The study is a first-of-its-kind, single-institution comparison of outcomes for both pediatric and adult patients undergoing liver transplantation for lethal genetic syndromes. Researchers found that children with genetic disorders that cause fibrosis, cirrhosis, and other liver conditions, which can affect other organs, have a good chance of still being alive five years, even 20 years after a liver transplant operation. Adults with these types of conditions also have high survival rates.
“If we had not transplanted these patients, long term, they
would have died,” said study lead author, Henrik Petrowsky, MD, who was
an attending transplant surgeon and assistant professor of surgery at
UCLA during the time the study was conducted.
Patients with genetic liver conditions are different from those
who developed liver diseases from a hepatitis C infection or
alcoholism. First, this patient population is less common. Dr.
Petrowsky estimates that only about 9 percent of liver transplants in
children and only 2 percent in adults are performed as a treatment to
correct genetic conditions. Second, the severity of genetic liver
disease may not be as obvious. Since donated livers are allocated
according to who needs them most, people with genetic liver diseases
often have to be given extra consideration when weighing how long they
can wait for a donor organ.
Although the genetic defect permeates every cell in the affected patient’s body,it expresses mainly in the liver. However, certain disorders could also affect other organs. During a transplant, when the old liver is replaced with a new one “it’s almost a form of gene therapy,” explains Dr. Petrowsky, who is now vice chair of the department of visceral and transplant surgery at the University Hospital Zurich in Switzerland. “The genetic defect is still in every cell, but since it’s mainly expressed in the liver, the genetic disorder is corrected by the transplanted liver which does not harbor the genetic defect.”
Dr. Petrowsky’s team wanted to evaluate the impact of the
transplant procedure on patients’ outcomes, especially because patients
families go through so much before a transplantable liver can be
procured.
Therefore, the investigators looked at patient records from the
UCLA liver transplant database for 74 children and 78 adults who had
received liver transplants between 1984 and 2012 to correct genetic
disorders. For 68 percent of those patients, the genetic disorder led
to cirrhosis, or scaring of the liver, making liver transplantation
their only hope for survival.
Five years later, 89 percent of children in the study were still alive, and 77 percent were still alive 20 years later. For adults, 73 percent were still alive after five years and 50 percent were still alive after 20 years.
“Without a transplant, the five-year survival rates are below 5
percent, depending on the severity of the liver disease,” Dr. Petrowsky
said.
Only one pediatric patient and one adult patient had a
recurrence of the underlying genetic disease. The pediatric patient
died 12 years after the transplant. The adult had another liver
transplant and was still alive 22 years later. “For certain genetic
conditions, replacing the liver is not enough,” Dr. Petrowsky explained,
because “other tissues and organs are expressing the mutated protein.
So the discussion now is should we do a combined liver and bone marrow
transplantation in these rare cases to improve the outcome?”
Only 13 percent of adult patients and 22 percent of pediatric
patients required another transplant. For pediatric patients, the
primary reasons for the additional procedure were blood clots in the
hepatic artery or the body rejected the new organ. The majority of
adults who needed another transplant had primary non-function, meaning
the transplanted organ simply didn’t work.
Despite the complications, Dr. Petrowsky said the high survival
rates also imply that liver transplantation is currently the best
available treatment for patients with genetic liver disease. “Liver
transplantation for lethal genetic syndromes represents a model of
personalized genomic medicine by providing gene therapy through solid
organ transplantation,” the authors wrote. Additionally, genetic
testing could be used to not only confirm the cause of liver disease,
but also predict it in people who have certain genetic markers. The
results of that finding could be used to guide treatment decisions.
The high survival rates also make up for the risks and the costs
of liver transplantation, which could be as high as $577,000 according
to the United Network of Organ Sharing.* “Transplantation saves
lives,” Petrowsky said. “Many of the patients go on to live a good
life. We have pediatric patients who were transplanted as infants. If
they had not received a transplant, they would not have survived. Many
of them are alive more than 20 years after transplant, are married,
and some of them have even kids, and have great careers,” he concluded.
Other participants in the study included F. Charles Brunicardi,
MD, FACS; Voon Meng Leow, MD; Robert S. Venick, MD; Vatche Agopian, MD;
Fady M. Kaldas, MD; Ali Zarrinpar, MD, PhD; Daniela Markovic, MS; Sue
V. McDiarmid, MD; Johnny C. Hong, MD, FACS, Douglas G. Farmer, MD,
FACS; Jonathan R. Hiatt, MD, FACS, and Ronald W. Busuttil, MD, FACS.
* Financing a Transplant. United Network for Organ Sharing. Available at http://www.transplantliving.org/before-the-transplant/financing-a-transplant/the-costs/. Accessed April 4, 2013.
Source: American College of Surgeons
