Adefovir Plus Vaccination in Transplant Patients Without Hepatitis B That Receive a Core Antibody Positive Liver

Study Overview
=================
Brief Summary
-----------------
The primary purpose of this study is to evaluate the efficacy of adefovir (ADV) in preventing de novo Hepatitis B in patients who receive Hepatitis B core antibody (HBcAb) positive grafts but who are not Hepatitis B Surface antigen (HBsAg) positive prior to transplant (Hepatitis B naive patients). The second objective is to evaluate the efficacy of accelerated vaccination with Hepatitis B in inducing innate immunity, thereby obviating the need for life-long antiviral therapy.

Detailed Description
-----------------
The investigators will conduct a prospective, open-label study of Hepatitis B naive patients who received HBcAb + livers and adefovir prophylaxis post-transplant. At one year to 18 months following transplantation, all study patients will then be vaccinated with standard Hepatitis B vaccine at double dose on a monthly basis for three months, at which point they will be tested for Hepatitis B surface antibody (HBsAb). Any study patients that have developed a sufficient antibody response (HBsAb >500 IU) will be given the option to discontinue anti-viral treatment in a monitored setting.

Official Title
-----------------
Prevention of de Novo Hepatitis B Infection With Adefovir Dipivoxil (ADV) and Hepatitis B Vaccination in HBsAg Seronegative Recipients of Liver Grafts From Hepatitis B Core Antibody Positive (HBcAb+) Donors

Conditions
-----------------
Hepatitis B, Liver Transplantation

Intervention / Treatment
-----------------
* Drug: Adefovir dipivoxil and hepatitis B vaccination


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Recipients who do not have evidence of hepatitis B surface antigen, regardless of HBcAb and HBsAb status, who: received liver transplantation with hepatitis B core antibody positive (and HBsAg negative) grafts, received adefovir treatment post transplantation, and who have not reached the 18 month post transplantation time period. Exclusion Criteria: Recipients with hepatitis B surface antigen positivity prior to liver transplant. Grafts from hepatitis B surface antigen positive patients. Previous intolerance to ADV therapy Recipients with pre-transplant creatinine > 1.6 mg/dL Patients younger than 21 years of age Patients who are pregnant or breastfeeding

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ADV plus hepatitis B vaccination<br>Adefovir dipivoxil and hepatitis B vaccination: All subjects will receive adefovir 10mg po daily, or adjusted for renal function and an option for Hepatitis B vaccination, double dose. | Drug: Adefovir dipivoxil and hepatitis B vaccination<br>* Adefovir 10mg po daily, or adjusted for renal function and option for Hepatitis B vaccination, double dose<br>* Other names: Hepsera;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Development of de Novo Hepatitis B Infection After Transplant With a Core Antibody Positive Liver | Determined by positive hepatitis B serology (tests positive for HBsAg) and HBV DNA viral load (>40 IU/mL). | Standard of care visits post-transplant for 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients With a Sustained Hepatitis B Surface Antibody Titer > 500 IU/mL Prior to and After Vaccination |  | 12-18 months post transplant | 
| Proportion of Patients Who Develop de Novo Hepatitis B Infection Post ADV Withdrawal, Which Will be Assessed at 6 Months Post Withdrawal |  | Six months after hepatitis B vaccination (2 years post transplant) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Vaccination, Immunocompromised Host, Antiviral Agents, Drug Resistance, Viral, Resource Allocation