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Detecting Occult HBV Infection in Liver Donors Positive for Antibody to Hepatitis B Core Antigen (Anti-HBc) (OBI)

Primary Purpose

Occult Hepatitis B, Liver Transplant; Complications

Status
Recruiting
Phase
Not Applicable
Locations
Hong Kong
Study Type
Interventional
Intervention
entecavir
Sponsored by
The University of Hong Kong
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Occult Hepatitis B focused on measuring occult hepatitis b, liver transplantation, novel biomarkers

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 1. Patient age ≥18 years undergoing liver transplantation
  • 2. Donor HBsAg- and anti-HBc+

Exclusion Criteria:

  • 1. Recipient of multiple solid organ transplants
  • 2. Patient undergoing re-transplantation

Sites / Locations

  • The University of Hong KongRecruiting

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

HBsAg-negative recipients

Arm Description

Recipients who are HBsAg-negative will undergo a panel of test to detect HBV viral markers. In addition, real-time PCR will be used to determine the presence of intrahepatic HBV DNA and cccDNA on the explant histology. Patients with evidence of OBI, as characterized by any one positive biomarker (serum HBV DNA, serum HBV RNA, serum HBcrAg, intrahepatic HBV DNA, intrahepatic cccDNA) in either the donor or recipient, will be commenced on life-long oral nucleos(t)ide analog therapy as part of their routine antiviral prophylaxis. For those without evidence of OBI, that is, negative for all biomarkers, no antiviral prophylaxis will be given.

Outcomes

Primary Outcome Measures

Proportion of HBsAg-negative recipients of an anti-HBc+ graft needing antiviral therapy
Proportion of HBsAg-negative recipients of an anti-HBc+ graft needing antiviral therapy

Secondary Outcome Measures

Prevalence of occult hepatitis B infection in HBsAg-/anti-HBc+ donors
Prevalence of occult hepatitis B infection in HBsAg-/anti-HBc+ donors

Full Information

First Posted
December 3, 2019
Last Updated
May 17, 2022
Sponsor
The University of Hong Kong
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1. Study Identification

Unique Protocol Identification Number
NCT04199819
Brief Title
Detecting Occult HBV Infection in Liver Donors Positive for Antibody to Hepatitis B Core Antigen (Anti-HBc)
Acronym
OBI
Official Title
The Use of Novel Hepatitis B Virus (HBV) Biomarkers to Detect Occult HBV Infection in Liver Donors Positive for Antibody to Hepatitis B Core Antigen (Anti-HBc) in Liver Transplantation
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Recruiting
Study Start Date
January 1, 2022 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The University of Hong Kong

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
After LT, long-term immunosuppressive therapy is required to prevent organ rejection. Therefore, for organs which may harbour OBI, there is a risk of reactivation which may result in liver graft failure. As a consequence, all patients who receive an anti-HBc positive graft will receive antiviral prophylaxis. Currently, all such patients will be commenced on life-long entecavir, which is highly effective in preventing reactivation.2 One major disadvantage of using such a blanket approach is that a significant proportion of anti-HBc donors may not actually have underlying occult HBV infection, and recipients of such grafts may not require lifelong antiviral therapy. Current markers such as HBsAg and HBV DNA are not sensitive enough to detect the presence of OBI. This is the first trial proposed to look at the efficacy of these novel HBV biomarkers in identifying occult HBV infection when used in combination, and to identify patients who will not need long term antiviral prophylaxis.
Detailed Description
Liver transplantation (LT) is potential curative for those with liver failure or hepatocellular carcinoma. In Hong Kong, where HBV infection remains endemic, chronic HBV (CHB) infection remains the leading indication for LT. Due to the low rate of organ donation, hepatitis B surface antigen (HBsAg) negative donors who are anti-HBc positive are frequently used. There is potential for anti-HBc positive donors to harbor OBI, defined as the presence of liver and/or serum HBV DNA without serological evidence of chronic infection (HBsAg negative).1 Hence, there is a risk of transmitting HBV infection when these grafts are transplanted to HBsAg negative recipients (de novo HBV infection). Nonetheless, anti-HBc positive donors represent an important source of organs in HBV endemic area, including Hong Kong, with a high prevalence rate (37%) of HBsAg negative but anti-HBc positive population. After LT, long-term immunosuppressive therapy is required to prevent organ rejection. Therefore, for organs which may harbour OBI, there is a risk of reactivation which may result in liver graft failure. As a consequence, all patients who receive an anti-HBc positive graft will receive antiviral prophylaxis. Currently, all such patients will be commenced on life-long entecavir, which is highly effective in preventing reactivation.2 One major disadvantage of using such a blanket approach is that a significant proportion of anti-HBc donors may not actually have underlying occult HBV infection, and recipients of such grafts may not require lifelong antiviral therapy. Current markers such as HBsAg and HBV DNA are not sensitive enough to detect the presence of OBI. More recently a panel of novel HBV biomarkers have emerged.3,4 These include quantification of anti-HBc, HBV RNA, hepatitis B core-related antigen (HBcrAg), and intrahepatic covalently closed circular DNA (cccDNA) levels. Some of these markers have been associated with OBI, and may predict HBV reactivation for immunosuppressed patients.5,6 This is the first trial proposed to look at the efficacy of these novel HBV biomarkers in identifying occult HBV infection when used in combination, and to identify patients who will not need long term antiviral prophylaxis

