PITTSBURGH, November 4, 1998 — Livers from hepatitis B positive donors were safely transplanted and a combination drug treatment prevented infection in recipients of those livers, a University of Pittsburgh Medical Center (UPMC) researcher will report at the 49th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Chicago Nov. 6–10. The results of the preliminary study are among more than 30 presentations by UPMC researchers, including three singled out by the AASLD for their scientific merits and study design.
In the face of a chronic shortage of organ donors, surgeons must often consider transplanting organs that may be considered less optimal or high risk. For example, if the only option available to save a patient’s life is to transplant a liver from a donor who tests positive for hepatitis B (anti-HBc positive), a surgeon may do so even if it places the recipient at an increased risk for becoming infected with the virus. Post-transplant hepatitis B infection, which is usually evident within six months, is difficult to treat and can eventually lead to cirrhosis of the transplanted liver, thus requiring a second transplant.
But according to the UPMC study, a combination therapy of hepatitis B immune globulin (HBIG) and lamivudine has the potential to stave off post-transplant infection in patients not immune to hepatitis B who receive hepatitis B positive livers. Twelve patients who received the combination therapy, which started during the transplant operation and continued for 18 months, all continue to be free of infection between five and 25 months post-transplant, according to the study’s lead author, Andrew Bonham, M.D., assistant professor of surgery at the Thomas E. Starzl Transplantation Institute . Four of these patients, who were ICU-bound before their transplants, had never been exposed to hepatitis (anti-HBs negative) and had no immunity to the virus (anti-HBc negative). Eight others, most of whom were also listed in the most urgent status categories, had previously been exposed to the virus but had not developed immunity.
One patient received only HBIG therapy because in 1996, at the time of his transplant, lamivudine was not available for these patients. The patient, who had not been exposed and had no immunity, became infected with the virus six months after transplantation.
The results of the study will be presented Sunday, Nov. 8, by S. Forrest Dodson, M.D., assistant professor of surgery at the Starzl Transplantation Institute.
Three other studies being presented by UPMC researchers will be featured as AASLD President’s Choice Posters. In reviewing abstracts submitted to the AASLD, a committee assigned scores to determine which ones would be accepted for poster presentation at the meeting, and those receiving scores that placed them in the top 10 percent were given the special recognition. Their results are as follows:
Drug Combination May Prove Effective to Prevent Recurrence of Hepatitis C After Transplantation
Hepatitis C is the most common indication for liver transplantation, yet it recurs in almost all patients after transplantation and cannot be successfully treated, even with alpha-interferon. A preliminary study of 20 liver transplant recipients who were treated with a combination of ribavirin and interferon for a year following their transplants suggests this drug regimen can be effective in eradicating the virus and be safely tolerated by patients. Thirteen patients completed the one-year treatment study conducted at the UPMC. Four patients did not respond to therapy as measured by detectable active virus in their blood. But in nine patients evidence of the virus disappeared, at least for the duration of the therapy, Dr. Dodson will report Saturday, Nov. 7. Five patients relapsed within one month of completing the one-year study, but four remained free of the virus three to five months after stopping the drug treatment. Dr. Dodson suggests earlier treatment, before significant liver damage has occurred, may be more effective.
Infants to Seniors: Seven Years’ Follow-up of 1,000 Liver Transplant Patients Taking Tacrolimus Indicates Children Have Best Survival
Children between the ages of 2 and 18 had the best survival rates among 1,000 liver transplant patients whose immunosuppression was managed with tacrolimus (formerly known as FK506 and now marketed as Prograf), Ashok Jain, M.D., assistant professor of surgery at the Starzl Transplantation Institute will report Sunday, Nov. 8. Researchers at the UPMC followed patients, ranging from infants to seniors, who were transplanted between 1989 and 1992, to determine their long-term survival using the anti-rejection drug developed at the UPMC. With 84 percent of the patients being hospital-bound at the time of transplantation, the overall one-year and seven-year patient survival was 84 percent and 66 percent, respectively. Survival rates for a subgroup of 91 children remained at 91 percent after seven years, the highest among the different age groupings. Survival rates for the other groups were also reported: 75 infants had one-year survival of 83 percent and seven-year survival of 77 percent; 630 adults between the ages of 18 and 60 had survival rates at one and seven years of 85 and 65 percent, respectively; 70 percent of the 204 patients older than 60 were alive at one year, and 49 percent were alive after seven years. Dr. Jain says that steroids were successfully weaned in about 70 percent of all the patients.
Liver Rejection Can Be Managed Long-Term in Children Switched to Tacrolimus
Children suffering from organ rejection or complications of their anti-rejection drugs can be successfully converted to tacrolimus with long-term benefits, according to a study of 85 liver transplant patients who were switched from cyclosporine to tacrolimus between 1989 and 1994. Children with acute rejection had better outcomes than those with chronic rejection, Jorge Reyes, M.D., associate professor of surgery at the Thomas E. Starzl Transplantation Institute and director of pediatric transplantation at Children’s Hospital of Pittsburgh, will report Sunday, Nov. 8. Patient and graft survival six years after being converted to tacrolimus was 91 and 87 percent, respectively, for those with acute rejection. But for children with chronic rejection, patient survival was 67 percent, and graft survival was 57 percent at six years. The advantages of tacrolimus (formerly known as FK506 and now marketed as Prograf) were also evident by virtue of the fact that 84 percent of the patients could be weaned off steroids, thus eliminating many of the side effects specific to children, such as stunted growth and puffy cheeks that give the appearance of a moon face. Fifty-eight percent were also able to be taken off antihypertensive medications.
The scientific meeting will also include a day-long series of debates on "Clinical and Administrative Controversies in Liver and Pancreas Transplantation" scheduled for Saturday, Nov. 7. The UPMC, which has strongly advocated for changes in the organ allocation system, will participate in two of three debates on this subject.