The liver transplant team realizes that surgery is just one step in the patient's long journey. University of Florida researchers play an important role in fostering an environment that blends sensitivity and science in the quest for answers to tough transplant questions.
Goal
Researchers at UF Health aim to identify improved therapies for liver transplant patients and transfer them from the laboratory to the bedside. Major focal points include clinical and basic science studies related to the pathogenesis of viral hepatitis and related treatments.
Hepatitis C Virus
End-stage liver disease secondary to hepatitis C virus is the leading indication for liver transplantation in the United States. Unfortunately, viral recurrence is universal following liver transplantation and recurrence of hepatitis C is responsible for allograft failure leading to death or graft loss in more than 10 percent of recipients by the fifth postoperative year. These observations suggest that disease from HCV is more aggressive in patients who are chronically immunosuppressed than in those with an intact immune response. An understanding of the mechanisms of disease injury in these circumstances may allow for improved organ allocation and patient management. In the setting of an increasingly acute shortage of cadaveric donor organs, the need to optimise outcomes following liver transplantation for hepatitis C has become one of the most pressing issues facing the transplant community. The Liver Transplant Program at UF Health is actively engaged in multiple research projects that focus on understanding the mechanisms of how HCV causes liver disease and strategies to improve outcomes.
- New antiviral strategies: We are currently evaluating the efficacy of pegylated interferons, immune-modulating agents and virus-specific molecules to eradicate hepatitis C virus.
- Prevention of graft re-infection : We are evaluating the ability of hepatitis C virus immunoglobulins to prevent the donor liver from becoming re-infected with hepatitis C virus at the time of transplant.
- Anti-fibrotic drug development : We are participating in a large, multi-center trial to evaluate drugs that may reverse fibrosis within the liver. Subjects with very advanced disease are being enrolled, with the ultimate goal to avoid the need for liver transplantation.
- Immunopathogenesis : Multiple basic science efforts are underway to better understand the factors that lead to hepatitis C virus disease recurrence after liver transplantation.
Hepatitis B Virus
Before the introduction of effective immunoprophylaxis, hepatitis B virus recurrence was routine after liver transplantation and accounted for significant graft loss and patient death. Fortunately, recent recognition of the impact of the level of hepatitis B virus replication before transplant and the protective effect of high dose hepatitis B immunoglobulin (HBIG) have led to effective measures to prevent graft reinfection by HBV.
Currently, UF Health is actively involved in studies to evaluate the role of nucleoside analogues in treating active disease and in the optimal use of HBIG. These strategies have allowed us to routinely perform successful transplantation for those with hepatitis B.
- Prevention of disease recurrence
- Treatment of active disease
Immunosuppression Strategies
Immunosuppression strategies in liver transplantation fall into the three time periods of initial (induction), maintenance and treatment of acute and chronic rejection. Many immunosuppressant agents are used for these periods after liver transplantation and all have unique pharmacology, side effects and toxicity. At UF Health, the transplant team is engaged at tailoring the immunosuppressive treatment to best fit the individual needs of each patient. Current research focus is aimed at the following efforts:
- Minimize rejection
- Prevent kidney damage
- Minimize effects on hypertension, diabetes and hyperlipidemia
Liver Cancer
Many advances have been achieved during the last decade in the management of patients with liver cancer. The refinement of imaging techniques and the better knowledge of the biology of this neoplasm have facilitated the establishment of useful criteria to select patients for transplantation. Following a strict selection policy (solitary tumors less than five cm or up to three foci each one less than three cm) patients with liver cancer may achieve the same survival as non-neoplastic subjects. Currently, the main problem is how to diminish the risk of tumor progression while waiting for a liver. Ongoing studies at UF Health are exploring new treatment options that will hopefully succeed in preventing disease progression and improve patient outcomes.
- Treatment : A multispecialty team is engaged in delivering “anti-tumor” care to patients with liver cancer. Treatment strategies range from currative resection to radiofrequency ablation and chemoembolization of the tumors. Ultimately, liver transplantation remains the final treatment option.
- Prevention of recurrence after transplant : We are currently evaluating the use of new immunosuppressive agents that may inhibit tumor growth and decrease the risk of tumor recurrence after transplantation
Quality of Life
UF clinical and health psychologists are assessing the effect that liver transplantation has on quality of life. The results have indicated dramatic improvements in physical and social functioning, degree of bodily discomfort and vitality post-surgery. These changes were noticeable in as little as six months after transplantation. In addition, current research interests are also focusing on the stress levels of family members and children of the transplant recipient.