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Occult Hepatitis B, Liver Transplant; Complications
Keywords
occult hepatitis b, liver transplantation, novel biomarkers

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
HBsAg-negative recipients
Arm Type
Other
Arm Description
Recipients who are HBsAg-negative will undergo a panel of test to detect HBV viral markers. In addition, real-time PCR will be used to determine the presence of intrahepatic HBV DNA and cccDNA on the explant histology. Patients with evidence of OBI, as characterized by any one positive biomarker (serum HBV DNA, serum HBV RNA, serum HBcrAg, intrahepatic HBV DNA, intrahepatic cccDNA) in either the donor or recipient, will be commenced on life-long oral nucleos(t)ide analog therapy as part of their routine antiviral prophylaxis. For those without evidence of OBI, that is, negative for all biomarkers, no antiviral prophylaxis will be given.
Intervention Type
Drug
Intervention Name(s)
entecavir
Other Intervention Name(s)
antiviral therapy
Intervention Description
Patients with evidence of OBI, as characterized by any one positive biomarker (serum HBV DNA, serum HBV RNA, serum HBcrAg, intrahepatic HBV DNA, intrahepatic cccDNA) in either the donor or recipient, will be commenced on life-long oral nucleos(t)ide analog therapy as part of their routine antiviral prophylaxis.
Primary Outcome Measure Information:
Title
Proportion of HBsAg-negative recipients of an anti-HBc+ graft needing antiviral therapy
Description
Proportion of HBsAg-negative recipients of an anti-HBc+ graft needing antiviral therapy
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Prevalence of occult hepatitis B infection in HBsAg-/anti-HBc+ donors
Description
Prevalence of occult hepatitis B infection in HBsAg-/anti-HBc+ donors
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 1. Patient age ≥18 years undergoing liver transplantation 2. Donor HBsAg- and anti-HBc+ Exclusion Criteria: 1. Recipient of multiple solid organ transplants 2. Patient undergoing re-transplantation
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
James Fung, MD
Phone
+852 22553830
Email
jfung@gastro.hk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
James Fung, MD
Organizational Affiliation
The University of Hong Kong
Official's Role
Principal Investigator
Facility Information:
Facility Name
The University of Hong Kong
City
Hong Kong
Country
Hong Kong
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
James Fung, MD
Phone
22553830
Email
jfung@gastro.hk
First Name & Middle Initial & Last Name & Degree
Man-Fung Yuen, DSc, MD, PhD
Phone
22553989
Email
mfyuen@hku.hk
First Name & Middle Initial & Last Name & Degree
James Fung, MD

12. IPD Sharing Statement

Learn more about this trial

Detecting Occult HBV Infection in Liver Donors Positive for Antibody to Hepatitis B Core Antigen (Anti-HBc)

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