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.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Small Research Grants (R03)
Project #
Application #
Study Section
Special Emphasis Panel (ZDK1-GRB-8 (M1))
Program Officer
Robuck, Patricia R
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Michigan Ann Arbor
Internal Medicine/Medicine
Schools of Medicine
Ann Arbor
United States
Zip Code