Effect of Entecavir Versus Tenofovir on HBV DNA Level in Peripheral Blood Mononuclear Cells

December 13, 2021 updated by: MAOmar, Assiut University

Comparative Study of the Effect of Entecavir Versus Tenofovir on the Presence of HBV DNA in the Peripheral Blood Mononuclear Cells in Chronic Hepatitis B Patients

Liver disease associated with persistent hepatitis B virus (HBV) infection remains an important public health problem with significant morbidity and mortality. In spite of the existence of an effective vaccine, worldwide approximately 260 million people are chronic HBV surface antigen (HBsAg) carriers and current treatment with interferon and/or nucleoside analogues (NA) is not able to achieve a complete cure.

The key obstacle to HBV eradication is the persistence of HBV DNA in the nuclei of infected hepatocytes, either integrated into the host genome or as a covalently closed circular DNA (cccDNA) episomal form.

While HBV integration is rare and its clinical implications still require investigation, cccDNA plays an essential role in the long-term persistence of HBV infection and can often be detected even following NA therapy and HBsAg seroconversion.

Since quantification of cccDNA in infected hepatocytes requires invasive liver biopsy, more accessible tissues, such as serum or peripheral blood mononuclear cells (PBMCs) have been investigated in different patient populations.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Some reports have shown that cccDNA in serum is a marker of off-treatment virological relapse, whereas others have not found cccDNA in the serum of chronic hepatitis B patients.

Some investigators speculate that PBMCs support HBV replication only partially, with linear and circular relaxed HBV DNA but not cccDNA formed in these cells, while others have detected cccDNA in PBMCs and/or plasma in a variable proportion of patients with chronic and occult HBV infection.

Although hepatocytes are recognized as the main target of HBV infection, HBV and other members of the hepadnaviral family, such as woodchuck hepatitis virus (WHV), have significant lymphotropic properties.

Hepadnaviral infection of lymphoid cells is an important mechanism by whitch virus escapes immune recognition and lymphoid reservoirs, particularly those harbouring drug-resistant HBV, may be the key to develop antiviral resistance.

Positive detection rate of HBV-DNA in neutrophils of chronic hepatitis B patients was 30.95%, After treatment of adefovir, the positive rate of HBV-DNA in neutrophils of chronic hepatitis B patients was 9.52% acting as asource of extrahepatic occult infection.

In liver transplant recipients, HBV in peripheral blood mononuclear cells has been implicated in graft reinfection with a specific lymphoid cell derived viral variant.

Additionally HBV intrauterine infection was primarily caused by maternal to fetal peripheral blood mononuclear cells transport in the second trimester of pregnancy.

The goal of treatment for chronic hepatitis B is to prevent liver disease progression and improve survival by long-term suppression of hepatitis B virus replication in a sustained manner.

A functional HBV cure, defined as a sustained hepatitis B surface antigen loss or seroconversion based on assays with a lower limit of HBsAg detection of 0.05 IU/mL, is a rare event in the natural history of chronic hepatitis B that is associated with a reduced risk of HCC.

Complete HBV cure is defined as an elimination of cccDNA together with durable HBsAg loss and undetectable serum HBV-DNA. Although liver biopsy is needed to measure intrahepatic cccDNA activity, serum biomarkers that reflect cccDNA levels are needed instead. Such as HBV RNA, hepatitis B core-related antigen, and/or quantitative HBsAg have been investigated. Quantification and ratio of large and middle proteins of HBsAg also showed specific patterns across different phases of hepatitis B that would predict the viral activity.

Entecavir (ETV) or tenofovir disoproxititis fumarate (TDF) are recommended as first line therapy in the treatment of naïve chronic hepatitis B because of their higher antiviral potency and higher genetic barriers than other antiviral agents.

In reality, ETV and TDF showed high virological responses of up to 93% and 100%, respectively, and a rare genotypic resistance of only 1.2% and 0%, respectively, during the 5- year follow-up in a cohort study.

In a study evaluating Dynamic changes of HBV-DNA in serum and peripheral blood mononuclear cells of chronic hepatitis B patients, concluded that HBV-DNA exists in PBMCs even after 48 weeks of lamivudine treatment that may reinfect hepatocytes again and cause the relapse of hepatitis.

Coffin., et al 2011; suggested that hepatitis B virus in lymphoid cells may be more resistant to antiviral therapy leading to a differential rate of HBV variant secretion in serum or plasma. Furthermore, HBV quasispecies diversity in liver correlated with antiviral drug resistance and this may have implications for the emergence of dominant resistant HBV variants over time.

Study Type

Observational

Enrollment (Anticipated)

100

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Mohamed Zakaria Ali Abu-Rahma, Assistent professor
  • Phone Number: 00201013443702
  • Email: mzaburahma@yahoo.com

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

All patients with chronic HBV receiving entecavir or tenofovir with sustained virological response for at least 2 years.

Description

Inclusion Criteria:

  1. Patients with chronic HBV
  2. Receiving anti-HB viral therapy (Entecavir or Tenofovir)
  3. Compliant on treatment
  4. Sustained virological response for at least 2 years

Exclusion Criteria:

  1. Patients co-infected with hepatitis C virus
  2. Less than 18 years old patients
  3. Cirrhotic patients
  4. Non compliant patients

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Only
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Entecavir group
Other: Detection of HBV-DNA in Peripheral Blood Mononuclear cells
Detection of HBV-DNA level in Peripheral Blood mononuclear cells
Tenofovir group
Other: Detection of HBV-DNA in Peripheral Blood Mononuclear cells
Detection of HBV-DNA level in Peripheral Blood mononuclear cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Compare the Effect of Entecavir versus Tenofovir on the Presence of HBV DNA in the Peripheral Blood Mononuclear Cells in Chronic Hepatitis B Patients
Time Frame: 1 week
Measurment of HBV-DNA level in Peripheral Blood Mononuclear cells
1 week

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assiut University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

February 1, 2022

Primary Completion (Anticipated)

February 1, 2023

Study Completion (Anticipated)

May 1, 2023

Study Registration Dates

First Submitted

December 13, 2021

First Submitted That Met QC Criteria

December 13, 2021

First Posted (Actual)

December 23, 2021

Study Record Updates

Last Update Posted (Actual)

December 23, 2021

Last Update Submitted That Met QC Criteria

December 13, 2021

Last Verified

December 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CSEEVTPHDPBMCCHBP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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