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

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ClinicalTrials.gov Identifier: NCT04199819
Recruitment Status : Not yet recruiting
First Posted : December 16, 2019
Last Update Posted : December 16, 2019
Sponsor:
Information provided by (Responsible Party):
James Yan Yue Fung, The University of Hong Kong

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.


Condition or disease Intervention/treatment Phase
Occult Hepatitis B Liver Transplant; Complications Drug: entecavir Not Applicable

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : January 1, 2020
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : December 31, 2022


Arm Intervention/treatment
HBsAg-negative recipients
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.
Drug: entecavir
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.
Other Name: antiviral therapy




Primary Outcome Measures :
  1. Proportion of HBsAg-negative recipients of an anti-HBc+ graft needing antiviral therapy [ Time Frame: 2 years ]
    Proportion of HBsAg-negative recipients of an anti-HBc+ graft needing antiviral therapy


Secondary Outcome Measures :
  1. Prevalence of occult hepatitis B infection in HBsAg-/anti-HBc+ donors [ Time Frame: 2 years ]
    Prevalence of occult hepatitis B infection in HBsAg-/anti-HBc+ donors



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04199819


Contacts
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Contact: James Fung, MD +852 22553830 jfung@gastro.hk

Sponsors and Collaborators
The University of Hong Kong
Investigators
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Principal Investigator: James Fung, MD The University of Hong Kong
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Responsible Party: James Yan Yue Fung, Principal Investigator, The University of Hong Kong
ClinicalTrials.gov Identifier: NCT04199819    
Other Study ID Numbers: occult HBV infection 01
First Posted: December 16, 2019    Key Record Dates
Last Update Posted: December 16, 2019
Last Verified: December 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by James Yan Yue Fung, The University of Hong Kong:
occult hepatitis b
liver transplantation
novel biomarkers
Additional relevant MeSH terms:
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Hepatitis A
Hepatitis B
Hepatitis
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Entecavir
Antiviral Agents
Anti-Infective Agents