Hepatitis B, Liver Transplantation
Conditions
Keywords
Vaccination, Immunocompromised Host, Antiviral Agents, Drug Resistance, Viral, Resource Allocation
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.
Interventions
DRUGAdefovir dipivoxil and hepatitis B vaccination
Adefovir 10mg po daily, or adjusted for renal function and option for Hepatitis B vaccination, double dose
Sponsors
Gilead Sciences
Columbia University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Recipients who do not have evidence of hepatitis B surface antigen, regardless of HBcAb and HBsAb status, who: 1. received liver transplantation with hepatitis B core antibody positive (and HBsAg negative) grafts, 2. received adefovir treatment post transplantation, and 3. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Development of de Novo Hepatitis B Infection After Transplant With a Core Antibody Positive Liver | Standard of care visits post-transplant for 2 years | Determined by positive hepatitis B serology (tests positive for HBsAg) and HBV DNA viral load (\>40 IU/mL). |
Secondary
| Measure | 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) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ADV Plus Hepatitis B Vaccination Group This group included recipients of Hepatitis B Core Antibody Positive livers who are negative for Hepatitis B infection. | 16 |
| Total | 16 |
Baseline characteristics
| Characteristic | ADV Plus Hepatitis B Vaccination Group |
|---|---|
| Age, Continuous | 54 years STANDARD_DEVIATION 11 |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 16 |
| other Total, other adverse events | 0 / 16 |
| serious Total, serious adverse events | 0 / 16 |
Outcome results
Primary
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).
Time frame: Standard of care visits post-transplant for 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ADV Plus Hepatitis B Vaccination Group | Development of de Novo Hepatitis B Infection After Transplant With a Core Antibody Positive Liver | 5 Participants |
Secondary
Proportion of Patients Who Develop de Novo Hepatitis B Infection Post ADV Withdrawal, Which Will be Assessed at 6 Months Post Withdrawal
Time frame: Six months after hepatitis B vaccination (2 years post transplant)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ADV Plus Hepatitis B Vaccination Group | Proportion of Patients Who Develop de Novo Hepatitis B Infection Post ADV Withdrawal, Which Will be Assessed at 6 Months Post Withdrawal | 3 Participants |
Secondary
Proportion of Patients With a Sustained Hepatitis B Surface Antibody Titer > 500 IU/mL Prior to and After Vaccination
Time frame: 12-18 months post transplant
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ADV Plus Hepatitis B Vaccination Group | Proportion of Patients With a Sustained Hepatitis B Surface Antibody Titer > 500 IU/mL Prior to and After Vaccination | 2 Participants |