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Research
You
can call (866) 548-3783 toll-free to make a referral to
researchers at the University of Florida.
The
liver transplant team realizes that surgery is just one
step in the patient's long journey. UF 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 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 (HCV)
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 ~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 is actively
engaged in multiple research projects that focus on understanding
the mechanisms of how HCV causes liver disease and strategies
to improve outcomes.
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New
antiviral strategies
: We are currently evaluating
the efficacy of pegylated interferons, immune-modulating
agents and virus-specific molecules to eradicate HCV.
-
Prevention
of graft re-infection
:
We are evaluating the ability of HCV immunoglobulins to
prevent the donor liver from becoming re-infected with
HCV at the time of transplant.
-
Anti-fibrotic
drug development
:
We are participating in a large, multicenter 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 HCV disease recurrence
after liver transplantation.
Hepatitis
B virus
Before the introduction of effective immunoprophylaxis,
hepatitis B virus (HBV) 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 HBV 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 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, 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 efforts to:
- Minimize
rejection
- Prevent
kidney damage
- Minimize
effects on hypertension, diabetes and hyperlipidemia
Hepatocellular
carcinoma
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 < 5cm or up
to 3 foci each one < 3 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 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 (QOL)
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.
Living
Donor Liver Transplantation
In response to a decreasing organ donor pool, living
donor liver transplantation (LDLT) has undergone widespread
use at many transplant centers. This allows patients to
bypass the UNOS waiting list by having a family member or
close friend donate half of his/her liver. Right lobe adult-to
adult LDLT is a recently developed procedure, but hundreds
have already been performed in the US and are currently
being performed at UF. Not only does LDLT avoid the lengthening
waiting period for a cadaveric transplant, it greatly reduces
the ischemic period of the transplanted organ, allows for
more time for evaluation of the donor and changes the operation
from an emergency into a scheduled procedure. Because of
the liver’s unique ability to regenerate, both the
donor and the recipient’s livers grow back to full
size in approximately 3 months following the surgery. LDLT
also provides a unique area to evaluate many research interests.
Just a few are highlighted below:
- Factors
involved in liver regeneration
- Stem
cell repopulation of the liver
- Effect
of HLA match/mismatch on disease recurrence
- QOL
and psychosocial aspects of liver donation
Statistics
Success rate and various other statistics regarding the
Shands Transplant Center at UF are available from the Scientific
Registry of Transplant Recipients at ustransplant.org.
Contact
For more information about the Shands Transplant Center
at UF, call us toll-free at (866) 548-3783.
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