis regression	Compare the difference in the 5-year incidence of cirrhosis regression in patients with chronic hepatitis B and cirrhosis with entecavir and control	5 years

Collaborators and Investigators

• Sponsor: CHA University
• Collaborators: Dong-A ST Co., Ltd.
• Investigators: Principal Investigator: SungKyu Hwang, MD, Principal Investigator

Study record dates

Study Major Dates

• Study Start (Actual): March 17, 2017
• Primary Completion (Anticipated): May 28, 2022
• Study Completion (Anticipated): August 26, 2022

Study Registration Dates

• First Submitted: November 22, 2020
• First Submitted That Met QC Criteria: November 22, 2020
• First Posted (Actual): November 30, 2020

Study Record Updates

• Last Update Posted (Actual): November 30, 2020
• Last Update Submitted That Met QC Criteria: November 22, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Liver Neoplasms; Enterovirus Infections; Picornaviridae Infections; Hepatitis B; Hepatitis; Carcinoma, Hepatocellular; Hepatitis A; Hepatitis B, Chronic; Hepatitis, Chronic
• Other Study ID Numbers: EN-REACH

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes