Medical Indications
for Liver Transplantation
March/April 2008
Despite great strides in surgical technique
and operative technologies, a variety of
challenging medical issues continue to
confront centers specializing in liver
transplantation. Chief among these are the
management of active HCV infection prior
to surgery, and the prevention of recurrent
liver disease and graft rejection in the
months following surgery.
Avoiding these threats, according to
Rajender
Reddy, MD, and Thomas
Faust, MD, of the Penn Transplant
Institute – where
combined liver transplant graft and patient
survival rates at one year exceed national
average rates by about 5 percent – involves a
concentrated, multidisciplinary effort to
optimize medical care for patients undergoing
liver transplantation.
Authors of The Clinician’s Guide to Liver
Disease (Slack, 2006), Drs. Reddy and Faust
have performed extensive research into chronic
viral hepatitis and other leading indications
for orthoptic liver transplantation (OLT).
At the Penn Transplant Institute, the findings
of these investigations have been applied to a
framework for the perioperative medical
management of transplant patients and to the
management of potentially intractable
complications in the postoperative period.
Penn has improved outcomes by tailoring
interventions to reflect the heterogeneity of the
transplant population. The majority of
patients in the liver transplant program at
Penn have chronic hepatitis
C (HCV) or
alcoholic liver disease; some have liver
cancer,
cholestatic hepatitis or other fatal conditions.
Given the continuing organ shortage, the
program strives to achieve an equitable
balance between these etiologies in the
transplant population.
The challenges inherent in optimizing
medical treatment in OLT are illustrated
by the treatment regimen for patients with
histological evidence of HCV infection
before and after surgery. Active HCV
infection is associated with posttransplantation
re-infection and graft
failure, and its presence mandates the use
of interferon-based therapies. Tolerance
for these drugs is typically low in patients
with HCV infection after transplantation as
a consequence of renal insufficiency and
other comorbidities that might be present.
“The
ideal candidate for therapy is someone who has
a positive HCV-RNA and abnormal ALT, with histologic
evidence of chronic hepatitis and absence of
decompensated liver disease."
– Rajender
Reddy, MD
Medical Director, Liver Transplantation |
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Patients with this
profile typically respond well to interferon and ribavirin,
the combination of drugs used to suppress viral
activity. The drugs are toxic, and rigorous
monitoring is necessary to minimize
complications, which may include anemia,
leucopenia and other side effects, as well as
drug interactions. Optimal dosing can be
maintained via patient education to promote
compliance and the addition of granulocyte
colony-stimulating factor or erythropoietin
when necessary.
Treatment of recurrent HCV infection in
the post-operative period is a paramount
concern, as well, says Dr. Faust, noting that
50 percent of liver recipients demonstrate
histological evidence of HCV-RNA within
the first year of surgery.
"Interferon and ribavirin can suppress
viral load in the majority of post-transplant
patients," said Dr. Faust, "but sustained
virologic clearance is uncommon."
To this end, current research at Penn is focusing on the
use of nucleoside analogues and other agents designed to
inhibit replication of the hepatitis C virus.
"With effective inhibition of HCV
replication," said Dr. Reddy, "the primary
indication for liver transplantation and the
prevailing threat to allograft failure would be
greatly diminished."
Moreover, Dr. Reddy observes, the
paradigm for liver transplantation would be
altered to permit greater access to organs for
patients with cancer, cholestatic hepatitis and
other compelling immediate needs.
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Referring Physicians: To speak with a Penn physician
or refer a patient, contact PennHealth through the secure online
referral form or by calling
1-800-789-PENN
(7366). |
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