Hepatitis B accounts for 4000 to 5000 deaths per year in the United States. Previous results with liver transplantation (OLT) for hepatitis B were poor with recurrence rates of greater than 80 percent. Recent studies found that continuous high dose HBIG and lamivudine monotherapy can decrease the rate of recurrent hepatitis B to less than 20 percent. Unfortunately, both therapies have to be administered indefinitely. However, HBIG is very expensive (30,000 dollars-50,000/dollars/yr), lamivudine is significantly more economical (greater than 1,500/dollars yr) but breakthrough infection due to resistant mutants has been observed in 20 percent of patients 1 year post-OLT. To date, there has been no report comparing HBIG with lamivudine or other new antiviral agents in the prevention of recurrent hepatitis B post-OLT. It is possible that combination of HBIG and lamivudine or combination antiviral therapy may further reduce the rate of recurrence and permit a shorter duration of maintenance prophylaxis. This proposal is for a planning grant in preparation for an R01 application to support a multi- center clinical trial to compare the long-term safety, efficacy and cost-effectiveness of existing therapies, singly or in combination in the prevention of recurrent hepatitis B post-OLT. A multi-center study is needed to have a sufficiently large sample size for definitive conclusions. The long-term goal of this study is to establish a safe and effective therapy that will completely prevent recurrent hepatitis B post-OLT.
The specific aims of the present proposal are to (1) review the world- wide data on existing therapies in the prevention of recurrent hepatitis B post-OLT; (2) to develop protocol for a prospective, randomized multi- center clinical trial to determine the most cost-effective therapy for the prevention of recurrent hepatitis B post-OLT; and (3) to develop the necessary infra-structure to ensure the success of the clinical trial. The planning study will be divided into three phases. Phase I will focus on the development of a draft protocol for the clinical trial and establishment of a data co-ordination center, a communication web page, and a central repository for blood and tissue samples. Phase 2 will be devoted to finalizing the clinical trial protocol, developing manual of operations for data and sample collection and transfer, and preparing for R01 grant submission. Phase 3 will concentrate on standardizing management of patients on the waiting list for OLT, and training of personnel on the utilization of data co-ordination center, central repository and central testing laboratories.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Small Research Grants (R03)
Project #
5R03DK054595-02
Application #
2906304
Study Section
Special Emphasis Panel (ZDK1-GRB-8 (M1))
Program Officer
Robuck, Patricia R
Project Start
1998-09-30
Project End
2001-01-31
Budget Start
1999-09-30
Budget End
2001-01-31
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109